Radiology of Infectious and Inflammatory Diseases - Volume 3: Heart and Chest [1st ed. 2023] 9819946131, 9789819946136

Table of contents :
Editorial Board of Radiology of Infectious and Inflammatory Diseases
Editors and Contributors of Radiology of Infectious and Inflammatory Diseases—Heart and Chest
Preface I
Preface II
Contents
About the Editors
Editor-in-Chief
Managing Editors
Part 1: General Introduction to Infectious and Inflammatory Diseases of Heart and Chest
1: Overview of Infectious and Inflammatory Diseases of Heart and Chest
1.1 Infection and Inflammation
1.2 Infectious and Inflammatory Diseases of Chest
1.3 Pathogenesis of Infectious and Inflammatory Diseases of Chest
1.4 Relationship Between Infection and Connective Tissue Diseases
1.5 Infectious and Inflammatory Diseases of Great Vessels in Heart
References
2: X-Ray Imaging and CT Imaging Techniques of Great Vessels in Chest and Heart
2.1 X-Ray Imaging Technique
2.2 CT Imaging Technique
2.2.1 CT Imaging Technique of Chest
2.2.2 CT Imaging Technique of Heart and Great Vessels
References
3: Magnetic Resonance Imaging and Nuclear Medicine Imaging Techniques of Great Vessels in Chest and Heart
3.1 Magnetic Resonance Imaging Technique
3.1.1 Magnetic Resonance Imaging of Chest
3.1.2 Cardiac Magnetic Resonance Imaging
3.1.3 Magnetic Resonance Imaging of Great Vessels
3.2 Nuclear Medical Imaging Technique
References
4: Pathological and Imaging Findings of Infectious and Inflammatory Diseases of Chest
4.1 Lesions Occurring in the Alveoli
4.2 Lesions Occurring in the Small Airway
4.3 Lesions Occurring in the Large Airway
4.4 Acute Lung Injury (Diffuse Alveolar Damage)
4.5 Lesions Occurring in Pulmonary Interstitium
4.6 Pulmonary Granulomatous Inflammation and Granulomatous Disease
4.7 Pulmonary Vasculitis
References
Part II: Infectious Diseases of Chest
5: Bacterial Infection
5.1 Streptococcus Pneumoniae
5.1.1 Overview
5.1.2 Pathological Manifestations
5.1.3 Imaging Manifestations
5.1.4 Diagnostic Key Points
5.1.5 Differential Diagnosis
5.1.6 Research Status and Progress
5.2 Staphylococcus
5.2.1 Overview
5.2.2 Pathological Manifestation
5.2.3 Imaging Manifestations
5.2.4 Diagnostic Key Points
5.2.5 Differential Diagnosis
5.2.6 Research Status and Progress
5.3 Klebsiella Pneumoniae
5.3.1 Overview
5.3.2 Pathological Manifestations
5.3.3 Imaging Manifestations
5.3.4 Diagnostic Key Points
5.3.5 Differential Diagnosis
5.3.6 Research Status and Progress
5.4 Moraxella Catarrhalis
5.4.1 Overview
5.4.2 Pathological Manifestations
5.4.3 Imaging Manifestations
5.4.4 Diagnostic Key Points
5.4.5 Differential Diagnosis
5.4.6 Research Status and Progress
5.5 Haemophilus Influenzae
5.5.1 Overview
5.5.2 Pathological Manifestations
5.5.3 Imaging Manifestations
5.5.4 Diagnostic Key Points
5.5.5 Differential Diagnosis
5.5.6 Research Status and Progress
5.6 Pseudomonas Aeruginosa
5.6.1 Overview
5.6.2 Pathological Manifestations
5.6.3 Imaging Manifestations
5.6.4 Diagnostic Key Points
5.6.5 Differential Diagnosis
5.6.6 Research Status and Progress
5.7 Legionella
5.7.1 Overview
5.7.2 Pathological Manifestations
5.7.3 Imaging Manifestations
5.7.4 Diagnostic Key Points
5.7.5 Differential Diagnosis
5.7.6 Research Status and Progress
5.8 Actinomycetes
5.8.1 Overview
5.8.2 Pathological Manifestations
5.8.3 Imaging Manifestations
5.8.4 Diagnostic Key Points
5.8.5 Differential Diagnosis
5.8.6 Research Status and Progress
5.9 Nocardia
5.9.1 Overview
5.9.2 Pathological Manifestations
5.9.3 Imaging Manifestations
5.9.4 Diagnostic Key Points
5.9.5 Differential Diagnosis
5.9.6 Research Status and Progress
References
6: Viral Infection
6.1 Influenza Virus
6.1.1 Influenza
6.1.1.1 Overview
6.1.1.2 Pathological Manifestations
6.1.1.3 Imaging Manifestations
6.1.1.4 Diagnostic Key Points
6.1.1.5 Differential Diagnosis
6.1.1.6 Research Status and Progress
6.1.2 Influenza A (H1N1)
6.1.2.1 Overview
6.1.2.2 Pathological Manifestations
6.1.2.3 Imaging Manifestations
6.1.2.4 Diagnostic Key Points
6.1.2.5 Differential Diagnosis
6.1.2.6 Research Status and Progress
6.1.3 Human Infection with Highly Pathogenic Avian Influenza
6.1.3.1 Overview
6.1.3.2 Pathological Manifestations
6.1.3.3 Imaging Manifestations
6.1.3.4 Diagnostic Key Points
6.1.3.5 Differential Diagnosis
6.1.3.6 Research Status and Progress
6.1.4 Human Infection with H7N9 Avian Influenza
6.1.4.1 Overview
6.1.4.2 Pathological Manifestations
6.1.4.3 Imaging Manifestations
6.1.4.4 Diagnostic Key Points
6.1.4.5 Differential Diagnosis
6.1.4.6 Research Status and Progress
6.2 Measles Virus
6.2.1 Overview
6.2.2 Pathological Manifestations
6.2.3 Imaging Manifestations
6.2.4 Diagnostic Key Points
6.2.5 Differential Diagnosis
6.2.6 Research Status and Progress
6.3 Coronavirus
6.3.1 Severe Acute Respiratory Syndrome
6.3.1.1 Overview
6.3.1.2 Pathological Manifestations
6.3.1.3 Imaging Manifestations
6.3.1.4 Diagnostic Key Points
6.3.1.5 Differential Diagnosis
6.3.1.6 Research Status and Progress
6.3.2 COVID-19
6.3.2.1 Overview
6.3.2.2 Pathological Manifestations
6.3.2.3 Imaging Manifestations
6.3.2.4 Diagnostic Key Points
6.3.2.5 Differential Diagnosis
6.3.2.6 Research Status and Progress
References
7: Fungal Infection
7.1 Aspergillus
7.1.1 Overview
7.1.2 Pathological Manifestations
7.1.3 Imaging Manifestations
7.1.4 Diagnostic Key Points
7.1.5 Differential Diagnosis
7.1.6 Research Status and Progress
7.2 Mucor
7.2.1 Overview
7.2.2 Pathological Manifestations
7.2.3 Imaging Manifestations
7.2.4 Diagnostic Key Points
7.2.5 Differential Diagnosis
7.2.6 Research Status and Progress
7.3 Cryptococcus Neoformans
7.3.1 Overview
7.3.2 Pathological Manifestations
7.3.3 Imaging Manifestations
7.3.4 Diagnostic Key Points
7.3.5 Differential Diagnosis
7.3.6 Research Status and Progress
7.4 Histoplasma
7.4.1 Overview
7.4.2 Pathological Manifestations
7.4.3 Imaging Manifestations
7.4.4 Diagnostic Key Points
7.4.5 Differential Diagnosis
7.4.6 Research Status and Progress
7.5 Coccidioides Immitis
7.5.1 Overview
7.5.2 Pathological Manifestations
7.5.3 Imaging Manifestations
7.5.4 Diagnostic Key Points
7.5.5 Differential Diagnosis
7.5.6 Research Status and Progress
7.6 Candida
7.6.1 Overview
7.6.2 Pathological Manifestations
7.6.3 Imaging Manifestations
7.6.4 Diagnostic Key Points
7.6.5 Differential Diagnosis
7.6.6 Research Status and Progress
References
8: Parasitic Infections
8.1 Pulmonary Schistosoma
8.1.1 Overview
8.1.2 Pathological Manifestations
8.1.3 Imaging Manifestations
8.1.4 Diagnostic Key Points
8.1.5 Differential Diagnosis
8.2 Paragonimus
8.2.1 Overview
8.2.2 Pathological Manifestations
8.2.3 Imaging Manifestations
8.2.4 Diagnostic Key Points
8.2.5 Differential Diagnosis
8.3 Pulmonary Echinococcus
8.3.1 Overview
8.3.2 Pathological Manifestations
8.3.3 Imaging Manifestations
8.3.4 Diagnostic Key Points
8.3.5 Differential Diagnosis
8.3.6 Research Status and Progress
8.4 Pneumocystis
8.4.1 Overview
8.4.2 Pathological Manifestations
8.4.3 Imaging Manifestations
8.4.4 Diagnostic Key Points
8.4.5 Differential Diagnosis
References
9: Mycoplasma Pneumonia
9.1 Overview
9.2 Pathological Manifestations
9.3 Imaging Manifestations
9.4 Diagnostic Key Points
9.5 Differential Diagnosis
9.6 Research Status and Progress
References
10: Chlamydia Pneumonia
10.1 Overview
10.2 Pathological Manifestations
10.3 Imaging Manifestations
10.4 Diagnostic Key Points
10.5 Differential Diagnosis
10.6 Research Status and Progress
References
11: Lobar Pneumonia
11.1 Overview
11.2 Pathological Manifestations
11.3 Imaging Manifestations
11.4 Diagnostic Key Points
11.5 Differential Diagnosis
11.6 Research Status and Progress
References
12: Lobular Pneumonia
12.1 Overview
12.2 Pathological Manifestations
12.3 Imaging Manifestations
12.4 Diagnostic Key Points
12.5 Differential Diagnosis
12.6 Research Status and Progress
References
13: Interstitial Pneumonia
13.1 Overview
13.2 Pathological Manifestations
13.3 Imaging Manifestations
13.4 Diagnostic Key Points
13.5 Differential Diagnosis
13.6 Research Status and Progress
References
14: Organizing Pneumonia
14.1 Overview
14.2 Pathological Manifestations
14.3 Imaging Manifestations
14.4 Diagnostic Key Points
14.5 Differential Diagnosis
14.6 Research Status and Progress
References
15: Lung Abscess
15.1 Overview
15.2 Pathological Manifestations
15.3 Imaging Manifestations
15.4 Diagnostic Key Points
15.5 Differential Diagnosis
15.6 Research Status and Progress
References
16: Pulmonary Tuberculosis
16.1 Primary Pulmonary Tuberculosis
16.1.1 Overview
16.1.2 Pathological Manifestations
16.1.3 Imaging Manifestations
16.1.4 Diagnostic Key Points
16.1.5 Differential Diagnosis
16.2 Hematogenous Disseminated Pulmonary Tuberculosis
16.2.1 Acute Hematogenous Disseminated Pulmonary Tuberculosis
16.2.1.1 Overview
16.2.1.2 Pathological Manifestations
16.2.1.3 Imaging Manifestations
16.2.2 Subacute and Chronic Hematogenous Disseminated Pulmonary Tuberculosis
16.2.2.1 Overview
16.2.2.2 Pathological Manifestations
16.2.2.3 Imaging Manifestations
16.2.2.4 Diagnostic Key Points
16.2.2.5 Differential Diagnosis
16.3 Secondary Pulmonary Tuberculosis
16.3.1 Overview
16.3.2 Infiltrative Pulmonary Tuberculosis
16.3.2.1 Pathological Manifestations
16.3.2.2 Imaging Manifestations
16.3.3 Caseous Tuberculosis
16.3.3.1 Pathological Manifestations
16.3.4 Tuberculoma
16.3.4.1 Pathological Manifestations
16.3.4.2 Imaging Manifestations
16.3.5 Chronic Fibrocavitary Pulmonary Tuberculosis
16.3.5.1 Pathological Manifestations
16.3.5.2 Imaging Manifestations
16.3.5.3 Diagnostic Key Points
16.3.5.4 Differential Diagnosis
16.4 Tuberculosis of Trachea and Bronchus
16.4.1 Overview
16.4.2 Pathological Manifestations
16.4.3 Imaging Manifestations
16.4.4 Diagnostic Key Points
16.4.5 Differential Diagnosis
16.5 Tuberculous Pleurisy
16.5.1 Overview
16.5.2 Pathological Manifestations
16.5.3 Imaging Manifestations
16.5.4 Diagnostic Key Points
16.5.5 Differential Diagnosis
16.5.6 Research Status and Progress
16.6 Drug-Resistant Tuberculosis
16.6.1 Overview
16.6.2 Pathological Manifestations
16.6.3 Imaging Manifestations
16.6.4 Diagnostic Key Points
16.6.5 Differential Diagnosis
16.6.6 Research Status and Progress
16.7 Diabetes Mellitus Complicated with Pulmonary Tuberculosis
16.7.1 Overview
16.7.2 Pathological Manifestations
16.7.3 Imaging Manifestations
16.7.4 Diagnostic Key Points
16.7.5 Differential Diagnosis
16.7.6 Research Status and Progress
References
17: HIV-Related Pulmonary Infection
17.1 Mycobacterium Tuberculosis
17.1.1 Overview
17.1.2 Pathological Manifestations
17.1.3 Imaging Manifestations
17.1.4 Diagnostic Key Points
17.1.5 Differential Diagnosis
17.1.6 Research Status and Progress
17.2 Nontuberculous Mycobacteria
17.2.1 Overview
17.2.2 Pathological Manifestations
17.2.3 Imaging Manifestations
17.2.4 Diagnostic Key Points
17.2.5 Differential Diagnosis
17.2.6 Research Status and Progress
17.3 Talaromyces Marneffei
17.3.1 Overview
17.3.2 Pathological Manifestations
17.3.3 Imaging Manifestations
17.3.4 Diagnostic Key Points
17.3.5 Differential Diagnosis
17.3.6 Research Status and Progress
17.4 Pneumocystis Jirovecii
17.4.1 Overview
17.4.2 Pathological Manifestations
17.4.3 Imaging Manifestations
17.4.4 Diagnostic Key Points
17.4.5 Differential Diagnosis
17.4.6 Research Status and Progress
17.5 Cryptococcus Neoformans
17.5.1 Overview
17.5.2 Pathological Manifestations
17.5.3 Imaging Manifestations
17.5.4 Diagnostic Key Points
17.5.5 Differential Diagnosis
17.5.6 Research Status and Progress
17.6 Rhodococcus Equi
17.6.1 Overview
17.6.2 Pathological Manifestations
17.6.3 Imaging Manifestations
17.6.4 Diagnostic Key Points
17.6.5 Differential Diagnosis
17.6.6 Research Status and Progress
17.7 Cytomegalovirus
17.7.1 Overview
17.7.2 Pathological Manifestations
17.7.3 Imaging Manifestations
17.7.4 Diagnostic Key Points
17.7.5 Differential Diagnosis
17.8 Toxoplasma Gondii
17.8.1 Overview
17.8.2 Pathological Manifestations
17.8.3 Imaging Manifestations
17.8.4 Diagnostic Key Points
17.8.5 Differential Diagnosis
17.8.6 Research Status and Progress
References
18: Non-HIV-Related Pulmonary Infection
18.1 Overview
18.2 Imaging Manifestations
18.3 Diagnostic Key Points
18.4 Differential Diagnosis
References
Part III: Non-infectious Inflammatory Diseases of Chest
19: Connective Tissue Disease-Associated Lung Disease
19.1 Rheumatoid Arthritis
19.1.1 Overview
19.1.2 Pathological Manifestations
19.1.3 Imaging Manifestations
19.1.4 Diagnostic Key Points
19.1.5 Differential Diagnosis
19.1.6 Research Status and Progress
19.2 Systemic Sclerosis
19.2.1 Overview
19.2.2 Pathological Manifestations
19.2.3 Imaging Manifestations
19.2.4 Diagnostic Key Points
19.2.5 Differential Diagnosis
19.2.6 Research Status and Progress
19.3 Polymyositis and Dermatomyositis
19.3.1 Overview
19.3.2 Pathological Manifestations
19.3.3 Imaging Manifestations
19.3.4 Diagnostic Key Points
19.3.5 Differential Diagnosis
19.3.6 Research Status and Progress
19.4 Systemic Lupus Erythematosus
19.4.1 Overview
19.4.2 Pathological Manifestations
19.4.3 Imaging Manifestations
19.4.4 Diagnostic Key Points
19.4.5 Differential Diagnosis
19.4.6 Research Status and Progress
19.5 Sjogren Syndrome
19.5.1 Overview
19.5.2 Pathological Manifestations
19.5.3 Imaging Manifestations
19.5.4 Diagnostic Key Points
19.5.5 Differential Diagnosis
19.5.6 Research Status and Progress
19.6 Mixed Connective Tissue Disease
19.6.1 Overview
19.6.2 Pathological Manifestations
19.6.3 Imaging Manifestations
19.6.4 Diagnostic Key Points
19.6.5 Differential Diagnosis
19.7 Relapsing Polychondritis
19.7.1 Overview
19.7.2 Pathological Manifestations
19.7.3 Imaging Manifestations
19.7.4 Diagnostic Key Points
19.7.5 Differential Diagnosis
19.7.6 Research Status and Progress
19.8 Ankylosing Spondylitis
19.8.1 Overview
19.8.2 Pathological Manifestations
19.8.3 Imaging Manifestations
19.8.4 Diagnostic Key Points
19.8.5 Differential Diagnosis
19.8.6 Research Status and Progress
19.9 Inflammatory Bowel Disease
19.9.1 Overview
19.9.2 Pathological Manifestations
19.9.3 Imaging Manifestations
19.9.4 Diagnostic Key Points
19.9.5 Differential Diagnosis
19.9.6 Research Status and Progress
References
20: Vasculitis
20.1 Microscopic Polyangiitis
20.1.1 Overview
20.1.2 Pathological Manifestations
20.1.3 Imaging Manifestations
20.1.4 Diagnostic Key Points
20.1.5 Differential Diagnosis
20.1.6 Research Status and Progress
20.2 Granulomatosis with Polyangiitis
20.2.1 Overview
20.2.2 Pathological Manifestations
20.2.3 Imaging Manifestations
20.2.4 Diagnostic Key Points
20.2.5 Differential Diagnosis
20.2.6 Research Status and Progress
20.3 Eosinophilic Granulomatosis with Polyangiitis
20.3.1 Overview
20.3.2 Pathological Manifestations
20.3.3 Imaging Manifestations
20.3.4 Diagnostic Key Points
20.3.5 Differential Diagnosis
20.3.6 Research Status and Progress
20.4 Behcet’s Disease
20.4.1 Overview
20.4.2 Pathological Manifestations
20.4.3 Imaging Manifestations
20.4.4 Diagnostic Key Points
20.4.5 Differential Diagnosis
20.4.6 Research Status and Progress
20.5 Polyarteritis Nodosa
20.5.1 Overview
20.5.2 Pathological Manifestations
20.5.3 Imaging Manifestations
20.5.4 Diagnostic Key Points
20.5.5 Differential Diagnosis
20.5.6 Research Status and Progress
20.6 Takayasu Arteritis
20.6.1 Overview
20.6.2 Pathological Manifestations
20.6.3 Imaging Manifestations
20.6.4 Diagnostic Key Points
20.6.5 Differential Diagnosis
20.6.6 Research Status and Progress
20.7 Antiglomerular Basement Membrane Antibody-Mediated Disease
20.7.1 Overview
20.7.2 Pathological Manifestations
20.7.3 Imaging Manifestations
20.7.4 Diagnostic Key Points
20.7.5 Differential Diagnosis
20.7.6 Research Status and Progress
20.8 Idiopathic Pulmonary Hemosiderosis
20.8.1 Overview
20.8.2 Pathological Manifestations
20.8.3 Imaging Manifestations
20.8.4 Diagnostic Key Points
20.8.5 Differential Diagnosis
20.8.6 Research Status and Progress
References
21: Hypersensitivity Pneumonitis
21.1 Overview
21.2 Pathological Manifestations
21.3 Imaging Manifestations
21.4 Diagnostic Key Points
21.5 Differential Diagnosis
21.6 Research Status and Progress
References
22: Aspiration Pneumonia
22.1 Overview
22.2 Pathological Manifestations
22.3 Imaging Manifestations
22.4 Diagnostic Key Points
22.5 Differential Diagnosis
22.6 Research Status and Progress
References
23: Radiation Pneumonia
23.1 Overview
23.2 Pathological Manifestations
23.3 Imaging Manifestations
23.4 Diagnostic Key Points
23.5 Differential Diagnosis
23.6 Research Status and Progress
References
24: Drug-Induced Lung Disease
24.1 Overview
24.2 Pathological Manifestations
24.3 Imaging Manifestations
24.4 Diagnostic Key Points
24.5 Differential Diagnosis
24.6 Research Status and Progress
References
25: Idiopathic Interstitial Pneumonia
25.1 Acute Interstitial Pneumonia
25.1.1 Overview
25.1.2 Pathological Manifestations
25.1.3 Imaging Manifestations
25.1.4 Diagnostic Key Points
25.1.5 Differential Diagnosis
25.1.6 Research Status and Progress
25.2 Idiopathic Pulmonary Fibrosis
25.2.1 Overview
25.2.2 Pathological Manifestations
25.2.3 Imaging Manifestations
25.2.4 Diagnostic Key Points
25.2.5 Differential Diagnosis
25.2.6 Research Status and Progress
25.3 Nonspecific Interstitial Pneumonia
25.3.1 Overview
25.3.2 Pathological Manifestations
25.3.3 Imaging Manifestations
25.3.4 Diagnostic Key Points
25.3.5 Differential Diagnosis
25.3.6 Research Status and Progress
25.4 Desquamative Interstitial Pneumonia
25.4.1 Overview
25.4.2 Pathological Manifestations
25.4.3 Imaging Manifestations
25.4.4 Diagnostic Key Points
25.4.5 Differential Diagnosis
25.4.6 Research Status and Progress
25.5 Respiratory Bronchiolitis-Associated Interstitial Lung Disease
25.5.1 Overview
25.5.2 Pathological Manifestations
25.5.3 Imaging Manifestations
25.5.4 Diagnostic Key Points
25.5.5 Differential Diagnosis
25.5.6 Research Status and Progress
25.6 Cryptogenic Organizing Pneumonia
25.6.1 Overview
25.6.2 Pathological Manifestations
25.6.3 Imaging Manifestations
25.6.4 Diagnostic Key Points
25.6.5 Differential Diagnosis
25.6.6 Research Status and Progress
25.7 Lymphocytic Interstitial Pneumonia
25.7.1 Overview
25.7.2 Pathological Manifestations
25.7.3 Imaging Manifestations
25.7.4 Diagnostic Key Points
25.7.5 Differential Diagnosis
25.7.6 Research Status and Progress
25.8 Idiopathic Pleuroparenchymal Fibroelastosis
25.8.1 Overview
25.8.2 Pathological Manifestations
25.8.3 Imaging Manifestations
25.8.4 Diagnostic Key Points
25.8.5 Differential Diagnosis
25.8.6 Research Status and Progress
References
26: Sarcoidosis
26.1 Overview
26.2 Pathological Manifestations
26.3 Imaging Manifestations
26.4 Diagnostic Key Points
26.5 Differential Diagnosis
References
27: Langerhans Cell Histiocytosis
27.1 Overview
27.2 Pathological Manifestations
27.3 Imaging Manifestations
27.4 Diagnostic Key Points
27.5 Differential Diagnosis
27.6 Research Status and Progress
References
28: Bronchiolitis Obliterans with Organizing Pneumonia
28.1 Overview
28.2 Imaging Manifestations
28.3 Diagnostic Key Points
28.4 Differential Diagnosis
References
29: Eosinophilic Lung Disease
29.1 Simple Pulmonary Eosinophilia
29.1.1 Overview
29.1.2 Pathological Manifestations
29.1.3 Imaging Manifestations
29.1.4 Diagnostic Key Points
29.1.5 Differential Diagnosis
29.1.6 Research Status and Progress
29.2 Acute Eosinophilic Pneumonia
29.2.1 Overview
29.2.2 Pathological Manifestations
29.2.3 Imaging Manifestations
29.2.4 Diagnostic Key Points
29.2.5 Differential Diagnosis
29.3 Chronic Eosinophilic Pneumonia
29.3.1 Overview
29.3.2 Pathological Manifestations
29.3.3 Imaging Manifestations
29.3.4 Diagnostic Key Points
29.3.5 Differential Diagnosis
29.4 Hypereosinophilic Syndrome
29.4.1 Overview
29.4.2 Pathological Manifestations
29.4.3 Imaging Manifestations
29.4.4 Diagnostic Key Points
29.4.5 Differential Diagnosis
References
30: Mediastinal Infection and Inflammatory Disease
30.1 Acute Mediastinitis
30.1.1 Overview
30.1.2 Imaging Manifestations
30.1.3 Diagnostic Key Points
30.1.4 Differential Diagnosis
30.1.5 Research Status and Progress
30.2 Fibrosing Mediastinitis
30.2.1 Overview
30.2.2 Pathological Manifestations
30.2.3 Imaging Manifestations
30.2.4 Diagnostic Key Points
30.2.5 Differential Diagnosis
30.2.6 Research Status and Progress
References
Part IV: Infectious Diseases of Great Vessels in Heart
31: Infective Endocarditis
31.1 Overview
31.2 Pathological Manifestations
31.3 Imaging Manifestations
31.4 Diagnostic Key Points
31.5 Differential Diagnosis
31.6 Research Status and Progress
References
32: Viral Myocarditis
32.1 Overview
32.2 Pathological Manifestations
32.3 Imaging Manifestations
32.4 Diagnostic Key Points
32.5 Differential Diagnosis
32.6 Research Status and Progress
References
33: Infective Pericarditis
33.1 Overview
33.2 Pathological Manifestations
33.3 Imaging Manifestations
33.4 Diagnostic Key Points
33.5 Differential Diagnosis
33.6 Research Status and Progress
References
34: Infectious Aortitis
34.1 Overview
34.2 Pathological Manifestations
34.3 Imaging Manifestations
34.4 Diagnostic Key Points
34.5 Differential Diagnosis
34.6 Research Status and Progress
References
35: Infection Complications After Cardiovascular Surgery
35.1 Overview
35.2 Pathological Manifestations
35.3 Imaging Manifestations
35.4 Diagnostic Key Points
35.5 Differential Diagnosis
35.6 Research Status and Progress
References
Untitled
Part V: Inflammatory Diseases of Great Vessels in Heart
36: Rheumatic Heart Disease
36.1 Overview
36.2 Pathological Manifestations
36.3 Imaging Manifestations
36.4 Diagnostic Key Points
36.5 Differential Diagnosis
36.6 Research Status and Progress
References
37: Immune-Mediated Myocarditis
37.1 Overview
37.2 Pathological Manifestations
37.3 Imaging Manifestations
37.4 Diagnostic Key Points
37.5 Differential Diagnosis
37.6 Research Status and Progress
References
38: Pericarditis
38.1 Overview
38.2 Pathological Manifestations
38.3 Imaging Manifestations
38.4 Diagnostic Key Points
38.5 Differential Diagnosis
38.6 Research Status and Progress
References
39: Vasculitis
39.1 Takayasu Arteritis
39.1.1 Overview
39.1.2 Pathology
39.1.3 Imaging Manifestations
39.1.4 Diagnostic Key Points
39.1.5 Differential Diagnosis
39.1.6 Research Status and Progress
39.2 Polyarteritis Nodosa
39.2.1 Overview
39.2.2 Pathological Manifestations
39.2.3 Imaging Manifestations
39.2.4 Diagnostic Key Points
39.2.5 Differential Diagnosis
39.2.6 Research Status and Progress
39.3 Kawasaki Disease
39.3.1 Overview
39.3.2 Pathological Manifestations
39.3.3 Imaging Manifestations
39.3.4 Diagnostic Key Points
39.3.5 Differential Diagnosis
39.3.6 Research Status and Progress
39.4 ANCA-Associated Vasculitis
39.4.1 Overview
39.4.2 Pathological Manifestations
39.4.3 Imaging Manifestations
39.4.4 Diagnostic Key Points
39.4.5 Differential Diagnosis
39.4.6 Research Status and Progress
39.5 IgG4-Related Diseases
39.5.1 Overview
39.5.2 Pathological Manifestations
39.5.3 Imaging Manifestations
39.5.4 Diagnostic Key Points
39.5.5 Differential Diagnosis
39.5.6 Research Status and Progress
References

Citation preview

Hongjun Li Jingzhe Liu Li Li Editors

Radiology of Infectious and Inflammatory Diseases - Volume 3 Heart and Chest

123

Radiology of Infectious and Inflammatory Diseases - Volume 3

Hongjun Li • Jingzhe Liu • Li Li Editors

Radiology of Infectious and Inflammatory Diseases - Volume 3 Heart and Chest

Editors Hongjun Li Department of Radiology Beijing You An Hospital, Capital Medical University Beijing, China

Jingzhe Liu Department of Radiology The First Hospital of Tsinghua University Beijing, China

Li Li Department of Radiology Beijing You An Hospital, Capital Medical University Beijing, China

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Editorial Board of Radiology of Infectious and Inflammatory Diseases

Editor-in-­Chief

Hongjun Li Beijing YouAn Hospital, Capital Medical University, Beijing, China

Editorial Board Members

(in alphabetical order of last name) Wenxiao Jia The First Affiliated Hospital of Xinjiang Medical University, Xinjiang, China Li Li Beijing YouAn Hospital, Capital Medical University, Beijing, China Jingzhe Liu First Hospital of Tsinghua University, Beijing, China Wenya Liu The First Affiliated Hospital of Xinjiang Medical University, Ürümqi, China Yubo Lyu Jiahui International Hospital, Shanghai, China Haibing Mei Ningbo Woman and Children’s Hospital, Zhejiang, China Shinong Pan Shengjing Hospital of China Medical University, Shenyang, China Zhongwei Qiao Fudan University Affiliated Children Hospital, Shanghai, China Wen Shen Tianjin First Central Hospital, Tianjin, China Wenwei Tang Womans Hospital of Nanjing Medical University, Nanjing, China Jian Wang The First Affiliated Hospital of Xinjiang Medical University, Xinjiang, China Shuang Xia Tianjin First Central Hospital, Tianjin, China Jianrong Xu Renji Hospital of Shanghai Jiao Tong University School of Medicine, Shanghai, China Xuening Zhang Second Hospital of Tianjin Medical University, Tianjin, China Jun Zhou Shenyang Fourth People’s Hospital, Shenyang, China

Editorial Secretary

Li Li Beijing YouAn Hospital, Capital Medical University, Beijing, China Meiji Ren Beijing YouAn Hospital, Capital Medical University, Beijing, China

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Editors and Contributors of Radiology of Infectious and Inflammatory Diseases—Heart and Chest

Managing Editors

Jingzhe Liu, Li Li

Associate Editors

Yufeng Xu, Ping Li, Yang Hou, Meiji Ren, Jun Xia, Xiangwu Zheng

Contributors

(in alphabetical order of last name) Feng Chen Beijing YouAn Hospital, Capital Medical University, Beijing, China Jianghong Chen Beijing Friendship Hospital, Capital Medical University, Beijing, China Tingting Chen The 2nd Affiliated Hospital of Harbin Medical University, Harbin, China Xujiao Chen Shengjing Hospital of China Medical University, Shenyang, China Yuxue Dang Shengjing Hospital of China Medical University, Shenyang, China Tingting Fan The 2nd Affiliated Hospital of Harbin Medical University, Harbin, China Liwei Fu The 2nd Affiliated Hospital of Harbin Medical University, Harbin, China Ying Guan The 2nd Affiliated Hospital of Harbin Medical University, Harbin, China Qingqiang Guo The First Affiliated Hospital of Xiamen University, Xiamen, China Yinglin Guo Harbin Taiping District People’s Hospital, Harbin, China Yang Hou Shengjing Hospital of China Medical University, Shenyang, China Renjun Huang The First Affiliated Hospital of Soochow University, Soochow, China Lili Kong Yeda Hospital, Yantai, China Li Li Beijing YouAn Hospital, Capital Medical University, Beijing, China Ping Li The 2nd Affiliated Hospital of Harbin Medical University, Harbin, China Guiying Li Beijing Geriatric Hospital, Beijing, China Hongjun Li Beijing YouAn Hospital, Capital Medical University, Beijing, China Huimin Li Inner Mongolia People’s Hospital, Hohhot, China Shijie Li Harbin Medical University Cancer Hospital, Harbin, China Yonggang Li The First Affiliated Hospital of Soochow University, Soochow, China Zhao Liu Beijing YouAn Hospital, Capital Medical University, Beijing, China Bailu Liu The 2nd Affiliated Hospital of Harbin Medical University, Harbin, China Jingzhe Liu First Hospital of Tsinghua University (Beijing Huaxin Hospital), Beijing, China Lili Liu The 2nd Affiliated Hospital of Harbin Medical University, Harbin, China Yiping Liu The First Affiliated Hospital of Harbin Medical University, Harbin, China vii

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Editors and Contributors of Radiology of Infectious and Inflammatory Diseases—Heart and Chest Yupeng Liu First Hospital of Qinhuangdao, Qinhuangdao, China Yibo Lu The Fourth People’s Hospital of Nanning, Nanning, China Zhehao Lyu The First Affiliated Hospital of Harbin Medical University, Harbin, China Yue Ma Shengjing Hospital of China Medical University, Shenyang, China Mingming Ma Peking University First Hospital, Beijing, China Quanmei Ma Guangdong Provincial People’s Hospital, Guangzhou, China Dan Mu The Affiliated Hospital of Nanjing University Medical School (Nanjing Drum Tower Hospital), Nanjing, China Meiji Ren Beijing YouAn Hospital, Capital Medical University, Beijing, China Jin Shang Shengjing Hospital of China Medical University, Shenyang, China Hengfeng Shi Anqing Municipal Hospital, Anqing, China Fugui Song BinHai Hospital of Peking University, Tianjin, China Shi Sui Shengjing Hospital of China Medical University, Shenyang, China Yue Teng The First Affiliated Hospital of Soochow University, Soochow, China Jingyi Tian Beijing Water Resources Hospital, Beijing, China Xiuxia Tian The 2nd Affiliated Hospital of Harbin Medical University, Harbin, China Qiuxia Wan The 2nd Affiliated Hospital of Harbin Medical University, Harbin, China Cen Wang Beijing Nuclear Industry Hospital, Beijing, China Fei Wang The 2nd Affiliated Hospital of Harbin Medical University, Harbin, China Ke Wang Peking University First Hospital, Beijing, China Dongkui Wang The First Affiliated Hospital of Harbin Medical University, Harbin, China Haibo Wang The 2nd Affiliated Hospital of Harbin Medical University, Harbin, China Jun Xia Affiliated Hospital of Guangdong Medical University, Guangdong, China Hongwei Xu The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China Xu Meiling The 2nd Affiliated Hospital of Harbin Medical University, Harbin, China Yufeng Xu Peking University First Hospital, Beijing, China Xuhua Yang Mudanjiang KangAn Hospital, Mudanjiang, China Shanshan Yu The 2nd Affiliated Hospital of Harbin Medical University, Harbin, China Wei Yuan The 2nd Affiliated Hospital of Harbin Medical University, Harbin, China Qi Zhang The First Affiliated Hospital of Harbin Medical University, Harbin, China Jifeng Zhang The 2nd Affiliated Hospital of Harbin Medical University, Harbin, China Xianhe Zhang The 2nd Affiliated Hospital of Harbin Medical University, Harbin, China Xiangwu Zheng The 1st Affiliated Hospital of Wenzhou Medical University, Wenzhou, China Jingfen Zhu The First Affiliated Hospital of Soochow University, Soochow, China Xiaolong Zhu The First Affiliated Hospital of Hebei North University

Editorial Secretary

Haibo Wang, Zhehao Lyu

Preface I

Socio-economic boom in modern times has changed people’s lifestyle and population mobility. As a result, human subsistence and socio-economic development are increasingly affected by infectious and inflammatory diseases. A document issued by the National Health Commission stresses that all the hospitals at level II and above need to set up an infectious diseases department and an infection control office, attaching unprecedented importance to the hazards of infectious diseases to human health. Over the past 30 years, the development of medical imaging diagnosis and treatment technologies has greatly boosted the improvement on diagnosis and treatment modes in modern times. Highly dependent on medical imaging technologies, modern medicine has entrusted medical imaging with an important mission in diagnosis and differential diagnosis of infectious and inflammatory diseases. During long-term clinical practices and scientific researches, my team and I have come to gain the following insight: Due to the neglect and lack of construction for key discipline systems of infectious and inflammatory diseases as well as researches on related theory systems and specification guidance, the quality and effectiveness of the diagnosis and treatment provided for patients have been adversely affected, resulting in the abuse of clinical antibiotics, thus compromising patients’ health and quality of life and increasing the financial burden on families and society. Based on the above considerations, this series of books gathers a large number of experts and scholars from the Infectious Diseases Group of the Chinese Society of Radiology, Infection Imaging Professional Committee of the Chinese Medical Doctor Association Radiological Branch, Professional Committee on Radiology of Infection and Inflammation of the Chinese Research Hospital Association, Working Committee on Infection (Infectious Disease) Imaging of Chinese Association of STD & AIDS Prevention and Control, Infectious Disease Imaging Group of Chinese Hospital Association Infectious Diseases Hospitals Branch, and Beijing Imaging Diagnosis and Treatment Technology Innovation Alliance. Clinical resources associated with infectious and inflammatory diseases nationwide are integrated, and the imaging characteristics and evolution rules of infectious and inflammatory disease are summarized herein. Meanwhile, this series of books has revealed the pathological basis of infectious and inflammatory diseases and put forward the essential points of imaging diagnosis and differential diagnosis of infectious and inflammatory diseases. I believe that the series of books will boost the academic development on prevention and control, rational prescription, and radiological diagnosis for infectious and inflammatory diseases, thereby effectively helping deliver accurate diagnosis and treatment in clinic. This series of books systematically introduces the theory of the radiology of infection and inflammation for the first time. The books are divided into six volumes (Brain and Spinal Cord, Head and Neck, Heart and Chest, Abdomen and Pelvis, Skeletal Muscle, and Children). This series of books covers four types of pathogens related to infectious diseases (bacteria, fungi, viruses, parasites) and inflammatory diseases such as autoimmune diseases. This series of books has three major features: (1) It provides clinically relevant data for a wide array of diseases ranging from clinically common and frequently occurring diseases to rare infectious and inflammatory diseases; (2) It provides complete data and objective basis of diagnosis, with a focus on the completeness, representativeness, consistency, and authenticity of cases, images and graphics therein; (3) By virtue of the editors’ accumulated clinical ix

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Preface I

e­ xperience and practice, they have contributed most of the data, and a small part of materials have been authorized by international peers. By absorbing and quoting the latest research results at home and abroad, this series of books offers readers many new findings and striking observations through reasonable layout and detailed contents. To ensure the successful publication of the books, we have established an advisory committee and an expert committee and spent over 1 year in accomplishing the compilation from outline designing to draft finalizing, while seeking for scientific design and systematic demonstration. In addition to the Chinese version, the English version is expected to be published simultaneously by the publisher Springer. The editorial board has put a high premium on the compilation of this series, and trained members of the editorial board on standardized writing, professional review, and finalization of drafts for several times, while assigning specific personnel to engage in the review, revision, and supplementation of the drafts. As the editor-in-chief, I would like to express my cordial thanks for their unremitting efforts. Sincere gratitude is also extended to all the members of the National Infectious Disease Imaging Group who devoted themselves to the compilation of this series of books. In view of the severe situation of prevention and treatment of infectious and inflammatory diseases, this series of monographs will serve as another powerful weapon fighting against infectious and inflammatory diseases and play a vital role in raising the physicians’ level of diagnosis and treatment, improving patients’ living quality and prolonging their lives. As science and technology evolve, we will gain deeper insight gradually. For this reason, deviations and errors are inevitable, so we sincerely welcome your criticism and suggestions to refine this series of books in the future. Beijing, China November 2019

Hongjun Li

Preface II

Infectious and inflammatory diseases are very common clinically. They have common inflammatory reaction and organ dysfunction, with many clinical similarities. For example, both infection and inflammation can cause fever. When infected by some low-virulence pathogens, patients are free of obvious symptoms of infection and poisoning, while takayasu arteritis can also cause high fever, but it does not necessarily lead to infection. Infectious and non-­infectious inflammatory diseases can sometimes coexist. For example, patients with connective tissue diseases may also suffer from infection in case of decreased immune function or drug effect. The complexity and individual differences between infectious and non-infectious inflammatory diseases make the diagnosis and differential diagnosis of them become the focuses and difficulties in clinical practice, and it is necessary to make comprehensive diagnosis based on the information of clinical manifestations, laboratory examinations, imaging and etiological examinations. As a volume of Radiology of Infectious and Inflammatory Diseases (multi-volume series), this book covers pathogen (bacteria, fungi, viruses, parasites, etc.) infection related to infectious diseases of great vessels in chest and heart, and autoimmune or inflammatory diseases. By introducing the clinical characteristics, pathological manifestations, and imaging features of the diseases, we strive to elaborate on and explain various infectious and inflammatory diseases in detail with concise language and refined contents, while providing a large number of typical case images and graphics, thus deepening readers’ understanding of the diseases with the help of illustrations. Each chapter provides the key points of diagnosis and differential diagnosis summarized concisely, which is helpful for readers to check quickly. Finally, the research status quo and progress of each disease are introduced to readers, thereby updating knowledge and keeping abreast of the times. Dozens of domestic experts on chest and cardiovascular imaging have been invited to participate in the compilation of this book. It was compiled by the contributors with many years of clinical experience, who absorb and quote the latest research results at home and abroad. This book showcases the wisdom and painstaking efforts of all contributors. The compilation of this volume has also received considerable support and assistance from Professor Hongjun Li, the editor-in-chief of the series. I would like to express my profound respect and gratitude here. This book is rich in content, clear in structure and practical in clinic, aiming to provide assistance for imaging departments and clinicians. Restricted by editors’ expertise, there are inevitably impropriety and errors in the book. We sincerely welcome readers and peers to feedback suggestions or corrections for the second edition in the future. Beijing, China May 10, 2022

Jingzhe Liu

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Contents

Part 1 General Introduction to Infectious and Inflammatory Diseases of Heart and Chest 1 Overview  of Infectious and Inflammatory Diseases of Heart and Chest�������������    3 Jingzhe Liu and Xiangwu Zheng 2 X-Ray  Imaging and CT Imaging Techniques of Great Vessels in Chest and Heart�������������������������������������������������������������������������������������������������������������������    7 Jingzhe Liu and Jun Xia 3 Magnetic  Resonance Imaging and Nuclear Medicine Imaging Techniques of Great Vessels in Chest and Heart �����������������������������������������������������������������������   11 Jingzhe Liu and Qingqiang Guo 4 Pathological  and Imaging Findings of Infectious and Inflammatory Diseases of Chest�������������������������������������������������������������������������������������������������������   17 Jingzhe Liu and Hengfeng Shi Part II Infectious Diseases of Chest 5 Bacterial Infection�����������������������������������������������������������������������������������������������������   33 Yonggang Li, Renjun Huang, Jingfen Zhu, Yue Teng, Bailu Liu, Zhehao Lyu, and Tingting Chen 6 Viral Infection�����������������������������������������������������������������������������������������������������������   61 Feng Chen, Li Li, Yupeng Liu, Wang Fei, Lili Kong, Yinglin Guo, Dan Mu, Xianhe Zhang, Xuhua Yang, Haibo Wang, and Zhao Liu 7 Fungal Infection �������������������������������������������������������������������������������������������������������  111 Bailu Liu, Zhehao Lyu, Qi Zhang, Dongkui Wang, Fugui Song, Ying Guan, and Tingting Chen 8 Parasitic Infections���������������������������������������������������������������������������������������������������  131 Jianghong Chen 9 Mycoplasma Pneumonia �����������������������������������������������������������������������������������������  141 Bailu Liu, Zhehao Lyu, and Meiling Xu 10 Chlamydia Pneumonia���������������������������������������������������������������������������������������������  145 Bailu Liu, Zhehao Lyu, and Xianhe Zhang 11 Lobar Pneumonia�����������������������������������������������������������������������������������������������������  149 Bailu Liu, Tingting Fan, and Shijie Li 12 Lobular Pneumonia �������������������������������������������������������������������������������������������������  153 Bailu Liu, Tingting Fan, and Shijie Li

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13 Interstitial Pneumonia ���������������������������������������������������������������������������������������������  157 Bailu Liu, Tingting Fan, and Shijie Li 14 Organizing Pneumonia���������������������������������������������������������������������������������������������  161 Bailu Liu, Tingting Fan, and Shijie Li 15 Lung Abscess�������������������������������������������������������������������������������������������������������������  165 Bailu Liu, Tingting Fan, and Shijie Li 16 Pulmonary Tuberculosis�������������������������������������������������������������������������������������������  169 Bailu Liu, Lili Liu, Li Li, Guiying Li, and Yiping Liu 17 HIV-Related Pulmonary Infection �������������������������������������������������������������������������  195 Li Li, Lili Kong, Lili Liu, Huimin Li, Yibo Lu, Meiji Ren, Zhao Liu, Liwei Fu, Xuhua Yang, and Yupeng Liu 18 Non-HIV-Related Pulmonary Infection �����������������������������������������������������������������  227 Li Li, Qiuxia Wan, and Fei Wang Part III Non-infectious Inflammatory Diseases of Chest 19 Connective  Tissue Disease-Associated Lung Disease���������������������������������������������  235 Yufeng Xu 20 Vasculitis �������������������������������������������������������������������������������������������������������������������  263 Ke Wang and Yufeng Xu 21 Hypersensitivity Pneumonitis ���������������������������������������������������������������������������������  289 Ping Li, Jifeng Zhang, and Xiuxia Tian 22 Aspiration Pneumonia ���������������������������������������������������������������������������������������������  293 Cen Wang and Yufeng Xu 23 Radiation Pneumonia�����������������������������������������������������������������������������������������������  297 Ping Li, Jifeng Zhang, and Xiuxia Tian 24 Drug-Induced Lung Disease������������������������������������������������������������������������������������  301 Yufeng Xu 25 Idiopathic Interstitial Pneumonia���������������������������������������������������������������������������  309 Ping Li, Jifeng Zhang, Wei Yuan, and Shanshan Yu 26 Sarcoidosis�����������������������������������������������������������������������������������������������������������������  325 Ping Li and Jifeng Zhang 27 Langerhans Cell Histiocytosis���������������������������������������������������������������������������������  331 Ping Li and Jifeng Zhang 28 Bronchiolitis  Obliterans with Organizing Pneumonia �����������������������������������������  337 Ping Li and Jifeng Zhang 29 Eosinophilic Lung Disease���������������������������������������������������������������������������������������  341 Mingming Ma and Yufeng Xu 30 Mediastinal  Infection and Inflammatory Disease�������������������������������������������������  349 Jingyi Tian and Yufeng Xu Part IV Infectious Diseases of Great Vessels in Heart 31 Infective Endocarditis�����������������������������������������������������������������������������������������������  357 Jingzhe Liu and Hongwei Xu

Contents

Contents

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32 Viral Myocarditis �����������������������������������������������������������������������������������������������������  365 Jingzhe Liu and Meiji Ren 33 Infective Pericarditis�������������������������������������������������������������������������������������������������  369 Jingzhe Liu and Meiji Ren 34 Infectious Aortitis�����������������������������������������������������������������������������������������������������  377 Jingzhe Liu and Meiji Ren 35 Infection  Complications After Cardiovascular Surgery���������������������������������������  381 Jingzhe Liu and Meiji Ren Part V Inflammatory Diseases of Great Vessels in Heart 36 Rheumatic Heart Disease�����������������������������������������������������������������������������������������  387 Yang Hou and Quanmei Ma 37 Immune-Mediated Myocarditis�������������������������������������������������������������������������������  395 Yang Hou and Yue Ma 38 Pericarditis�����������������������������������������������������������������������������������������������������������������  399 Yang Hou and Shi Sui 39 Vasculitis �������������������������������������������������������������������������������������������������������������������  407 Yang Hou, Yuxue Dang, Xiaolong Zhu, Jin Shang, Xujiao Chen, and Quanmei Ma

About the Editors

Editor-in-Chief Hongjun Li  Doctor of Medicine, chief physician, professor, doctoral supervisor. He serves as Director of the Medical Imaging Center of Beijing YouAn Hospital, Capital Medical University and Deputy Director of the Medical Imaging Department of Capital Medical University. He is listed in the first batch of Beijing “Ten Hundred Thousand Excellent Health Professionals.” He is included in the first batch of academic leaders (backbones) of senior health talents in Beijing 215 talent training program (namely, selection of 20 leading talents, 100 academic leaders, and 500 academic backbones). He is a chief editor of Journal Radiology of Infectious Diseases and an associate editor of BMC Neurology. Now he acts as the head of the Lemology Group of the Chinese Society of Radiology, Chairman of the Infection Imaging Professional Committee of the Chinese Association of Radiologists, Chairman of the Professional Committee on Radiology of Infection and Inflammation of the Chinese Research Hospital Association, Chairman of the Working Committee on Infection (Infectious Disease) Imaging of Chinese Association of STD & AIDS Prevention and Control, and President of the Beijing Imaging Diagnosis and Treatment Technology Innovation Alliance. He mainly focuses on the imaging diagnosis for infectious diseases and inflammatory diseases and has trained more than 20 doctoral and master students. In recent years, he has undertaken more than 10 research and development projects. Among them, there is one National Science and Technology Major Project, one key project funded by the National Natural Science Foundation of China, and two general projects. He has been editor-in-chief of 2 textbooks, 28 Chinese or English monographs, chief translator of 3 monographs, and the total number of downloads of the monographs in English has reached 160,000. Radiology of HIV/AIDS and Radiology of Infectious Diseases 1-2, for which he acts as managing editor, were granted 2014 and 2015 Excellent Exported Book Award, respectively. Besides, the two books won the 2017 General Award issued by the State Administration of Press, Publication, Radio, Film and Television of the PRC. He has published more than 200 papers, including more than 60 SCI articles. He has won 2 national invention patents and 16 intellectual property registrations. He has won 9 prizes at provincial and ministerial level, including the Chinese Medical Science and Technology Award. He was awarded the title “Accomplished Teacher for xvii

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Training an Apprentice” by Beijing Federation of Trade Unions. The scientific research team led by him was given the title “Science & Technology Innovation Cultivation Team” by the Beijing Municipal Administration of Hospitals, and the title “Staff Innovation Studio at Municipal Level” was awarded jointly by the Beijing Federation of Trade Unions and the Beijing Municipal Science and Technology Commission.

Managing Editors Jingzhe Liu  chief physician and professor. Director of Radiology Department and Director of Nuclear Medicine Department of the First Affiliated Hospital of Tsinghua University (Beijing Huaxin Hospital). She has been engaged in clinical, teaching, and scientific research of medical imaging for a long time, good at cardiovascular and gastrointestinal imaging diagnosis. She has presided over or participated in multiple projects supported by scientific research fund and published more than 20 papers as the first author or corresponding author. She has been editor-in-chief, chief translator, and editor of multiple monographs. She presides over national and Beijing municipal continuing education programs. She serves as Principal Investigator of Imaging Clinical Trial Base. She currently serves as a member of Beijing Medical Association Radiological Branch, Standing Committee Member of Radiological Imaging and Imaging Engineering Branch of Chinese Society of Cardiothoracic and Vascular Anesthesiology, Standing Committee Member of China Association for Disaster Emergency Rescue Medicine Imaging Branch, Standing Committee Member of Professional Committee on Cardiovascular Imaging of Chinese Research Hospital Association, Council Member of Beijing Association for Medical Education, and a member of Beijing Chaoyang District Youth Federation. She is an expert in laboratory animal technology (senior). She is a reviewer of Chinese Journal of Radiology and an editorial board member of Journal of Chinese Research Hospitals. Li  Li  doctor of medicine, associate chief physician. She is currently working in Beijing YouAn Hospital, Capital Medical University. She serves as a member of the Lemology Group of the Chinese Society of Radiology. She is Standing Committee Member of the Professional Committee on Radiology of Infection and Inflammation of the Chinese Research Hospital Association, Standing Committee Member of AIDS Radiology Branch of Chinese Association of STD & AIDS Prevention and Control, a member of Endocrinology and Rheumatology Group of Beijing Medical Association Radiological Branch, Executive Council Member of the Beijing Imaging Diagnosis and Treatment Technology Innovation Alliance, and an editorial board member of Radiology of Infectious Disease.

About the Editors

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She mainly focuses on imaging diagnosis, scientific research and teaching of infectious diseases; she is good at imaging diagnosis of thoracic and abdominal infectious diseases. She has published more than 30 papers and participated in the compilation of expert consensus on imaging diagnosis of major infectious diseases such as hydatid disease, AIDS, tuberculosis, and COVID-19. She is a co-editor, an associate e­ ditor, and an editorial board member of more than 20 Chinese or English medical imaging monographs and textbooks. She has participated in multiple projects supported by national, provincial, and ministerial scientific research fund, such as National Science and Technology Major Project and International Cooperation Key Research and Development Project. She was awarded the title Apprentice of “Accomplished Teacher for Training an Apprentice” by Beijing Federation of Trade Unions in 2019.

Part 1 General Introduction to Infectious and Inflammatory Diseases of Heart and Chest

1

Overview of Infectious and Inflammatory Diseases of Heart and Chest Jingzhe Liu and Xiangwu Zheng

1.1 Infection and Inflammation Inflammation refers to the defensive response of living tissues with a vascular system, including recognition, clearance, and repair of infectious and noninfectious injury factors. According to the disease course, inflammation can be divided into acute inflammation (2 months). Any factor that can lead to tissue injury can become the cause of inflammation, including: (1) physical factors, such as high temperature, low temperature, radiation, and ultraviolet rays; (2) chemical factors, such as exogenous acid and alkali corrosion stimulation and some endogenous chemical toxins produced by the body; (3) mechanical factors, such as cutting, extrusion, and impact; (4) infection by pathogenic microorganisms, in which case immune response will also occur in the body; in addition to redness, swelling, heat, and pain at the infected site, there is usually fever; and (5) immune reactions, such as various allergic reactions, which can cause injury to tissues and cells and lead to inflammation [1, 2]. Infection refers to the pathophysiological changes caused by the interaction between pathogens and the host immune system. The severe pathological injury and obvious clinical symptoms caused by pathogens are called apparent infections; those without obvious clinical symptoms are called silent infections. Infection can also manifest as latent infection and carrier state. Latent infection refers to an infection in which pathogens parasitize host cells in a hidden state, which mostly occurs after apparent infection or silent infection. Under certain conditions, latent pathogens can be actiJ. Liu (*) First Hospital of Tsinghua University (Beijing Huaxin Hospital), Beijing, China X. Zheng The 1st Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

vated to cause clinical infection again. Carrier state refers to the survival state of pathogens in the body after the clinical infection symptoms have disappeared [2]. Therefore, according to the above concepts, infection can cause inflammatory reaction, as one of the major causes of inflammation, but inflammation is not exclusively caused by infection, and latent infection and carrier state may not always cause inflammation.

1.2 Infectious and Inflammatory Diseases of Chest Inflammation is the body’s self-defensive response to various stimuli and is also a common pathological feature in the occurrence and development of numerous infectious and noninfectious diseases in clinical practice [3]. Infectious disease is a general term for diseases in which pathogens invade human body and proliferate in tissues, body fluids, or cells, causing inflammation or organ dysfunction. Because the airway and lungs are connected to the outside environment, they are susceptible to infection caused by pathogens. Pulmonary infection, also known as infectious pneumonia clinically, can be classified in many ways according to its clinical symptoms, pathogens, or anatomical features. According to the occurrence environment, pulmonary infection can be divided into community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP). According to the immune status of patients, pulmonary infection can be divided into pulmonary infection in immunocompetent people and pulmonary infection in immunocompromised people. According to the anatomical features, pulmonary infection is mainly divided into lobar pneumonia, bronchopneumonia, and interstitial pneumonia and less common infections include bronchitis, septic pulmonary embolism, miliary pulmonary infection, and lung abscess. According to the types of pathogens, pulmonary infection can be divided into bacterial pneumonia, viral pneumonia, mycoplasma

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pneumonia, chlamydia pneumonia, and fungal pneumonia, as well as pulmonary parasitic disease. Noninfectious inflammation is a general term for a range of diseases including inflammation or organ dysfunction caused by various stimuli other than pathogens. Noninfectious inflammation is also common in the chest. Connective tissue disease is a kind of chronic inflammatory disease with autoimmune abnormalities involving multiple systems, including rheumatoid arthritis, systemic lupus erythematosus (SLE), Sjogren syndrome, scleroderma, dermatomyositis, and mixed connective tissue disease. Connective tissue disease often involves the lungs and the heart with specific clinical symptoms and imaging manifestations. Idiopathic interstitial pneumonia (IIP) is a group of unexplained interstitial lung diseases characterized by diffuse pulmonary alveolitis and pulmonary fibrosis caused by alveolar structure disorder. The etiology of idiopathic interstitial pneumonia is unknown for many patients, and different pathological types are related to different pathogenic factors. The aggregation of inflammatory eosinophils in alveolar space and adjacent interstitial tissue caused by various reasons can also lead to inflammation, which is called eosinophilic lung disease. Drugs and radiation can also cause lung tissue injury and then lead to inflammation. Clinically, besides those diseases caused by pathogens, many diseases featuring acute or chronic lung inflammation have unclear etiology and pathogenesis, while some diseases have clear pathogenic factors. For the diagnosis and treatment of patients, it is very important to correctly understand the clinical features, imaging manifestations, and etiology of pulmonary inflammation. Infectious and noninfectious inflammatory diseases feature common inflammatory reaction and organ dysfunction and may have many similarities in clinical practice. For example, both patients with infectious inflammatory diseases and patients with noninfectious inflammatory diseases can show fever symptoms. In cases of infections by low virulence pathogens or chronic infections, patients do not show significant systemic inflammatory response syndrome, making differentiation from noninfectious inflammatory diseases difficult. Although microbial specimen culture is the “gold standard” for diagnosis of infection, the positive rate is relatively low and sometimes the diagnosis of infection cannot be exclusively dependent on the microbial culture. Infectious and non-infectious diseases can sometimes coexist. Many patients with diffuse connective tissue disease will also be infected due to the decline of immune function or drug effect. Lung and upper respiratory tract are the most common infection sites, and there are many kinds of pathogenic microorganisms, including various bacteria, fungi, and viruses. Due to the complexity of and individual differences between infectious and noninfectious inflammatory diseases, sometimes the diagnosis and differential diagnosis of the two

J. Liu and X. Zheng

are a clinical priority and a difficult task and comprehensive diagnosis should be made based on combining clinical laboratory examination, imaging, and pathogen examination.

1.3 Pathogenesis of Infectious and Inflammatory Diseases of Chest Microorganisms can reach the lungs through three routes: airway inhalation, hematogenous dissemination, and direct spread of extrapulmonary lesions. Inhalation or accidental inhalation of contaminated air or infectious oropharyngeal secretions is the most common route of infection. Direct inhalation is considered to be a major route of pulmonary infection by mycobacterium tuberculosis, endemic fungi, mycoplasma, Legionella, and many respiratory viruses. The routes of hospital-acquired pneumonia bacteria entering the respiratory tract include microinhalation of oropharyngeal secretions containing pathogenic bacteria, accidental inhalation of gastric contents, inhalation of contaminated aerosol, distant hematogenous dissemination, and direct invasion from adjacent infection foci, direct entry from endotracheal intubation, and so forth. Among them, microinhalation of oropharyngeal secretions containing pathogenic bacteria is the most common route. The response of lung tissue after pathogens enter the lungs and the resulting imaging findings depend on the virulence of pathogens, the number of pathogens, and the defense and immune function of the host. Pulmonary host defense mechanisms can be divided into innate or nonspecific immunity (such as mechanical barrier and phagocytosis) and acquired or specific immunity (such as cell-mediated defensive immunity and humoral immunity). The upper respiratory tract is the anatomical first line of defense. The cilia and mucus of trachea, bronchi, and terminal bronchioles form a mechanical barrier, and the mechanical clearance is affected by the physical properties of inhaled infectious agents and dust. Granules larger than 10  μm in diameter are filtered out in the upper respiratory tract (nasopharynx), and granules 5–10  μm in diameter reach the trachea and bronchi and are cleared by mucus-cilia. Only 1–2 μm granules can reach alveoli. After pathogens reach the terminal bronchioles, the phagocytosis of the lung is mainly performed by monocytes, macrophages, and polymorphonuclear cells. Alveolar macrophages are the first line of alveolar defense. If the number and virulence of pathogens are dominant or the macrophage function is impaired, macrophages act as antigen-presenting cells, which process pathogens and present them to T cells and B cells to induce acquired immunity, which includes humoral immunity and cellular immunity. Immune response is a “doubleedged sword”, and appropriate immune response is protective, which plays the role of immune defense, immune homeostasis, and immune surveillance. Inappropriate immune response

1  Overview of Infectious and Inflammatory Diseases of Heart and Chest

can mediate pathological injury. Over-response will produce severe systemic inflammatory reaction or allergic reaction, while under-response will easily induce serious infection [4].

1.4 Relationship Between Infection and Connective Tissue Diseases Infection has long been considered to be related to connective tissue diseases. One of the most important speculations is that infection may induce specific immune response by affecting immune regulation. The role of pathogenic infection in the pathogenesis of connective tissue diseases has attracted increasing attention of researchers. At present, according to the molecular mimicry which has been well established, the components of pathogens have similar epitopes to autoantigens and there may be antigen receptors that recognize both autoantigen epitopes and pathogen epitopes in the body. When there is no infection by related pathogens, these potential autoreactive lymphocytes will be subjected to the peripheral immune tolerance mechanism. However, in the case of infection by pathogens, a considerable number of cross-reactive pathogen epitopes may be presented in the inflammatory environment caused by pathogens, which may break the peripheral immune tolerance, initiate the activation of autoreactive lymphocytes, and cause immunopathological injury. Infection usually occurs several years before the clinical symptoms of connective tissue disease, and it is involved in the process of breaking immune tolerance and inducing autoimmune response in connective tissue disease [5]. Epstein–Barr virus (EBV) is a kind of herpes virus, which is widely prevalent worldwide. It mainly spreads through saliva. Cellular immunity and humoral immunity are involved in the primary EBV infection. Studies have shown that EB virus infection is related to the development of systemic lupus erythematosus, rheumatoid arthritis, Sjogren syndrome, and systemic sclerosis. Other studies have found that Mycobacterium tuberculosis may initiate or activate autoreactive cells and produce a large number of autoantibodies, causing autoimmune diseases [6]. Patients with connective tissue diseases often have severe immune dysfunction and extensive immunopathological injury, which leads to the disruption and inefficiency of the body’s resistance mechanism against infection by external pathogens, thus providing a convenient route for pathogen invasion. Commonly used therapeutic drugs for connective tissue diseases include glucocorticoids, cytotoxic immunosuppressants, and some biological agents, all of which reduce anti-infection immunity and increase the risk of infection to some extent. Therefore, various pathogenic infections have become common complications of connective tissue diseases. It has been reported that 33.2% of SLE patients mainly

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died of infection and infection has become the leading cause of death of SLE patients in China [7]. Whether infection is one of the pathogenic factors of connective tissue disease or an important complication of connective tissue disease, there is a close relationship between them so it is necessary to correctly understand the relationship between them in clinical and imaging diagnosis.

1.5 Infectious and Inflammatory Diseases of Great Vessels in Heart Inflammatory lesions of great vessels in heart can be caused by infectious and noninfectious factors. Infective endocarditis refers to the inflammation of heart valve or ventricular wall intima, chordae tendineae, artificial valve, and implant caused by infection of various pathogens. Rheumatic heart disease is heart inflammation and scar formation caused by autoimmune reaction of group A streptococcus infection. Structural cardiac abnormalities, such as rheumatic endocardial lesions, congenital heart disease, senile degenerative valvular disease, and prosthetic valve replacement, are the predisposing factors of infective endocarditis. Myocarditis is a localized or diffuse acute or chronic inflammatory lesion of myocardium. The etiology of myocarditis can be divided into infective myocarditis, immune-­ mediated myocarditis, and toxic myocarditis. Virus is the most common pathogen in infective myocarditis. Immune-­ mediated myocarditis can be secondary to some autoimmune diseases, such as systemic lupus erythematosus and rheumatoid arthritis. Pericarditis is an inflammatory lesion of visceral layer and parietal layer of pericardium caused by many factors. According to the etiology, it can be divided into infective pericarditis and noninfective pericarditis. Infective pericarditis can be caused by viruses, bacteria, and other pathogens invading pericardium. Acute pericarditis is mostly caused by infection. After the first episode of acute pericarditis, the probability of recurrent pericarditis is 15–30%. The etiology of recurrent pericarditis is not fully understood. It is generally believed that immune-mediated mechanism may play a major role in the pathogenesis. Most patients have no clear etiological basis, and there are nonspecific myocardial antibodies in serum, which is called idiopathic recurrent pericarditis and is the most important type. Infection exists in some patients with recurrent pericarditis, and especially, viral infection is the most common. Pseudoaneurysms are formed by local destruction of aortic wall and local expansion of aortic lumen caused by pathogenic microorganism infection, which is often called infectious aortitis or infected aneurysm clinically at present. Infectious aneurysms account for 0.7–2.6% of all aortic aneurysms. The clinical misdiagnosis rate of the disease is

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high, with many complications and poor prognosis. The main causes of death are rupture and hemorrhage of aneurysms caused by infection and systemic infection complications. Inflammatory granulomatous vasculitis can involve different blood vessels, including macroangiitis mainly involving aorta and its main branches, polyarteritis nodosa involving small and medium arteries, and ANCA-related vasculitis involving small vessels.

References 1. Liu J.  Reflections on the relationship between immunity and inflammation in systemic infection. Chin J Emerg Med. 2017;26(11):1230–5.

J. Liu and X. Zheng 2. Chen J, Li G.  Pathology. Beijing: People’s Medical Publishing House; 1990. 3. Shen C, Ma L, Zhao C. Reflections on the confusion between infection and non-infection and clinical practice. J Intern Intensive Med. 2018;24(3):185–7. 4. Xiao Z, Qian G, Xia Q. Progress of research on mechanism of lung nonspecific defense. Immunol J. 2001;17(Z1):129–31. 5. Wang X, Li Y. Relationship between infection and diffuse connective tissue disease. J Clin Intern Med. 2018;35(9):646–8. 6. Cao X, Wu D, Hou Y.  Association of Epstein-Barr Virus infection with connective tissue diseases. Chin J Allergy Clin Immunol. 2016;10(4):402–6. 7. Li Z.  Research on systemic lupus erythematosus and bacterial infection should be expanded in depth. Chin J Rheumatol. 2016;20(3):145–7.

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X-Ray Imaging and CT Imaging Techniques of Great Vessels in Chest and Heart Jingzhe Liu and Jun Xia

2.1 X-Ray Imaging Technique Conventional X-ray examination is an important part of imaging for chest and is a widely used examination technique. Normal lungs are filled with air and have good natural contrast. X-ray examination has important clinical value in demonstrating lung diseases. Because the conventional X-ray image is a kind of overlapping image, the standard position of clinical X-ray examination for evaluating the chest image includes AP (posterior or anterior position) and LAT (lateral position) projection and the combination of AP and LAT allows for better assessment of lung disease. For the heart, conventional X-ray images cannot directly show the internal structure of the heart, so the enlargement of the heart, atriums, and ventricles can only be determined by analyzing the edge and contour of the heart, which has certain limitations. At present, posterior or anterior position is the basic position of cardiac X-ray examination and oblique position or left lateral position can be selected as needed by the disease. 1. AP (posterior or anterior position): The patient stands upright with the anterior chest wall close to the film, and the X-ray passes horizontally across the chest from posterior to anterior. Such position can be used to measure the heart and cardiac dimensions. To reduce the distortion caused by magnification, the X-ray machine tube should be at least 1.8  m away from the film (cassette) during projection. 2. LAT (lateral position): The patient takes lateral position, with left or right chest wall close to the film. Generally,

J. Liu (*) First Hospital of Tsinghua University (Beijing Huaxin Hospital), Beijing, China J. Xia Affiliated Hospital of Guangdong Medical University, Guangdong, China

the affected side is close to the film during chest X-ray examination, while the left side is close to the film during heart X-ray examination. 3. Oblique position. (a) Right anterior oblique position: The patient stands upright and rotates 45° to the left, with the right shoulder close to the film. (b) Left anterior oblique position: The patient stands upright and rotates 60° to the right, with the left shoulder close to the film. In the oblique position, barium can be administered, which is beneficial to determine the enlargement of cardiac chambers. 4. Bedside radiography: The patient generally takes semisitting anterior or posterior positions, which are mainly used for acute and severe patients and patients who cannot stand upright for radiography before recovery after operation. It should be noted that the image quality in bedside radiography is affected to some extent due to the great influence of position and respiration and there are considerable errors in determining heart size and heart shadow, which should be comprehensively determined in combination with clinical and other examinations.

2.2 CT Imaging Technique Computed tomography (CT) is a revolution in the history of medical imaging. Since the advent of CT machines in the 1970s, CT machines have been roughly upgraded in five generations, but with the emergence and popularization of spiral CT machines, the previous CT machines have been phased out [1]. Spiral CT can be divided into single-slice spiral CT and multislice spiral CT (MSCT). MSCT has the advantages of high scanning speed, wide coverage, high spatial resolution, and multiple post-processing techniques and can scan almost all organs of human body including the heart.

© Science Press 2023 H. Li et al. (eds.), Radiology of Infectious and Inflammatory Diseases - Volume 3, https://doi.org/10.1007/978-981-99-4614-3_2

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2.2.1 CT Imaging Technique of Chest

J. Liu and J. Xia

ECG-triggered or ECG-gated technique is the most important feature that distinguishes cardiac CT from other The rapid development of CT technology is of great value CT examinations. Heartbeat is a periodic motion. Assuming for improving the imaging diagnosis of chest diseases. CT is that the cardiac motion is in the same phase at the same currently the most important imaging examination method time in different cardiac cycles, ECG-triggered/gated techfor respiratory diseases. For respiratory diseases, CT plain nique should be used for data acquisition and reconstrucscan should be performed first and patients should hold their tion in cardiac CT examination, thus obtaining continuous breath during the scanning. Spiral CT can be used for thin-­ images of the entire heart [2]. Prospective ECG-triggered layer reconstruction, thus obtaining a thin-layer image of data acquisition is usually called prospective ECG-gated about 1 mm. Conventional CT requires adjustment of win- acquisition, which refers to setting exposure windows and dow width and position for observation, and the window can data acquisition in the cardiac cycle, thereby continuously be divided into lung window and mediastinal window. Bone obtaining cardiac images at different slices at the same window should be used when analyzing bony lesions in the phase in different cardiac cycles. With the advantage of the wide-body detector of MSCT, the examination of the entire chest wall. High-resolution CT (HRCT): Thin slice and high spatial heart can be completed in less than 3–4 cardiac cycles. The resolution algorithm (bone algorithm) are used to improve most important advantage of prospective ECG-gated acquithe spatial resolution and sharpness of CT images. HRCT is sition is to significantly reduce the X-ray radiation dose, suitable to be used for small intrapulmonary lesions, bron- but the heart rate of the subjects is generally under strict chiectasis, and diffuse intrapulmonary lesions. Due to the requirement. At present, prospective ECG-gated acquisidevelopment of MSCT equipment, conventional MSCT scan tion is mainly used for the cases where the heart rate is slow for reconstruction with 1–1.25  mm slice thickness can (less than 65 beats/minute) and the heart rhythm is uniform. replace HRCT currently. Retrospective ECG-gated acquisition refers to continuous CT enhanced scan: Iodine-containing contrast agent is injected intravenously to visualize the blood supply to CT scan in all cardiac phases while obtaining ECG data and lesions. It is generally used for the examination of chest then selecting the data during image reconstruction to use the space occupying lesions and vascular lesions but is rarely data of specific phases, thus obtaining cardiac CT images of used in the assessment of chest infection or inflammatory specific cardiac phases. Retrospective ECG-gated acquisilesions. CT enhanced scan is mainly used for differential tion is the most commonly used technique in cardiac CT examination at present, which is less demanding on the heart diagnosis or assessment of vascular complications. CT image post-processing technique: Multiplanar recon- rate and is suitable for most subjects. Its advantage is that the struction (MPR) is the most commonly used post-processing acquired data covers the entire cardiac cycle, and the images technique in the diagnosis of chest diseases. MPR can dis- of different phases of the cardiac cycle can be reconstructed play lesions from different directions and multiple planes. for cardiac function measurement. Its disadvantage is the The post-processing technique of MSCT includes maximum high dose of X-ray radiation. Non-ECG-gated acquisition: For patients who are uncointensity projections (MIPs), curved planar reconstruction operative or have significant arrhythmias, ECG-gated acqui(CPR), and volume rendering technology (VRT). sition cannot be implemented and conventional spiral scan can be used for the examination of non-ECG-gated cardiac CT. The advantages of non-gated acquisition are fast scan2.2.2 CT Imaging Technique of Heart ning speed and low radiation dose, but the motion artifact and Great Vessels interference of the image is significant, causing poor visualDue to the continuous beating of the heart, the speed of con- ization of the subtle structures of the heart and the inability ventional CT scan is not adequate for cardiac imaging and to perform coronary imaging. At present, non-ECG-gated the function of cardiac CT examination has been signifi- acquisition is mainly used for cardiac CT examination of cantly limited in a long period of time. The application of infant patients requiring no coronary artery visualization. Contrast enhancement: The blood in cardiac chambers MSCT has greatly promoted the development of cardiac CT and blood vessels has no natural contrast with myocardium examination technique, and the temporal resolution of 64-slice or above MSCT can even reach 200  ms or even and vessel walls. To improve the contrast of cardiac cham100 ms, and the spatial resolution can reach isotropic 0.5– bers and blood vessels, high-concentration iodine-containing 0.625 mm. MSCT is suitable for the examination of various contrast agent (350 mg/mL or 370 mg/mL) and high injeccardiac and macrovascular diseases, and CT angiography tion flow rate (usually 4–5 mL/s) should be used in MSCT (CTA) of arteries including coronary arteries has even imaging of heart and 30–40  mL normal saline should be injected at the same flow rate. become a routine clinical examination.

2  X-Ray Imaging and CT Imaging Techniques of Great Vessels in Chest and Heart

The duration for contrast agent to maintain a high concentration in cardiac chambers and blood vessels is limited, so it is necessary to accurately grasp the timing for exposure scanning. At present, the setting of scan delay time mainly involves low-dose contrast agent bolus injection testing technique, and contrast agent bolus injection tracking technique.

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References 1. Tang G, Qin N. Modern whole body CT diagnostics. 4th ed. Beijing: China Medical Science and Technology Press; 2019. 2. Li K.  Chinese clinical medical imaging  - cardiovascular. Beijing: Peking University Medical Press; 2016.

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Magnetic Resonance Imaging and Nuclear Medicine Imaging Techniques of Great Vessels in Chest and Heart Jingzhe Liu and Qingqiang Guo

3.1 Magnetic Resonance Imaging Technique 3.1.1 Magnetic Resonance Imaging of Chest 1. As a noninvasive imaging method, magnetic resonance imaging (MRI) of the lung has shown great superiority in the examination of other tissues in the human body. MRI of the lung was proposed as early as 1979. However, due to the low proton density in lung parenchyma, the influence of large magnetic susceptibility artefacts at gas tissue interface, and motion artifacts, traditional MRI techniques cannot obtain clear images of lung tissue. In recent years, with the booming MRI techniques, and the development and application of various fast imaging and short TE sequences, MRI has been increasingly used in the diagnosis and assessment of various lung diseases [1–3]. MRI features a higher resolution than CT in detecting soft tissue, especially sensitive to inflammatory exudates. Studies have shown that MRI has greater value in evaluating lung parenchyma and pleura in complex pulmonary infections as well as lymph node lesions. The results of a prospective study of 71 children show that MRI plain scan and MSCT enhanced scan have comparable diagnostic efficiency in finding chest abnormalities. It is suggested that MRI plain scan should be used instead of MSCT enhanced scan as the preferred tomographic imaging method for children’s chest diseases, thereby reducing the potential harm of radiation exposure and intravenous contrast agent to children [2]. Although CT is the most commonly used imaging method to diagnose and evaluate interstitial lung diseases, J. Liu (*) First Hospital of Tsinghua University (Beijing Huaxin Hospital), Beijing, China Q. Guo The First Affiliated Hospital of Xiamen University, Xiamen, China

CT remains controversial in evaluating the progress and response to therapy in interstitial lung diseases, mainly because CT has limitations in differentiating active inflammation from chronic fibrosis in interstitial lung diseases. Although MRI of the lung is not comparable to CT in spatial resolution and lung anatomical details, a growing number of studies in recent years have shown that lung MRI is helpful in differentiating active interstitial inflammation from fibrosis (Fig.  3.1). Active inflammation is characterized by T2WI hyperintensity in interstitium, while fibrosis is characterized by isointensity, which has important clinical significance for evaluating the condition of interstitial lung disease and predicting its response to therapy [1]. MRI of the lung can also be used to evaluate airway diseases. Larger tracheal and bronchial walls show hyperintensity on MRI, in obvious contrast to surrounding hypointense air. In addition, MRI can also evaluate pulmonary nodules and determine their benignity and malignancy. It can be used for the diagnosis and staging of lung cancer, with good clinical value and application prospect. 2. Hyperpolarized inert gas lung ventilation imaging: Traditional MRI uses the signal of hydrogen protons for imaging, but for the lung, the density of hydrogen proton is low, so the traditional MRI technique is not ideal for lung imaging. In recent years, hyperpolarized 3He and 129 Xe have been used to replace hydrogen protons in traditional MRI, thereby obtaining clear lung images. At present, the hyperpolarized inert gas MRI lung imaging technique mainly focuses on lung ventilation and lung perfusion [4]. Hyperpolarized inert gas MRI can perform 3D imaging of lung ventilation and perfusion, for quantitative or semiquantitative measurements that reflect local lung function. At present, its research at home and abroad is mainly used in asthma, chronic obstructive pulmonary disease, lung transplantation complications, cystic fibrosis, and pediatric patients, showing certain clinical value.

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Fig. 3.1  Comparison of CT and MRI of the lung with interstitial pneumonia. (a) CT lung window showed interstitial pneumonia in the lower lobes of both lungs, reticular opacities with ground-glass opacity, and

However, hyperpolarized inert gas MRI must use special devices to make the inert gas hyperpolarized and has special requirements for radio frequency (RF) coils, so its clinical routine application still has many limitations. 3. MRI of other chest diseases: MRI has good resolution for soft tissue and is an important examination method to evaluate mediastinal and chest wall diseases. MRI can clearly visualize mediastinal lesions, inflammatory edema features T2WI hyperintensity, so MRI can accurately evaluate the extent of mediastinal infection or inflammation, as well as the blood vessels and lymph nodes in mediastinum.

J. Liu and Q. Guo

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bronchiectasis; (b) MRI T2WI fat suppression sequence, interstitial pneumonia in lower lobes of both lungs, with patchy hyperintensity, suggesting the activity of interstitial pneumonia

1. Inversion recovery sequence, also known as black-blood technique, can highlight the tubular wall and myocardial tissue through multiple inversion with the blood showing hypointense signal. Inversion recovery sequence can well display the intracardiac structure and is the clearest scanning sequence to observe myocardial morphology and lesions. 2. Cardiac magnetic resonance cine imaging, also known as white blood technique, mainly uses fast steady-state equilibrium free precession sequence to make blood flow show hyperintensity. This sequence of images features high signal-to-noise ratio and short scanning duration. It can be used for ECG-gated dynamic scanning without intervals, dynamically observe the ventricular 3.1.2 Cardiac Magnetic Resonance Imaging wall motion of the whole cardiac cycle, quantitatively analyze and measure cardiac function parameters In recent years, with the rapid development of hardware and including ventricular volume, myocardial mass, stroke software of MRI, cardiac magnetic resonance imaging volume, and ejection fraction, and display valve stenosis (CMRI) has been increasingly used in clinical practice and and regurgitation. plays an important role in the diagnosis of cardiac diseases, 3. Myocardial (first-pass) perfusion imaging and delayed especially cardiomyopathy. A single cardiac MRI examinacontrast-enhanced magnetic resonance imaging refers to tion can provide a variety of information such as the structhe imaging methods of assessing myocardial perfusion ture of cardiac great vessels, cardiac motor function, cardiac by intravenous bolus injection of gadolinium-based conblood flow, cardiac perfusion, and metabolism, so it is called trast agent and dynamic acquisition of a series of images one-stop cardiac imaging examination [5]. Due to its advanof contrast agent passing through myocardium for the tages of multiparameter, multiplane, multisequence imaging first time by using fast imaging sequence. The delayed and high resolution of soft tissue, CMRI has become the 10–20 min scan after the injection of gadolinium-based “gold standard” for noninvasive assessment of cardiac struccontrast agent is called delayed enhanced scan, which can ture and function. At present, the conventional clinical applibe used to assess myocardial activity. cation of the cardiac MRI technique includes inversion 4. Other inspection techniques. recovery (IR) sequence, cardiac magnetic resonance cine (a) Quantitative imaging technique: T1 and T2 are intrinimaging, myocardial perfusion imaging, delayed contrast-­ sic properties of tissue and have specific values under enhanced cardiac magnetic resonance imaging, etc. specific field strengths. T1 and T2 mapping can

3  Magnetic Resonance Imaging and Nuclear Medicine Imaging Techniques of Great Vessels in Chest and Heart

directly measure the T1 and T2 values of myocardial tissue. (b) Magnetic resonance blood flow measurement: Magnetic resonance phase contrast velocityencoded cine imaging technique is generally used. Two-­ dimensional phase contrast technique can quantitatively measure the blood flow velocity and 2. flow of great vessels in heart and calculate the peak pressure difference of left ventricular outflow tract or heart valve according to the flow velocity. Four-­ dimensional blood flow analysis (4D flow) can obtain phase flow velocity-encoded data in three vertical spatial directions by using ECG-gated technique and diaphragm navigation technique. Through the change of velocity vector in three-dimensional space, the state and change of blood flow can be described in three-­dimensional visual forms such as velocity diagram, streamline diagram, and trace diagram, and conventional flow and velocity, hemodynamic parameters such as wall shear force, pulse wave velocity, pressure gradient, and energy loss can also be measured [6].

3.1.3 Magnetic Resonance Imaging of Great Vessels At present, the commonly used methods of magnetic resonance angiography (MRA) include time of flight (TOF), phase contrast (PC), contrast enhancement MRA (CE-MRA), and vascular wall imaging (VWI). 1. Time leap method and phase contrast method: They do not use contrast agent, but is mainly based on the natural contrast between hemodynamic characteristics and surrounding static tissues to clearly display the blood vessels in the corresponding parts. The two methods can be divided into 2D acquisition and 3D acquisition. 2D acquisition has fast imaging speed, but poor resolution, and is not as good as 3D acquisition in displaying small lesions. MRA examination without contrast agent has some disadvantages: (1) The long duration acquisition requires the cooperation of patients, and children or restless patients may have obvious artifacts; (2) because of the long scanning duration and saturation effect, the blood flow signal decreases and the small branches of blood

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vessels are not well displayed; (3) blood flow route and blood vessels with nonvertical or distorted scanning plane will cause signal loss and artifacts due to saturation, which may easily cause misdiagnosis; and (4) vascular stenosis or turbulence at bifurcations may also cause local signal loss, which may easily cause misdiagnosis. Contrast-enhanced MRA: Intravenous injection of paramagnetic gadolinium-based contrast agent (Gd-DTPA) can significantly shorten the T1 value of blood and enhance the contrast between blood vessels and background tissues, thus significantly improving the image quality of MRA, which is more reliable than MRA without contrast agent, and significantly reduces artifacts and illusions. CE-MRA is the best sequence to show the anatomical structure of blood vessels. In recent years, some new CE-MRA sequences have been used, such as TRICKS (time-resolved imaging of contrast kinetics sequence), which can shorten the scanning duration to 2–6  s each time, perform multiple dynamic scans, and dynamically display the inflow and outflow of contrast agents in cardiac chambers and great vessels, which is more similar to the traditional angiocardiography images. 3. Vascular wall imaging: Magnetic resonance high-­ resolution vascular wall imaging is an imaging method that uses magnetic resonance principle to suppress the signals of blood flowing in blood vessels to obtain vascular wall images [7]. Commonly used scanning sequences include spin echo, turbo spin echo (TSE), and black-­ blood technique. Black-blood technique can suppress the signals of blood flowing in the lumen of blood vessels and retain the signals of vascular wall. Multicontrast sequences based on black-blood sequences (T1WI plain scan and enhanced scan, and T2WI and proton density-­ weighted imaging) are currently the main sequences for clinical vascular wall imaging (Fig. 3.2). With the development of MRI technology, vascular wall imaging has entered a new stage from two-dimensional (2D) imaging to three-dimensional (3D) imaging. High-resolution 3D MRI technologies such as SPACE, VISTA, THRIVE, and CUBE have the advantages of higher isotropic resolution, faster imaging speed, and larger coverage, thus showing the vascular wall structure more accurately. VWI can be used for the assessment of atherosclerotic plaque and the diagnosis of wall lesions in vascular inflammatory diseases [8].

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J. Liu and Q. Guo

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Fig. 3.2  Vascular wall imaging (VWI) of Takayasu arteritis. (a) MRI T2WI black-blood technique fat suppression sequence showed that the abdominal aorta vessel wall annular thickening with increased signal;

(b) T1WI black-blood technique fat suppression sequence also clearly showed the annular thickening of vascular wall

3.2 Nuclear Medical Imaging Technique

ificity, positive predictive value, and negative predictive value of 18F-FDG PET for the diagnosis of vascular implant infection are 93%, 70%, 82%, and 88%, respectively, which are significantly higher than those of CT [10]. 18 F-FDG PET has certain value for the diagnosis and assessment of inflammatory diseases, such as sarcoidosis and Takayasu arteritis, which is helpful for the diagnosis and staging of multiple parts of the whole body, and for the treatment assessment and activity determination of systemic inflammatory diseases (Fig.  3.3). In addition, 67Ga-citrate, 111 In-leukocyte, 99mTc-monoclonal antibody, 111In-human immunoglobulin, and other radiopharmaceuticals can also be used for the imaging of infectious and inflammatory diseases.

The value of radionuclide imaging in the diagnosis of infectious and inflammatory diseases is increasingly recognized in clinical practice. 18F-FDG is a commonly used tracer in tumor diagnosis at present, with a large amount of uptake in many tumors. Studies have shown that cells involved in inflammation and infection, especially neutrophils, mononuclear macrophages, and proliferating fibroblasts, all feature high uptake of tracers. Therefore, 18F-FDG PET can be used to identify inflammation or infection lesions, especially for the etiological diagnosis of fever of unknown origin [9]. 18F-FDG PET is increasingly used to detect and assess cardiac and vascular implant infection. A study has shown that the sensitivity, spec-

3  Magnetic Resonance Imaging and Nuclear Medicine Imaging Techniques of Great Vessels in Chest and Heart

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Fig. 3.3  PET/CT evaluation of sarcoidosis. (a) 18F-FDG imaging showed multiple concentrated radionuclide uptakes in mediastinum and supraclavicle area and mild radionuclide uptake in left ilium; (b) at the 18 F-FDG PET/CT mediastinal lymph node, mediastinal lymph node concentrated radionuclide uptake indicated active lesions; and (c) at the

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References

5. Li K. Chinese clinical medical imaging - cardiovascular. Beijing: Peking University Medical Press; 2016. 6. Stankovic Z, Allen BD, Garcia J, et  al. 4D flow imaging with MRI. Cardiovasc Diagn Ther. 2014;4(2):173–92. 7. Jung SC, Kang DW, Turan TN.  Vessel and vessel wall imaging. Front Neurol Neurosci. 2017;40:109–23. 8. Raman SV, Aneja A, Jarjour WN. CMR in inflammatory vasculitis. J Cardiovasc Magn Reson. 2012;14(1):82. 9. Li H. Diagnostic imaging of infections and inflammatory diseases. Beijing: Science Press; 2018. 10. Liu S, Shi H.  Application of 18F-FDG PET/CT in cardiovascular infection. Chin J Nucl Med Mol Imaging. 2018;38(12):821–3.

1. Romei C, Turturici L, Tavanti L, et al. The use of chest magnetic resonance imaging in interstitial lung disease: a systematic review. Eur Respir Rev. 2018;27(150):180062. 2. Gorkem SB, Coskun A, Yikilmaz A, et  al. Evaluation of pediatric thoracic disorders: comparison of unenhanced fast imaging sequence 1.5T MRI and contrast-enhanced MDCT.  AJR Am J Roentgenol. 2013;200(6):1352–7. 3. Zhang L, Liu J, Li X. Research progress of MRI in children with pulmonary diseases. Int J Med Radiol. 2014;37(4):337–41. 4. Chen S, Sun X, Zhou K.  Study on hyperpolarized MRI.  J Pract Radiol. 2009;25(2):284–8.

F-FDG PET/CT left ilium, mild radionuclide uptake indicated left iliac bone lesion, suggesting sarcoidosis (case images by courtesy of Professor Jianhua Zhang, Department of Nuclear Medicine, Peking University First Hospital)

4

Pathological and Imaging Findings of Infectious and Inflammatory Diseases of Chest Jingzhe Liu and Hengfeng Shi

Inflammation is the common pathological basis of infectious and noninfectious lesions. The basic lesions of inflammation include deterioration, exudation, and hyperplasia. Deterioration means degeneration and necrosis of local tissues and cells of inflammation [1]. Exudation means that body fluids and cellular components in blood vessels in inflammatory lesions enter the surrounding tissue space through the vascular wall. Hyperplasia is the proliferation of tissue cells in inflammatory lesions stimulated by inflammatory factors. Infectious or inflammatory diseases have these three basic changes in pathology, but each disease is different in severity of changes. The three changes are interrelated and mutually transformed. For example, tuberculosis is mainly manifested by hyperplasia. If the body’s resistance declines, it can turn into deterioration and exudation. X-ray and CT are the most commonly used imaging methods for chest diseases. Chest X-ray radiography (hereinafter referred to as chest radiography) is the preferred screening method for suspected chest infection or inflammation, and its value lies in finding abnormalities consistent with pneumonia, monitoring treatment effect, assessing lesion scope, and finding complications such as cavity, abscess, pneumothorax, and pleural effusion. CT has better histological and spatial resolution, can provide anatomical details similar to gross pathological examination, and is more sensitive to the detection of chest infection and inflammatory diseases. CT can evaluate chest abnormalities from large airway to secondary pulmonary lobules and alveoli, and it can find a variety of air cavity lesions, including ground-glass opacities, consolidation, air bronchograms, air cavity nodule, and “tree-in-bud” sign. CT can also evaluate interstitial lesions such as thickened interlobular septa, retic-

J. Liu (*) First Hospital of Tsinghua University (Beijing Huaxin Hospital), Beijing, China H. Shi Anqing Municipal Hospital, Anqing, China

ular nodule, and honeycomb lung, which is helpful for the diagnosis and differential diagnosis of infectious and inflammatory diseases, as well as excluding other potential lung diseases. Imaging is a “mirror” of pathology, and various imaging signs of diseases are consistent with their pathological changes. A specific disease may have a variety of pathological changes, and correspondingly, the imaging manifestations are also diverse. Understanding the pathological changes of the disease is crucial for understanding the imaging features [2].

4.1 Lesions Occurring in the Alveoli Bronchus enters the lung through the hilum and is divided into lobar bronchi and segmental bronchi at first and then continues to branch into bronchioles, terminal bronchioles, respiratory bronchioles, alveolar ducts, alveolar sacs, and alveoli in about 24 grades. Pulmonary alveoli are the terminal part of bronchial tree, which are polyhedral vesicles and the main site for gas exchange in the lung. One side of the alveoli is open to the alveolar sac, alveolar duct, or respiratory bronchiole, and the other sides are alveolar walls and connected with adjacent alveoli. The alveolar wall is composed of a single layer of squamous epithelium, and the thin layer of connective tissue between adjacent alveolar walls contains dense capillary network, which is called alveolar septum. Alveoli communicate with each other through interalveolar pores (pores of Kohn). Generally, there can be 1–6 Kohn pores on one alveoli. The pore is a channel for communicating gas in adjacent alveoli. If a bronchiole is blocked, collateral ventilation can be established through the pore and some alveolar lesions can also spread to adjacent lung tissues through the pores of Kohn. Infectious or inflammatory lesions occurring in the alveolar space mainly include the following categories:

© Science Press 2023 H. Li et al. (eds.), Radiology of Infectious and Inflammatory Diseases - Volume 3, https://doi.org/10.1007/978-981-99-4614-3_4

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1. Lobar pneumonia: It is mainly inflammation caused by Streptococcus pneumoniae infection, mainly manifested by pulmonary fibrinous exudation. The lesion begins in alveoli, and its histological features are exudative edematous fluid and neutrophils filling gas-filled alveolar space, usually starting from lung tissue adjacent to visceral pleura and rapidly spreading to several lung segments and even the whole lung lobe through interalveolar pores, making the bronchi remain inflated. Involvement of pleura causes exudative inflammation of the pleura. Chest X-ray radiography and CT show that homogeneous lung consolidation and adjacent lung segments may be involved, and air bronchograms can be seen in lung consolidation. Ground-glass opacity areas around consolidation are sometimes seen on CT, representing incomplete alveolar filling (Fig. 4.1). 2. Eosinophilic pneumonia: Simple eosinophilic pneumonia is characterized by a large number of eosinophils in alveolar exudate, widened alveolar septum, infiltration of eosinophils, lymphocytes and plasma cells in interstitium, and compensatory emphysema in lung tissue far away from lesions. The exudate in alveolar space is manifested by transient and migratory consolidation or ground-glass opacity area on chest radiograph and CT, and the infiltration of inflammatory cells in pulmonary interstitium shows smoothly thickened interlobular septa on CT (Fig. 4.2).

a

3. Alveolar hemorrhage: Diffuse alveolar hemorrhage can occur in various alveolar hemorrhage syndromes, including pulmonary hemorrhage-nephritis syndrome, idiopathic hemosiderosis, Wegener’s granulomatosis, and systemic lupus erythematosus. Pathological manifestations are diffuse alveolar hemorrhage, fresh hemorrhage in alveolar space, and hemosiderin, which is usually deposited in alveolar macrophages or deposited extracellularly. It is manifested by thickened alveolar septum and proliferated alveolar epithelial cells. X-ray and CT show ground-glass opacities and consolidations evenly distributed in both lungs, and air bronchograms can be seen in large patchy consolidation (Fig.  4.3). Repeated chronic hemorrhage shows persistent reticular nodules, suggesting interstitial lesions. CT shows diffuse 1–3 mm centrilobular nodules, thickened interlobular septa, and intralobular septa (Fig. 4.4). 4. Organizing pneumonia: It is often secondary to pneumonia not be completely absorbed. Pathologically, loose fibrous polypoid tissue composed of fibroblasts can be seen in alveolar space, which can reach adjacent alveolar space through interalveolar pores. Sometimes, organizing fibrous polypoid tissue can extend into the bronchioles. Chest X-ray radiography and CT show patchy consolidation at the basal part of both lungs.

b

Fig. 4.1  Lobar pneumonia. (a) Chest X-ray radiograph showed large patchy consolidation in the upper lobe of the right lung with homogeneous opacity (long arrow) and (b) CT lung window showed homoge-

neous patchy consolidation in the upper lobe of the right lung, with air bronchogram (short arrow) and a small amount of ground-glass opacity around (long arrow)

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4.2 Lesions Occurring in the Small Airway The airway features an asymmetrical branched dendritic tubular structure, and each bronchus is subdivided into asymmetrical inferior bronchus. Clinically, cartilage-free bronchioles with inner diameter less than 2 mm are usually called small airways. Small airway features small airflow resistance but easy obstruction. Bronchioles can be divided into membranous bronchioles, terminal bronchioles, and respiratory bronchioles. Bronchial tree is anatomically and physiologically continuous. At present, it is impossible to distinguish the small airway from other bronchial structures, but they have different clinical and physiological abnormalities, so whether the disease involves the small airway or the large airway should be distinguished. Fig. 4.2  Eosinophilic pneumonia. CT lung window showed subpleural patchy consolidation of both lungs (long arrow) and thickened interlobular septa (short arrow)

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Fig. 4.3  Alveolar Hemorrhage (I). (a) CT lung window showed large patchy ground-glass opacity (arrow) evenly distributed in both lungs, suggesting a small amount of alveolar hemorrhage in alveolar space

1. Bronchiolitis mainly involves inflammatory changes of bronchioles less than 2 mm in diameter, including follicu-

b

and (b) the low density of a small amount of hemorrhage in the alveolar space caused chest X-ray radiograph negative

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a

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Fig. 4.4  Alveolar Hemorrhage (II). (a) CT lung window showed symmetrical ground-glass opacities in the lower lobes of both lungs with a small number of reticular nodules, suggesting that repeated alveolar hemorrhage leads to interstitial lesions; (b) chest X-ray radiograph

c

showed symmetrical patchy ground-glass opacities in the lower lobes of both lungs, and reticular nodules occurred in the lesions; and (c) after 5 days, alveolar hemorrhage was absorbed and reticular nodule opacities were more significant (arrow)

4  Pathological and Imaging Findings of Infectious and Inflammatory Diseases of Chest

lar bronchiolitis, cellular bronchiolitis, respiratory bronchiolitis, diffuse panbronchiolitis, bronchiolitis obliterans, and so on [2]. (a) Follicular bronchiolitis: It is a proliferative lesion of bronchus-associated lymphoid tissue, which is limited to bronchiolar lymphoid tissue hyperplasia. The histopathological features are local lymphoid tissue aggregation and hyperplasia around bronchiolar wall and lymphoid follicles formation, air cavity compressed and narrowed, and lymphoid tissue hyperplasia can also be seen in adjacent interstitium around bronchioles. Such feature can be seen in rheumatoid arthritis, Sjogren syndrome, and other connective tissue diseases and immunodeficiency diseases. (b) Cellular bronchiolitis: Inflammation located in bronchioles may or may not be accompanied by fibrosis or metaplasia surrounding bronchioles. It can be divided into acute bronchiolitis, chronic bronchiolitis, and mixed bronchiolitis (acute and chronic ­bronchiolitis). Acute bronchiolitis is characterized by acute inflammatory cells filling the bronchiolar lumen and wall of bronchioles with or without epithelial necrosis and exfoliation. Chronic bronchiolitis features chronic inflammation in the lumen and wall with or without lymphatic follicles. Acute and chronic bronchiolitis can occur in infections (bacterial, viral, or mycoplasma infections), connective tissue diseases, inflammatory bowel diseases, etc. (c) Respiratory bronchiolitis: Also known as smoker bronchiolitis, with the lesions distributed along respiratory bronchioles. In addition, macrophage aggregation can also be seen in adjacent alveolar ducts and alveolar spaces. (d) Diffuse panbronchiolitis: Pathologically, it is mainly manifested as bronchiolitis and peribronchiolitis centered on respiratory bronchioles, with thickened bronchial wall, infiltration of inflammatory cells such as lymphocytes, plasma cells, and histiocytes, and the lesions involve the whole wall of bronchioles, thus becoming panbronchiolitis. Typical diffuse panbronchiolitis is distributed in both lungs. (e) Bronchiolitis obliterans: The pathological features are mucosa concentric fibrosis of terminal bronchioles and respiratory bronchioles, resulting in small airway stenosis or occlusion. It is often secondary to viral infection, rheumatoid arthritis, and drug injury. • X-ray: Bronchiolitis can be manifested as small nodules or reticular nodules, hyperinflation in the involved lung field, etc. However, due to the small lesions, X-ray has limited value in the diagnosis

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Fig. 4.5  “Tree-in-bud” sign of bronchiolitis. CT lung window showed scattered centrilobular nodules in both lungs, and typical “tree-in-bud” sign occurred in the lower lobe of the right lung (arrow)

and differential diagnosis of bronchiolitis. HRCT has become the preferred imaging method for bronchiolitis patients. • CT: Normal bronchioles are about 0.6  mm in diameter and 0.1  mm in wall thickness, which cannot be displayed by HRCT.  CT findings of different types of bronchiolitis can be divided into direct signs and indirect signs. Direct signs are thickened bronchiolar wall or fibrosis, which is characterized by centrilobular nodules and branching line shadows, similar to sprouting branches, called “tree-in-bud” sign (Fig.  4.5). Centrilobular nodules represent inflammation and thickened wall of bronchioles. The edges of centrilobular nodules in infectious bronchiolitis and panbronchiolitis are often clear and sharp, while those in respiratory bronchiolitis are blurred (Fig.  4.6). Indirect signs are caused by reflex vasoconstriction secondary to airway obstruction, and blood flow redistribution of uninvolved lung results in uneven lung density, which is called mosaic attenuation (Fig.  4.7). Small airway obstruction caused by bronchiolitis can also lead to local air-trapping, which is characterized by increased transparency of affected lung field. Expiratory CT is more sensitive to detect air retention. 2. Exogenous allergic alveolitis, also known as hypersensitivity pneumonitis, is an allergic inflammatory lung disease caused by inhalation of various organic matters or inorganic dust. Inhaled allergens are mostly

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Fig. 4.6  Centrilobular nodules. (a) Panbronchiolitis features diffuse centrilobular nodules (arrow) in both lungs, with clear and sharp edges and (b) centrilobular nodules (arrow) with blurred edges in respiratory bronchiolitis

Fig. 4.7  Mosaic attenuation. CT lung window showed uneven density of both lungs, and centrilobular nodules were visible in hypodense area (arrow)

deposited in bronchioles and alveolar epithelium, causing bronchiolitis and alveolitis, and membranous bronchioles and proximal respiratory bronchioles are the most serious lesions. The main manifestations are bronchiolar inflammatory cell infiltration, and small non-necrotizing granuloma can be seen around bronchioles and pulmonary interstitium. Chronic hypersensitivity pneumonitis can cause pulmonary parenchymal fibrosis. The typical imaging findings of acute allergic alveolitis are ground-glass opacity and centrilobular nodules with blurred edges in both lungs, representing alveolitis and bronchiolitis, respectively (Fig. 4.8). In the chronic stage, the disease is manifested by thickened interlobular septa, traction bronchiectasis, and honeycomb lung changes.

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Fig. 4.8  Allergic alveolitis. (a) CT lung window showed diffuse centrilobular nodules with blurred edges in both lungs and (b) in another patient, diffuse patchy ground-glass opacity (arrow) centrilobular nodules with blurred edges occurred in both lungs

4.3 Lesions Occurring in the Large Airway The lesion of the large airway refers to the lesion involving the larger bronchus in lobes or segments and subsegments with cartilage (before the sixth-grade branch). 1. Bronchopneumonia: The peribronchial patchy inflammation is different from lobar pneumonia, which may be related to the formation of less inflammatory edema in bronchopneumonia, stronger pathogen virulence, and severe tissue injury. Lesion progression can also cause consolidation of lung lobes and segments. The main pathogenic bacteria are Staphylococcus aureus, Haemophilus influenzae, Pseudomonas aeruginosa, and Escherichia coli. X-ray radiograph shows bilateral multiple patchy consolidation, and typical CT findings include thickened bronchial wall, alveolar nodules, and multiple lobular consolidation foci (Fig. 4.9). 2. Chronic bronchitis: Chronic nonspecific inflammation of bronchial wall. It is manifested as epithelial degeneration and necrosis of bronchial mucosa, hyperplasia, congestion and edema of mucosal capillaries, infiltration of chronic inflammatory cells, and increased mucus in bronchial cavity, sometimes accompanied by acute inflammatory cell infiltration. X-ray examination results may show no abnormality, while CT often shows thickened bronchial wall and concomitant emphysema, pulmonary bullae, and other changes. 3. Bronchiectasis: It refers to chronic irreversible enlargement of bronchus. Common pathogenesis includes bronchial obstruction, bronchial wall injury, and pulmonary

parenchymal fibrosis (traction bronchiectasis). Bacterial and viral infections, cystic fibrosis, and immunodeficiency diseases in childhood can all cause bronchiectasis. Pulmonary fibrosis caused by pulmonary tuberculosis, sarcoidosis, and pulmonary fibrosis can also lead to traction bronchiectasis. According to the morphology, bronchiectasis can generally be divided into columnar, varicose, and cystic dilatation in pathology. Histologically, thickened bronchial wall can be manifested by chronic inflammatory cell infiltration. X-ray radiograph shows the thickened bronchial wall, with visible parallel linear opacities (“double track” sign), while cross-sectional observation features blurred annular shadows. Multiple cystic bronchiectasis is characterized by multiple thin-walled annular shadows, often with gas–liquid plane. CT shows dilatation of bronchial lumen, and the inner diameter of bronchus is larger than that of accompanying pulmonary artery (Fig. 4.10). 4. Bronchial mucus impaction: The general pathological manifestation is that the dilated bronchial lumen is full of mucus, mixed with mucus, fibrin, eosinophils, neutrophils, and cell necrosis debris. Bronchial mucus impaction can be seen in asthma, chronic bronchitis, and cystic fibrosis. Allergic bronchopulmonary aspergillosis can also cause bronchial mucus impaction. X-ray radiograph shows bronchus filled with mucus manifested by tubular or oval shadows. CT can directly show the dilated bronchial lumen filled with density foci similar to fluid, and no enhancement can be obtained with enhanced scan (Fig. 4.11).

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Fig. 4.9  Bronchopneumonia. (a) CT lung window showed thickened bronchial wall (arrow) in basal segment of lower lobe of right lung, suggesting bronchial inflammation and (b) multiple lobular consolidation (arrow) occurred in the lower lobe of the right lung Fig. 4.10  Bronchiectasis. CT lung window showed dilatation of bronchial lumen in the middle and upper lobe of right lung (arrow)

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Fig. 4.11  Bronchiectasis with mucus impaction. (a) CT lung window showed bronchiectasis in the lower lobe of the left lung, and mucus impaction (arrow) occurred in the bronchus and (b) with enhanced scan, mediastinal window showed no enhancement of lesions

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4.4 Acute Lung Injury (Diffuse Alveolar Damage)

4.5 Lesions Occurring in Pulmonary Interstitium

Diffuse alveolar damage (DAD) is a pathologic descriptive name characterized by alveolar and interstitial edema, hyaline membrane formation, and type II alveolar epithelial hyperplasia. According to the pathogenesis of the disease, the pathological changes of diffuse alveolar damage can be divided into acute stage (exudation stage) and proliferative stage (organizing stage), which are in a continuous process without clear boundary and may exist simultaneously. Acute stage is manifested as edema in pulmonary interstitium and alveoli accompanied by unequal erythrocyte exudation and fibrin deposition. Since the first day or in several days after the disease onset, a hyaline membrane rich in cytoplasmic substances and cell debris forms close to the alveolar wall and gradually increases. Inflammatory cells such as lymphocytes, plasma cells, and phagocytes infiltrate in lung interstitium. Under normal circumstances, about 95% of the type I alveolar epithelial cells in the lung covers the alveolar wall. In case of diffuse alveolar damage, the type I alveolar epithelial cells swell, degenerate, and shed in large quantities and type II alveolar epithelial cells proliferate [3]. The proliferative stage begins 1 week or more after onset, and its pathological features are fibroblast proliferation and inflammatory cell infiltration in alveolar septum, and edema in interstitial and alveolar spaces decreases, and lesions may eventually lead to pulmonary interstitial fibrosis and peribronchial fibrosis. Diffuse alveolar damage can be caused by many pathogenic mechanisms, including infection, radiation pneumonitis, drug-induced pneumonitis, and systemic lupus erythematosus. X-ray radiograph mainly shows patchy consolidation in the middle and lower fields of both lungs. CT shows extensive ground-glass opacity and consolidation in both lungs (Fig. 4.12).

1. Interstitial pneumonia: The histological characters of interstitial pneumonia are infiltration of mononuclear inflammatory cells in alveolar septum and interstitium around small vessels. The most common pathogens are Mycoplasma pneumoniae, virus, and Pneumocystis jirovecii. Small airway involvement (bronchiolitis), edema, and inflammatory cell infiltration in peribronchiolar tissues and interlobular septa are common in Mycoplasma pneumoniae and viral infection. Chest radiograph shows extensive distribution of increased lung markings and reticular nodules. On CT, bronchiolitis is manifested as small centrilobular nodules and branched linear opacities (“tree-in-bud” sign). Pneumonia caused by Pneumocystis jirovecii is the most common opportunistic lung infection in HIV-infected patients. Pneumocystis jirovecii survives on the surface of alveoli and histologically shows inflammatory exudate filling in alveolar space, accompanied by lymphocyte and plasma cell infiltration in adjacent interstitium to varying degrees. The most common X-ray findings of Pneumocystis jirovecii pneumonia are blurred ground-glass opacities or fine reticular nodules in both lungs. CT shows typical bilateral patchy or ground-glass opacity lesions, with map-like appearance, mainly involving the perihilar area or upper lobe of lung, and pulmonary reticular opacities or thickened interlobular septa are manifested in some patients (Fig. 4.13). 2. Idiopathic interstitial pneumonia (IIP) is a group of interstitial lung diseases with unknown etiology. The common features of pathological manifestations are unexplained pulmonary inflation and terminal pulmonary interstitial deformation, accompanied by inflammation and/or fibro-

Fig. 4.12  Acute alveolar injury. CT lung window showed extensive distribution of ground-glass opacity and consolidation in both lungs

Fig. 4.13  Interstitial pneumonia (Pneumocystis jirovecii pneumonia). CT lung window showed ground-glass opacity and pulmonary reticular opacities in both upper lobes

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sis to varying degrees. Histopathological classification plays an important role in distinguishing different subtypes of IIP and guiding the treatment and prognosis of IIP. In 2013, the new IIP classification scheme [4] jointly formulated by American Thoracic Society (ATS) and European Respiratory Society (ERS) includes two categories: (1) common interstitial pneumonia, idiopathic pulmonary fibrosis, idiopathic nonspecific interstitial pneumonia, respiratory bronchiolitis, desquamative interstitial pneumonia (DIP), cryptogenic organizing pneumonia, acute interstitial pneumonia, etc. and (2) rare interstitial pneumonia, idiopathic lymphocytic interstitial pneumonia, pleuropulmonary fibroelastosis, and unclassified interstitial pneumonia. Idiopathic interstitial pneumonia has various imaging manifestations, which will be described in detail in Chap. 24.

necrotizing granulomas composed of epithelial cells. Immunocompromised patients may show nonspecific inflammatory reactions such as histiocyte infiltration, acute, and chronic inflammation. Pulmonary tuberculosis is manifested as ill-defined nodules on chest radiograph, involving the upper lobe or the dorsal segment of the lower lobe of the lung. On CT, pulmonary tuberculosis is manifested as small centrilobular nodules and branched linear opacities (“tree-­ in-­ bud” sign), which represented endobronchial dissemination of pulmonary tuberculosis. Consolidation and cavitation may occur during lesion progression (Fig. 4.14). (b) Granuloma caused by fungi: Most of them are caused by Histoplasma, Cryptococcus, Blastomyces, Coccidiococcus, and Aspergillus. According to the host immune status and fungal virulence, the pathological changes are different. Acute stage features 4.6 Pulmonary Granulomatous mostly acute granulomatous pneumonia, showing Inflammation and Granulomatous acute fibrinous inflammation, followed by epithelioid Disease granuloma and multinucleated giant cell reaction, granuloma formation, and necrosis in the center. The 1. Necrotizing epithelioid cell granuloma. imaging manifestations of pulmonary fungal infec (a) Tuberculous granuloma: It is currently the most comtion are diverse, typically showing single or multiple mon pulmonary inflammatory granulomatous disnodules, lung consolidation, miliary nodules, and a ease in China. The lesion is necrotizing granulomatous few cavities (Fig. 4.15). inflammation. The typical lesion is a confluent epi- 2. Non-necrotizing epithelioid cell granulomatous sarcoidthelioid cell nodule with caseous necrotic tissue at osis: The pathological feature is granulomatous inflamthe center and fibrous connective tissue and chronic mation. Granuloma is composed of tufted epithelial cells, inflammatory cell infiltration at the periphery. The multinucleated giant cells, a small number of lymphopathological changes of pulmonary infection with cytes, and other inflammatory cells, without caseous non-tuberculous mycobacteria are similar to those of necrosis. Most of the lesions are located in pleura, interMycobacterium tuberculosis, which are often necrolobular septa, and along bronchial vessels. Early granulotizing granulomatous inflammation or non-­ matous inflammation can be completely dissipated. With a

b

Fig. 4.14  Tuberculosis. (a) CT lung window showed nodules and masses with blurred edges in left upper lobe of lung and (b) the other side showed the cavities formed in the mass, with surrounding “tree-in-bud” sign (arrow)

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Fig. 4.15  Pulmonary mycosis. (a) CT lung window showed multiple nodules scattered in both lungs with blurred edges (arrow) and (b) the other side showed patchy consolidation and ground glass opacity (arrow)

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Fig. 4.16  Pulmonary sarcoidosis. (a) CT lung window showed multiple small nodules (arrow) scattered in both lungs, distributed along bronchovascular bundle, pleura, and interlobular fissure and (b) mediastinal window showed bilateral hilar enlarged lymph nodes (arrow)

the progress of lesions, granulomas can be connected with each other, accompanied by fibrous tissue. The imaging findings are mainly hilar and mediastinal lymph node enlargement, bilateral pulmonary nodules, and reticular nodules (Fig. 4.16). 3. Pulmonary granuloma with vasculitis. (a) Wegener’s granulomatosis: Typical Wegener’s granulomatosis is characterized by necrotizing granuloma with necrotizing vasculitis. Pathologically, it is mostly manifested as irregular nodular masses of different sizes, with necrotic areas or cavities in the center of the lesions. There are large patchy necrotic areas at the lesion site, with epithelioid histiocytes around the necrotic areas. Small-to-medium-sized arteries and veins in the lesion areas show localized



or generalized vasculitis, mostly involving the media of vascular wall, with occasional necrosis, epithelioid granulomas, or multinucleated giant cell aggregation. The typical X-ray findings are multiple nodules with a diameter of 1–4 cm, 75% of which were bilateral, with thick-walled cavities in the nodules. CT findings show multiple nodules randomly distributed with cavities (Fig. 4.17). (b) Churg–Strauss syndrome: A rare vasculitis and granulomatous disease. Histologically, there are three basic changes: medium-sized arteriovenous vasculitis, eosinophilic infiltration in lung tissue, and extravascular granuloma. Typical lung manifestations are asthmatic bronchitis, eosinophilic pneumonia, extravascular granuloma, and vasculitis. The most com-

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Fig. 4.17  Wegener’s granulomatosis. (a) CT lung window showed multiple nodules scattered in both lungs, with cavities in the nodules of the dorsal segment of the right lower lobe and (b) patchy ground-glass opacities visible in both lungs (arrow)

mon imaging manifestation is transient patchy nonsegmental lung consolidation, which is similar to the lesion distribution of eosinophilic pneumonia. 4. Eosinophilic granulomatosis. (a) Langerhans cell histiocytosis: An unexplained pulmonary interstitial lesion characterized by Langerhans cell tumor-like hyperplasia. According to the disease development process, it can be divided into early lesions, hyperplastic lesions, and fibrotic lesions. The early stage is manifested by cell infiltration in the interstitium of membranous bronchioles and proximal respiratory bronchioles. The cells mainly include Langerhans cells, eosinophils, lymphocytes, plasma cells, and a small amount of neutrophils, with local nodular granulomatous changes. Eosinophils in nodules are markedly increased, which may form eosinophilic abscess, and occasionally the nodules show cystic changes. In the advanced stage of the lesion, the cellular infiltration spreads to the alveolar interstitium adjacent to the affected airway, with central fibrosis and epithelial cell hyperplasia. With further progress of the lesion, the granulomatous changes disappear and the fibrosis of lung tissue becomes more obvious. In the later stage of the disease, the lungs are almost replaced by fibrous tissue and cystic space. X-ray radiograph shows Langerhans cell histiocytosis manifested as small nodules with a diameter of 1–10 mm in early stage,



diffusive in both lungs, mainly in upper and middle lungs. It develops into reticular nodules in the advanced stage and shows thick pulmonary reticular opacities in the end stage with cystic changes, which is consistent with its pathological evolution. The most common abnormalities on CT are diffuse nodules and cystic degeneration. Most of the nodules are 1–5 mm in diameter and show centrilobular distribution mostly, corresponding to peribronchiolar granulomatous inflammation on pathological results (Fig. 4.18). The advanced stage is mainly manifested by cystic degeneration, with the diameter of cysts ranging from several millimeters to several centimeters and round or irregular shape. In the later stage, fibrosis occurs in the lung, showing diffuse honeycomb lung changes. (b) Parasitic granuloma: A variety of parasites including pulmonary schistosomiasis, paragonimiasis, or pulmonary hydatid, can cause exudative inflammation in the lung, mainly manifested as congestion, hemorrhage, and eosinophilic infiltration. There may be epithelioid cells and multinucleated giant cells around parasites or their eggs, possibly with fibrosis and granuloma. Imaging findings of inflammation caused by larval migration are characterized by patchy, migratory consolidation or ground-glass opacity, and small nodules with blurred edges or rare reticular nodules.

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Fig. 4.18  Langerhans cell histiocytosis. (a) CT lung window showed scattered multiple centrilobular nodules in both lungs (arrow) and (b) cystic degeneration occurred in some nodules (arrow)

4.7 Pulmonary Vasculitis The pathological feature of pulmonary vasculitis is inflammatory reaction of vascular wall, involving vascular full-­ thickness, as well as large, medium, and small arteries and veins. Microscopically, polyvasculitis mainly involves small pulmonary vessels, including arterioles, capillaries, and venules. Behcet’s disease involves vessels of all diameters, including pulmonary arteries, pulmonary veins, and alveolar septal capillaries. Arteritis can cause thrombosis, arteriovenous fistula, and periadventitial fibrosis, possibly followed by pulmonary hemorrhage, pulmonary infarction, and pneumonia. In fact, vasculitis may occur in many diseases, such as Wegener’s granulomatosis, Churg–

Strauss syndrome, lung infection, and connective tissue disease.

References 1. Huang Q, Wang Q. Pathology. 3rd ed. Beijing: Science Press; 2013. 2. Liu T.  Diagnostic pathology. 3rd ed. Beijing: People’s Medical Publishing House; 2013. 3. Tang G.  Diffuse lung diseases  - clinical features, pathology, HRCT. Beijing: People’s Military Medical Press; 2009. 4. Travis WD, Costabel U, Hansell DM, et  al. An official American Thoracic Society/European Respiratory Society statement: update of the international multidisciplinary classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med. 2013;188(6):733–48.

Part II Infectious Diseases of Chest

5

Bacterial Infection Yonggang Li, Renjun Huang, Jingfen Zhu, Yue Teng, Bailu Liu, Zhehao Lyu, and Tingting Chen

5.1  Streptococcus Pneumoniae Yonggang Li

5.1.1 Overview Streptococcus pneumoniae usually inhabits the nasopharyngeal cavity of normal people, most of which are not pathogenic, and only a few are virulent. If the body’s resistance decreases, it can often invade lung tissue and cause pneumonia. In addition, septicemia, sinusitis, otitis media and purulent meningitis may also occur in this case. Streptococcal pneumonia, formerly called lobar pneumonia (accounting for about 90% of out-of-hospital-acquired pneumonia), features typical symptoms such as sudden chills, high fever, cough, rust-colored sputum and chest pain. Streptococcus pneumoniae is a common pathogen of pneumonia, and it is also the most common pathogen among hospitalized patients with pneumonia. Young and middle-aged men are prone to Streptococcus pneumoniae, which occurs frequently in winter and spring. There are usually inducements such as getting caught in the rain, catching a cold, fatigue and drunkenness, and most of the patients have prodromal symptoms of upper respiratory tract infection. However, in recent 20 or 30 years, the resistance of Streptococcus pneumoniae to antibiotics has been increasing, causing some difficulties to clinical treatment.

Y. Li (*) · R. Huang · J. Zhu · Y. Teng The First Affiliated Hospital of Soochow University, Soochow, China B. Liu · T. Chen The 2nd Affiliated Hospital of Harbin Medical University, Harbin, China Z. Lyu The First Affiliated Hospital of Harbin Medical University, Harbin, China

The occurrence of Streptococcus pneumoniae is mostly related to the infection of respiratory tract by Streptococcus pneumoniae, which is a common bacterial infectious pneumonia in clinical practice and a common type of community-­ acquired pneumonia. Streptococcus pneumoniae can often be cultured in the nasopharynx of healthy people. However, because normal respiratory tract has many protective mechanisms to prevent pulmonary infection, such as ciliary movement, cough reflex and macrophage phagocytosis, Streptococcus pneumoniae cannot cause diseases under normal circumstances. This disease occurs only when the number of bacteria entering the airway is too large or the normal defense function of the respiratory tract is compromised. Clinically, most of the symptoms are acute onset, high fever, accompanied by chills, cough with brown sputum, purulent sputum or bloody sputum, chest pain, increased C-reactive protein (CRP) and significant increase in the total number of peripheral blood leukocytes. Lung consolidation signs: (1) In the early stage, the decreased respiratory movement amplitude and respiratory sound of the affected thoracic cavity; (2) In the middle stage, the percussion dullness, enhanced tremor and pathological bronchial respiratory sound; (3) In the later stage, if moist rales involve pleura, there are pleural fricative sound [1].

5.1.2 Pathological Manifestations Upper respiratory tract infection often damages the integrity of bronchial mucosa, which affects mucociliary activity, thus leading to mucus accumulation, preventing bacteria from phagocytosis, and affecting the ability of respiratory tract to remove bacteria. Once the mucus containing bacteria is inhaled into the alveoli, the bacteria will grow and multiply in the alveoli, resulting in alveolar telangiectasia, congestion and exudation of the alveolar serous fluid, so the alveolar space will be filled with inflammatory exudate (early consolidation). Then a large number of neutrophils phagocytize

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bacteria, accompanied by red blood cell exudation (red hepatization). Due to the exudation of a large number of red blood cells and fibrin, and the accumulation of a large number of dead bacteria and cell debris, the lungs are generally gray (gray hepatization). Five to ten days after bacterial infection, specific antibodies are usually formed, and then phagocytes appear in exudate, which phagocytize bacteria and remove cell debris. The alveolar exudate will be dissolved and absorbed, and the alveoli will be reinflated (dissipation period). Because the alveolar wall is not damaged during the whole course of disease, the lung tissue will completely return to normal after the pneumonia is cured. If the body’s resistance is poor or the virulence of bacteria is strong, the lesion may involve several lung lobes. In severe cases, it may even cause peripheral circulatory failure and blood pressure drop, and in severe cases, it may lead to shock (i.e., pneumonia with shock). In streptococcal pneumonia, only 25–30% of cases have bacteremia, and secondary extrapulmonary migratory lesions, such as arthritis, meningitis and endocarditis.

5.1.3 Imaging Manifestations There are often three types of imaging manifestations: consolidation (lobar pneumonia), bronchopneumonia (lobular pneumonia) and ground-glass opacity. 1. Most of X-ray chest radiographs are inconclusive for diagnosis. (a) For the manifestation of lobar pneumonia, its chest radiographs are different because of the different pathological stages. (1) Congestive stage: Usually, there is no abnormality, or only locally increased lung markings, and the transparency of lung field decreases. (2) Consolidation stage: It shows a large uniform opacity increasing. Its morphology and extent are consistent with the involved lobes and segments (Fig. 5.1a, b). Air bronchogram is visible with large patchy opacities. (3) Dissipation stage: The opacity of consolidation area gradually decreases, showing patchy opacities with different sizes and irregular distribution. Inflammation can eventually be completely absorbed and dissipated, or only a few stripe-like opacities are left. (b) If it is manifested as lobular pneumonia, chest radiograph may show the following symptom: thickened lung markings and blurred edges; nodular and patchy opacities increasing in the lung fields on both sides, distributed along bronchus, with most of the lesions located in the inner zone of the lower fields of both lungs (Fig. 5.2a); obstructive emphysema; cavitation (pyogenic bacterium infection is prone to pneumato-

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cele, showing round thin-walled cavity); pleural effusion. In a few cases, it can also be manifested as focal nodules or masses, which are called “spherical pneumonia,” and the chest radiograph shows spherical or quasi-round hyperdensities. Cavity and abscess are rare. About 10% of patients show signs of pleural effusion. 2. CT. (a) When it is manifested as lobar pneumonia, it is different in different pathological stages: (1) In congestive stage, the lesions are ground-glass-like opacities with blurred edges; (2) Consolidation stage is manifested by dense consolidation distributed along the lobes or lung segments, with visible air bronchogram inside (Fig.  5.1c, d); (3) In the dissipation stage, with the absorption of lesions, the opacities of consolidation decrease, showing scattered patchy opacities with different sizes, which can be completely absorbed at last, or only a few stripe-like opacities are left. The typical imaging manifestation of lobar pneumonia is that the consolidation lesion starts from the periphery of the lung lobe, immediately adjacent to the pleura, and then gradually spreads to the center of the lung field. (b) For the manifestation of lobular pneumonia, because of being mostly centered on the bronchioles, the lesions start from bronchioles and spread to the surrounding alveoli. CT shows increased patchy and nodular opacities distributed along bronchi (Fig. 5.2b), obstructive emphysema, cavitary lesions and pleural effusion. Fifty percent or less patients may be complicated with empyema. If “spherical pneumonia” is formed, it is manifested as spherical hyperdensities with blurred edges and irregularity, showing air bronchogram opacities inside.

5.1.4 Diagnostic Key Points 1. Most of patients are young and middle-aged people who have been in good health in the past. Before the onset of the disease, they have inducements of catching a cold, being caught in the rain, fatigue and others, or have a history of upper respiratory tract infection. 2. Acute onset is manifested as chills, high fever, chest pain, cough with rust-colored sputum or bloody sputum. 3. Lung consolidation signs are accompanied by moist rales in some cases. 4. The total number of leukocytes and the proportion of neutrophils in peripheral blood are increased (>80%). 5. X-ray radiograph and CT show patchy hypodensities and lung consolidation with air bronchograms. 6. Pathogenic bacteria are found in sputum or blood bacteria examination.

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a

b

c

d

Fig. 5.1  Lobar pneumonia. (a and b) The frontal and lateral chest radiographs showed patchy spherical uniform hyperdensities in the right upper lung field with blurred edges; (c) CT lung window showed

a

lobular hyperdensities under the left lung, with air bronchogram inside; (d) Mediastinal window showed the opacities of soft tissue in the lower lobe of the left lung, and air bronchogram inside

b

Fig. 5.2  Lobular pneumonia. (a) Chest X-ray radiograph showed multiple patchy and nodular hyperdensities with blurred edges in both lung fields, mainly distributed along bronchus; (b) CT lung window showed patchy hyperdensities with blurred edges along bronchus in both lungs

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5.1.5 Differential Diagnosis

5.1.6 Research Status and Progress

1. Mycoplasma pneumonia: Streptococcal pneumonia and mycoplasma pneumonia are common types of community-­ acquired pneumonia, and their imaging manifestations are similar and overlapped. The onset of mycoplasma pneumonia is slow, and the systemic symptoms are significant. Various forms of infiltration opacities can be seen on chest radiographs, showing segmental distribution, which is more common in the lower field of the lung and sometimes extends outward from around the hilum of the lung. Studies have shown that streptococcal pneumonia has more irregular lung consolidation than mycoplasma pneumonia, and there are significant differences in pulmonary morphology between the two. The probability of ground-glass opacities and thickened bronchi in streptococcal pneumonia is less than that in mycoplasma pneumonia. Diagnosis can be made by cold agglutination test, mycoplasma IgM antibody assay, nucleic acid hybridization and PCR technology or pathogen culture [2–5]. 2. Chlamydia pneumonia: The incidence of bronchiectasis and thickened bronchovascular bundle in chlamydia pneumonia is higher than that in streptococcal pneumonia. Therefore, if bronchovascular bundle thickening and bronchiectasis are shown on thin-layer CT, but there is no significant consolidation of lung tissue, it indicates that chlamydia infection is more likely than streptococcal infection. However, mycoplasma pneumonia is more prone to reticular and linear fuzzy image, bronchiectasis and emphysema [6]. 3. Staphylococcal pneumonia: Patients are mostly manifested by high fever, chills, rapid onset, accompanied by significant fatigue, night sweats and other toxemia symptoms. The total number of peripheral blood leukocytes increases significantly. X-ray radiograph or CT shows typical imaging features, such as pneumatocele, fuzzy image and may be accompanied by cavity and gas–liquid plane. 4. Caseous pneumonia: It is also called tuberculous pneumonia, which has symptoms of tuberculosis poisoning. X-ray radiograph or CT shows that the lesions are often distributed in typical locations, such as the apical segment/apical posterior segment/posterior segment of the upper lobe or the dorsal segment of the lower lobe of both lungs or unilateral lung, with uneven opacity and no dissipation for a long time. X-ray radiograph or CT shows cavities and intrapulmonary dissemination. Acid-fast bacilli can be found in sputum.

1. X-ray: Studies have shown that streptococcal pneumonia consolidation starts from the peripheral air cavity of the lung, so it is almost always close to the surface of the visceral pleura or the interlobar part of the convex surface of the lung [7]. In rare cases, the infection is manifested as a spherical consolidation, similar to a mass (spherical pneumonia), which is more common in children than in adults [8]. CT: It can provide some important findings that cannot be displayed on chest radiographs, including necrosis, abscess, pleural disease and pericardial effusion. Some studies show that CT can detect lesions that are not displayed on chest radiographs. CT can show at least one important manifestation that is not displayed on chest radiographs [9]. Hodina et  al. have reviewed the chest radiographs and CT images of 9 children in pediatric ICU [10]. Although given sufficient antibiotics, they still suffered from persistent or progressive pneumonia, respiratory distress or sepsis, including 4 cases of streptococcal pneumonia. Chest radiographs showed consolidation in 8 of 9 patients. CT showed that cavitary necrosis was confined to one lobe in 2 cases, cavitary necrosis in multiple lobes or bilaterally in 7 cases, and cavitary necrosis in 3 of 9 cases, which was only shown on CT images at first, and the time of appearance on chest radiographs was 5–9  days later than CT.  Peripulmonary effusion was shown on chest radiograph in 3 cases and CT in 5 cases, and bronchopleural fistula was only shown on CT images in 3 cases.

5.2 Staphylococcus Yonggang Li and Renjun Huang

5.2.1 Overview Staphylococcus is a gram-positive coccus, which can be divided into coagulase-positive staphylococci (mainly Staphylococcus aureus) and coagulase-negative staphylococci (such as saprophytic staphylococcus and staphylococcus epidermidis, etc.). Staphylococcus aureus pneumonia can be divided into two types: (1) Primary infectious pneumonia, which is caused by respiratory tract inhalation; (2) Secondary infectious pneumonia, usually caused by infectious diseases in other parts of the body, in which the pathogen spreads into the lungs through blood.

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Staphylococcal infection accounts for 11–25% of hospitalacquired pneumonia. The onset of staphylococcal infection is usually rapid, with high fever, chills, chest pain, body temperature as high as 39–40 C, a large amount of purulent sputum, with bloodshot or pink milky systemic toxemia. Phlegm sounds and dry and moist rales can be heard during auscultation of lungs. The symptoms of toxemia are significant, with sore muscles and joints and listlessness. Moreover, in severe cases, peripheral circulatory failure and corresponding organ damage may occur in the early stage. Nosocomial infections usually have insidious onset, with gradually rising body temperature and purulent sputum. Among them, Staphylococcus aureus pneumonia is more common, which is an acute purulent pulmonary inflammation caused by Staphylococcus aureus. It often occurs in the elderly with underlying diseases, such as blood diseases, diabetes, liver diseases, AIDS or preexisting bronchopulmonary disease. Hospital-acquired pneumonia is common in ICU and intravenous patients. Children are also susceptible to the disease if they have measles or influenza. The early clinical signs of staphylococcal infection are often not parallel to severe poisoning symptoms and respiratory symptoms, and then moist rales scattered in both lungs may occur. Lung consolidation may occur if the lesions are large or confluent. Pneumothorax or pyopneumothorax has corresponding signs. The pathogenic substances of Staphylococcus are mainly toxins and enzymes, such as leukin, hemolytic toxin, enterotoxin, etc. They have the functions of hemolysis, necrosis, killing leukocytes and causing vasospasm. The pathogenicity of staphylococcus can be measured by plasma coagulase, and the pathogenicity to patients with positive plasma coagulase is stronger. Staphylococcus aureus is positive, which is the main cause of purulent infection. However, other coagulase-­negative Staphylococcus can also cause infection complications. With the increase of nosocomial infection, pneumonia caused by coagulase-negative Staphylococcus has also been found. Outbreaks of methicillin-resistant Staphylococcus aureus (MRSA) in hospitals have also been reported in recent years.

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cantly change the function of isogenic strains. Mutant strains still have surface adhesion ability, but lose accumulation function, and then specifically mediate bacterial adhesion. Receptor-ligand interaction occurs between epitopes and related structures of matrix proteins. Then the accumulation means that bacteria proliferate on a surface and develop toward the surface of other bacteria. This is due to a mechanism of intercellular adhesion, which enables them to accumulate and grow into cell population. Muramic acid is a complex polymer containing phosphorus, which exists in the outer layer of staphylococcus, and can stimulate the body to produce corresponding antibodies. The determination of muramic acid antibody is helpful for etiological diagnosis.

5.2.3 Imaging Manifestations 1. X-ray: The lesions on chest radiograph show multiple patchy and nodular opacity distribution, which progress rapidly and often involve more than 2 lung lobes, manifested by typical honeycomb lucency shadow (Fig. 5.3), cavity and pneumatocele. Pneumatocele is an important feature in the diagnosis of this disease. Multiple and annular small pneumatoceles are located in the middle and outer zones of the middle and upper field of both

5.2.2 Pathological Manifestation Staphylococcus usually adheres to the surface of skin and mucous membrane, and its adhesion is nonspecific in a protein-­free environment. If foreign matter enters human tissues or blood vessels, it will be quickly surrounded by matrix proteins. Two substances are very important in adhesion. One is linear homoglycan N-acetyl-D-(+)-glucosamine called intercellular adhesin. The other is NOKD2 protein. Removal of polysaccharide or protein genes will signifi-

Fig. 5.3  Staphylococcal pneumonia (I). Chest radiograph showed diffuse small nodules in both lung fields and pneumothorax on the right side

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lungs, more common near the edge of the lungs. Large pneumatoceles are the characteristic manifestation of primary Staphylococcus aureus pneumonia in infants and young children. One or several large pneumatoceles may occur 1–2 days after onset of the disease. Large pneumatoceles are often complicated with pyopneumothorax, which can compress lung tissue and cause atelectasis. Two-third patients may develop pleural effusion, and some of them show encapsulated effusion. Pneumothorax (Fig.  5.3), pyopneumothorax, cardiac shadow enlargement, pericardial pneumatosis and mediastinal emphysema may occur [11–13]. Thirty percent of patients have cavities, and the rapid progress of the disease can be observed on the series of chest radiographs in dynamic reexamination, and even significant imaging changes can be observed within a few hours.

2. CT. (a) Pneumatocele: Thin-walled, hypertonic and multiple clustered pneumatoceles are one of the most characteristic manifestations of hematogenous Staphylococcus aureus pneumonia (Fig. 5.4a). (b) Inflammatory exudative lesions: The manifestations are diverse, ranging from multiple small centrilobular nodules to mass consolidation. The main manifestations are small patchy or wedge-shaped hyperdense subpleural lesions, which are mainly located in the outer zone of the lower lobe of both lungs. The edge of the lesions is blurred, closely related to blood vessels, with common dense consolidation. Most of the lesions develop rapidly, and some patients can develop rapidly from single lesion to multiple lesions within a few hours or one day after examination.

a

b

c

d

Fig. 5.4  Staphylococcal pneumonia (II). (a) CT lung window showed multiple nodular hyperdensities in both lungs and multiple small cavities; (b) The mediastinal window showed bilateral pleural effusion; (c) Lung window showed the middle and lower lobe-like hyperdensities of

the right lung with cavity formation in the lesion; (d) The mediastinal window showed patchy soft tissue opacities with cavity formation in the right lung and bilateral pleural effusion (especially in the right side)

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Most of the inflammatory exudates fuse with each other into large-scale hyperdensities or ice-melting pulmonary infarction changes. (c) Pleural effusion, pneumothorax and hydropneumothorax: Hematogenous Staphylococcus aureus pneumonia can invade pleura in the early stage, causing hydropneumothorax, empyema and pyopneumothorax. Thickened pleura and enhancement may occur in empyema patients (Fig. 5.4b, d). (d) Liquefaction and necrosis of lung abscess: The necrotic foci are closely related to blood vessels, and the lung tissue around the necrotic foci shows infection such as increased density. The central liquefied necrotic foci can reach bronchus and form cavities. CT shows scattered round cavities (thin-walled or thickwalled) (Fig. 5.4c, d). In the early stage, the disease is manifested as large patchy ground-glass opacities, which gradually increase. After treatment, the cavities can be absorbed or there are residual fibrous lesions. (e) Multiple nodules or masses: Such symptoms can be seen in septic pulmonary embolism caused by hematogenous dissemination of pathogens. Sometimes the edges of nodules are blurred or confluent with each other. In 40–70% of patients, a blood vessel reaches the nodule (“vasa vasorum” sign), which is usually the draining pulmonary vein. Most nodules eventually form cavities. Finally, septic infarct also forms subpleural wedge-shaped consolidation areas, which are often multiple and occur at the same time as nodules [15]. (f) Fibrous stripe-like opacities. (g) Pericardial effusion.

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ties [16]. Therefore, the pneumatocele formed on the basis of abscesses is relatively rare, and ground-glass opacities and patchy opacities are the most common manifestations on CT.

5.2.4 Diagnostic Key Points 1. Rapid onset, high fever, chills, accompanied by significant fatigue, night sweats and other toxemia symptoms. 2. Patients may have purulent, blood-clotted or pink milky sputum. 3. The total number of peripheral blood leukocytes increases significantly. 4. X-ray or CT shows typical imaging features, such as pneumatocele, multifocal consolidation, which may be accompanied by cavities and gas-liquid plane. 5. This disease can be diagnosed if staphylococci are detected by smear and culture of respiratory secretion or blood culture.

5.2.5 Differential Diagnosis

1. Other bacterial pneumonias: Including Streptococcus pneumoniae, Klebsiella pneumoniae, Escherichia coli and Pseudomonas aeruginosa. The clinical manifestations are similar, and lung consolidation may occur. Imaging findings show multiple lung consolidations and cavity formation. No single imaging sign can characterize the pathogen of infection, which needs comprehensive judgment. Examination of pathogenic microorganisms in sputum or blood is helpful to determine the diagnosis. The above manifestations often coexist in many types 2. Viral pneumonia: The imaging manifestations are mostly [14]. centrilobular nodules, “tree-in-bud” signs and multiple Studies have shown that imaging manifestations of non-­ patchy ground-glass opacities. Linear opacities around AIDS Staphylococcal pneumonia patients are mostly lung hilum, thickened bronchial wall, atelectasis and air-­ abscess and empyema, while the imaging manifestations of trapping are more common. AIDS patients with Staphylococcal pneumonia are mostly 3. Tuberculosis: Patients generally have symptoms of tuberpatchy consolidation, nodules, cavities and pleural effusion, culosis poisoning. X-ray radiograph or CT shows that which may be accompanied by enlargement of hilar and medimost of the lesions have typical distribution sites, such as astinal lymph nodes, but there is no significant correlation the apical segment/apical posterior segment/posterior between etiology and chest CT findings [14]. Some studies segment of the upper lobe of both lungs or unilateral have reported the following findings: After surgery, radiotherlungs or the dorsal segment of the lower lobe. The opaciapy and chemotherapy and other antitumor treatments, the ties are uneven and do not dissipate for a long time, with patients are immunocompromised, especially prone to seccavities and intrapulmonary dissemination. Acid-fast ondary Staphylococcus aureus pneumonia. However, their bacilli can be found in sputum. manifestations are different from those of ordinary patients with Staphylococcus aureus infection. Pulmonary Staphylococcus aureus infection secondary to malignant 5.2.6 Research Status and Progress tumor often shows multiple coexisting CT signs. Patients often have no significant purulent tendency of infected lesions According to chest CT, pulmonary cystic fibrosis infected by because of bone marrow suppression and leukopenia after MRSA can be scored. MRSA is a major pathogen of pulmotreatment, and show ground-glass opacities and patchy opaci- nary cystic fibrosis. The scoring of pulmonary cystic fibrosis-­

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related pulmonary structural changes can describe and quantify bronchiectasis, mucus obstruction, peribronchial thickening, consolidation, perilobular and centrilobular hyperdilation. The main finding of the study is as follows: CT score of MRSA is worse or similar to that of patients with Pseudomonas aeruginosa infection, and worse than that of patients without Pseudomonas aeruginosa infection. Similar results can be obtained by comparing the total score with the bronchiectasis score. Therefore, MRSA infection is related to the structural changes of lung parenchyma, which is similar to the structural changes of lung related to Pseudomonas aeruginosa infection [17, 18].

5.3  Klebsiella Pneumoniae Yonggang Li and Jingfen Zhu

5.3.1 Overview Klebsiella pneumoniae is a gram-negative bacillus, which usually exists in human intestinal tract or respiratory tract and is a conditional pathogen. Klebsiella pneumoniae infection accounts for 1–5% of all community-acquired pneumonia and about 15% of hospital-acquired pneumonia [19]. It can be divided into 80 subtypes by capsular antiserum test. Type 1–6 are common in respiratory tract infection, among which Klebsiella pneumoniae subsp. pneumoniae, Klebsiella pneumoniae subsp. rhinoscleromatis and Klebsiella pneumoniae subsp. ozaenae are the most common [19]. In recent years, with the widespread use of antibiotics, the incidence of multidrug-resistant Klebsiella pneumoniae has been increasing year by year. According to the National Bacterial Resistance Monitoring Report, the number of reported strains of Klebsiella pneumoniae ranked second among gram-negative bacteria in 2015, and the drug resistance rates to the third-generation cephalosporins and carbapenem drugs were 36.5% and 7.6%, respectively [20]. Chung et  al. reported that the multidrug resistance rate of Klebsiella pneumoniae was as high as 44.7% among hospital-acquired infections and ventilation-related pulmonary infections in Asia, ranking second [21]. In 2018, Yao et al. discovered the drug resistance mechanism of highly pathogenic Klebsiella pneumoniae [22]. Klebsiella pneumoniae pneumonia mostly occurs in the elderly, especially those with underlying diseases, such as alcoholic, immunocompromised patients (with cancer history and diabetes) and those with chronic lung underlying diseases. In a death risk assessment of Klebsiella pneumoniae pneumonia in hospitalized patients [23], ICU hospitalization, solid tumor and complications with other bacterial or viral pneumonia are the main risk factors leading to death of patients.

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The clinical onset of Klebsiella pneumoniae pneumonia is rapid, which is mainly manifested as high fever, chills, chest pain and thick sputum difficult to cough up. Typical patient’s sputum may be brick red and jam-like. Bacteriological detection is the basis of diagnosis.

5.3.2 Pathological Manifestations Pulmonary lesions are manifested as exudative inflammation of lobar or lobule fusion. The viscous exudate can cause necrosis and liquefaction of lung tissue and form abscess. The exudate can invade pleura and cause empyema. In acute stage, fibrinous exudation can often be found on the pleural surface. Microscopical examination shows congested and swollen alveolar wall, viscous alveolar exudate, necrosis of alveolar wall, parenchymal destruction and abscess formation. Patients at chronic stage have multiple lung abscesses with obvious fibrosis of lung parenchyma, thickened pleura and adhesion.

5.3.3 Imaging Manifestations 1. X-ray: Community-acquired Klebsiella pneumoniae pneumonia is similar to Streptococcus pneumoniae pneumonia, and the typical manifestation is lobar pneumonia. Compared with Streptococcus pneumoniae pneumonia, acute Klebsiella pneumoniae pneumonia can produce a large amount of inflammatory exudate, which leads to the expansion of lung lobes and the bulging of interlobar fissure, forming “stalactite” sign, and also leads to the formation of abscess and cavity [24]. With the extensive application of antibiotics and the emergence of a large number of immunosuppressed people, Korvick et  al. found that the chest radiographs of patients with ­Klebsiella pneumoniae pneumonia showed abnormal manifestations, mostly bilateral lung lesions, without bulging or cavity formation of interlobar fissure (Fig. 5.5), and most of his reported cases were hospital-acquired, which may be due to the fact that drug-resistant Klebsiella pneumoniae is more common in hospital-acquired pneumonia, and its virulence is lower than that of nondrugresistant strains [25]. Chest radiograph is not sufficient to show subtle imaging signs, so it has limited value in etiological diagnosis of pneumonia, and can be used to find lesions and reexamine after treatment. 2. CT. (a) Lobar-wide exudative consolidation: Lobar-wide (nonsegmental) air cavity consolidation is more common in community-acquired pneumonia, and the scope of exudative lesions often spans lung segments, more common in the upper lung. Because the exu-

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Fig. 5.6  Klebsiella pneumoniae pneumonia (II). The patient, an 80-year-old male. After femoral head replacement, the patient had the following manifestations: infection, consolidation of right upper lobe (no tail arrow), thickened interlobular septa and interlobular septa of both upper lungs (arrow), thickened bronchial wall and bilateral pleural effusion Fig. 5.5  Klebsiella pneumoniae pneumonia (I). The patient, an 81-year-old male, developed hospital-acquired Klebsiella pneumoniae pneumonia after operation on a fracture of the left femoral neck. Chest radiograph showed that the fields of both lungs are mostly different in size, with patchy consolidation and blurred edge

date of this disease is abundant and viscous, it can lead to interlobular fissure bulging or falling, which is called “stalactite” sign. Cavity or secondary empyema can be formed in consolidation, and those who occur in lower lung can even involve subphrenic or lateral chest wall, forming subphrenic abscess or chest wall abscess [25–27]. (b) Multiple patchy consolidation or ground-glass opacity: This imaging manifestation is more common in hospital-acquired pneumonia, showing patchy opacity increasing with blurred edge, thickened bronchial wall in the lesions, and often complicated with interlobular septal thickening and small centrilobular nodules (Figs. 5.6 and 5.7). Okada et al. evaluated the CT manifestations of 198 cases of acute Klebsiella pneumoniae pneumonia. The CT manifestations were mainly ground-glass opacities (100%), consolidation (91.4%), thickened intralobular septa (85.9%), mostly distributed in the peripheral areas of both lungs (96%) and often accompanied by pleural effusion (53%) [28]. In addition, thickened bronchial wall, thickened interlobular septa, central nodules and other signs can be seen. (c) Cavity formation: Moon et al. analyzed 11 cases of Klebsiella pneumoniae pneumonia with complica-

tions. All patients showed consolidation areas of lung tissue and hypodense areas with blurred edges and multiple small cavities, suggesting necrotizing pneumonia [26]. Among them, 9 patients showed scattered enhanced structures in the necrotic area of consolidated lung tissue, which may suggest dilated lung tissue and pulmonary blood vessels. (d) Pleural effusion and empyema: Empyema is common in community-acquired pneumonia, with strong bacterial virulence, which can invade chest wall and subdiaphragm, and some patients may have brain abscess. Imaging findings showed diffuse thickened pleura and enhanced structure. Pleural effusion is common in patients with community-acquired and hospital-acquired Klebsiella pneumoniae infection.

5.3.4 Diagnostic Key Points 1. Community-acquired pneumonia: CT often shows lobar lung consolidation, “stalactite” sign, cavity or empyema, with certain characteristics. Hospital-acquired pneumonia usually shows multiple consolidations, ground-glass opacities thickened intralobular septa, thickened bronchial wall, pleural effusion and other diverse noncharacteristic manifestations. 2. A clinical feature of Klebsiella pneumoniae infection is brick red or jam-like sputum. 3. Sputum or blood culture, gene detection of sputum samples, etc. are helpful for the final diagnosis.

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a

Fig. 5.7  Klebsiella pneumoniae pneumonia (III). The patient, a 52-year-old female. (a) CT lung window showed ground-glass opacities of the upper lobe of the right lung and dilatation and thickened

5.3.5 Differential Diagnosis

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b

bronchial wall (arrow); (b) Nodular ground-glass opacities in the left lower lung, with small bronchi and slightly thickened bronchiolar wall (arrow)

acquired pneumonia, especially in immunocompromised patients and ICU patients. The imaging manifestations of 1. Streptococcus pneumoniae pneumonia: It can cause lobu- drug-resistant Klebsiella pneumoniae pneumonia are similar lar or lobar lung consolidation, with blurred edges of the to those of other bacterial pneumonia, with few abscesses lesion and no “stalactite” sign. Generally, there is no and empyema, which may be due to the fact that drug-­ necrosis, liquefaction and cavity formation. If the treat- resistant strains carry more drug-resistant genes and less ment is timely, generally no scar will form after the lesion virulence genes. Mao et  al. analyzed the clinical and CT manifestations of 18 cases of multidrug-resistant Klebsiella is absorbed. 2. Staphylococcus aureus pneumonia: Multiple patchy con- pneumoniae pneumonia, and all of them were inpatients and solidations and cavities occur in the lungs, mostly in the 13 cases were postoperative patients [29]. Among them, inner zone of the lower lobe of the two lungs, distributed pleural effusion, consolidation and thickened bronchial wall along the bronchial branches. Pneumatocele has the char- were more common, manifested in 16 cases, 12 cases and 15 cases respectively. Ground-glass opacities were manifested acteristics of random distribution and rapid progress. 3. Mycoplasma pneumoniae pneumonia: Manifested by the in 10 cases, and scattered central pulmonary nodules were coexistence of interstitial inflammation and alveolar manifested in 9 cases. There were 6 cases of thickened interinflammation. Lesions can be confluent with each other, lobular septa and 5 cases of intralobular septa thickening. but lobar consolidation is rare. Generally, there is no Multiple imaging manifestations coexisted and were mainly necrosis and cavity. Positive serum cold agglutination test randomly distributed (Fig.  5.7). No abscess, empyema and rapid progression of strong pathogenic changes were found has diagnostic value. 4. Pulmonary tuberculosis: The lesions of chronic Klebsiella in 18 cases, suggesting that the virulence of drug-resistant pneumoniae pneumonia in the upper lobe needs to be dis- strains was weak. Klebsiella pneumoniae can also be complicated with tinguished from pulmonary tuberculosis, and the diversity of tuberculosis lesions is more significant, and other pathogenic microorganism infection, which increases “stalactite” sign is rare. Bronchial dissemination often the difficulty of imaging diagnosis. Okada et al. analyzed the clinical and CT manifestations of simple acute Klebsiella occurs in patients with cavities. pneumoniae pneumonia and pneumonia complicated with mixed infection [30]. There were 80 cases of simple Klebsiella pneumoniae pneumonia, 55 cases of methicillin-­ 5.3.6 Research Status and Progress resistant Staphylococcus aureus and 25 cases of Pseudomonas In recent years, according to the imaging comparison aeruginosa. Patients in mixed infection group were mostly between drug-resistant Klebsiella pneumoniae infection and accompanied by serious underlying diseases clinically. CT nondrug-resistant strain infection, drug-resistant Klebsiella showed that the incidence of centrilobular nodules, thickpneumoniae pneumonia has been more common in hospital-­ ened bronchial wall, cavitation, bronchiectasis, nodules and

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pleural effusion in the mixed infection group was significantly higher than that in the simple Klebsiella pneumoniae pneumonia group.

5.4  Moraxella Catarrhalis Yonggang Li and Yue Teng

5.4.1 Overview Moraxella catarrhalis is an aerobic gram-negative coccus. “Moraxella” comes from Victor Morax, a Swiss doctor who first described the bacterium, while “catarrhalis” comes from “catarrh” in Greek, which means “flowing down.” Moraxella catarrhalis is a normal colonizing bacterium of human upper respiratory tract, and human is the only host of Moraxella catarrhalis. Moraxella catarrhalis is the second most common cause of respiratory infection after Streptococcus pneumoniae and Haemophilus influenzae, which mainly causes opportunistic infection, especially in patients with impaired immune system or chronic underlying diseases (such as chronic obstructive pulmonary disease, bronchiectasis, congestive heart failure). Moraxella catarrhalis colonization is the inducement of infection. Moraxella catarrhalis colonization in nasopharynx is very common in infancy, and the reported prevalence rate is 30–100%. By adulthood, the prevalence rate drops to 1–5%. In adults with chronic obstructive pulmonary disease (COPD), the colonization rate is higher [31]. Therefore, Moraxella catarrhalis is the main cause of otitis media, COPD exacerbation and acute bacterial sinusitis in children.

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ability to remove pathogens, while enhancing the resistance of pathogens to antibiotics. In acute otitis media, adhesion to the mucous membrane surface alone is not sufficient to cause disease, so cofactors such as viral infection may be involved to promote bacteria to spread to the middle ear through the Eustachian tube. Moraxella catarrhalis often coexists with Streptococcus pneumoniae or Haemophilus influenzae in respiratory tract culture, and may promote infection by protecting these organisms from complement-mediated immune, promoting biofilm formation and releasing β-lactamase into local environment. A similar pathogenesis may also exist in acute bacterial sinusitis, in which bacterial infection often precedes viral infection and eventually leads to mixed infection.

5.4.3 Imaging Manifestations 1. X-ray: Moraxella catarrhalis infection may be localized (segmental or lobar pneumonia) [33, 34], or diffuse (bronchopneumonia) [34]. 2. CT: Moraxella catarrhalis pulmonary infection mainly occurs in the elderly, especially in patients with emphysema. The main manifestations of Moraxella catarrhalis pneumonia are ground-glass opacities, thickened bronchial wall and centrilobular nodules (Figs. 5.8, 5.9, 5.10, and 5.11). Among them, the first two often occur at the same time. Lung consolidation may occur in about half of patients, and bronchiectasis may occur in one-third patients. Pleural effusion and lymphadenectasis are rare in Moraxella catarrhalis pneumonia [35].

5.4.2 Pathological Manifestations The pathogenesis of Moraxella catarrhalis infection involves the complex interaction among viruses, bacterial pathogens and host immune response. For most Moraxella catarrhalis infections, the first step is the adhesion and colonization of bacteria on the mucosal surface. Moraxella catarrhalis can be manifested by a variety of adhesins, each with different specificities for the host [32]. After adhesion, bacteria can invade respiratory mucosa, and the main cellular targets include epithelial cells, antigen-presenting cells, neutrophils and lymphocytes of respiratory mucosa. Adhesion and invasion can trigger excessive proinflammatory immune response, which will damage host tissues and promote the spread of infection. Proinflammatory reaction can also cause a large amount of mucus in respiratory tract. As bacteria aggregate, biofilms will form, thereby reducing the host’s

Fig. 5.8  Moraxella catarrhalis pneumonia (I). The patient, a 42-year-­ old male, with a history of diabetes. CT lung window showed consolidation of upper lobe of right lung, ground-glass opacities, thickened bronchial wall (long arrow) and centrilobular nodule (short arrow)

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Fig. 5.9  Moraxella catarrhalis pneumonia (II). The patient, a 75-year-­ old male, with emphysema. CT lung window showed consolidation of the upper lobe of the right lung, ground-glass opacities and thickened bronchial wall (arrow) with a small amount of pleural effusion

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Fig. 5.11  Moraxella catarrhalis pneumonia (IV). The patient, a 76-year-old male, with emphysema. CT lung window showed ground-­ glass opacities and thickened bronchial wall at the tracheal crest level (arrow)

2. Acute otitis media caused by Moraxella catarrhalis has no substantially different signs and symptoms from otitis media caused by other pathogens. Common manifestations usually include fever, ear pain and tympanic membrane bulging. 3. Acute sinusitis is characterized by fever, nasal congestion, runny nose, facial pain and headache. 4. For most patients, empiric therapy usually does not require microbiological diagnosis. Gram staining and bacterial culture are helpful to confirm the diagnosis of patients who have failed empirical antibiotic therapy.

5.4.5 Differential Diagnosis

Fig. 5.10  Moraxella catarrhalis pneumonia (III). The patient, a 72-year-old female, with cardiovascular disease and renal failure. CT lung window showed the central nodule of subpleural lobule (black arrow), thickened bronchial wall (white arrow) and mild bronchiectasis in the lower lobe of the right lung

5.4.4 Diagnostic Key Points 1. Common symptoms of acute attack of COPD include cough, sputum production, purulent sputum (color change) and dyspnea. Chest X-ray radiograph or CT findings are nonspecific. COPD can be manifested as lobar consolidation or bronchopneumonia. Pleural effusion and mediastinal lymphadenectasis are rare.

1. Pulmonary infection caused by Streptococcus pneumoniae and Haemophilus influenzae: Pulmonary infection caused by Moraxella catarrhalis is similar to that caused by Streptococcus pneumoniae and Haemophilus influenzae, and there are no specific clinical and imaging features to help distinguish infection caused by Moraxella catarrhalis from that caused by the two common pathogens. 2. Staphylococcus aureus pneumonia: The patient shows acute onset, severe clinical symptoms and rapid progress. Common symptoms include chills, high fever, chest pain, pus and blood sputum, shortness of breath, toxemia symptoms and shock. The imaging manifestations are multiple pulmonary nodules with blurred edges or clusters of pneumatoceles, which can quickly fuse into mul-

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tiple cavitary lesions, and may invade pleura in the early stage, resulting in hydropneumothorax, empyema and pyopneumothorax, etc. The imaging manifestations change rapidly. 3. Klebsiella pneumoniae pneumonia: It is divided into community-acquired pneumonia and hospital-acquired pneumonia. Community-acquired Klebsiella pneumoniae pneumonia has certain characteristics, severe clinical symptoms, a large amount of viscous sputum, showing typical brick-red jelly status. The imaging manifestations are consolidation of lung lobes or segments, with cavities in them. Falling interlobar fissures and “stalactite” sign are also its main features, which can form empyema and subphrenic abscess. Hospital-acquired Klebsiella pneumoniae pneumonia is mostly caused by the infection of drug-resistant strains, the virulence of bacteria is weaker than that of nondrug-resistant strains, and the imaging manifestations are noncharacteristic, and difficult to be distinguished from Moraxella catarrhalis pneumonia. 4. Pseudomonas aeruginosa pneumonia: Clinical manifestations include cough and a large amount of emerald purulent sputum, which is one of its characteristic manifestations. The symptoms of toxemia are significant, mainly including chills, fever, restlessness, dyspnea, rapid heartbeat and even coma. The imaging findings are multiple nodular or patchy hyperdensities in the lungs, and some patients may show cavities, pleural effusion or empyema. 5. Legionella pneumonia: Patients often have prodromal symptoms, such as fatigue, lethargy, etc. The clinical manifestations are dry cough, high fever, muscular soreness, etc. At the same time, they can be complicated with other systemic symptoms. The chest imaging manifestations are diverse lesions, including nodules, patchy blurred opacities, stripe-like opacities, cavities and pleural effusion, etc. The lesions are distributed in multiple lobes and segments, progressing rapidly and dissipating slowly.

5.4.6 Research Status and Progress 1. X-ray: It is difficult to use clinical and imaging features for distinguishing pneumonia caused by other bacteria. 2. CT: Okada et  al. studied 109 patients with Moraxella catarrhalis pulmonary infection, and found that Moraxella catarrhalis pneumonia is more prone to thickened bronchial wall and lobular nodules, which are significantly more common in the elderly, compared with Klebsiella pneumoniae pneumonia, Streptococcus pneumoniae pneumonia and Chlamydia pneumoniae pneumonia [35]. The consolidation rate of Moraxella catarrhalis pneumonia was lower than that of Klebsiella pneumoniae

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and Streptococcus pneumoniae pneumonia, while the intralobular ground-glass opacities are significantly less common than that of Klebsiella pneumoniae pneumonia and Chlamydia pneumoniae. Moraxella catarrhalis, as a normal colonizing bacterium of respiratory tract, has gradually more visible role in persistent bacterial bronchitis. O'Grady et  al. found that the detection of Moraxella catarrhalis in nasal swabs of children with acute respiratory infection is the only microbiological risk factor for its development into chronic cough, suggesting that clinicians should pay attention to the role of Moraxella catarrhalis in the pathogenesis of chronic cough [36]. Wang et al. measured the minimum inhibitory concentration of commonly used antibiotics and the enzyme production rate of β-lactamase of 401 strains of catarrhalis isolated from children [37]. PCR amplification combined with restriction endonuclease analysis was used for BRO genotyping. It was found that the β-lactamase production rate of Moraxella catarrhalis isolated from children’s respiratory tract was high (96.5%, 387/401), and the enzyme-producing strain mainly carried BRO-1 gene (93%), and its ability to tolerate some β-lactams and macrolide antibiotics was significantly higher than that of BRO-2 gene strains. Therefore, the epidemiological characteristics and drug resistance of Moraxella catarrhalis infection should be closely monitored in clinical diagnosis and treatment.

5.5  Haemophilus Influenzae Yonggang Li

5.5.1 Overview Haemophilus influenzae (HI) is a gram-negative rod-shaped bacterium, which usually inhabits the nose, pharynx, eyes and vaginal mucosa of normal people, and generally coexists with normal colonies. Most infections of Haemophilus influenzae spread directly from nasopharynx to lower respiratory tract. At the same time, it is also a common pathogen in community-­ acquired pneumonia, second only to Streptococcus pneumoniae, and can cause primary suppurative infection and secondary infection. HI is mostly secondary to other viral infections and influenza, and can invade multiple organs in human body. Bronchitis and sinusitis often occur after infection in adults, while purulent meningitis, sinusitis, nasopharyngitis, pneumonia, purulent arthritis and pericarditis are common in children. This disease often occurs in the elderly and children. The risk factors include chronic obstructive pulmonary disease (COPD), alcoholism,

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diabetes, anatomical or functional spleen deficiency, immunoglobulin deficiency, advanced age and AIDS.  COPD patients are especially prone to acute exacerbation, and have a very high morbidity and mortality. The main cause of death is infection [38]. Haemophilus influenzae infection has the highest incidence in winter, with slow clinical onset, subacute course, severe clinical manifestations and diverse clinical manifestations, including high fever, cough, chest pain, dyspnea, similar to those of Streptococcus pneumoniae infection. However, the former has the following characteristics: spastic cough, similar to whooping cough, and sometimes bronchiolitis. Systemic symptoms are severe and poisoning symptoms are significant. The total number of leukocytes increases significantly, sometimes accompanied by relative or absolute increase of lymphocytes. X-ray chest manifestations are diversified. Small infants are prone to complication with empyema, pericarditis, septicemia, meningitis and suppurative arthritis, often with sequelae of bronchiectasis.

5.5.2 Pathological Manifestations Haemophilus influenzae can be divided into encapsulated strains and nonencapsulated strains. It is known that encapsulated Haemophilus influenzae type B (i.e., Haemophilus influenzae type B) is the main pathogenic bacterium, and encapsulated strains are bacterial colonies with certain spatial configuration, of which the components include coated bacteria, lipopolysaccharide, matrix protein and nucleic acid. After being infected with encapsulated strains, the body can produce specific antibodies against encapsulated strains and obtain immune protection. Specific capsular polysaccharide can neutralize antibodies formed in the process of infection, resist phagocytosis of leukocytes in host, without triggering complement-mediated lysis, while inhibiting the activity of respiratory mucociliary, and causing primary infection. The nonencapsulated strains are less aggressive, and their pathogenicity mainly comes from endotoxin produced by bacteria, which often causes secondary infections, such as epiglottitis. In addition, Haemophilus influenzae can also produce histamine to contract bronchial smooth muscle and secrete mucus, which increases the permeability of epithelial cells and disturbs ciliary movement. Pathogenic Haemophilus influenzae secretes IgA protease, which can hydrolyze secretory IgA in respiratory mucosa and cause disease. Usually, parasitic Haemophilus influenzae is not pathogenic, and bacteria are generally excreted by cilia after being inhaled into trachea or bronchus from oropharynx. On the other hand, secretory IgA in respiratory mucosal secretions can protect the body from infection. However, the body’s reduced resistance and imperfect immune function

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can cause infection, Haemophilus influenzae pneumonia, even septicemia and purulent meningitis, which are life-threatening.

5.5.3 Imaging Manifestations 1. X-ray: Haemophilus influenzae infection can be localized (segmental or lobar pneumonia) or diffuse (bronchopneumonia). Adult chest radiographs show diversity but no specificity. Most of the pulmonary lesions involve the lung segments first, and gradually change from pulmonary interstitial involvement to alveolar infiltration. Most of manifestations are patchy or segmental consolidation, which can be unilateral or bilateral, and mostly occurs in the peripheral zone of the lung with sharp edges. Bronchopneumonia is manifested by scattered multiple small nodules or reticular nodules, which can exist alone or occur along with alveolar consolidation. Pleural effusion occurs in 50% of patients, while empyema is not common. 2. CT: The main manifestations are patchy or segmental consolidation in one or both lungs, accompanied by thickened bronchial wall (Fig.  5.12), and sometimes ground-glass opacity lesions may occur. Centrilobular nodules and “treein-bud” signs in the peripulmonary zone are common manifestations of bronchopneumonia, and diffuse centrilobular nodules in both lungs may occur in some cases, with a diameter generally less than 5 mm. Confluent changes can be seen in frequently-occurring diseases. About 50% of patients show unilateral or bilateral pleural effusion. Bronchiectasis and cavity are not common. Thoracic lymphadenectasis is also rare [39, 40].

Fig. 5.12  Haemophilus influenzae pneumonia. CT lung window showed hyperdensities in the right lower lobe with thickened bronchioles wall

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5.5.4 Diagnostic Key Points 1. The onset is slow, and most patients have prodromal symptoms of catching a cold. 2. Spasmodic cough, severe systemic symptoms, obvious poisoning symptoms, often accompanied by high fever, dyspnea and respiratory failure. 3. The total number of leukocytes in peripheral blood is significantly increased, usually up to (15–30) × 109/L, sometimes accompanied by relative or absolute increase of lymphocytes. 4. X-ray radiograph or CT manifestations are mainly lobar consolidation, and some of them are bronchopneumonia, which may be accompanied by pleural effusion. 5. This disease can be diagnosed if the bacterial culture of blood or respiratory secretion confirms the existence of Haemophilus influenzae. 6. Haemophilus influenzae cultured in pleural effusion can also diagnose this disease.

5.5.5 Differential Diagnosis Streptococcus pneumoniae pneumonia: Before the onset, patients often have inducements of catching a cold, being caught in the rain, fatigue, drunkenness or a history of viral infection. Acute onset, high fever, may be accompanied by chills, purulent sputum, brown sputum or bloody sputum, and chest pain. X-ray radiograph and CT show patchy hypodensities and lung consolidation with air bronchograms. 1. Staphylococcus aureus pneumonia: It often occurs in patients with underlying diseases, with acute onset, manifested as chills, high fever, chest pain, coughing up pus and blood sputum, shortness of breath, toxemia symptoms and shock. The X-ray radiograph shows that multiple pneumatoceles in clusters are rapidly fused into multiple cavitary lesions, which could invade pleura in the early stage and cause hydropneumothorax, empyema and pyopneumothorax, accompanied by thickened pleura. 2. Klebsiella pneumoniae pneumonia: It is manifested by acute onset, chills, high fever and significant systemic symptoms. The patient has a large amount of viscous sputum, showing typical brick-red jelly status. X-ray radiograph shows consolidation of lung lobes or segments, with multiple small cavities and honeycomb changes, which may quickly fuse into a large cavity. Falling interlobar fissures are also its main feature. 3. Pseudomonas aeruginosa pneumonia: The clinical manifestations include cough and a large amount of emerald purulent sputum, which is one of the characteristic manifestations of Pseudomonas aeruginosa pneumonia. The

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patient has obvious symptoms of toxemia, mainly including chills, fever, restlessness, dyspnea, rapid heartbeat and even coma. X-ray examination shows multiple nodular hyperdensities in the lungs, some of which are fused into large patches. Pleural effusion with empyema often occur in patients. 4. Legionella pneumonia: Patients often have prodromal symptoms, such as fatigue and lethargy. The clinical manifestations are dry cough, high fever and muscle soreness. The digestive system manifestations are nausea, vomiting and diarrhea, and the nervous system manifestations are headache, unconsciousness and lethargy. Cardiovascular system manifestations are mainly pericarditis and endocarditis, and renal damage which will lead to renal failure. The chest X-ray examination shows no specificity, and the symptoms are usually patchy infiltration and consolidation in the peripheral zone or lower lobe of lung. The lesions progress rapidly and dissipate slowly. During the treatment, the imaging manifestations often change continuously [41].

5.5.6 Research Status and Progress 1. X-ray: According to clinical and imaging features, it is difficult to distinguish this disease from pneumonia caused by other bacteria. However, Kofteridis et al. studied the clinical characteristics of 45 cases of lower respiratory tract infection caused by Haemophilus influenzae, and found that advanced age, complications, respiratory failure and segmental consolidation on chest radiographs can be regarded as the relative characteristic changes of Haemophilus influenzae infection [42]. 2. CT: Nei et  al. described the CT manifestations of patients with mycoplasma pneumoniae pneumonia and community-­acquired pneumonia, including 12 patients with Haemophilus influenzae pneumonia. They found that thickened bronchial wall was more common in CT manifestations of patients with Haemophilus influenzae pneumonia than patients with Streptococcus pneumoniae [43]. CT findings are closely related to prognosis, Okada et al. followed up patients infected by Haemophilus influenzae. All 211 patients in the study were treated with antibiotics. Among the 102 patients with community-­ acquired infection, 99 (97.1%) patients showed improvement in their initial respiratory symptoms and follow-up CT and chest radiographs, but in the remaining 3 (2.9%) patients with emphysema and pulmonary heart disease (cor pulmonale), the imaging manifestations such as ground-glass opacities and lesion fusion progressed, and the patients died subsequently [39]. Among 109 patients with nosocomial infection, 101 patients (92.7%) showed

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improvement in their initial respiratory symptoms and CT or chest X-ray radiograph, while the remaining 8 patients (7.3%) had their pulmonary parenchymal lesions and pleural effusion worsening, and then died, including patients with emphysema, bronchial asthma, laryngeal cancer surgery, diabetes and heart disease [39]. Tufvesson et  al. followed up the clinical manifestations and CT features of COPD patients infected with Haemophilus influenzae for a long time [44]. According to their research, the increase of bacteria in sputum of COPD patients in stable stage is positively correlated with the degree of emphysema. Compared with patients without bronchiectasis, the number of bronchiectasis patients colonized with Haemophilus influenzae in  vivo increased. They believed that the degree of bronchiectasis and emphysema can be used as imaging indicators to evaluate the degree of bacterial colonization and inflammatory infection.

5.6  Pseudomonas Aeruginosa Yonggang Li

5.6.1 Overview Pseudomonas aeruginosa, a nonfermentative gram-negative bacillus, is a conditional pathogen and has become one of the main pathogens of nosocomial infection at present [45]. It is widely distributed in water, air and skin, respiratory tract and intestinal tract of normal people [46].This strain has the characteristics of wide drug resistance spectrum, high drug resistance rate and complex drug resistance mechanism. Patients with advanced age, underlying diseases (such as malignant tumor, pulmonary infection, liver and kidney insufficiency, diabetes and other metabolic diseases), admission to ICU, long hospitalization time, use of immunosuppressants and various invasive operations (such as invasive ventilation, arteriovenous catheterization, indwelling catheter, etc.) are the main risk factors of infection [47]. The internal and external toxins produced by Pseudomonas aeruginosa can cause damage to organs, and the resulting clinical manifestations depend on the affected sites. Pseudomonas aeruginosa often causes postoperative wound infection, and can also cause pressure sores, abscesses, suppurative otitis media and so on. The common clinical manifestations of Pseudomonas aeruginosa pulmonary infection are cough, expectoration, fever, chest pain and hemoptysis. Physical examination may show dry and moist rales in the lungs. The prominent feature is that the infection can easily lead to hypoxemia, but it has no significance for differential

diagnosis in clinical practice [48]. Some patients may also show dyspnea, shoulder pain, back pain, etc., and some patients only show unilateral shoulder pain. Pseudomonas aeruginosa usually persists in the later stage of cystic fibrosis and develops into chronic infection [49]. In addition, Pseudomonas aeruginosa is a common pathogen of urinary tract infection. In tropical climates, Pseudomonas aeruginosa is an important pathogen causing microbial keratitis [50]. Severe patients may have septicemia and multiple organ failures, with high morbidity and mortality.

5.6.2 Pathological Manifestations Pseudomonas aeruginosa contains O antigen (bacterial antigen) and H antigen (flagellar antigen). O antigen contains two components: one is outer membrane protein, which is a protective antigen; the other is lipopolysaccharide, which is specific. Its pathogenic mechanism is complex, mainly due to: (1) Adhesins, including extracellular capsule, type IV fimbriae, etc.; (2) Secretion of extracellular products that can destroy cells and tissues, such as fluorescent pigments, proteases, phospholipases and glycosyltransferases; (3) Pathogenic factors carried by outer membrane, cytoplasm and inner membrane, such as β-lactamase, outer membrane protein and penicillin binding protein; (4) Biofilm barrier, active transport system and drug-resistant plasmid which prevent drugs from reaching their targets. All these factors together constitute the pathogenic mechanism of multidrug-­ resistant Pseudomonas aeruginosa [51]. The drug resistance mechanism of multidrug-resistant Pseudomonas aeruginosa is very complex, including the barrier of outer membrane permeability, the change of action target, the production of antibacterial inactivating enzymes, the formation of biofilm and so on [48].

5.6.3 Imaging Manifestations 1. X-ray: Pseudomonas aeruginosa pneumonia may be manifested as multiple nodular opacities in both lungs, or multiple patchy hyperdense consolidation areas, in which translucent cavities may occur [52]. In some patients, chest radiographs may only show thickened and blurred lung markings. In case of pleural effusion, chest radiographs may show that one or both costophrenic angles become blunt. 2. CT: Multiple nodules may occur in both lungs, showing a quasi-round hyperintensities. Some patients may show bronchopneumonia-like changes, manifested as small patchy consolidation and ground-glass opacities distributed or scattered along bronchus, or partially fused into large patches. Focal necrosis of lung parenchyma may

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fested as chills, high fever, chest pain, coughing up pus and blood sputum, shortness of breath, toxemia symptoms and shock. The X-ray features are multiple pneumatoceles distributed in clusters, which quickly fuse into multiple cavitary lesions, and may invade pleura in the early stage, resulting in hydropneumothorax, empyema and pyopneumothorax, accompanied by thickened pleura. 3. Klebsiella pneumoniae pneumonia: It has acute onset, manifested as chills, high fever and significant systemic symptoms; the patient has a large amount of viscous sputum, showing typical brick-red jelly status. X-ray radiograph shows consolidation of lung lobes or segments, with multiple small cavities and honeycomb changes, which could quickly fuse into large cavities. Falling interlobar fissures are also its main feature. Fig. 5.13  Pseudomonas aeruginosa pneumonia. CT lung window showed ground-glass opacity with local consolidation in the middle 4. Haemophilus influenzae pneumonia: It has slow clinical lobe of the right lung and lobular consolidation with cavities in the onset, severe and diverse symptoms, including high fever, lower lobe of the left lung cough, chest pain, dyspnea. Patients have spastic cough, similar to whooping cough, and sometimes similar to bronchiolitis. Systemic symptoms are severe and poisonoccur to form diffuse small abscesses, and then fuse into ing symptoms are significant. X-ray radiograph shows large cavities. If cavities persist for a long time, thick-­ diverse manifestations. Infants are prone to empyema, walled cavities may be formed [53] (Fig. 5.13). pericarditis, septicemia, meningitis and suppurative arthritis, often with sequelae of bronchiectasis. 5. Legionella pneumonia: Patients often have prodromal 5.6.4 Diagnostic Key Points symptoms, such as fatigue and lethargy. The clinical manifestations are dry cough, high fever and muscle sore 1. Pneumonia-related clinical manifestations, such as ness. The digestive system manifestations are nausea, cough, expectoration or aggravation of original respiravomiting and diarrhea, and the nervous system manifestatory disease symptoms, fever, etc. tions are headache, unconsciousness and lethargy. 2. Lung consolidation signs and/or moist rales. There is Cardiovascular system manifestations are mainly pericarpurulent secretion in bronchi. ditis and endocarditis, and renal damage which will lead 3. The total number of leukocytes in peripheral blood is sigto renal failure. The chest X-ray examination shows no nificantly increased, usually >10 × 109/L. specificity, and the symptoms are usually patchy infiltra 4. New or progressive infiltration, consolidation or ground-­ tion and consolidation in the peripheral zone or lower glass opacities can be seen on X-ray radiograph or CT. lobe of lung. The lesions progress rapidly and dissipate 5. If bacterial culture of blood or respiratory secretion conslowly. During the treatment, the imaging manifestations firms the existence of Pseudomonas aeruginosa, this disoften change continuously [48]. ease can be diagnosed.

5.6.5 Differential Diagnosis

5.6.6 Research Status and Progress

1. Streptococcus pneumoniae pneumonia: Before its onset, patients often have inducements of catching a cold, being caught in the rain, fatigue, drunkenness or a history of viral infection. This disease features acute onset and high fever. It may be accompanied by chills, expectoration of purulent sputum, brown sputum or blood sputum, chest pain and other manifestations. X-ray radiograph and CT show patchy hypodensities and lung consolidation with air bronchograms. 2. Staphylococcus aureus pneumonia: It often occurs in patients with underlying diseases, with acute onset, mani-

1. X-ray: It is reported that Pseudomonas aeruginosa pneumonia is most often involved in the upper lobe of the right lung, and about two-third patients show consolidation of the upper lobe of the right lung on the first chest radiograph [54]. 2. CT: Studies show that the lack of connection between Pseudomonas aeruginosa pneumonia and abnormal chest CT findings in patients under the age of 1 can be attributed to aggressive eradication therapy interventions [49]. The potential influence of other pathogens on the results has also been discussed, but is not significant. It is cur-

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rently considered that Pseudomonas aeruginosa infection in the early stage of cystic fibrosis may not affect the lungs of school-age children. Takajo et  al. analyzed a patient with community-­ acquired Pseudomonas aeruginosa pneumonia. Chest X-ray and CT showed consolidation of the whole upper lobe of the right lung, suggesting lobar pneumonia, and the patient died of respiratory failure with bronchial hemorrhage on the day of admission [55]. After autopsy, it was found that the alveoli of the whole upper lobe of the right lung were filled with dense inflammatory cells, mainly composed of macrophages and neutrophils. Therefore, some scholars believe that lobar pneumonia composed of dense neutrophils and macrophages, accompanied by whole lung congestion and edema, may be the feature of community-acquired Pseudomonas aeruginosa pneumonia in healthy adults. Salciccioli et al. reported a case of Pseudomonas aeruginosa pneumonia in a 31-year-old female with systemic lupus erythematosus [56]. Chest radiographs of the patient showed cavitary lesions in the upper lobe of the right lung with ground-glass opacity changes around it. Pseudomonas aeruginosa was found in blood culture on the day of admission, and Pseudomonas aeruginosa was found in sputum sample and pleural fluid culture. Pseudomonas aeruginosa is a rare cause of cavitary lung injury and is associated with immunocompromised hosts. Most reported cavitary Pseudomonas aeruginosa lesions found in immunocompromised patients are secondary to HIV infection, and current studies suggest the possibility of infection in patients undergoing immunosuppressive therapy.

5.7 Legionella Yonggang Li and Jingfen Zhu

5.7.1 Overview Legionella, an aerobic gram-negative bacillus, is a facultative intracellular parasite of human monocytes and macrophages, which widely exists in natural fresh water or artificial water bodies. Currently, 58 species and 3 subgroups have been found [57]. The one most closely related to human beings is Legionella pneumophila. Legionella pneumophila can be divided into 15 serotypes. The most common pathogenic serotype in the United States and Europe is type 1, accounting for 80% of the total cases; it is reported that among Legionnaires’ disease cases in Australia and New Zealand, only 50% are caused by Legionella pneumophila type 1 and 30% are caused by Legionella Long Beach. This

strain has the endotoxin of other gram-negative bacilli, exotoxin of lysing cells and a variety of active enzymes, so it has strong pathogenicity. The exact incidence of Legionnaires’ disease is unclear worldwide, mainly due to differences in awareness levels, diagnostic methods and reporting systems among countries. The prevalence and spread of Legionnaires’ disease is closely related to artificial water environment. Investigation data at home and abroad show that central air conditioning cooling tower and water supply system are the primary risk factors leading to Legionella pneumonia outbreak [58, 59]. Legionnaires’ disease occurs frequently in summer and autumn, and may also be endemic. The incidence ratio of male to female is 2:1 or 3:1. People are generally susceptible, mainly in people with low immune function. Susceptible factors include advanced age (over 50 years old), long-term smoking, alcoholism, underlying diseases such as COPD, malignant tumor, organ transplantation, liver failure, renal failure and so on. Legionella is the main pathogen of lung infection especially in liver transplant recipients [58–60]. Legionnaires’ disease has been listed in the scope of infectious disease report by WHO and many countries, and it has been listed as one of 14 new infectious diseases in China. Clinically, Legionnaires’ disease can be divided into pneumonia type and nonpneumonia type. Legionella pneumonia (LP) belongs to the category of atypical pneumonia, which is severe and is usually defined as bacterial pneumonia caused by microorganisms such as Mycoplasma, Chlamydia and Legionella. Its clinical features are acute lower respiratory tract infection symptoms, with typical manifestations of pneumonia, such as cough, expectoration, chest pain, muscle pain, headache, without specificity. Pontiac fever is a nonpneumonia Legionnaires’ disease similar to influenza, which is mild, with symptoms like cold, chills, fever, headache, muscle pain, and no pneumonia. Most of patients can recover in a short time [58, 61]. Legionella strain isolated by culture is the gold standard in laboratory diagnosis and epidemiological investigation, but it is difficult to culture Legionella strains. Urinary detection of Legionella antigen in urine is simple, rapid and sensitive, and has been widely used in rapid diagnosis of Legionella. The commonly used antigen detection methods include radioimmunoassay and enzyme-linked immunosorbent assay (ELISA), providing a sensitivity of 80–90% and a specificity of 90–100% [62, 63].

5.7.2 Pathological Manifestations The pathological features of Legionella pneumonia are widespread multifocal fibrinous suppurative inflammation, often accompanied by fibrinous and a small amount of mucinous exudative pleurisy. After being inhaled, Legionella is first

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phagocytized by alveolar macrophages, and neutrophils and more alveolar macrophages can be recruited through cellular immunity, finally forming exudative alveolitis rich in fibrin [64]. Pulmonary vascular muscular arteries often show nonnecrotizing vasculitis changes, and about one-third patients involve pleura, showing serous, serous fibrinous or suppurative pleurisy changes. Pneumonia can be repaired, but it may not be absorbed completely, thus causing interstitial inflammation and fibrosis.

5.7.3 Imaging Manifestations 1. X-ray. (a) Rapidly progressive exudative consolidation: The imaging manifestations are mainly filled alveolar spaces, including large consolidation, patchy opacity with blurred edge and ground-glass opacity, showing pneumonia changes in lung lobes and segments. Early involvement of unilateral lung is more common, which can develop from one lobe to multiple lobes and multiple segments. Involvement in multiple lobes and multiple segments is more common, mostly located in the periphery of lung (Figs.  5.14 and 5.15). Although effective antibiotics have been used early, the disease can progress rapidly, involving multiple lobes or contralateral lung tissues within

Fig. 5.14 Community-acquired Legionella pneumonia (I). Chest X-ray radiograph showed patchy opacities with blurred edges in the left lower lung field

Fig. 5.15 Community-acquired Legionella pneumonia (II). Chest X-ray radiograph showed large patchy consolidation in both lung fields with blurred edges, and small patchy opacities with blurred edges in the right upper lung field

3–4 days [65, 66]. Tan et al. analyzed the X-ray manifestations of 43 cases of Legionella pneumonia, and found that 40 patients had pulmonary lesions on the initial chest radiograph, 77% patients showed patchy opacities with blurred edge in the lung, and 16% patients showed lesion fusion trend or progression to lobar pneumonia [66]. More than two-third of the patients with patchy opacities with blurred edge were involved only one lung in the early stage. With the progression of the lesion, both lungs may be involved, and stripe-like opacities and interstitial changes may occur in the later stage of the lung. (b) Cavitation and pleural effusion: The incidence of cavitation varies greatly in different reports, which may be related to the specific immune status of the host. Most cases are accompanied by a small amount of pleural effusion, which is caused by peripheral lung inflammation spreading to pleural space [66, 67]. Cavities is common in immunocompromised patients [61, 65]. (c) Some patients, especially those with impaired immune function, have hilar lymph node enlargement [68]. 2. In the past, most Legionella pneumonias can be diagnosed by CT depending on clinical manifestations and chest radiographs. With the popularization of CT examination, the reports on CT features of Legionella pneumonia are gradually increasing. CT has high resolution for

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a

b

Fig. 5.16 Community-acquired Legionella pneumonia (III). (a) CT lung window showed a large patchy consolidation in the lower lobe of the left lung with air bronchograms inside; (b) After 51 days, reexami-

opacity representation, and can often find more lesions and some subtle imaging signs. At present, it is reported in domestic and foreign literatures that the CT findings of Legionella pneumonia are nonspecific, mainly manifested as consolidation and ground-glass opacities with clear edges in multiple lobes or segments, and the two symptoms often appear together. Sarkai et al. conducted a retrospective analysis on the CT manifestations of 38 patients with Legionella pneumonia, and found that 23 patients had lesions involving both lungs, with no specificity in the involved upper or lower lungs [69]. The consolidation in 24 patients was segmental or subsegmental, often accompanied by scattered ground-glass opacities, and the consolidation areas were mostly located around the lung with clear edges. Yu et al. conducted a retrospective analysis on the CT manifestations of 23 patients with sporadic Legionella pneumonia, and found that consolidation with ground-glass opacities was the main imaging manifestation [67]. Air bronchograms were seen in consolidation of 22 patients, and pleural effusion was seen in most cases. In this group of cases, the lesions had no obvious segmental distribution specificity, and most of lesions are involved in multiple segments and lobes. Lei et  al. studied 35 patients with Legionella pneumonia, including 31 patients with polymorphic lesions, mainly including centrilobular nodules, acinar nodules, small patchy opacities, large patchy opacities, cavities, stripe-­ like opacities, reticular opacities, honeycomb shadow and pleural effusions [70]. Among them, 25 cases showed multilobe and multisegment lesions, which showed the characteristic that Legionella pulmonary lesions often coexisted in various forms, and their distribution was characterized by multilobe and multisegment distribu-

nation showed the lesions of the left lower lobe completely absorbed, only stripe-like opacities were found, with mildly dilated bronchus locally

tion. Moreover, the lesions were often complicated with interstitial fibrosis, cavities and pleural effusion in the later stage (Figs. 5.16 and 5.17). Many literatures have reported that the imaging dynamic changes of Legionella pneumonia are generally later than the changes of clinical symptoms, and the imaging abnormalities may persist or worsen after the clinical symptoms have improved or disappeared [70–72]. A foreign study reported that 57% of patients still had respiratory symptoms, including dyspnea, 13–19 months after recovery. CT examination of 33 cases with decreased carbon dioxide diffusivity showed that there were still residual lesions in lung parenchyma in 21 cases, including strip-like hyperdensities in 21 cases (100%), subsegmental or segmental consolidation in 8 cases (38%), tracheal or bronchiolar dilatation in 7 cases (33%) and pneumatoceles in 4 cases (19%). Mechanical ventilation needed in the acute stage of the disease, inadequate antibiotic treatment which is not standardized, and COPD are considered as the high risk factors for persistent lung abnormalities [73].

5.7.4 Diagnostic Key Points 1. Legionella pneumonia is a noncommunicable disease, which is caused by inhaling aerosol containing Legionella. High-risk factors include chronic lung disease, smoking, advanced age, travel history and immunosuppressant application. 2. Imaging manifestations often include unilateral lower lobe exudation in the early stage, which can rapidly progress to multiple lobes. Most of them are complicated with

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a

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b

c

Fig. 5.17 Community-acquired Legionella pneumonia (IV). (a) CT lung window showed large patchy consolidation in the lower lobe of the left lung with air bronchograms inside. Multiple patchy opacities with blurred edges occurred in both lungs. A small amount of pleural effusion can be found in bilateral thoracic cavities; (b) After 58 days, reex-

amination showed patchy ground-glass opacities after parenchyma exudation absorbed in both lungs, some with interstitial changes, and some with mildly dilated bronchus locally; (c) After 58 days, reexamination showed nodular and strip-like hyperdensities in the lower lobe of the left lung, with pleural effusion absorbed more than before

a small amount of pleural effusion. The incidence of cavitation and hilar lymphadenopathy increases in immunocompromised patients. 3. Legionella strains isolated from culture are the gold standard for diagnosis of Legionella infection.

single lung lobe. After the lesion is absorbed, there is generally no scar formation. However, Legionella disease often invades lung tissue at multiple lobes and segments and usually causes interstitial inflammation and fibrosis in the later stage. 2. Mycoplasma pneumoniae pneumonia: Manifested as the coexistence of interstitial inflammation and alveolar inflammation. Lesions can fuse with each other, but lobar consolidation is rare. Positive serum cold agglutination test has diagnostic value. 3. Pulmonary interstitial fibrosis: Idiopathic interstitial pneumonia generally develops from the peripheral part of the lower lung to the central part and the upper lung. Hormone therapy is effective for ground-glass opacities and consolidation in acute stage, and traction bronchiectasis is common. The fibrosis of this disease is mainly around the

5.7.5 Differential Diagnosis The imaging manifestations of Legionella pneumonia are complex, which are similar to those of typical pneumonia and atypical pneumonia. The residual lesions in the later stage need to be differentiated from interstitial fibrosis. 1. Pneumococcal pneumonia: It often causes lobar consolidation. The lesion edge is blurred, and mostly limited to a

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focus, and the traction of the central bronchus is rare. Most interstitial pneumonia has no clinical symptoms of typical pneumonia such as fever and expectoration.

5.7.6 Research Status and Progress The mortality of Legionella pneumonia remains high, and the existence of underlying diseases and immunosuppression further increases the chance of Legionella infection, but the specific reasons and interactions are still unclear. The study on the regulatory mechanism of lung injury caused by Legionella infection has improved the understanding of lung injury caused by Legionella infection [74]. Early pathogenic detection for suspected patients, early diagnosis and proper anti-Legionella treatment are the key to improve the success rate of treatment and reduce the mortality. Molecular biological techniques developed in recent years have the advantages of rapidity, simplicity, specificity and sensitivity, and have played a certain role in the detection of Legionella pneumophila and rapid diagnosis of Legionnaires’ disease. The second-generation sequencing, also known as high-throughput sequencing (HTS), can sequence hundreds of thousands to millions of nucleic acid molecules at a time. It has greatly reduced the time and cost of sequencing, facilitating sequencing technology application in real-time monitoring and analysis of epidemics. Sequencing technology also provides a large number of high-quality bioinformatics data, which makes the research of Legionella pneumophila more detailed and in-depth. The imaging changes of Legionella pneumonia are inconsistent with the clinical manifestations in stages, but its scope, morphology and fibrosis degree reflect the severity, prognosis and outcome of its lesions to a certain extent, especially the fibrosis degree has a great influence on the latter two. Therefore, analyzing and studying the imaging features of Legionella pneumonia can make timely and accurate diagnosis, with great guiding significance for the selection of treatment scheme and treatment duration.

5.8 Actinomycetes Yonggang Li and Jingfen Zhu

5.8.1 Overview Actinomycetes are gram-positive anaerobic or microaerobic bacteria, which grow slowly and have no spores [75]. Actinomycetes mostly exist in the oral cavity of normal ­people, and can also be found in gastrointestinal tract and

genitourinary tract, belonging to the normal flora of human body. Pulmonary actinomycosis is a rare disease, accounting for 15–30% of all cases of actinomycete infection, second only to head and neck, abdominal cavity and pelvic actinomycete infection [75–77]. Most of the diseases are due to aspiration of oral or gastrointestinal secretions, and most of the actinomycetes causing lung infection are Israeli actinomycetes [75, 76]. The susceptible factors of actinomycosis include poor oral hygiene, periodontal disease, alcoholism, smoking, chronic wasting diseases (diabetes) and basic lung diseases [75–77]. Clinical manifestations are lack of specificity, and most of patients are middle-aged and elderly men. Common respiratory symptoms such as cough, expectoration, hemoptysis, dyspnea and chest pain may occur. Pleural effusion and empyema may occur when pleura is involved, and sulfur-like granules may be excreted if fistula is formed in the involved chest wall, but it is extremely rare [75, 78]. Pathological examination is the gold standard for diagnosis of pulmonary actinomycosis. Lung puncture biopsy can quickly and effectively determine the diagnosis of pulmonary actinomycosis, but it should be noted that one biopsy may not get enough lesion tissue for definite diagnosis, and multiple biopsies are needed to improve the diagnostic rate. Literature shows that 41–52% of pulmonary actinomycosis can only be finally diagnosed by surgical and pathological findings [79].

5.8.2 Pathological Manifestations Actinomycosis is a chronic granulomatous inflammation manifested by suppuration, sulfur-like granules, abscesses, and sinus formation [80, 81]. The pathological manifestations were inflammatory reaction locally in bronchial mucosa and lung tissue with infiltration of neutrophils, macrophages, plasma cells and lymphocytes, showing peripheral fibrotic changes and granulation tissue hyperplasia. CT images and related histological findings of patients undergoing lobectomy show that the hypodense foci in the center of CT image represents abscess containing sulfur-like granules or dilated bronchus containing inflammatory cells and actinomycete colonies, and the peripheral enhancement of hypodense area represents new blood vessels in abscess wall or granulation tissue around lung parenchyma [81, 82]. Sulfur-like granules are mostly found in sinuses and necrotic secretions. Sulfur-like granules in sputum may be suggestive for the diagnosis of pulmonary actinomycosis, but cannot be used as the basis for the diagnosis of pulmonary actinomycosis. For example, sulfur-like granules similar to those in actinomycosis may also appear in nocardiosis, chromomycosis and eumycetoma [82, 83].

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5.8.3 Imaging Manifestations 1. X-ray: It can show lumpy and large patchy opacities mainly in subpleural and peripheral lung tissues, mostly involving unilateral lung, and the details of cavities, bubbles and necrotic foci in lesions are unclear, which has limited diagnostic value for this disease. 2. CT: The characteristic CT findings include focal or patchy consolidation, often accompanied by central hypodense foci or cavities (Fig. 5.18). CT enhancement scan shows the periphery of the lesions, and typical cases show thickened adjacent pleura [78, 84, 85]. Cheon et al. reviewed the chest radiographs and CT images of 22 patients with pulmonary actinomycosis [78]. The lesions were unilateral in all patients, with an average diameter of 6.5 cm (ranging from 2 to 12 cm). CT showed patchy air cavity consolidation (n = 20) or mass (n = 2). Among 20 patients with consolidation of air cavity, 15 patients had hypodense focus in the center of consolidation area. 13 of 15 cases underwent enhanced CT scan, and 10 of 13 cases (77%) showed annular edge enhancement around the central hypodense focus. Cheon et al. reported 22 cases of pulmonary actinomycosis, of which 16 cases (16/22, 73%) showed thickened focal pleura in the consolidation area. The central hypodense focus in CT images of lobectomy patients represents an abscess containing sulfur-like granules or a residual dilated bronchus containing inflammatory cells and actinomycete colonies. Peripheral enhancement of hypodense areas represents neovascularization in the wall of small abscess or granulation tissue around lung parenchyma. Kim [81] and Han [84] divided pulmonary actinomycosis into pulmonary parenchymal type, bronchiectasis a



type, endobronchial type related to broncholithiasis, endobronchial type related to foreign body and extrapulmonary type. (a) Pulmonary parenchymal type: The imaging manifestations of early, middle and late pulmonary actinomycosis are different. In the early stage, it is generally noncharacteristic, which can be manifested as irregular patchy consolidation or localized strip-like opacities of peripheral lung tissue, and the periphery can be accompanied by “halo” sign formed by ground-­ ­ glass opacities, with or without thickened interlobular septa. The formation of ground-glass opacities is related to the infiltration of neutrophils, lymphocytes and inflammatory cells, as well as fibrinous exudate in surrounding alveoli. In the middle and later stages, the volume of lesions gradually increases, showing patchy or mass opacities. The lesions may be distributed in segments of the lung at first, but may involve the whole lung lobe in the later stage. The direct spread of actinomycete lesions mostly occurs around the lesions, and the lesions involve a wide scope, often across segments, lobes and anatomical spaces. Both plain scan and enhanced scan show central hypodense focus, accompanied by cavities or multiple quasi-round small vacuoles, and the cavity wall has been significantly enhanced [85]. The sign of “air-space consolidation” is the characteristic manifestation of this disease. Gas suspension has nothing to do with gravity, and the cavity is in a vacuum state, so the gas is suspended inside, and generally does not form a gas-liquid plane [86]. Hilar and mediastinal lymphadenectasis, thickened local pleura, pleural effusion and so on can also be found.

b

Fig. 5.18  Pulmonary actinomycosis. (a and b) CT showed a agglomerate consolidation area in the lower lobe of the right lung, and a hypodense necrosis area in the center of the lesion (case images by courtesy of Qiuzhen Xu, Zhongda Hospital Southeast University)

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(b) Bronchiectasis type: It is reported in the literature that actinomycetes are easy to colonize in the damaged lung tissue and cause diseases, such as bronchiectasis and pulmonary tuberculosis lesions complicated with actinomycete infection. CT manifestations are local bronchiectasis and uneven thickened bronchial wall with or without local lung abscess. (c) Endobronchial type related to broncholithiasis: Broncholithiasis is a calcification of the hilum or bronchi, which leads to local bronchial luminal stenosis with secondary actinomycete infection. CT findings shows hyperdense bronchial calcification at the proximal end of the lesion with obstructive pneumonia at the distal end, and abscesses or cavities may be formed in the lesions of obstructive pneumonia. (d) Endobronchial type related to foreign body: The CT manifestations of this type are similar to those of endobronchial type related to broncholithiasis, and foreign bodies can be chicken bones, fish bones, peas or grape seeds. (e) Extrapulmonary type: Due to the use of antibiotics, the reported cases of extrapulmonary type have been reduced. Actinomycetes can produce proteolytic enzymes, which can destroy the adjacent anatomical barrier and directly spread and involve other areas. For example, peripheral pneumonia often involves pleura and mediastinum, resulting in empyema, or invades chest wall, destroying ribs or vertebrae. The imaging manifestations of chest wall involvement include chest wall soft tissue mass, which is usually connected with lung lesions, in which hypodense necrotic areas, empyema, local rib periosteal reaction, bone destruction of ribs or vertebrae can also be found, and chest wall sinus tract can be formed in some cases in the later stage. The involvement of mediastinum can cause mediastinal infection, abscess, and even invade esophagus to form bronchoesophageal fistula.

5.8.4 Diagnostic Key Points 1. Clinical history and risk factors, including poor oral hygiene, periodontal disease, alcoholism, smoking, chronic wasting diseases (diabetes), underlying lung diseases, etc. 2. Sulfur-like granules often appear in sinus tracts and necrotic secretions. Sulfur-like granules in sputum may be suggestive for the diagnosis of pulmonary actinomycosis, but cannot be used as the basis for the diagnosis of pulmonary actinomycosis.

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3. The common manifestations of X-ray examination are unilateral patchy consolidation in peripheral lung tissue and lower lobe. CT often shows hypodense area caused by abscess formation in common consolidation. The sign of “air-space consolidation” is the relative characteristic manifestation of this disease.

5.8.5 Differential Diagnosis 1. Peripheral lung cancer: Lung cancer has lobules and burrs, and the inner wall of cancerous cavity is often not smooth, with wall nodules. Actinomycetes have no obvious lobules and burrs, and hypodense area or the sign of “air-space consolidation” is common in lesions. 2. Pulmonary tuberculosis: Most of the patients have a history of tuberculosis, which usually occurs in the posterior segment of the upper lobe and the dorsal segment of the lower lobe. There are scattered satellite foci around the lesions, and the cavity wall is thin and sometimes the gas-­ liquid plane is visible. 3. Lung abscess: Compared with actinomycetes, the onset is more acute, with faster progress and absorption, often showing the clinical manifestations of fever and chills. Lung abscess often shows thick-walled cavities with visible gas-liquid plane. The lesions may involve multiple lung segments, but interlobar fissures are rarely involved.

5.8.6 Research Status and Progress The diagnosis of pulmonary actinomycosis should be made by combining clinical symptoms, imaging findings and histological or microbiological examination results. The management of actinomycosis usually requires extended course of antibiotic treatment, and penicillin is the preferred drug. More complex cases may also require surgical intervention, such as patients with infections in important spaces (such as epidural infections, brain abscesses), massive hemoptysis, or patients with extensive abscesses and fistulas. The following situations need to be vigilant, such as bronchitis, pulmonary infection with poor treatment effect, lung abscess with unknown causes and pleural effusion. Gene sequencing, PCR and 18F-FDG PET/CT are expected to be the means of in vitro rapid diagnosis of this disease in the future.

5.9 Nocardia Bailu Liu, Zhehao Lyu, and Tingting Chen

5  Bacterial Infection

5.9.1 Overview Nocardia is an aerobic filamentous bacterium, and an opportunistic infection pathogen. Nocardia asteroides is the main pathogen to human body, and other pathogens include Nocardia brasiliensis and Nocardia guinea pigs. Nocardia does not cause endogenous infection, because it is not a normal flora of human body. Nocardia can cause nocardiosis, which is an acute or chronic purulent or granulomatous lesion, mostly caused by respiratory tract inhalation of pathogens or traumatic infection, common in immunocompromised patients. Nocardia exists in soil, rotten matter and organic water. At present, there are four Nocardia species known to cause diseases to human body: N. asteroids, N. farcinica, N. titidiscaviarum and N. brasiliensis. Nocardia has different virulence in different growth stages. Mycobacteric acid is contained in the cell wall of Nocardia in logarithmic growth stage, which can enhance the virulence of Nocardia and may also affect the ability of Nocardia to aggregate in some tissues. After infection with Nocardia, the neutrophils of the host can inhibit Nocardia but cannot kill Nocardia. Activated macrophages can stimulate cellular immunity, thus killing Nocardia. Blood routine examination of pulmonary nocardiosis can find that neutrophil count increases, and the total number of erythrocytes decreases and hemoglobin decreases. Pulmonary infection caused by Nocardia has no significant clinical specificity, and its early symptoms include fever, chills, cough, expectoration, chest pain, chest tightness and weight loss. Patients who have been sick for a long time and cough a lot of yellow purulent sputum should be differentiated from those with pulmonary tuberculosis. For patients who have been treated with antituberculosis for a long time and have coughed up a large amount of yellow purulent sputum, the possibility of Nocardia infection should be especially considered. The respiratory tract of patients with pulmonary nocardiosis is stimulated by chronic suppurative inflammation for a long time, thereby showing bronchial deformation and long-term dilatation. Chest CT can show cystic columnar dilatation of multiple small bronchi, so this disease should be distinguished from bronchiectasis. The diagnosis of this disease depends on the culture results of sputum, lower respiratory tract secretion or pleural effusion, as well as pathological examination of lung biopsy. Serological methods and skin tests have no diagnostic significance.

5.9.2 Pathological Manifestations There are white hyphae on the surface of Nocardia asteroids colony, but there are white hyphae on the surface of Nocardia brasiliensis colony. In liquid culture medium, bacterial

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membrane often grows on the surface, and the lower liquid is clear. The pathological changes of Nocardia are purulent inflammation, with infiltration of a large number of neutrophils, lymphocytes and plasma cells. There were no giant cells or caseous necrosis. The main pathological changes of pulmonary Nocardiosis are pyogenic granuloma with infiltration of a large number of neutrophils, plasma cells and histiocytes, tissue necrosis and abscess, which tends to fuse. Hyphae can be found in abscess, and aggregate to form loose granules, and its sheath is not obvious.

5.9.3 Imaging Manifestations The imaging findings of this disease have no characteristics. 1. Localized or diffuse infiltrative changes can be manifested as ground-glass opacities and patchy opacities, and most of them are mainly consolidation. 2. There are single or multiple pulmonary nodules or masses (similar to primary cancer or metastases), with different nodules of different sizes. Miliary nodules can be found in the early stage, most of which are large nodules and masses, which are easy to form cavities. Nocardia colonizes in the respiratory tract and causes bronchopneumonia. Its pathological changes include inflammatory changes in bronchial and bronchiolar walls, as well as exudation of adjacent alveoli. Therefore, thickened bronchial wall and centrilobular nodules can be seen in patients with bronchopneumonia, sometimes forming “tree-in-bud” sign and mucus impaction [87, 88, 90, 91]. 3. The lesion is purulent infection, necrotic and discharged, so cavities are often formed. 4. Pleural effusion may occur if pleura is involved. 5. As for the CT features of pulmonary nocardiosis, the review mentioned that discrete nodules are often related to immunosuppression, and lung consolidation (64.2%) is the most common imaging manifestation, followed by pulmonary nodules (57%) and cavities (40%). Other studies have not found any significant difference between immunocompromised patients and immunocompetent patients. It is considered that the main CT manifestations of pulmonary nocardiosis in immunocompromised patients and immunocompetent patients include pulmonary nodules, consolidation and cavities. Studies have shown that lung consolidation, nodules and masses are also common CT features of Nocardia disease, and cavities can also be seen in some cases. Pleural effusion, bronchiectasis and “halo” sign are rare manifestations of this disease, but their incidence varies greatly among different studies, which may be caused by the limited number of patients in these studies.

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6. HRCT can show the detailed changes of lung structure and lesions more clearly, and is usually used to evaluate the abnormal changes of lung parenchyma and interstitium. Compared with conventional chest radiograph and common chest CT scan, HRCT can detect the characteristics of early and late pulmonary nocardiosis, and the diagnosis of pulmonary nocardiosis still needs histopathological examination or culture [89–92].

5.9.4 Diagnostic Key Points 1. Single-lobe or multilobe consolidation and infiltrative opacities of both lungs. 2. Single or multiple pulmonary nodules, masses, cavities, pulmonary fibrosis and diffuse pulmonary interstitial lesions. 3. Hilar and mediastinal lymphadenovarix, empyema and thickened pleura, occasionally invading chest wall. 4. Blood routine examination shows the increased neutrophil count, the decreased total number of erythrocytes, and the decreased hemoglobin level. 5. The diagnosis depends on culture of sputum, lower respiratory tract secretion or pleural effusion, and pathological examination of lung biopsy.

5.9.5 Differential Diagnosis 1. Lung abscess: It has clinical symptoms such as infection, fever, purulent smelly sputum. The imaging manifestations are uniform thick-walled cavities with gas-liquid plane and “halo” sign. The enhanced cavity wall is annular and markedly enhanced. A small amount of pleural effusion can be seen in involved pleura. 2. Pulmonary tuberculosis: It has clinical symptoms of tuberculosis poisoning, and most of the tuberculosis indicators in laboratory examination are positive. Pulmonary tuberculosis occurs mostly in the posterior segment of the upper lobe apex and the dorsal segment of the lower lobe of both lungs. The cavity wall is thin and irregular, surrounded by satellite lesions, mostly dry cavities without liquid or gas-liquid plane. Dynamic observation shows that the lesions progress slowly and no major changes occur in short term. 3. Granulomatosis with polyangiitis: More than 70% of patients are first involved in upper respiratory tract, with positive ANCA.  It is characterized by granulomatous inflammation and necrotizing vasculitis. Multiple nodules of different sizes occur in both lungs. “Three-multi and one cavity” (“Three-multi” is multiform, multichange and multidistribution) is the manifestation feature. Some patients are accompanied by hilar or

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mediastinal lymphadenovarix. Pleural effusion occurs in 10% of patients. 4. Central lung cancer: Clinical symptoms are mostly mild, without fever or purulent sputum. Hemoptysis occurs in most of patients. The edges of the lesions are clear and irregular. The cavity wall is thick and uneven. The internal cavities are mostly eccentric, with irregular inner edges. There is no gas-liquid plane in the cavities, often accompanied by hilar and mediastinal lymphadenectasis.

5.9.6 Research Status and Progress Posttransplant patients are at risk for pulmonary nocardiosis, a life-threatening opportunistic infection caused by Nocardia. In view of the limitations of conventional diagnostic techniques (microscopic observation and culture), the current research focus is to detect Nocardia based on polymerase chain reaction (PCR). In a prospective study of PCR detection of Nocardia in lung transplant patients [93], about one-­ fourth (5/21) of bronchoalveolar lavage fluid samples were positive, but there were no other tests supporting nocardiosis detection (microscopic observation, culture or 6-month follow-­ up), which may represent airway colonization of Nocardia. Another study showed that Nocardia colonization was found in 46 of 101 healthy U.S. soldiers when screened with swabs from nostrils, oropharynx and groin [94]. In addition, some patients with pulmonary tuberculosis and HIV infection can also show positive results of Nocardia PCR [95]. A recent prospective study evaluated the diagnostic sensitivity and specificity of Nocardia PCR to be 88% and 74% for patients at high risk of nocardiosis [96].

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60 52. Gao W, Xiao Y, Shi B, et al. Pseudomonas aeruginosa community-­ acquired pneumonia: two cases report and literature review. Int J Respir. 2014;34(6):413–8. 53. Han D, He W. Imaging evaluation of hospital acquired pneumonia. Chin Comput Med Imag. 2010;16(5):375–8. 54. Zhang R, Huang X, Li M, et al. A case of fatal community-acquired Pseudomonas aeruginosa pneumonia. Chin J Tubercul Respir Dis. 2019;42(12):950–2. 55. Takajo D, Iwaya K, Katsurada Y, et al. Community-acquired lobar pneumonia caused by Pseudomonas aeruginosa infection in Japan: a case report with histological and immunohistochemical examination. Pathol Int. 2014;64(5):224–30. 56. Salciccioli JD, Woodcock H, Darmalingam M. Pseudomonas aeruginosa as an unusual cause of cavitating lung lesion. BMJ Case Rep. 2017;2017:bcr2017220527. 57. Cunha BA, Burillo A, Bouza E.  Legionnaires’ disease. Lancet. 2016;387(10016):376–85. 58. Bartram J, Chartier Y, Lee J, et al. Legionella and the prevention of legionellosis. Geneva: World Health Organization; 2007. 59. Fraser DW. Legionellosis: evidence of airborne transmission. Ann N Y Acad Sci. 1980;353:61–6. 60. Atlas RM.  Legionella: from environmental habitats to disease pathology, detection and control. Environ Microbiol. 1999;1(4):283–93. 61. Mittal S, Singh AP, Gold M, et  al. Thoracic imaging features of Legionnaire’s disease. Infect Dis Clin N Am. 2017;31(1):43–54. 62. Jarraud S, Descours G, Ginevra C, et al. Identification of legionella in clinical samples. Methods Mol Biol. 2013;954:27–56. 63. Olsen CW, Elverdal P, Jørgensen CS, et al. Comparison of the sensitivity of the Legionella urinary antigen EIA kits from Binax and Biotest with urine from patients with infections caused by less common serogroups and subgroups of Legionella. Eur J Clin Microbiol Infect Dis. 2009;28(7):817–20. 64. Newton HJ, Ang DKY, van Driel IR, et al. Molecular pathogenesisof infections caused by Legionella pneumophila. Clin Microbiol Rev. 2010;23(2):274–98. 65. Coletta FS, Fein AM.  Radiological manifestations of Legionella/Legionella-like organisms. Semin Respir Infect. 1998;13(2):109–15. 66. Tan MJ, Tan JS, Hamor RH, et al. The radiological manifestations of Legionnaire’s disease. Chest. 2000;117(2):398–403. 67. Yu H, Higa F, Hibiya K, et al. Computed tomographic features of 23 sporadic cases with Legionella pneumophila pneumonia. Eur J Radiol. 2010;74(3):e73–8. 68. Lanternier F, Tubach F, Ravaud P, et al. Incidence and risk factors of Legionella pneumophila pneumonia during anti-tumor necrosis factor therapy: a prospective French study. Chest. 2013;144(3):990–8. 69. Sarkai F, Tokuda H, Goto H, et al. Computed tomographic features of Legionella pneumophila pneumonia in 38 cases. J Comput Assist Tomogr. 2007;31(1):125–31. 70. Lei Z, Feng K, Jia W, et al. Imaging appearances and its diagnostic value of Legionella pneumonia. Chin J Med Imaging Technol. 2006;22(11):1668–71. 71. Godet C, Frat JP, Moal GL, et al. Legionnaire’s pneumonia: is there really an interstitial disease? Eur J Radiol. 2007;61(1):150–3. 72. Dietrich PA, Johnson RD, Fairbanks JT, et al. The chest radiograph in Legionnaire’s disease. Radiology. 1978;127(3):577–82. 73. Jonkers RE, Lettinga KD, Pels Rijcken TH, et al. Abnormal radiological findings and a decreased carbon monoxide transfer factor can persist long after the acute phase of Legionella pneumophila pneumonia. Clin Infect Dis. 2004;38(5):605–11. 74. Liang S, Chen Y.  Research advances on regulation mechanism of lung injury caused by Legionella infection. Int J Respir. 2021;41(3):229–35. 75. Kim SR, Jung LY, Oh IJ, et al. Pulmonary actinomycosis during the first decade of 21st century: cases of 94 patients. BMC Infect Dis. 2013;13:216.

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6

Viral Infection Feng Chen, Li Li, Yupeng Liu, Wang Fei, Lili Kong, Yinglin Guo, Dan Mu, Xianhe Zhang, Xuhua Yang, Haibo Wang, and Zhao Liu

6.1 Influenza Virus

virus. According to the antigenic characteristics of virus nucleoprotein, influenza virus can be divided into type A, 6.1.1 Influenza type B and type C. Rapid mutation and evolution is a major feature of influenza virus. Influenza virus mutation is mainly Feng Chen due to structural changes of hemagglutinin and neuraminidase antigens, especially hemagglutinin. The variants of 6.1.1.1 Overview hemagglutinin and neuraminidase are constantly combined Influenza is an acute respiratory infectious disease caused by into new mutant strains, which feature large number enough influenza virus, which is mainly transmitted by droplets. It is to prevent the immune defense established by the original highly contagious and likely to cause outbreaks or pandem- epidemic strains from playing an effective protective role as ics, and its incidence ranks first among statutory infectious long as the immunity of the population drops to a low level diseases. The main clinical features of this disease are acute sufficiently for the mutant strains to invade the susceptible onset of high fever, fatigue, systemic muscle soreness and population and cause outbreaks, which is an important reamild respiratory symptoms. It features high incidence in son for the recurrence of influenza pandemics. Significant autumn and winter. Influenza has a short course and is self-­ mutations occur mainly in influenza A virus, while influenza limiting, but infants, the elderly, patients with cardiopulmo- B virus is less common, and influenza C virus generally does nary diseases and other chronic diseases and not mutate (Table 6.1). immunocompromised people are prone to pneumonia or Influenza patients and latent infected persons are the main other serious complications, which can lead to death. sources of influenza infection. It is contagious from the end In 1971, the World Health Organization (WHO) unified of latent period to the acute stage after onset, and the most the naming system of influenza virus. Influenza virus is RNA contagious period is first 2–3  days at the beginning of the disease. During the period of seasonal influenza (without complications) in adults and older children, the virus typically releases toxins in respiratory secretions for 3–6 days. F. Chen · L. Li (*) · Z. Liu Beijing Youan Hospital, Capital Medical University, Beijing, China Hospitalized adult patients can spread infectious viruses for a week or more after onset of the disease. Y. Liu First Hospital of Qinhuangdao, Qinhuangdao, China Studies have shown that long-term toxin release is common (1–3 weeks) in infant influenza cases or human H5N1 W. Fei · X. Zhang · H. Wang The 2nd Affiliated Hospital of Harbin Medical University, avian influenza cases. In addition, patients with AIDS and Harbin, China other immunodeficiency also have the phenomenon of proL. Kong longed period of virus toxin release. Yeda Hospital, Yantai, China Air droplet transmission is the main route of transmisY. Guo sion. Influenza virus exists in respiratory secretions of Harbin Taiping District People’s Hospital, Harbin, China patients or latently infected persons, and spreads in the air in D. Mu the form of droplets or aerosols through talking, coughing or The Affiliated Hospital of Nanjing University Medical School sneezing, so that susceptible persons are infected after inha(Nanjing Drum Tower Hospital), Nanjing, China lation. It can also spread through direct or indirect contact X. Yang with mucous membranes in oral cavity, nasal cavity and Mudanjiang Kangan Hospital, Mudanjiang, China

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Table 6.1  Comparison of influenza A, B and C viruses Contrast item Genome Structure

Host Viral variability

Clinical features

Type A 8 gene segments

Type B 8 gene segments

10 viral proteins M2 is unique to type A Human, pig, horse, etc. Antigenic drift and displacement

10 viral proteins NB is unique to type B Seems to infect only human Antigenic drift, more than one variant can be prevalent at the same time Generally does not cause a pandemic

May cause a pandemic with high mortality

Type C 7 gene segments 9 viral proteins HEF is unique to type C Human, pig Antigenic drift, multiple variants

Most of them are sporadic and the condition is mild

eyes. Influenza is highly contagious, spreads rapidly and is prevalent extensively. Its transmission speed is related to population density. People are generally susceptible to influenza, regardless of gender, occupation, etc. Patients have a certain immunity after recovery. The antibodies appear at 1 week after infection, reaching its peak at 2–3 weeks, and began to decline at 1–2  months after infection. Antibodies exist in blood and nasal mucosa secretions. There is no cross immunity among influenza A, B and C and different subtypes of influenza A, and the disease can occur repeatedly. After infection, the immune protection is not maintained for a long time. Although antibodies exist in blood, patients can still be infected by the same virus again. Influenza viruses often mutate, and the infection rate is usually higher among teenagers. The following specific people are more likely to have severe cases after being infected with influenza virus, which should be paid great attention to, influenza virus-related tests and other necessary examinations should be conducted as soon as possible, and targeted treatment measures should be provided. (1) Pregnant women; (2) Patients accompanied by the following diseases or conditions: Chronic respiratory diseases, Cardiovascular diseases (except hypertension), liver and kidney diseases, blood system diseases, nervous system and neuromuscular diseases, metabolic and endocrine system diseases, immunosuppressive persons (including immunocompromised persons with immunosuppressive agent administration or HIV infection), and care recipients living collectively in nursing homes or other chronic disease convalescent institutions, and those under 19 years old who take aspirin for a long time; (3) Obese persons [body mass index (BMI)  >  30  kg/m2]; (4) Children under 5  years old (children under 2 years old are more prone to serious complications); (5) Old people aged ≥65 [1, 2].

Laboratory examination: In acute stage, the total number of peripheral blood leukocytes decreases, while the lymphocyte count increases relatively, and eosinophils may disappear. The total number of leukocytes and the proportion of neutrophils increase in case of complication with bacterial infection. Nasopharyngeal mucosal epithelial cells are smeared for virus antigen detection, and necrosis of columnar ciliated epithelial cells and eosinophilic inclusions in cytoplasm can be found. Immunofluorescence or enzyme-­ labeled staining is sensitive to detect viral antigens in exfoliated cells. Monoclonal antibodies can identify influenza A, B and C.  Serological examination of antibodies to influenza virus is performed by taking double sera in the acute phase and 3–4  weeks after illness in hemagglutination inhibition test, enzyme-linked immunosorbent assay and complement fixation test. If the titer of influenza virus has increased more than 4 times, it will be of diagnostic significance. The positive rate can reach 60%–80%. PCR can detect influenza virus genes directly from respiratory tract samples of patients, which is more sensitive and rapid than virus culture. Influenza virus culture and isolation is the gold standard for the diagnosis of influenza.

6.1.1.2 Pathological Manifestations Influenza A and B viruses initiate infection by binding their hemagglutinin (HA) to sialic acid receptors on the surface of respiratory epithelial cells. Influenza virus enters cells through endocytosis, and viral genome is transcribed and replicated in the nucleus. A large number of new progeny virus granules are replicated, which spread through respiratory mucosa and infect other cells. After influenza virus infects human body, it can induce cytokine storm, which leads to systemic inflammatory reaction, acute respiratory distress syndrome, shock and multiple organ failure. Acute necrotizing encephalopathy may occur in children. The main pathological changes are cluster exfoliation of airway ciliated epithelial cells, ciliated epithelial cells metaplasia, congestion and edema of mucosal cells in lamina propria complicated with monocyte infiltration and other pathological changes. Diffuse alveolar damage may occur in severe pneumonia [3]. 6.1.1.3 Imaging Manifestations Imaging manifestations reflect the severity of lesions, and high-risk groups are the focus of chest imaging examination. In addition, attention should be paid to the imaging manifestations of the original underlying diseases in the lung, and differential diagnosis. X-ray examination is the most commonly used method, mainly for the diagnosis of influenza viral pneumonia or influenza complicated with bacterial pneumonia. 1. Influenza virus pneumonia.

6  Viral Infection

(a) X-ray: Interstitial pneumonia and bronchopneumonia are the main manifestations, with enhanced lung markings and blurred edges in the early stage. The manifestations are significant in bilateral lower lung fields with ground-glass hyperdensities. Because the early clinical symptoms are not obvious, the diagnosis is difficult. The progression of the disease is manifested as reticular opacities and reticular nodular opacities in the lung field, and the nodules are generally less than 5 mm. This sign can coexist with enhanced and blurred lung markings, and the lesions are mostly distributed in the lower fields of both lungs and around the hilum (Figs. 6.1 and 6.2). Pathological manifestations are exudative inflammation of alveolar walls and interlobular septa. In the later stage, due to inflammatory obstruction of small bronchi, cystic changes of different sizes appear, showing honeycomb lung, with reduced lung volume, lifted diaphragm and interlobar fissure displacement. About 30% of cases are confirmed as pulmonary interstitial fibrosis by lung biopsy, but chest X-ray examination shows normal condition. X-ray examination is not sensitive to alveolitis and lacks specificity. (b) CT: Compared with traditional X-ray examination, CT examination can comprehensively and objec-

Fig. 6.1  Influenza virus pneumonia (I). The patient, a 4-year-old female, coughed for 9 days and had fever for 5 days, with the highest body temperature of 39.2°C.  Laboratory examination: WBC 5.26 × 109/L, L 24.3%, N 71.4%, CRP 2.7 mg/L, positive for influenza A virus antigen. Chest X-ray radiograph showed the thickened bilateral lung markings. Dotted and small patchy opacities along the lung markings occurred in the middle and inner zones of bilateral lung fields, with blurred edges

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Fig. 6.2  Influenza virus pneumonia (II). The patient, a male aged 72, had cough, fever and dyspnea for 7 days, with the highest body temperature of 39.5°C.  Laboratory examination: WBC 2.99  ×  109/L, L 9.4%, N 84.9%, CRP 45 mg/L, positive for influenza A virus antigen. Chest X-ray radiograph shows the thickened bilateral lung markings, dotted and small patchy opacities and fibrous strip-like opacities distributed along the lung markings in the middle and lower fields of both lungs

tively evaluate the disease condition, which is conducive to accurately judging the degree, scope and location of lung damage. Through the adjustment of window width and window position, the subtle dynamic changes and distribution of lesions can be found, thereby obtaining more information than chest radiographs. CT findings include large consolidation of lung lobes or segments with air bronchograms, small nodules, ground-glass opacities, “tree-in-bud” sign and mosaic perfusion, as well as thickened interlobular septa, thickened subpleural curvilinear shadow, thickened adjacent pleura, pleural effusion, etc. (Figs. 6.3 and 6.4). 2. Influenza complicated with bacterial pneumonia. (a) X-ray: Bacterial pneumonia is characterized by alveolar pneumonia (lobar pneumonia) and bronchopneumonia (lobular pneumonia). Alveolar pneumonia is manifested as alveolar consolidation, which is seen in pneumococcus, pneumobacillus, Legionella infection, etc. The lesions involve one or more lung lobes. Chest X-ray examination mainly shows lobar consolidation or hyperdense uniform consolidation in most lobar part, and gas-filled bronchi shadows can be found inside. According to the different parts of the lung lesions, the imaging findings are different.

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a

b

Fig. 6.3  Influenza virus pneumonia (III). The same patient as that in Fig. 6.2. (a) and (b) are CT cross-sectional images and coronal MPR images, respectively. There were scattered reticular opacities in both lungs and thickened interlobular septa, especially in the left lung

Fig. 6.4  Influenza virus pneumonia (IV). The same patient as that in Fig.  6.1. CT lung window showed small nodular opacities scattered along bronchovascular bundles in both lungs, with blurred edges, thickened bilateral pleura and a small amount of pleural effusion

Intrapulmonary lesions were mostly absorbed within 2 weeks. In addition to the above pathogenic bacteria infection, bronchopneumonia is also found in infections by Haemophilus influenzae, Staphylococcus aureus and others. It is more common in infants, the elderly and extremely frail patients. Chest X-ray examination shows that the lung markings are enhanced and thickened, with blurred nodular opacities with a diameter of 6–8 mm or blurred patchy opacities with a diameter of 10–25  mm, while the larger uneven patchy opacities with blurred edges are caused by the overlapping opacities of most lobular alveolitis

Fig. 6.5  Influenza complicated with bacterial pneumonia (I). The patient, a 51-year-old female, had fever and cough for 7 days, with the highest body temperature of 39°C.  Laboratory examination: WBC 7.31 × 109/L, L 13.3%, N 80.1%, CRP 18.0 mg/L, positive for influenza B virus antigen. Chest X-ray radiograph showed the thickened bilateral lung markings. Irregular agglomerate opacities occurred in the middle and outer zones of right lower lobe lung field, with blurred edges

(Figs. 6.5 and 6.6). Mucus obstruction of bronchi can be manifested as lobular atelectasis or focal emphysema in the lesion area, and bronchiole obstruction

6  Viral Infection

can form small triangular atelectasis. Most of the lesions are located in the inner zone of the lower field of both lungs, and there are more lesions in the posterior part of the lung lobe than in the anterior part, which are distributed along bronchial branches, and

Fig. 6.6  Influenza complicated with bacterial pneumonia (II). The patient, a 14-year-old female, had fever and sore throat for 4 days, with the highest body temperature of 40.2°C. Laboratory examination: WBC 6.4 × 109/L, L 10.2%, N 88.0%, CRP 251.1 mg/L, positive for influenza A virus antigen. Chest X-ray radiograph showed the thickened bilateral lung markings, decreased transparency in the left lung field, uniform hyperdense consolidation in the middle and lower fields of the left lung, and small patchy opacities distributed along the lung markings in the right lung field, with blurred edges. Left diaphragmatic surface and costophrenic angle disappeared

a

Fig. 6.7  Influenza complicated with bacterial pneumonia (III). The same patient as that in Fig. 6.5. (a) and (b). CT lung windows showed wedge-shaped consolidation in the lower lobes of both lungs with bron-

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the bronchi of the lung segments and lobes are unobstructed. Mucosal congestion, edema and inflammatory exudation of terminal bronchioles can cause obstructive emphysema, which is manifested as increased transparency of both lung fields, enlarged thorax, widened intercostal space and flattened diaphragm. (b) CT: Chest CT examination is mainly for early detection, evaluation of lesions and differentiation from other diseases. The vascular features of CT images include consolidation consistent with the distribution of pulmonary lobes, air bronchograms, nodular and patchy opacities with different sizes and blurred edges along bronchial bundles, and lobular atelectasis or focal emphysema (Fig. 6.7). 3. Imaging manifestations of influenza complicated with pneumonia in special population. (a) Influenza in children: Infants and preschool children are the population with high incidence of influenza. Healthy children infected with influenza virus may be manifested by mild influenza. Influenza in newborns is rare but easy to be complicated with pneumonia (Figs. 6.8 and 6.9). (b) Influenza in the elderly: The elderly patients often have underlying diseases because of their relatively low immune function. Therefore, after being infected with influenza virus, their illness is more severe, and their illness progresses rapidly. With high probability of pneumonia, they are easy to have severe pneumonia which leads to death [4] (Fig. 6.10). (c) Influenza in pregnant women: Pneumonia, acute respiratory distress syndrome and even death are easy to occur in pregnant women in the middle and b

chial opacities, and blurred nodule opacities, small patchy opacities and ground-glass opacities distributed along bronchovascular bundles in both lungs

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a

b

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d

Fig. 6.8  Influenza complicated with bacterial pneumonia (IV). The patient, a 3-year-old female. Cough and expectoration for 3  weeks, fever for 2  weeks, with the highest body temperature of 39.6°C.  Laboratory examination: WBC 13.32  ×  109/L, L 14.7%, N 81.4%, CRP 9.5 mg/L, positive for influenza A virus antigen. (a) Chest X-ray radiograph showed the thickened bilateral lung markings, and

patchy blurred opacities distributed along the markings of both lungs, with partial fusion and consolidation; (b–d) CT cross-sectional images (b, d) and coronal MPR reconstructed images (c) showed the thickened bronchovascular bundles in both lungs, multiple wedge-shaped consolidation with different scopes in both lungs, with air bronchogram inside

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b

Fig. 6.9  Influenza complicated with bacterial pneumonia (V). The same patient as that in Fig. 6.1. (a) The first chest radiograph showed the thickened bilateral lung markings, dotted and small patchy opacities distributed along bilateral lung markings in the middle and inner zones

of both lungs, with blurred edges; (b) 5 days after treatment, bilateral lung markings were clearer than before, and the original scope of dotted and small patchy opacities in both lungs was significantly narrower than before

late gestation period after being infected with influenza virus (Fig. 6.11). (d) Influenza in people with immunodeficiency or immunocompromise: People with immunodeficiency have a high probability of severe influenza after being infected with influenza virus, and are prone to various complications (Fig. 6.12).

2. Confirmed diagnosis: The case has the above clinical manifestations of influenza, and one or more of the following pathogenic test results are positive: (1) Positive results of influenza virus nucleic acid test; (2) Positive results of influenza virus isolation and culture; (3) The level of double-sera influenza virus specific IgG antibody in acute and convalescent stage has increased by 4 times or more. 3. Imaging manifestations: To a certain extent, the manifestations can reflect the severity of the lesion. There is no obvious abnormality in chest imaging examination of patients with mild symptoms, or the manifestation is only interstitial pneumonia with thickened and blurred lung markings. If patients with severe symptoms are ­complicated with bacterial infection, a large scope of consolidation may occur in the lungs. The lesions may be distributed according to the shape of lung lobes or segments. Some patients are complicated with pulmonary edema and acute respiratory distress syndrome, with multiple diffuse lesions in both lungs, which change rapidly and may endanger patients’ life occasionally.



6.1.1.4 Diagnostic Key Points This disease can be easily diagnosed during influenza epidemic, according to clinical symptoms and in the principle of stratification diagnosis. However, the early cases of sporadic influenza should be comprehensively diagnosed according to epidemiological history, clinical manifestations and laboratory examination. Diagnostic basis includes influenza exposure history, typical symptoms and signs, and etiological examination. The diagnosis depends on the detection of influenza virus or virus antigen from nasal and pharyngeal secretions of patients, or the detection of corresponding serum antibodies. 1. Clinical diagnosis: The case has the above-mentioned influenza manifestations, epidemiological evidence or positive influenza rapid antigen test results. Other diseases that can cause influenza-like symptoms have been excluded.

6.1.1.5 Differential Diagnosis 1. Common cold: Also known as acute rhinitis or catarrhal inflammation of upper respiratory tract. The viruses causing this disease include rhinovirus, parainfluenza virus,

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c

Fig. 6.10  Influenza complicated with bacterial pneumonia (VI). The same patient as that in Fig. 6.2. (a) Chest X-ray radiograph showed the thickened bilateral lung markings, dotted and small patchy opacities distributed along bilateral lung markings, with blurred edges; (b and c)

CT cross-sectional images and coronal MPR images respectively showed small nodular and patchy opacities scattered along bronchovascular bundles in both lungs with blurred edges, thickened bilateral pleura and a small amount of pleural effusion

respiratory syncytial virus, Echovirus, etc. Among them, rhinovirus mostly causes the cold of adults, while parainfluenza virus and respiratory syncytial virus mainly cause the cold of children (Table 6.2). 2. Other viral pneumonias: Including adenovirus pneumonia, respiratory syncytial virus pneumonia, measles virus pneumonia and so on. The imaging manifestations are mainly ground-glass opacities in lung. (a) Adenovirus pneumonia: Its X-ray manifestations are closely related to the disease condition and disease stage. In the early stage, the lung markings are thickened and blurred, and small nodules distributed along the lung markings can be found in the middle and inner zones of the middle and lower fields of both

lungs. Three to five days after onset of the disease, lung consolidation occurs, with patchy lesions or confluent lesions of different sizes, more common in the lower fields of both lungs and the upper lobe of the right lung. The density of lesions increases with the development of the disease, and the lesions increase, distributed widely and fused with each other. Emphysema is common. Pleural effusion may occur in a few cases. (b) Respiratory syncytial virus pneumonia: Respiratory syncytial virus is the most common pathogen causing viral pneumonia in children, and its typical change is diffuse interstitial infiltration. In most cases, there are small patchy opacities, mostly in 2–3 lobes of the

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Fig. 6.11  Influenza complicated with bacterial pneumonia (VII). The patient, a 22-year-old female, was 39 weeks pregnant, with fever and chills for 5 days, and the highest body temperature of 39°C. Laboratory examination: WBC 13.25 × 109/L, L 11.8%, N 90.1%, CRP 45.3 mg/L, SaO2 85%, positive for influenza A virus antigen. Chest X-ray radiograph showed the decreased transparency of both lung fields, with blurred lung markings. Large patchy uniform hyperdensities were found in both lungs, with blurred edges, and blurred diaphragmatic surface and costophrenic angle on both sides

a

lung. About one-third cases have different degrees of emphysema or hyperairiness of the lung tissue. About 15% of cases only show hyperairiness of the lung tissue by X-ray examination. Lung consolidation or atelectasis occurs in about one-fourth cases, with limited distribution below the lung segment, mostly in the upper lobe of the right lung. The absorption of lung consolidation significantly lags behind the improvement of symptoms and signs. (c) Measles virus pneumonia: It is more common in infants and immunocompromised patients, and it mostly occurs in the early stage of the disease. Chest radiographs mainly show patchy or diffuse ground-­ glass opacities and/or thickened bronchovascular bundle. CT findings include centrilobular nodules with blurred edges, ground-glass opacities, thickened interlobular septa and lobular or segmental lung consolidation. 3. Pneumonia caused by other pathogens. (a) Mycoplasma pneumonia: Acute respiratory infection with pneumonia caused by Mycoplasma pneumoniae. Both children and adults can be affected, and most of them are positive in cold agglutination test. In the early stage, chest X-ray examination only shows increased lung markings with blurred edges, followed by fuzzy cloud opacities or uniform

b

Fig. 6.12  AIDS and influenza complicated with bacterial pneumonia. The patient, a 35-year-old male, with positive HIV antibody. Fever for 4 days, accompanied by chest pain and fatigue, with the highest body temperature of 38.7°C. Laboratory examination: WBC 10.0 × 109/L, L 11.8%, N 90.1%, CRP 45.3 mg/L, SaO2 85%, positive for influenza A

virus antigen. A. Chest X-ray radiograph showed the decreased transparency of both lung fields, with patchy blurred opacities widely distributed in the lung, especially in the left side; B.  CT lung window showed ground-glass opacities distributed along bronchovascular bundles in both lungs

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Table 6.2  Differentiation between influenza and common cold Contrast item Pathogen

Influenza Influenza virus

Pathogenic detection of influenza Infectivity Seasonal onset

Positive

Degree of fever

High fever (39–40°C) with chills 3–5 days Nonsignificant in early stage Significant

Duration of fever Respiratory symptoms Systemic symptoms Course of disease Complications

High Significant seasonal onset

5–10 days May be complicated with pneumonia, myocarditis, encephalitis or meningitis

Common cold Rhinovirus, parainfluenza virus Negative

Low Nonsignificant seasonal onset No fever or mild fever 1–2 days Significant Mild or none 5–7 days Rare

o­ pacities, mostly distributed in the middle and lower lung fields. The opacities near hilar part are dense, gradually lighter outward, with blurred edges, which usually does not invade the whole lobe. Mycoplasma pneumonia with lobar lesions cannot be distinguished from lobar pneumonia caused by other pathogens. CT findings mainly include ground-glass opacities, nodular or small patchy consolidation of air cavity (characteristic manifestation), thickened bronchial vascular bundle, “tree-in-bud” sign, large consolidation, sometimes with mediastinal lymphadenectasis and pleural effusion. Pulmonary lesions are usually absorbed in 2  weeks, and up to 4–6  weeks in the elderly. (b) Hypersensitivity pneumonitis: A group of nonasthmatic allergic lung diseases caused by different allergens. Chest X-ray radiograph shows normal or diffuse interstitial fibrosis. Common manifestations include bilateral patchy or nodular infiltration, thickened lung markings, or small acinar-like changes. Hilar lymphadenectasis and pleural effusion are rare. CT shows thickened bronchovascular bundle, small patchy opacities and ground-glass opacities along the bronchovascular bundles with blurred edges. CT findings are irregular, and the severity of imaging manifestations may be inconsistent with clinical symptoms. (c) Klebsiella pneumoniae pneumonia: It is an acute lung inflammation caused by Klebsiella pneumoniae, which mostly occurs in chronic alcoholism, malnutrition and the elderly. Chest X-ray manifestations include three types:

(1) Increased lung markings; (2) Lobular or diffuse pneumonia; (3) Lobar consolidation or lung abscess formation. CT examination can show lesions more clearly than X-ray examination. The early consolidation of Klebsiella pneumoniae pneumonia is distributed along lobular, with patchy or irregular hyperdensities mostly scattered distribution, involving multiple lung segments. Soon, the lesions fuse with each other to form lobar consolidation, which is more common in the upper lobe of the right lung. The exudate in the lesion is thick and heavy, so it causes falling interlobar fissures. The lesions are prone to necrosis, so lung abscesses can be formed, most of which are small cavities with a diameter less than 2 cm, and the healing process is slow, often leaving extensive fibrosis. 4. Acute respiratory distress syndrome (ARDS) is an acute respiratory failure syndrome, which is caused by severe diseases inside and outside the lung, based on diffuse injury and enhanced permeability of pulmonary capillaries, with pulmonary edema, hyaline membrane formation and atelectasis as the main pathological changes, and with progressive respiratory distress and refractory hypoxemia as the clinical features. This symptom is a typical manifestation of acute lung injury in the later stage. The abnormal imaging manifestations of ARDS are related to the alveolar epithelium injury or diffuse destruction of alveolar wall, which leads to the leakage of protein-rich edema fluid to fill alveolar space. Chest radiographs often show diffuse opacities in both lungs, and imaging changes characteristic of underlying diseases, such as severe pneumonia caused by various pathogens. CT findings show uneven distribution of lesions: (1) nongravity-dependent areas (mainly in the anterior chest in supine posture) are normal or almost normal; (2) The anterior and middle areas show ground-glass opacities; (3) Gravity-dependent areas show consolidation. In the absence of pulmonary capillary membrane injury, patchy opacities in both lungs are evenly distributed, without gravity-dependent phenomenon or gravity-dependent change after changing posture. This feature is helpful to distinguish this disease from pulmonary infectious diseases. In the later stage of ARDS, the manifestations include bronchial distortion and traction, lung segment or lobe volume reduction, reticular opacities, stripe-like opacities and honeycomb shadow. Honeycomb lung occurs in severe cases [5].

6.1.1.6 Research Status and Progress The main imaging manifestations of influenza complicated with pneumonia are multiple ground-glass opacities and consolidation in both lungs, involving multiple lobes and segments, and bilateral lower lung fields show significantly

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thickened markings, and may be accompanied by pleural effusion and/or pericardial effusion. Influenza virus pneumonia in children may be complicated by influenza-related encephalopathy and acute necrotizing encephalitis, which should also be paid attention to. The imaging findings of different types of influenza complicated with pneumonia are generally similar. Studies have shown that the level of lactate dehydrogenase (LDH) in blood is highly correlated with the severity of the disease. With the aggravation of the disease, the level of LDH will gradually increase, which also became an effective indicator to evaluate the severity of influenza A virus pneumonia [6].

6.1.2 Influenza A (H1N1) Li LiYupeng Liu, and Wang Fei

6.1.2.1 Overview Influenza A (H1N1) is an acute respiratory infectious disease caused by the mutated new influenza A virus H1N1 subtype. Most cases are mild, while a few cases are severe, progressing rapidly and even leading to death. The structure of influenza A (H1N1) virus is similar to other influenza A virus, but different from seasonal influenza viruses prevalent in the past. This virus is a new variant virus, which contains the gene fragments of avian, swine and human influenza viruses, as a “mixture” formed by gene recombination [7]. Influenza A (H1N1) has spread rapidly to the whole world since it broke out in Mexico in March 2009, and the first case in China was found in May 2009. In June, 2009, WHO raised the warning level of influenza pandemic to the highest level 6, officially declaring a new influenza pandemic all over the world. By August 2010, the WHO announced that the influenza A (H1N1) pandemic had ended and entered the postinfluenza pandemic period. Since then, the virus activity has returned to seasonal phenomenon [8]. The incubation period of influenza A (H1N1) virus generally lasts for 1–7 days. The main clinical manifestations are influenza-like symptoms such as fever, cough, runny nose, headache and fatigue. The conditions of some patients progress rapidly, with sudden high fever and secondary pneumonia. Patients in severe cases may experience acute respiratory distress syndrome, respiratory failure, multiple organ injury and even death. The original underlying diseases can also be aggravated, and most of the patients are young adults. Pneumonia is the most common complication of influenza A (H1N1), which can be caused by primary viral pneumonia or secondary bacterial infection.

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6.1.2.2 Pathological Manifestations Influenza A (H1N1) virus mainly replicates in tracheobronchial epithelium and alveolar epithelium, causing diffuse alveolar damage, accompanied by hyaline membrane formation, alveolar septal edema, necrotizing bronchiolitis and alveolar hemorrhage. 6.1.2.3 Imaging Manifestations 1. Adult influenza A (H1N1) virus pneumonia: It is manifested as viral pneumonia in the early stage, followed by mixed viral and bacterial pneumonia, or only secondary bacterial pneumonia. The mild cases are characterized by interstitial pneumonia, namely ground-glass opacity (GGO) distributed by lobes in the lung. HRCT shows thickened reticular interlobular septa. Severe cases show diffuse distribution of GGO in the lungs, mostly in middle and lower lung fields, with significant air cavity consolidation. HRCT shows interstitial lesions and alveolar consolidation. (a) X-ray: In the initial stage of the lesion (within 3 days of onset), inflammation occurs in and around the peripheral bronchioles. X-ray radiograph shows thickened and blurred lung markings and small patchy opacities (Fig. 6.13). The lesions are mostly located in the lower lung field and around the hilum

Fig. 6.13  Influenza A (H1N1) virus pneumonia (I). Chest X-ray radiograph showed increased markings in both lungs, and flocculent opacities at the cardiac edge of the left lower lung

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Fig. 6.14  Influenza A (H1N1) virus pneumonia (II). (a) Chest X-ray radiograph showed increased markings in both lungs, flocculent blurred opacities in both lower lungs, and enlarged and thickened hilar opacities; (b) After 2 days of treatment, the lesions progressed, showing multiple flocculent opacities in both lungs with blurred edges, unclear hilar

a

c

structure and slightly blunt right costophrenic angle; (c) After 4 days of treatment, re-examination showed the lesions absorbed and improved, and the markings of both lungs increased with patchy blurred opacities

b

Fig. 6.15  Influenza A (H1N1) virus pneumonia (III). (a, b) HRCT showed multiple patchy GGOs in both lungs, and the lesions were mostly distributed around bronchovascular bundle and subpleural, and the subpleural lesions in the lower lobe of right lung showed “reversed halo” sign

[9], and the lesions of both lungs are more common. GGO and consolidation are predominant manifestations in the advanced stage (3–7  days after onset) [10]. Multiple scattered lesions fuse rapidly and can involve multiple segments (Fig. 6.14). During convalescence, the lesions are basically absorbed, and stripe-like opacities, reticular opacities and localized emphysema may remain in the lungs. Bao et  al. reported that pulmonary bullae left in convalescence were considered to be caused by local hyperventilation of the lung caused by inflammation involving terminal bronchioles [11].



(b) CT: The main manifestations on HRCT are diffuse or multiple patchy GGOs in the lung, with or without consolidation, mostly distributed around bronchovascular bundles or under pleura (Fig. 6.15) [12]. As the lesions progress, multiple patchy GGOs fuse rapidly with each other to become hyperdensities (Fig.  6.16), accompanied by patchy consolidation inside or outside the GGO (Fig. 6.17). There are also patients only with consolidation, but without GGO (Fig. 6.18). Qi et al. used CT semiquantitative visual scoring method to quantitatively display the degree of intrapulmonary lesions, and found that the CT

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Fig. 6.16  Influenza A (H1N1) virus pneumonia (IV). (a, b) CT lung window showed multiple ground-glass opacities under bilateral pleura, with different sizes and shapes and clear edges

Fig. 6.17  Influenza A (H1N1) virus pneumonia (V). CT lung window showed wedge-shaped ground-glass opacities in the lower lobe of the left lung, with small patchy consolidation and strip-like bronchial opacities

score of semiquantitative GGO was positively correlated with fever duration, while semiquantitative consolidation CT score was not correlated with fever duration [13]. It indicates that the progression of influenza A pneumonia in the early stage after onset is characterized by the expansion of GGO scope. The absorption of lesions is manifested by the decreased GGO and consolidation density and the narrowed scope. Some cases in convalescence may show thickened interlobular septa, thickened bronchovascular bundles and even fibrosis. The presumable reasons are as follows: The lesions are limited to bronchial mucosa in the early stage, followed by inflammatory cell infiltration, edema and fibrosis around bronchi

Fig. 6.18  Influenza A (H1N1) virus pneumonia (VI). CT lung window showed large patchy consolidations of the right lung, with air bronchogram opacities inside

and interlobular septa [14]. Although the lesions in air cavity (alveoli and respiratory bronchioles) are in remission, the interstitial lesions are aggravated. GGO is the most common manifestation of this disease in both early stage and advanced stage, and the high incidence of GGO is a rare sign in other pneumonias. In the early stage of lesions, quasi-­ round GGOs distributed under pleura or around bronchial vessels is a typical feature of this disease. Centrilobular nodules can also be seen in GGO center, and cavities can be seen in centrilobular nodules [15], for which the possible reason is that viruses invade bronchial epithelial tissues and then spread to surrounding bronchial tissues, causing immune

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a

b

c

d

Fig. 6.19  Influenza A (H1N1) virus pneumonia (VII). (a–d) CT lung window showed multiple consolidations and ground-glass opacities in both lungs, with air bronchogram opacities inside

response, and leading to bronchial stenosis and local hyperventilation of lungs. In some cases, patients may have a small amount of pleural effusion, but generally without small airway change, such as pulmonary nodules, “tree-in-bud” sign, mosaic perfusion and so on. The chest imaging features of severe influenza A pneumonia complicated with ARDS: (1) The lesions are diverse in shape, including small patchy and large patchy consolidation, patchy fusion opacities or cloud flocculent blurred opacities, and large patchy ground-glass opacities (Fig.  6.19). If the lesions invade one or more lobes, the density of lung consolidation will be uniform and consistent, showing the sign of “white lung.” (2) The lesion site and scope show multilobular infiltration and migratory changes. (3) The pulmonary interstitium and parenchyma are involved. (4) The imaging manifestations change rapidly. (5) Complications are common, such as

pneumothorax, mediastinal and subcutaneous emphysema, even retroperitoneal pneumatosis and fungal infection. In some cases, patients have local lung tissue injury and fibrosis, with honeycomb lung and incomplete recruitment of pneumothorax. The prognosis of mild cases is good. Generally, the lesions can be completely absorbed or significantly alleviated within 2 weeks, and there is generally no fibrosis or only mild peripheral interstitial thickening. Pulmonary lesions in patients with serious diseases can be absorbed rapidly and disappear in 1–2  days. The pulmonary lesions in critically ill patients progress rapidly, and even change greatly within one day [4], which may be complicated with ARDS, pneumothorax, mediastinal and subcutaneous emphysema, and even retroperitoneal pneumatosis. Agarwal et al. reported that 36% of patients with severe influenza A (H1N1) virus infection developed acute pulmonary embolism during hospitalization,

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which may be secondary to hypercoagulable state caused by ARDS [9]. 2. Children influenza A (H1N1) virus pneumonia: The early chest imaging findings of influenza A pneumonia are not characteristic, without significant difference with common pulmonary infection. Pulmonary parenchymal lesions are the main manifestations in advanced stage, and interstitial changes are the main manifestations in absorption stage. (a) X-ray: (1) Pulmonary parenchymal lesions and parenchymal infiltration are the main manifestations of this disease, mostly bilateral, and some studies think that unilateral cases are more than bilateral cases, and the right-side cases are more than the left-­ side cases. The lesions are mainly located in the inner and middle zones. The upper, middle and lower lung fields can be involved. The middle and lower lung fields are involved commonly. However, some studies suggested that the lesions are mainly at the basal part. Parenchymal infiltration can be manifested as single or multiple small patchy opacities, which can also be fused into large opacities and/or GGO.  Children are mainly characterized by patchy opacities, while infants are mostly characterized by patchy flocculent opacities. (2) Lung interstitial lesions show that lung markings are increased, thickened and blurred, with different degrees of reticular opacities and nodular opacities. Some scholars have suggested that there is no interstitial change in chest radiographs in the early stage of children’s lesions, which may be related to the limitations of chest radiographs and the disease course [16]. (3) In severe cases, children can also show increased lung markings with hyperinflation, and the degree of lung hyperinflation is consistent with the degree of dyspnea and course of disease in clinical children patients [17]. (4) In the absorption stage, the main interstitial changes are blurred lung markings, poor transparency of both lungs and uneven inflation. (5) Other manifestations include pleural involvement, pleural effusion, mediastinal and hilar lymphadenectasis. (b) CT: The chest CT findings are basically the same as those of X-ray radiographs (Fig.  6.20), and the advantage of CT is that it can clearly show subtle lesions, which is helpful for evaluating the degree of lesions. 3. Influenza A (H1N1) virus pneumonia in pregnant and postpartum women: Mild symptoms are GGOs of single or multiple lung lobes and small flocculent hyperdensities. Severe manifestations are flocculent opacities of multiple lung lobes, GGOs and air bronchogram. The lesions progress within 24 h, showing diffuse hyperdense

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Fig. 6.20  Influenza A (H1N1) virus pneumonia (VIII). CT lung window showed multiple patchy ground-glass opacities around bilateral bronchial vessels

foci in both lungs, some accompanied by atelectasis, which may be complicated with unilateral or bilateral pleurisy, pleural effusion, pericardial effusion, etc. [18].

6.1.2.4 Diagnostic Key Points 1. During the epidemic period of influenza A (H1N1), the patient has been to the epidemic area within 7 days before the onset of influenza, in close contact with the infected persons, and with other epidemiological history. 2. Flu-like symptoms such as fever, cough, headache and fatigue. 3. Chest imaging shows multiple GGOs in both lungs, mostly in the lower lung field, and the lesion is manifested as large consolidation. 4. The important basis for the diagnosis of this disease include: The isolation of influenza A (H1N1) virus from respiratory specimens of patients, or the detection of influenza A (H1N1) virus nucleic acid, or the increase of specific antibody level of influenza A (H1N1) virus by 4 times or more in double sera. 6.1.2.5 Differential Diagnosis 1. Adenovirus pneumonia: It is more common in children, mainly tracheal, peribronchial inflammation and alveolitis. X-ray radiograph shows thickened, blurred and exudative opacities of lung markings, often accompanied by emphysema. The disease course is short, antiviral treatment is effective, and the incidence of respiratory failure is low. 2. Mycoplasma pneumonia: It is characterized by enhanced, blurred and reticular lung markings in the early stage, limited or extensive patchy blurred opacities in the advanced stage, and large fan-shaped opacities extending from hilum to the periphery of lung field, which may or

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may not be distributed according to lung lobes and segments. CT can show early pulmonary interstitial inflammation, reticular opacities and thickened interlobular septa. 3. Hypersensitivity pneumonitis: The foci change rapidly, with minor pulmonary opacities, and the foci can be absorbed quickly after treatment. The onset is related to allergens, and the pathology is mainly exudative alveolitis and interstitial pneumonia. 4. Severe acute respiratory syndrome: It is manifested as small patchy opacities in the lungs in the early stage, which can develop into large or diffuse lesions in the advanced stage, and may be complicated with lung consolidation, similar to severe influenza A pneumonia. SARA has a long course of disease, so pathogenic testing is required for identification.

6.1.2.6 Research Status and Progress Mineo et al. followed up patients of influenza A pneumonia for 4  months, showing that 75% of patients had common pneumonia, and 25% patients were complicated with ARDS. The clinical and lung X-ray manifestations of common pneumonia cases completely returned to normal at the end of the follow-up period [19]. Among the patients complicated with ARDS, 20% of them died, 60% of them showed peripheral pulmonary fibrosis on chest CT and 20% of them showed progressive resolution of chest CT abnormalities after 4 months. Liu et al. followed up 24 patients with severe influenza A pneumonia complicated with moderate to severe ARDS requiring mechanical ventilation [20]. It was found that 46% of the patients had abnormal chest CT 1 year later, mainly showing different degrees of reticular opacities, and a few patients had a small amount of ground-glass changes and local emphysema. The reticular opacities on CT have no correlation with the abnormal degree of chest CT, the worst oxygenation index, the duration and condition of mechanical ventilation in acute stage, but Murray acute lung injury score has a positive correlation with the degree of lung fibrosis at the end of follow-up, indicating that the comprehensive score of lung injury can better reflect the severity of lung lesions and be helpful for predicting long-term lung abnormalities.

6.1.3 Human Infection with Highly Pathogenic Avian Influenza Li Li and Lili Kong

6.1.3.1 Overview Human infection with highly pathogenic avian influenza (human avian influenza) is an acute respiratory infectious disease caused by some strains of some subtypes of avian influenza A virus.

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According to the degree of pathogenicity, avian influenza viruses can be highly pathogenic, low pathogenic and nonpathogenic. Among them, H5 and H7 subtype strains (represented by H5N1 and H7N7) can cause severe avian diseases and are highly pathogenic influenza viruses. Avian influenza A virus features host specificity. It has been confirmed that the main subtypes of avian influenza virus that can infect human beings are H5N1, H9N2, H7N7, etc. Among them, H5N1 subtype makes infected patients seriously ill with a high mortality. In 1997, human cases of H5N1 subtype avian influenza first appeared in Hong Kong, China, and then occurred in many countries. According to WHO statistics [21], from 2003 to January 29, 2021, 862 cases of human infection with H5N1 subtype avian influenza were confirmed in laboratories worldwide, of which 455 patients died; 53 cases were confirmed in China, of which 31 patients died, with a mortality rate up to 58%. The infectious source of this disease is poultry suffering from avian influenza or carrying avian influenza. Human avian influenza can be transmitted through respiratory tract, and patients can also be infected by close contact with secretions and excretions of sick birds, items and water contaminated by viruses. People generally lack immunity to avian influenza virus. There are many children with serious illness, and there is no significant gender difference. Incubation period of this disease lasts for 1–7 days, and most of the diseases have acute onset. The early symptoms are influenza-like symptoms, with fever and cough as the main clinical manifestations. The body temperature is generally above 39°C, often accompanied by nasal congestion, sore throat, muscle soreness and general malaise. Some patients may have gastrointestinal symptoms such as nausea, diarrhea and abdominal pain. Severe symptoms of patients develop rapidly, and patients generally have pneumonia, which may lead to ARDS, pulmonary hemorrhage, pleural effusion, Reye syndrome and other complications. For the patients of severe symptoms, the total number of leukocytes and lymphocytes decreases, and the platelet count decreases slightly to moderately.

6.1.3.2 Pathological Manifestations Postmortem pathological findings of three patients with H5N1 subtype avian influenza in Hong Kong, China, showed that the lung lesions of the patients were typical viral interstitial pneumonia changes. Among them, 2 cases were mainly characterized by lesion organization, diffuse alveolar damage and pulmonary interstitial fibrosis [22]. One case showed consolidation of both lungs with diffuse hemorrhage, edema, fibrin exudation and alveolar infiltration. Histopathology showed diffuse alveolar damage, interstitial fibrosis and air cavity dilatation. Other manifestations include interstitial

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lymphocytes and plasma cells infiltration, as well as scattered histiocytes [23].

6.1.3.3 Imaging Manifestations X-ray radiographs and CT mainly show patchy GGOs or consolidation in the lung with blurred edges and air bronchograms in the lesion. 1. In the early stage (1–4  days after onset), 90% of the patients show focal patchy opacities, consolidation or GGOs, with single and multiple patchy opacities, more common in the right lung and periphery distribution. Qureshi et al. reported that more than 90% of patients had multiple lesions, 80% of patients had bilateral pulmonary involvement, and the lesion scope involved more than 4 lung fields or 10 lung segments [24]. In addition, symptoms were accompanied by a small amount of pleural effusion and pulmonary interstitial lesions. 2. In the advanced stage (5–14 days after onset), the lesions progressed and aggravated, showing multiple or diffuse large patchy GGOs and consolidation, with air bronchograms inside (Fig. 6.21a–c). Significant changes occurred in severe cases within 1–2 days after onset. The lesions developed from unilateral lung to bilateral lung, from one lung field to multiple lung fields, and from GGO to consolidation [25]. Most patients have the most serious lung infiltration within 8–14 days after onset, which is called the peak period or “fastigium” of lesions. 3. In the stable stage (15–21 days after onset), the pulmonary parenchyma and interstitial changes coexist, and the lesions begin to be absorbed gradually (Fig.  6.21d). ­Alveolar inflammation can be absorbed relatively quickly, while interstitial changes such as interstitial edema, hyperplasia and early fibrosis can only be absorbed relatively slowly. In addition, the lesions at the latest invaded site are absorbed quickly, while the lesions at the first invaded site are absorbed slowly. 4. During convalescence (22–30  days after onset), most patients’ lesions can be completely absorbed, while a few patients have mainly pulmonary interstitial changes, such as stripe-like opacities, reticular opacities, thickened interlobular septa and subpleural curvilinear shadow (Fig. 6.21e). In the early stage, the lesion of children is manifested as single patchy opacity. In the advanced stage, the lesions progress rapidly and the lesions are widely distributed. In a short time, unilateral lesions develop into bilateral lesions, changing from GGO to lung consolidation. 12 months after onset, CT re-examination can show that pulmonary lesions are still being slowly absorbed. Lung volume decreases in

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the early and advanced stage after onset; GGO can be found in the early stage, advanced stage and recovery stage of lesions. Mediastinal hernia can be found in advanced stage [26]. Lu et al. summarized the chest imaging features of H5N1 subtype human avian influenza pneumonia [27]: (1) Large patchy hyperintensities and GGO can be found in the lung field in the early stage after onset; (2) Diffuse and exudative changes can be found in multiple lobes and segments of both lungs, and “white lung” change occurs if complicated with ARDS; (3) The lesions change rapidly; (4) Pulmonary parenchyma and pulmonary interstitium can be involved at the same time, but lung consolidation is the main manifestation; (5) The lesions can be slowly absorbed (Fig. 6.21f–h).

6.1.3.4 Diagnostic Key Points 1. During the epidemic of avian influenza, high-risk people are those who have been to the epidemic area within 1  week before the onset of the disease, or have a confirmed history of contact with sick and dead birds and their secretions and excretions, or have close contact with human avian influenza patients. 2. Diagnose can be easily determined by combining clinical manifestations with laboratory examination, virus isolation and serological antibody detection. 3. Chest imaging manifestations include multilobe and multisegment GGO or consolidation in both lungs, and “white lung” change occurs if complicated with ARDS. 6.1.3.5 Differential Diagnosis 1. Staphylococcus aureus pneumonia: It has an acute onset, rapid progression of lesions, with increased total number of leukocytes. Chest imaging manifestations include large patchy inflammatory exudation, with air bronchogram inside, and cavities are common. If inflammatory lesions are absorbed, small air sacs and pneumatoceles can be found in the lungs, even with empyema or pyopneumothorax. 2. Adenovirus pneumonia: The imaging manifestations include thickened and blurred lung markings and exudative opacities of the lung, often complicated with bacterial pneumonia, causing lung consolidation. The lesions are widely distributed, but without migration. Pleural effusion is rare. The imaging manifestations are consistent with clinical severity. 3. Hypersensitivity pneumonitis: The cloudy opacities are light and can be distributed in any part of the lungs. The lesions change rapidly, featuring migration. Patients have a clinical history of allergy. Laboratory examination can show that the total number of leukocytes increases significantly, mainly eosinophils.

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a

c

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Fig. 6.21  H5N1 subtype human avian influenza pneumonia. (a) On the fifth day of the disease, chest radiograph showed small patchy blurred opacities in the left upper lung. (b) On the ninth day of the disease, the lesions in the left upper lung rapidly expanded and spread to the middle and upper lung field, accompanied by collapse of lung lobes and air bronchogram. There were patchy blurred opacities in the right lung. (c) On the 13th day of the disease, the lesions in the left lung spread to the whole lung field and showed “white lung” changes, and the lung collapse aggravated. The lesions in the right lung increased. (d) On the 15th day of the disease, CT lung window showed that the left thorax collapsed, and a large number of patchy and stripe-like opacities were found in the upper lobe of the left lung and the right lung, with air bronchogram inside. Part of lung tissue herniated into the anterior supe-

rior mediastinum, and the mediastinum shifted to the left. (e) On the 22nd day of the disease, the lesions in both lungs were absorbed, left lung collapsed and mediastinal hernia worsened. (f) On the 31st day of the disease, the lesions in both lungs were significantly absorbed, and the absorption of anterolateral lesions of left lung was more significant than that of posteromedial lesions. (g) On the 53rd day of the disease, there were multiple stripe-like opacities in both lungs, ground-glass opacities in the upper lobe of the right lung, and mediastinum shifted to the left. (h) After 11 months, CT re-examination still showed stripe-like opacities in the left lung, and the mediastinum slightly shifted to the left (case images by courtesy of Puxuan Lu of the Third People’s Hospital of Shenzhen)

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e

f

g

h

Fig. 6.21 (continued)

6.1.3.6 Research Status and Progress 1. The study on the evolution of H5N1 subtype avian influenza virus is of great significance to the development of avian influenza vaccines and the prevention of avian influenza pandemic. 2. The study on the transmission dynamics of H5N1 subtype avian influenza virus is of great significance for establishing the intermeadow transmission dynamics model of H5N1 avian influenza virus in China, exploring its internal transmission mechanism, estimating the basic reproduction number (R0) of H5N1 avian influenza virus transmission in China, analyzing the sensitivity of R0 by numerical simulation, and quantitatively evaluating the effects of prevention and control measures [28].

6.1.4 Human Infection with H7N9 Avian Influenza Li Li and Yinglin Guo

6.1.4.1 Overview Human infection with H7N9 avian influenza (H7N9 avian influenza) is an acute respiratory infectious disease caused by H7N9 avian influenza virus. Since its first report in China in March 2013, human infection with H7N9 avian influenza has gone through eight epidemic seasons as of July 2020. This disease has a short incubation period, rapid progress and high mortality, thus arousing widespread concern all over the world.

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H7N9 avian influenza virus belongs to influenza A virus of Orthomyxoviridae family, which is a new type of triple-­ reassortant virus. Similar to other influenza A virus, its genome also has 8 segments. Existing evidence has shown that the new H7N9 virus may have at least three origins, all of which come from avian influenza viruses, without any gene segments of human influenza viruses. Studies have shown that some key amino acids of H7N9 avian influenza virus receptor binding site have been mutated, such as G186V and Q226L mutations, which enhance the binding ability of avian influenza virus to SAα2, 6-Cal receptors in human upper respiratory epithelial cells, and promote the virus to spread directly from poultry to human in a large scope [8]. Exposure to live poultry is a key risk factor for human infection with H7N9 avian influenza virus, and most cases are caused by direct or indirect exposure to the environment contaminated by infected live poultry or virus-carrying poultry. From the perspective of family clustering epidemic, transmission by limited person-to-person close contact cannot be ruled out, but there is no evidence of interpersonal transmission at present. Occupational groups in direct contact with poultry, the elderly and the patients suffering from underlying diseases are the high-risk groups of this disease. This disease has no specificity in the early stage, and is generally manifested as flu-like symptoms such as fever, cough and expectoration, accompanied by headache, muscle soreness, diarrhea and other general discomfort symptoms. Pneumonia is the main manifestation of this disease, and only a few patients show mild symptoms. Severe symptoms of patients develop rapidly, mostly with body temperature above 39°C, and severe pneumonia occurs in 5–7  days. Patients have dyspnea and hemoptysis, and can the disease can rapidly progress to ARDS, septic shock. Patients may even die due to multiple organ dysfunction. Some patients may have mediastinal emphysema and pleural effusion. Severe cases show poor treatment effect and high mortality.

6.1.4.2 Pathological Manifestations In the early stage of the disease, patients have diffuse alveolar epithelial injury in the lungs, accompanied by alveolar hemorrhage and hyaline membrane formation. Fibrous tissue hyperplasia can be found in the later stage. 6.1.4.3 Imaging Manifestations X-ray and CT examination play an important role in the diagnosis, condition monitoring and curative effect evaluation of H7N9 avian influenza pneumonia. According to its evolution process, the disease can be divided into four stages: (1) Onset stage, within 3  days after onset; (2) Advanced stage, 3–6  days after onset; (3) Absorption period, 7–15 days after onset; (4) Stable stage, more than 15 days after onset [29].

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1. X-ray: In the early stage of infection, the manifestations are mostly small patchy opacities with blurred edges, and most of them are in the lower and middle fields of both lungs. In the advanced stage, the lungs show large patchy opacities with uneven density, clear or blurred edges, as well as air bronchograms. ARDS patients may show changes similar to “white lung.” During convalescence, the absorption of the above lesions gradually decreases, and the stripe-like opacities and reticular opacities gradually increase. 2. CT: Multiple or single lesions are mainly distributed in both lungs or one lung. Wang et  al. reported that the lesions in the early stage of onset were mainly in the right lung, more often in the lower field of both lungs than in the upper field of both lungs [30]. Lung parenchyma lesions are the main manifestations, mainly GGO and consolidation. For mild disease with small lesion scope, GGO is the main manifestation. For severe infection, the lesions involve multiple lobes, and the proportion of consolidation increases. The consolidations of adjacent lung segments can fuse, and the lesions can also spread to adjacent lung lobes across interlobar fissures [31]. Air bronchograms are common in consolidation. Pulmonary interstitial changes are mainly manifested as thickened interlobular septa and interlobular interstitium within the lesion scope, often showing reticular changes (Figs. 6.22 and 6.23). Pulmonary interstitial changes and pulmonary fibrosis are more significant in absorption stage. GGO can appear in the early stage, advanced stage and absorption stage of the disease. In the early stage, the edge of GGO is blurred, suggesting exudative lesions. In advanced stage, the scope and density of GGO increase. In absorption stage, the scope is reduced, the edge is gradually clear, and the density is reduced, suggesting the interstitial lesion. The main imaging manifestations of severe pneumonia are rapid progress of lung consolidation and GGO.  The lesions mainly occur in the lower lobes and back of both lungs. The lesions in the right lung are wider than those in the left lung, and the consolidation occurs earlier. Most patients have showed severe pneumonia at the first imaging examination, or progressed to severe pneumonia in a short period (3–6 days in the faster cases) after onset. The patchy opacities of severe pneumonia involve multiple lung lobes, and generally extend to 3 lung fields on chest radiographs. The lesions progress rapidly and increase by 50% within 1–2 days [32]. The proportion of intralung consolidation significantly increase, or the overall density of lesions increases, indicating severe alveolar lesions. Pleural effusion can indicate the severity of the disease to a certain extent: There is no pleural effusion in mild infection, and a small amount of bilateral pleural effusion can be found in severe pneumonia. Some patients may have pneumothorax, subcutaneous

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Fig. 6.22  Human infection with H7N9 avian influenza pneumonia (I). The patient, a 72-year-old male. Fatigue for 10 days, cough, fever and chest tightness for 1 week, with the highest body temperature of 38.4°C, without clear history of contact with birds. (a) CT lung window showed

“paving stone” changes in the lower lobe of the right lung and small subpleural nodules in the left side; (b) After 3 days of treatment, chest radiograph showed multiple large patchy consolidation of both lungs

emphysema and mediastinal emphysema. Hilar and mediastinal lymphadenectasis is rare. If severe pneumonia is complicated with ARDS, the lesion scope accounts for more than 60% of the whole lung field, or the consolidation in the lung increases, with “white lung” changes (Fig. 6.24). Lu et al. believed that pleural effusion is one of the imaging features of H7N9 avian influenza, which may be related to the direct attack of H7N9 avian influenza virus on pleura or the production of a large number of cytokines after binding with sialic acid receptor, thus inducing cytokine storm and leading to systemic inflammatory reaction [33]. Yang et al. found that H7N9 avian influenza is prone to thickened pleura and thin-walled cavities [34]. Thickened pleura is considered to be caused by late treatment of patients, long-­ term stimulation of pleura by pleural effusion, and fibrin attachment to chest wall or granulation tissue hyperplasia in pleural effusion. Thin-walled cavities are related to lung parenchymal necrosis and valve-caused bronchial stenosis. Absorption of lesions begins with GGO and consolidation near the central area of the hilum. The density of consolidation decreases to form sparse consolidation, and the consoli-

dated lung tissue gradually expands. In the process of absorption, the lesions that occur earliest in the early and advanced stages are absorbed later, and the lesions that occur later are absorbed earlier [33]. Chen et al. reported the chest CT findings of 56 patients with H7N9 avian influenza during the clinical follow-up, in which the absorption of GGO, consolidation, reticular opacity and other lesions was found within 6  months after discharge, but there was no obvious change in the lesions after 6 months [35].

6.1.4.4 Diagnostic Key Points 1. Within 10 days before onset of the disease, patients had contact with poultry and their secretions or excretions, or had been to the live poultry market, or had a history of close contact with human infection with H7N9 avian influenza [36]. 2. Patients have flu-like clinical symptoms. 3. Imaging examinations show multiple GGOs and consolidations in both lungs or unilateral lungs, air bronchograms, accompanied by interstitial pulmonary lesions

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Fig. 6.23  Human infection with H7N9 avian influenza pneumonia (II). The patient, a 20-year-old female. Fever, cough and expectoration for 8  days, with the highest body temperature of 39°C.  The patient denied any contact with poultry. (a) CT lung window showed multiple patchy and nodular consolidations in both lungs, mainly in the lower

lungs, surrounded by ground-glass opacities, and the left lung lesions crossed the interlobar fissure; (b) After 8  days of treatment, HRCT showed that the lesions in both lungs were reduced and absorbed; (c) After 16 days of treatment, HRCT showed that the lesions of both lower lungs were significantly absorbed, mainly fibrous strip-like opacities and honeycomb opacities

such as thickened interlobular septa. Patients in severe cases may have pleural effusion, “white lung” and other changes. 4. The H7N9 avian influenza virus isolated from respiratory tract samples or the virus nucleic acid test are positive, or the specific antibody level of H7N9 avian influenza virus in double serum samples has been increased by 4 times or more.

the main manifestations, without the above distribution characteristics. In addition, influenza A (H1N1) has mild lesions and clinical progression, and only a few critically ill patients die after developing ARDS, while the lesions of H7N9 avian influenza develop rapidly, and are prone to rapid progression to ARDS and even multiple organ dysfunction. In terms of fusion speed, scope of involvement and incidence of complications, the lesions of H7N9 avian influenza progress faster with a higher incidence of complications than those with influenza A (H1N1) virus pneumonia, and the condition of patients with H7N9 avian influenza is more likely to relapse during treatment. 2. Severe acute respiratory syndrome (SARS): The CT findings are diffuse GGO in both lungs and extensive consoli-

6.1.4.5 Differential Diagnosis 1. Influenza A (H1N1) virus pneumonia: The early manifestation is GGO distributed around bronchovascular bundle or subpleura, and it develops into extensive alveolar consolidation after the lesion progresses. However, in the early stage of H7N9 avian influenza, the exudation changes of single or multiple lung segments or lobes are

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a

b

Fig. 6.24  Human H7N9 avian influenza pneumonia complicated with ARDS. The patient, a 56-year-old male. Fever for 1 week, unconsciousness for 2 hours, with the highest body temperature of 39.5°C, and no recent history of contact with poultry. (a) CT lung window showed large patchy consolidation in the lingular segment of left lung, in which air bronchogram was found; (b) After 7  days of treatment, the chest

c

radiograph showed large patchy consolidations in both lungs, especially the right lung, showing “white lung” changes; (c) After 11 days of treatment, re-examination showed the consolidations of both lungs were significantly absorbed, and the density and scope of lesions were reduced

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dation in the lungs. The lesions in the lungs progress rapidly, but most of them are located around the lungs, mainly involving the subpleura. HRCT shows thickened interlobular septa, with “paving stone” changes. Human infection with H7N9 avian influenza has the similar symptoms, but the interstitial changes are not as significant as those of SARS, and there is no characteristic of peripulmonary distribution. 3. Human infection with highly pathogenic H5N1 avian influenza: Human infection with H7N9 avian influenza and human infection with highly pathogenic H5N1 avian influenza cannot be easily distinguished in imaging, both of which show pulmonary segmental and lobar consolidation and progress rapidly. The diagnosis depends on virus isolation and detection. 4. Pulmonary edema: It is mainly around the hilum of both lungs, showing confluent GGO, with moderate pleural effusion and enlarged cardiac shadow. The clinical manifestations include heart failure and abnormal renal function.

6.1.4.6 Research Status and Progress Dong et al. reported that ultrasound examination of patients with severe human infection with H7N9 avian influenza showed that the larger oblique diameter of the right lobe of liver before treatment than that after treatment and that of the control group, suggesting that H7N9 subtype virus may induce acute liver injury [37]. In addition, ultrasound examination can also detect the changes of hemodynamic state before thrombosis, such as slow blood flow velocity of deep veins of lower limbs, which is beneficial to taking preventive measures in clinical practice.

6.2 Measles Virus Li Li and Dan Mu

6.2.1 Overview Measles is an acute respiratory infectious disease caused by measles virus. The main clinical manifestations are catarrhal symptoms such as fever, cough and runny nose, as well as conjunctivitis. It is characterized by oral measles mucosa (Koplik spots) and skin maculopapules. Mainly spread by droplets, this disease is highly contagious and common in children. Pneumonia is the most common complication of measles, which is more common in children under the age of 5, and is the main cause of death in children. Pneumonia in the course of measles can be divided into two categories: Pulmonary lesions directly caused by measles virus (measles pneumo-

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nia), and pulmonary infection caused by bacterial or viral infection on the basis of measles virus infection (measles complicated with pneumonia). Children in the rash stage are often complicated with mixed infection of other pathogens because of their weak constitution and low immunity. Most of the clinical symptoms of measles pneumonia are not severe, but secondary infection is the main reason for the aggravation of measles patients. The clinical manifestations include sudden aggravation of the condition, cough, purulent sputum, flapping of the nose, cyanosis of the lips and obvious rales in the lungs. Laboratory examination can show that the total number of leukocytes decreases and the proportion of lymphocytes increases relatively. If the total number of leukocytes increases, especially the increase of neutrophils, it will indicate the secondary bacterial infection. If lymphocytes are severely reduced, it will mostly indicate poor prognosis. Aminotransferase, serum creatinine and urea nitrogen can be significantly increased in patients with severe conditions. In severe cases, patients have electrolyte disturbance, elevated myocardial enzyme spectrum, abnormal coagulation function, often complicated with respiratory failure, hypoxemia, acidosis and so on.

6.2.2 Pathological Manifestations The invasion of measles virus to lung tissue has certain characteristics. After measles virus invades the respiratory tract, it spreads along the airway, gradually invades bronchioles at all levels, even up to alveolar space, causing catarrhal inflammation of the airway mucosa. Meanwhile, the inflammation caused by virus develops beyond the airway, invades the bronchial wall, involves the bronchial and perivascular spaces, and causes bronchial and perivascular inflammation. The alveolar septum is also involved, damaging the alveolar epithelium, and the inflammation further extends to the lung parenchyma [38, 39]. In the early stage, there is no obvious inflammatory exudate or only a small amount of serous exudation in alveolar space. The bronchioles and alveolar epithelial cells proliferate and swell, forming multinucleated giant cells, in which virus inclusion bodies can be found. If the disease is not effectively controlled, it will further damage the alveolar epithelium, and promote the activation of alveolar macrophages and inflammatory reaction chain, resulting in an inflammatory reaction in the lung. The pathological manifestation is diffuse alveolar damage in the lung [40]. Recent studies have shown that interstitial pneumonia not only originates from bronchi and perivascular pulmonary interstitium, but also involves bronchioles and alveolar spaces [41]. The pathological manifestations of severe measles pneumonia include the infiltration of a large number of inflamma-

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tory cells in pulmonary interstitium and alveolar space, thus forming abscesses around the bronchioles. The alveolar wall is necrotic, the lung structure is seriously damaged and inflammation spreads among the lobules, with diffuse lung consolidation [42, 43].

6.2.3 Imaging Manifestations 1. Measles pneumonia: Its imaging manifestations are mainly pulmonary interstitial changes [44]. (a) Measles pneumonia in children. • X-ray: Typical patients mostly have interstitial inflammation, mainly manifested as reticular changes in lung markings. Early X-ray radiographs show increased, thickened and blurred lung markings, which are significant in bilateral middle and lower lungs and the inner and middle zones of the lung, accompanied by patchy blurred opacities (Figs.  6.25 and 6.26) [45]. Localized emphysema is a common X-ray manifestation of interstitial measles pneumonia, mostly in younger children. With the progress of the disease, the lung parenchyma is involved, and patchy blurred opacities or consolidations of different sizes may occur in the lung. The hilar shadow is enlarged, thickened and blurred, which is more common in one side, with incidence higher than that of adults. • According to chest radiographs, Jiang et  al. divided measles pneumonia into four types: emphysema type, pulmonary interstitial type, pulmonary lobular type and lung consolidation type [46]. –– Emphysema type: It is the early manifestation of measles pneumonia, which is caused by congestion, edema and exudation of bronchiolar mucosa. Inflammatory reaction is mainly limited to bronchial mucosa at all levels, and the degree of lesions is relatively mild. –– Pulmonary interstitial type: With the development of the disease, measles virus invades pulmonary interstitial, pulmonary interstitial inflammation aggravates, and interstitial measles pneumonia is mainly manifested as increased lung markings and blurred opacities. –– Pulmonary lobular type: If alveolar cells representing lung parenchyma are gradually damaged, the exudation in alveoli will increase. Because the lesions are relatively early with mild degree, the interlobular septa is not significantly damaged, and the inflammatory reaction is still limited to the pulmonary lobules,

Fig. 6.25  Measles pneumonia in children (I). After 4 days of hospitalization, chest X-ray radiograph showed thickened and blurred lung markings, small reticular opacities in the inner and middle zones of the left upper lung field, and patchy blurred opacities in the right lower hilum

Fig. 6.26  Measles pneumonia in children (II). Chest X-ray radiograph showed thickened and blurred lung markings, multiple dense opacities in bilateral lung fields, and increased and thickened right hilar opacities

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forming lobular measles pneumonia changes in quite limited scope. –– Lung consolidation type: If the inflammatory reaction breaks through the pulmonary lobules and spreads among the lobules, thus forming segmental or lobular consolidation, and chest X-ray radiograph shows obvious consolidation. • CT: The pulmonary interstitial changes are the main symptoms characterized by thickened peribronchovascular interstitium, interlobular septa and interlobular interstitium, especially interlobular septa showing reticular and ground-glass opacities. The reticular nodules are mainly distributed in the middle and inner zones of the middle and lower lung fields. The size, density and distribution of the nodules are uneven. Most of them are small nodules of 1–3  mm. In addition, emphysema, hilar enlargement, alveolar or lobular atelectasis and other changes can be found. Emphysema or pulmonary hyperinflation mainly occurs in the outer zone of the lung tissue, which is considered to be related to early small airway obstruction or small airway reaction. “Mosaic perfusion” sign may be a manifestation of localized emphysema on HRCT [47]. Inflammation involves pulmonary interstitium, resulting in regional imbalance of pulmonary blood flow/ventilation ratio. HRCT shows “map-like” mosaic perfusion sign with uneven density. (b) Adult measles pneumonia. • X-ray: Measles virus invades pulmonary interstitium, manifested as increased lung markings (Fig.  6.27), disorder, reticular nodule opacities, ground-glass opacities (Fig.  6.28), emphysema, etc. Wang et al. divided the X-ray manifestations of adult measles pneumonia into three types [48]. –– Reticular type (Type I): The lung markings are increased, thickened and blurred, showing a reticular structure, which is obvious in the middle and inner zones and lower part of the lung field. Obstructive emphysema occurs in both lungs. –– Reticular nodule type (Type II): On the basis of Type I, extensive reticular opacities can be found in both lungs, and small dotted blurred opacities distributed along bilateral lung markings. The diameter of small nodules is 5–8 mm, with blurred edges. Most of the lesions are distributed in the inner zone of the middle and lower lung fields. Obstructive atelectasis occurs in both lungs. –– Reticular nodule infiltration type (Type III): On the basis of Type II, small patchy and large

Fig. 6.27  Measles pneumonia in adults (I). Chest X-ray radiograph showed increased lung markings in the lower lobe of right lung

Fig. 6.28  Measles pneumonia in adults (II). Chest X-ray radiograph showed diffuse ground-glass opacities in both lungs

patchy blurred opacities are distributed along the markings of both lungs, which are obvious in the inner and middle zones of both lower lungs. The size of the lesions ranges from 1 to 3 cm, with infiltrative changes.

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• CT: In the early stage of the lesion, due to the incomplete obstruction of inflammatory secretion in bronchioles, CT may show lung hyperinflation. After measles virus has infected alveolar cells, inflammatory secretions continue to increase, resulting in alveolar atelectasis, alveolitis or peribronchiolitis. CT may show dotted and small nodular blurred opacities along bronchi, which are

Fig. 6.29  Measles pneumonia in adults (III). CT lung window showed multiple patchy ground-glass opacities in the posterior segment of the upper lobe of the right lung

a

Fig. 6.30  Measles complicated with pneumonia in children. (a) Chest X-ray radiograph showed that the markings of both lungs were enhanced and blurred, and there were multiple patchy opacities in both

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unevenly distributed and mostly located in reticular opacities, mostly with diameters 90%, but other invasive fungal infections cannot be excluded. 4. “Air crescent” sign indicates necrosis in the center of nodules. 5. Patients with aspergillus tracheobronchitis should be diagnosed by bronchoscopy.

7.1.5 Differential Diagnosis 1. Pulmonary tuberculoma: There are clinical symptoms of tuberculosis poisoning, and most of the related indicators of tuberculosis in laboratory examination are positive. It usually occurs in the posterior segment of the upper apex and the dorsal segment of the lower lobe of both lungs, with large cavities, thin and irregular walls. Most of them are dry cavities without liquid or gas–liquid plane, and the spherical contents in the cavities can be caseous necrotic masses with uneven density, irregular edges and without mobility. Cavities are surrounded by satellite lesions. The lesions progress slowly, with insignificant change in a short time. 2. Peripheral lung cancer: The cavities are uneven in thickness, the outer edge is lobulated and the spherical nodules on the cavity wall are irregular without mobility. The finding of cancer cells in sputum is helpful for the diagnosis of this disease.

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2. MRI: The lack of detectable protons in air-filled space and the potential artifacts between air–tissue interface has limited the wide application of lung MRI imaging. However, longitudinal studies in mice have shown that Aspergillus fumigatus lung lesions can be observed and quantified by MRI. Using advanced MR pulse sequences with ultrashort echo time, the pathological changes of pulmonary infection can be detected with high sensitivity. Dynamic contrast-enhanced MRI (DCE-MRI) can also be used to detect invasive pulmonary aspergillosis in immunosuppressed patients with acute myeloid leukemia [8, 9]. 3. 18F-FDG: It can be used for the imaging of fungal infection, distinguishing noninvasive pulmonary aspergillosis from invasive pulmonary aspergillosis, identifying extrapulmonary infection and monitoring treatment. However, a recent study combining PET and MRI (PET/MRI) to detect Aspergillus fumigatus pulmonary infection in vivo has shown that the increased uptake of 18F-FDG in pulmonary aspergillosis cannot be distinguished from aseptic inflammation or bacterial pulmonary infection caused by Streptococcus pneumoniae and Yersinia enterocolitica, indicating that this method has no specificity [10–12].

7.2 Mucor Bailu LiuZhehao Lyu, Qi Zhang and Dongkui Wang

7.2.1 Overview

Mucor circinelloides is a conditional pathogen, distributed in air, soil and spoiled food, and grows well in conditions of high temperature, high humidity and poor ventilation [13]. It 1. SPECT/CT: Clinical studies using MORF oligomers tar- can enter the body through inhalation, ingestion or direct geting fungal ribosomal RNA have shown that when dermal inoculation. If the immunity of the body is low, 99m Tc labeled aspergillus-specific probes are combined mucor can quickly invade mucous membrane, blood vessels, with SPECT, the specificity of CT examination can be bone and other structures, resulting in tissue necrosis and significantly improved. At present, AGEN (genus-­ spreading to adjacent tissues. If not treated in time, it can specific) and AFUM (Aspergillus fumigatus-specific) cause serious consequences in a short time. probes have been studied. SPECT/CT imaging results of In immunocompromised patients, pulmonary mucormyexperimental mice have shown that the level of 99mTc cosis is mainly caused by mucor entering the upper respiralabeled probes in Aspergillus fumigatus-infected lungs tory tract through nasal cavity and oral cavity and invading has increased by two times compared with the control bronchus and alveoli. If the natural or acquired immune bargroup without invasive pulmonary aspergillosis. AGEN rier of the body is defective, phagocytes cannot engulf pathooligomer is cross-reactive with Candida albicans, and genic bacteria, and the ability of T cells to kill target cells AFUM oligomer can exclude the detection of infectious decreases; it will lead to mucor colonizing in the lungs and aspergillus fungi except Aspergillus fumigatus, but the eventually causing inflammation. The clinical manifestations diagnostic efficiency of CT can still be greatly improved of this disease are fever (treatment with broad-spectrum by using specific pathogen probes [7]. ­antibiotics is ineffective), cough, hemoptysis, with or with-

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out chest pain, complicated with airway stenosis and wheezing rales. Mucormycosis can be divided into nose–brain type, lung type, gastrointestinal type and brain type according to the infection site. Clinically, nose–brain type is the most common, while brain type is rare. Rhizopus and mucor in mucorales are common pathogens. The former often invades nose, paranasal sinuses, brain and digestive tract, while the latter often invades lungs. The predisposing factors of mucormycosis include neutropenia, immunosuppression, diabetes and penetrating trauma. Laboratory examination show no specific. The inflammatory indicators such as leukocytes, specificity serum procalcitonin and C-reactive protein are mostly normal, and the erythrocyte sedimentation rate may be slightly increased [14].

7.2.2 Pathological Manifestations Mucor is highly angiotropic. Once mucor grows and multiplies in the infected area, it can release elastase-like proteolytic enzyme and quickly invade adjacent blood vessels (mainly arterial blood vessels). After hyphae have invaded vascular endothelium, it can lead to suppurative arteritis. Spores can proliferate in arterial elastic layer and make it peel off from tunica media, eventually leading to vasculitis, thrombosis, vascular occlusion and tissue infarction. The pathological features are vascular infarction and tissue necrosis. Macroscopic examination shows lung consolidation with poor elasticity, and section examination shows extensive hemorrhage with recent infarction. Microscopic examination shows edema, congestion, massive hemorrhage and necrosis in different degrees, accompanied by neutrophils and plasma cell infiltration. Sometimes macrophages can be found. Most of the tissues show suppurative changes, rarely with granuloma. Hyphae with a width of 10–15  μm can be found in the vascular wall. HE staining shows light blue hyphae, and hexamethylenetetramine-silver staining shows the clearest image. Tissues infected by mucor are often accompanied by edema and neutrophil infiltration, but the pathological manifestations have no specificity.

7.2.3 Imaging Manifestations The predisposing factors of more than 80% patients with pulmonary mucormycosis are diseases of blood system, especially hematological malignancies [15]. Less than half of patients with pulmonary mucormycosis have neutropenia at diagnosis. Therefore, even if patients do not have neutropenia, mucormycosis should not be excluded from differential diagnosis. The most common imaging manifes-

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tation of this disease is the rapid lesion progress. Chest CT shows the changes of pulmonary mucormycosis as follows: Consolidation can be found in the initial lesion center, surrounded by ground-glass opacities, manifested as “halo” sign. As mucor invades blood vessels and causes hemorrhage, “reversed halo” sign can be found. The latest studies have shown that “reversed halo” sign is the most important imaging sign [16]. Other signs include large ground-glass “halo,” where the ground-glass opacity area is much larger than the solid component area of the central lesion. Its wide range indicates that pulmonary mucormycosis is more likely to lead to extensive pulmonary hemorrhage than other vascular invasive infections, such as aspergillosis, which usually shows only a small “halo” around the nodule. The disease can continue to develop and is manifested as central necrosis, peripheral consolidation and late abscess formation with gas–liquid plane. By enhanced scanning, the lesions are mildly to moderately enhanced, which sometimes cannot be easily distinguished from lung tumors [14, 17]. Most of the vascular invasiveness of mucor shows “halo” sign on chest CT images. If the lesions have chronical outcome, the exudation around the nodule can be absorbed, with smooth and sharp edge. Necrotizing pneumonia accompanied by “air crescent” sign can be found after infarction. The number of lesions in upper lobe is often more than that in middle and lower lobe, more in the outer zone of the lung field than in middle and the middle and inner zones of the lung field [18]. Another common imaging feature of this disease is that the lesions are distributed around the peripheral area of the lung, and sometimes the vascular truncation sign related to these lesions can be found, which is consistent with the process of pulmonary infarction caused by distal vascular involvement [19]. In the case of neutropenia, the manifestation similar to pulmonary septic embolus can be found, which shows the process of pulmonary mucormycosis spreading through blood, and even pulmonary arterial hypertensive endocarditis caused by septic pulmonary embolism can be found in patients with pulmonary mucormycosis [20]. Studies have confirmed that pleural effusion is an independent risk factor for mucor pneumonia. The lung parenchyma involved by mucor can form thick-walled cavities locally, with smooth cavity wall. Liquefaction and necrosis are easy to occur inside the lesions [21]. Enhanced scanning shows uneven enhancement or irregular annular enhancement, and the solid component is significantly enhanced, but mostly with delayed enhancement. Hilar lymphadenectasis, miliary nodules in both lungs and bronchiectasis can be occasionally found. Thickened interlobular septa may also be found. Bronchial occlusion and pulmonary pseudoaneurysm are rare [22, 23].

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7.2.4 Diagnostic Key Points 1. Manifestations are exudation, wedge-shaped consolidation, unilateral or bilateral nodular lesions. 2. Solitary or multiple masses and cavities form “halo” sign, and the edge is enhanced after injection of contrast medium. Imaging examinations of patients with mucormycosis often include “reversed halo” sign. 3. The “air crescent” sign can be formed between the lesions and normal tissues. 4. Symptoms of acute bronchitis involving the lungs cause lung consolidation and lung abscess, accompanied by signs of thrombosis and infarction. 5. The histopathological features of pulmonary mucormycosis are nonspecific, mainly based on the large hyphae without septum or with sparse septum found in tissue sections.

7.2.5 Differential Diagnosis 1. Nodular cavities: Most occur in the posterior segment of the upper apex or the dorsal segment of the lower lobe, which are mostly thin-walled cavities with relatively slow progress and often accompanied by satellite foci. Pulmonary mucormycosis cavities have no prone location, are mostly thick-walled, progress rapidly and are prone to pulmonary embolism. 2. Cancerous cavities: Most are eccentric cavities, often with wall nodules, obvious lobulation on the outer wall and many short burrs, often accompanied by lymphadenectasis in hilum and mediastinum. Pulmonary mucormycosis cavities are multiple, mostly with smooth inner wall, and the outer wall may have long burrs, while short burrs are rare. 3. Pulmonary aspergillosis: Most show thin-walled cavities. Aspergillosis balls and cavities form “air crescent” sign, which belongs to its characteristic changes, and those accompanied by aspergillosis balls can be easily identified.

7.2.6 Research Status and Progress MRI examination of pulmonary mucormycosis shows hypointense signal edge in T2WI lesions, which may represent blood related to hemorrhagic infarction, or may be concentrated metals in fungal organisms, such as iron, magnesium or manganese. In addition, enhanced MRI shows no enhancement in the lesion, which is called “black hole” sign [20]. Detection of mucorales in bronchoalveolar lavage fluid (BALF) by polymerase chain reaction (PCR) can help identify the pathogen of fungal pneumonia and detect mixed

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aspergillosis infection. Studies have shown that serum mucormycosis PCR is the earliest evidence for diagnosis of pulmonary mucormycosis in most cases, Positive BALF mucormycosis PCR is not only a biological test method for detecting pulmonary mucormycosis but also a method to help diagnose complicated aspergillosis. Therefore, this new tool can actually provide necessary microbiological evidence for rapid and effective treatment against mucor [24, 25].

7.3 Cryptococcus Neoformans Bailu LiuZhehao Lyu, Fugui Song and Ying Guan Cryptococcus is a saccharomycete widely distributed in nature, especially in soil and poultry feces. Cryptococcus includes 17 species and 18 varieties, but only Cryptococcus neoformans and its varieties (Cryptococcus gattii and Cryptococcus neoformans var.grubii) are pathogenic. Cryptococcus infection is more likely to occur in immunosuppressive population with HIV infection, malignant tumor, organ transplantation, hematological diseases, long-term use of glucocorticoid and others [26]. Cryptococcus can infect any tissue and organ of human body, mainly central nervous system, lung and skin. Ninety percent of the lesions are limited to the lung, and only 10% can spread to other organs through blood.

7.3.1 Overview Pulmonary cryptococcosis (PC) is an acute or chronic pulmonary mycosis caused by Cryptococcus neoformans infection. Pulmonary cryptococcal infection that invades the lungs alone without other primary lung diseases and structural abnormalities is called primary pulmonary cryptococcosis. The incidence of PC ranks the second in that of various pulmonary mycoses, only lower than that of pulmonary aspergillosis, and it occurs slightly more in male patients than in female patients. Cryptococcus is inhaled through respiratory tract and enters the outer zone of lung, leading to subpleural infection, causing pulmonary granulomatous lesions and extensive interstitial infiltration of the lung. In the hosts with normal immune function, the annual incidence of PC is (0.4– 0.9)/100,000. Those with immune impairment, especially HIV infection, account for 6–10% of the total number of patients. In recent years, there have been increasing reports of cryptococcal infection in immune normal hosts. In China, about 70% of PC patients have no obvious risk factors. This section mainly introduces pulmonary cryptococcosis in patients with normal immune function. The clinical manifestations of this disease are nonspecific, and the symptoms vary in severity. According to the

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severity of clinical manifestations, it can be divided into the following three types. (1) Asymptomatic type. For normal hosts, most of the infections are discovered by chance during chest X-ray examination, and these patients basically have no clinical symptoms. (2) Chronic type. Often with occult onset, clinical manifestations are cough, expectoration, chest pain, fever, night sweats, shortness of breath, weight loss, systemic fatigue and hemoptysis. Generally, physical examination shows no positive finding. (3) Acute type. It is especially common in AIDS patients. The clinical manifestations include high fever, obvious anhelation and hypoxemia, occasionally with acute and severe lower respiratory tract infection, leading to acute respiratory failure, which is very similar to the symptoms of pneumocystis pneumonia. In addition to anhelation and cyanosis, thin moist riles in both lungs can be heard during physical examination, and very few patients may have corresponding clinical signs due to the complication with pleural effusion. Mycoscopic examination of fungi is the most effective laboratory diagnostic method. Positive results can confirm fungal infection, but negative results cannot rule out the diagnosis. Serological examination can be carried out by Eiken test, namely the pretreatment of serum with protease, which can significantly improve the sensitivity of detection. Besides serum, antigen titration in sputum, pleural effusion and bronchoalveolar lavage fluid (BALF) can also be detected. In addition, foreign studies have confirmed that the detection of serum cryptococcal capsular polysaccharide antigen has high diagnostic value for cryptococcal infection, with sensitivity and specificity of 93%–100%. Therefore, latex agglutination test of cryptococcal capsule antigen is the most efficient and most valuable diagnostic method for cryptococcosis at present.

7.3.2 Pathological Manifestations Cryptococcus neoformans is large spherical in tissue fluid or culture, with a diameter of 5–20 μm, surrounded by hypertrophic capsule. It is highly refractive and cannot be easily found by common staining. PAS staining shows that the outer membrane of Cryptococcus is bright red, and hexamine silver staining shows that the cell wall is brown-black, with clear outline [27]. Microscopic examination with ink negative staining shows that bacterial cells are wrapped in transparent capsules, often budding, but not forming pseudohyphae. Much inflammatory cell infiltration occurs in the lesions, mainly monocytes, lymphocytes and plasma cells. Neutrophils are rare because of the inhibitory effect of capsule on neutrophils. Granuloma is formed by the aggregation of a large number of histiocytes, epithelioid cells and multinucleated giant cells. Fungal spores can be found inside and outside epithelioid cells and multinucleated giant cells

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[27]. The cells in granuloma are diffuse, rarely form nodules, and the necrosis is incomplete. The reticular fiber scaffold exists, which can be distinguished from proliferative pulmonary tuberculosis. Cryptococcus pathogen must be found in pathological examination before the diagnosis can be confirmed.

7.3.3 Imaging Manifestations PC imaging examination mainly depends on CT examination, and PC is mainly distributed in the peripheral lung area under the pleura on CT [27]. Patients with normal immune function mostly show single pulmonary nodule or mass, and consolidation is rare. If the immune status of the body is good, Cryptococcus infection in the lungs can induce significant delayed hypersensitivity and form granulomatous nodules. At the same time, good immunity can promote macrophages to phagocytize immune complexes, and finally activate CD  +  T cells to kill target cells, thus limiting the infection scope of Cryptococcus pulmonary infection and prevent it from spreading widely in the lungs and even involving the central nervous system. The pathological manifestations of nodular type PC are noncaseous granulomatous lesions, with necrosis in the center of solitary granuloma, macrophages and multinucleated giant cells can be found inside, and a large number of cryptococcal spores can be found in cytoplasm. The exudation of inflammatory cells and red blood cells can be found in alveolar space, with the infiltration of inflammatory cells in interstitium and alveolar wall, and the necrosis around bronchial wall suggests the possibility of Cryptococcus invading from airway inside to outside. 1. Nodular lesions: As the most common manifestations of PC patients with normal immune function, multiple clustered nodules are the main manifestation, which can be often misdiagnosed as metastases, followed by single nodule [28]. Pulmonary nodules of PC infection are often irregular in shape, suggesting infectious nodules [29]. The situation of lesions distributed around the lung field is significantly more often than in the central area and mixed situation. The lesions are generally located under the pleura, especially in bilateral lower lungs but rarely in upper lungs, which may be due to the easier colonization of cryptococcal spores in the peripheral zone. Some patchy and nodular opacities distributed along bronchovascular bundles suggest that Cryptococcus grows and multiplies from inside to outside along the airway. 2. Mass-like lesions: PC masses vary in size, showing single or multiple lesions, with clear edges. “knife cutting” sign and “straight” sign can be found, among which “knife cutting” sign is common in subpleural nodules. ­Lobulation

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and burrs can be found in some lesions, but the lobulation is shallow and the burrs are slender, which are mostly burr shadows in the “halo” sign. The pleural depression sign is less [27]. Air bronchogram can be found in the masses, which is the most characteristic manifestation of mass-like lesions in PC patients with normal immune function. The pathological basis may be similar to that of pneumonia, as an inflammatory reaction around pathogens, which is characterized by alveolar consolidation. The lung stent structure is complete and the bronchial stent structure is undamaged. Therefore, if PC shows air bronchogram, it is characterized by deep lesions near the hilar bronchus, with natural route and smooth bronchial wall, which is different from that of malignant lesions such as lung cancer [30, 31]. By enhanced scanning, the lesions show mild-to-moderate enhancement, and delayed enhancement can also be found. Various enhancement methods may also show uneven enhancement or annular enhancement. About two-third cases of the disease show pores between the pleura, and one-third cases of the disease show connection with the pleura, manifested as “wall papering” sign, in which the pleura near the lesion is thickened and the fat space outside the pleura is widened [26]. 3. “Halo” sign: Blurred ground-glass opacities can be found around or adjacent to the lung field of PC lesions, namely the “halo” sign (Fig.  7.5). The pathological basis of “halo” sign is nodular hemorrhage, tumor cell infiltration, inflammatory exudation, while the pathological manifestations of PC include granulomatous inflammation and surrounding inflammatory exudation [26]. 4. Infiltrating consolidation-like lesions: The lesions are distributed in lobes or segments, mainly in the lower lobes of both lungs, followed by the middle lobes and the poste-

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rior segment of the upper lobe apex. The density of the lesion middle area is high, and the density of the surrounding area is low, with blurred edges. Multiple scattered necrotic lesions can be found inside, and air bronchogram can be found in the consolidation, which is a more characteristic sign of patients with normal immune function, suggesting that it is alveolar exudative lesion. Air bronchogram can reach the distal end or blockage occurs at the proximal end. The bronchus in the blockage area is normal or slightly dilated, with normal route [26]. 5. Cavity-like lesions: Such lesions are rare in PC patients with normal immune function, mainly coagulative necrosis, which can occur in nodules, mass opacities or lung consolidation, with a diameter of 0.3–2.2 cm and smooth inner wall. Mural nodules and septa can also be found in the cavities. Its occurrence often suggests local severe fungal infection, which requires more potent antifungal treatment [32, 33].

7.3.4 Diagnostic Key Points 1. The possibility of PC should be considered for polymorphic, multifocal and multiple pulmonary lesions, which are mainly located outside the lung, with the clinical symptoms inconsistent with the imaging findings. 2. PC patients with good immune status mainly show single and nodular masses, while PC patients with underlying diseases mainly show multiple infiltrative consolidations, mostly mixed types. The main CT signs of both are air bronchogram, “halo” sign and cavity. 3. The onset of PC is insidious, with atypical symptoms, which often causes misdiagnosis. For the lumpy opacity lesions in the lungs due to poor antibiotic treatment effect, early biopsy should be used for pathological diagnosis.

7.3.5 Differential Diagnosis

Fig. 7.5  Pulmonary cryptococcosis. CT lung window showed a subpleural quasi-round mass in the upper lobe of the right lung, with “halo” sign around

1. Solitary nodules and mass-like lesions need to be differentiated from peripheral lung cancer: PC often shows no obvious enhancement, and “halo” sign can be found at the edge. The edge of lung cancer is irregular, with deep lobulation, spinous protuberance, short burr sign, vessel convergence sign, “small vacuole” sign and pleural traction sign. Inflammatory lesions can be found at the distal end, surrounded by ground-glass opacities with clear edges. Bronchial blockage can be found at the proximal end. The CT value changes mostly from 20 to 60 HU before and after enhancement. 2. Multiple nodular lesions need to be differentiated from multiple lung metastases: PC lesions have various shapes, different sizes, unclear edges and often gathered

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d­ istribution. Patients with lung metastases have a history of primary disease, and the nodules are mostly quasiround, with smooth edges, uniform density and random distribution. The lesions are generally cotton-shaped with burrs. “Halo” and “vacuole” signs are rare, often complicated with lung metastases in other areas. 3. Diffuse miliary lesions need to be differentiated from acute hematogenous disseminated pulmonary tuberculosis: Acute hematogenous disseminated pulmonary tuberculosis has typical clinical symptoms, sputum bacteria and mostly positive T-SPOT detection. 4. Mixed-type lesions need to be differentiated from pulmonary tuberculosis: PC mainly shows nodules and masses. Pulmonary tuberculosis mainly shows patchy, dotted and stripe-like opacities. Pulmonary tuberculosis is mostly located in the posterior segment of the upper lobe apex and the dorsal segment of the lower lobe, and may be accompanied by bronchial dissemination. Cryptococcal lesions are mostly located under the pleura of the lower lobe of both lungs. Tuberculosis calcification is common, but cryptococcal calcification is rare. “Tree-in-bud” sign and satellite foci can be seen around tuberculosis. Small “halo” signs with burrs can be seen around cryptococcal lesions, which are connected with blood vessels. Tuberculosis can be enhanced in outer zone and Cryptococcus can be enhanced uniformly. 5. Consolidation lesions need to be distinguished from pneumonia: PC has significant imaging manifestations but mild clinical symptoms. Consolidation distribution is scattered, with higher density of lesions than that of lobar pneumonia, but the surrounding density shadow is significantly lighter and sparse. In addition, most airway signs are limited to the proximal end of the consolidated lung, which is significantly different from the air bronchogram of lobar pneumonia penetrating the consolidated lung, and the general anti-inflammatory treatment effect is poor. Inflammation usually starts with acute onset, with increased total number of leukocytes, increased percentage of neutrophils, mostly with fever, and significant clinical symptoms, which is consistent with lung changes. 6. Consolidation lesions need to be distinguished from pneumonia lung cancer: The density of consolidation area of pneumonia lung cancer is reduced. By enhanced scanning, many areas with reduced density show enhancement. Swelling and contraction can also be found at the edge; the internal bronchus is often distorted and deformed. The proximal obstruction is narrow, with stiff route of internal blood vessels. “Honeycomb” sign can be found in the lesion, surrounded by ground-glass opacities with clear edges. Mediastinal lymph nodes and distant metastasis can be found.

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7.3.6 Research Status and Progress The extensive use of 18F-FDG PET/CT imaging shows that nuclear medicine has made great progress in modern oncology, which changes the diagnosis and treatment of lung cancer and lymphoma, and provides the staging function for noninvasive cancer. Some studies have shown that the SUV value of pulmonary cryptococcosis can range from 0.93 to 4.85, which is related to the serum cryptococcal antigen level. Therefore, it is still difficult to distinguish pulmonary cryptococcosis from pulmonary malignant tumor by 18F-­ FDG PET/CT alone. Excessive SUV value may lead to excessive evaluation of diseases by 18F-FDG PET/CT and affect clinical diagnosis. Active inflammation should be considered in clinical lesions with high FDG uptake, while normal FDG uptake indicates no active inflammation. Therefore, 18 F-FDG PET/CT is mainly used to guide treatment planning and select the best biopsy site. Mediastinal lymphadenitis associated with pulmonary cryptococcosis is rare. Generally, lymphadenitis can be confirmed by mediastinoscopy, CT-guided lymph node biopsy or intrabronchial ultrasound-­ guided needle aspiration biopsy. Other studies have shown that 18F-FDG PET/CT scanning can provide information for detecting mediastinal lymph nodes [34–37].

7.4 Histoplasma Bailu LiuZhehao Lyu, and Fugui Song

7.4.1 Overview Pulmonary histoplasmosis is a primary mycosis caused by histoplasmosis capsulatum infection. Histoplasma capsulatum is a biphasic fungus. It is of yeast-type in tissues and hyphae-type at room temperature, and the latter is more infectious. Pulmonary histoplasma mainly exists in the soil with rotten feces of bats or birds. Human activities cause aerosols with spores in the topsoil, which are then inhaled into the body to cause lung infection [38], and systematic dissemination may occur in immunocompromised people. This disease is common in patients with acquired immunodeficiency syndrome, organ transplantation, malignant hematological diseases, taking hormones and immunosuppressive drugs, etc. [39–41]. The clinical manifestations of pulmonary histoplasmosis vary in severity, which is related to the exposure intensity of the bacterium and the immunity of the host. Clinically, the disease includes asymptomatic type, acute self-limited type, acute severe pneumonia type, subacute type and chronic pulmonary histoplasmosis type. According to the onset dura-

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tion, the disease may be acute (within 1  month), subacute (1–3 months) and chronic (>3 months). The clinical symptoms of acute and subacute pulmonary histoplasmosis are usually influenza-like manifestations (fever, chills, fatigue, malaise, headache and dry cough). Pericarditis, erythema nodosum, pleurisy and acute arthritis may also occur. Patients with mild symptoms may improve themselves within a few weeks, while patients with severe symptoms may have diffuse bilateral lung exudation leading to respiratory failure. Chronic infection mainly occurs in elderly (>50 years old) male smokers, with clinical symptoms including cough, expectoration, dyspnea, chest pain, night sweats and weight loss during the deterioration of the disease [42]. The diagnosis methods of acute or subacute pulmonary histoplasmosis include histopathological analysis, culture and serological histoplasmosis antibody test, antigen detection and PCR determination. Because the sensitivity and specificity of a single examination method are less than 100%, multiple examination methods should be adopted for suspected cases. The sensitivity of blood and urine antigen detection and serological detection is high, but there is still a lack of serological detection reagents currently in China, so their applications in China are limited [43].

7.4.2 Pathological Manifestations The pathological changes caused by this bacterium invading various organs are similar. After invading human body, histoplasmosis spores or mycelium are phagocytized by leukocytes and macrophages, and transformed into yeast type, resulting in specific cell-mediated immune response, that is, delayed hypersensitivity reaction. With the enhancement and prolongation of inflammatory reaction, fibrous granuloma is formed, and dystrophic calcification occurs in the central tissue of granuloma nodules, forming “target” sign or diffuse calcification. Before the formation of cell-mediated immune response, histoplasmosis can be carried by macrophages for distant spreading, and then reach mediastinal lymph nodes through lymphatic pathway or reticuloendothelial system through blood flow, resulting in enlarged and calcified mediastinal and hilar lymph nodes, often accompanied by pulmonary nodules or consolidation [44, 45]. Pulmonary pathological changes in patients with pulmonary histoplasmosis are related to bacterial content and immune status of the body, manifested as inflammatory exudation or granulomatous inflammation and diffuse alveolar damage in severe cases. People with normal immune function often show granulomatous inflammation with or without necrosis, which needs to be differentiated from other fungi and tuberculous granulomatous inflammation. Special staining of lung tissue may show histoplasma, manifested as yeast-like fungus, with a diameter of 2–5 μm, deep staining

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dots in nucleus and peripheral hollow halo. PAS staining and hexamine silver staining in pathological sections of lung biopsy show no pulmonary histoplasmosis spores, which is related to the relative difficulty of histoplasma staining, the normal immune function of patients, the short exposure duration to infection environment and the relatively late biopsy time after infection.

7.4.3 Imaging Manifestations The function of imaging examination is to exclude and assist in diagnosis and classification, understand the degree and scope of lesion invasion and evaluate the therapeutic effect. 1. Active stage: Lung lesions are composed of granulation tissue in lung parenchyma and inflammatory lesions in lung interstitium, which are mostly characterized by multiple scattered lung infiltration and hilar lymphadenectasis. Pulmonary lesions have various shapes, which can be stripe-like, patchy, large patchy and nodular. The specific manifestations are as follows. (a) Pneumonia type: It is more common in the early stage of pathological changes, showing interstitial pneumonia, bronchiolitis, lobular or lobar pneumonia. The lesions are scattered in both lung fields, with blurred edges, often showing lobular or segmental pneumonia changes, which are more common under pleura, and the scope may spread to the whole lung lobe or lung segment, with cavities inside. It cannot be easily distinguished from lobar pneumonia when involving the whole lung lobe. If the lesions are in bilateral upper lung fields, the manifestations are similar to those of pulmonary tuberculosis. The manifestations are similar to those of bronchopneumonia. If the cavity occurs, it looks like a lung abscess, with smooth inner wall and exudation outside the wall. Enhancement scan can show the slightly enhanced lesions. (b) Nodular type: The lesions progress further, and gradually form single or multiple round or oval hyperdensities with a size of 0.5–2 cm, with uniform density, clear edge, burrs and incomplete ground-glass opacities at the edge. The formation of ground-glass halo may be caused by the high density of nodules and the different density between nodule edge and lung parenchyma. This sign is different from ground-glass nodules of lung, which means the whole round and quasi-round nodule with clear and complete edge, similar to ground-glass opacity nodules, which often indicates preinvasive lesions or microinvasive adenocarcinoma of the lung [46]. Large nodular lesions may be single or multiple spherical opacities in the

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lungs, scattered in the middle and inner zones of the two lung fields, similar to primary or metastatic lung tumors, which may form cavities or cause dotted annular calcification. Enhancement scan can show mildly enhanced lesions. If invading pleura, it can cause pleurisy, pleural effusion or thickened pleura, adhesion, and even involve ribs. (c) Miliary dissemination type: Miliary-like nodules are diffuse in both lungs, mainly in the inner and middle zones of the middle and lower lung fields, with uniform density and round size ranging from 1 to 4 mm. The larger ones are sparsely distributed, while the smaller ones are densely distributed, but fusion rarely occurs. The lung tissue between lesions is normal, and fibrosis or calcification may occur in the lung tissue in several years. (d) Lymphadenectasis type: Lymphadenectasis can coexist with pulmonary lesions or occur alone. 2. Healing stage: Pneumonia type can be gradually absorbed without leaving traces, while nodular type, miliary dissemination type and lymphadenectasis type are often manifested as fibrosis and calcification after healing. Calcified nodules are mostly round or oval, with smooth and dense edges. (a) Pulmonary changes: Usually dense round calcification, with high density, similar to lipiodol retained after bronchography. The edges are sharp, surrounded by stripe-like opacities. According to the manifestations, pulmonary changes can be divided into nodular calcification and miliary dissemination calcification. Nodular calcification is manifested by round hyperdensities scattered in both lungs, with different sizes, as small as needle tips or as large as beans (0.1–4.0 cm), with clear edges, and can also be manifested by aggregated distribution of calcification in the center of multiple nodules, forming “shotgun” sign [45]. Miliary dissemination calcification is usually manifested by diffuse nodules of similar size (0.2–0.5  cm) in both lungs, with uniform density, smooth and sharp edges, uniformly distributed in the middle and lower fields, and rarely occurs in apex pulmonis. (b) Hilar changes: Hilar shadows are enlarged, widened and thickened, with eggshell-like calcification of lymph nodes. (c) Pleural changes: A small amount of pleural effusion and thickened pleura can be found [47–50].

7.4.4 Diagnostic Key Points 1. X-ray manifestations show that the pulmonary changes are not proportional to clinical symptoms. Pulmonary lesions are similar to tuberculosis or pneumonia lesions.

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Complications include extrapulmonary lesions, such as hepatosplenomegaly, pancytopenia, etc. 2. CT manifestations show that both lungs have scattered exudative lesions with different sizes or nodular lesions with clear edges. Lesions can be single or multiple. Exudate shadows occur around the lesion. The enhancement is not significant. 3. Pulmonary changes are not proportional to or in line with clinical symptoms. Anti-inflammatory and antituberculosis treatment is ineffective, and sputum tuberculosis bacterium test result is negative. 4. The gold standard for diagnosis of this disease is to culture histoplasma from tissues or body fluids, but this method is very slow and takes 1–6 weeks, which is not conducive to early clinical diagnosis. 5. Histoplasma found by histopathology or bone marrow cytology is a reliable diagnostic basis.

7.4.5 Differential Diagnosis 1. Acute hematogenous disseminated pulmonary tuberculosis: The lesions can be distributed throughout the lung, the edges of proliferative lesions are clear, and the edges of exudative nodules are blurred and tend to be fused. After calcification, the nodules are irregular, which is different from the nodules of this disease with uneven distribution, round and smooth edges. 2. Bronchial calculi: The clinical manifestations are mostly repeated hemoptysis, accompanied by coughing up bean-­ sized calculi. Bronchial obstruction or tracheoesophageal fistula may aggravate the disease [42]. The imaging manifestations show that the calculi are irregular in shape and different in size, mostly distributed along bronchus, and are more common in the lower lung fields. 3. Alveolar microlithiasis: Patients often have a family history of the disease. Imaging manifestations show that hyperdense caviar-like white dot calculus shadows are distributed in the whole lung field, most densely in the inner zone of the middle and lower lung field, and the cardiac outer edge and lung markings are not displayed. The shape is similar to flame, often accompanied by calcification of pleura and pericardium, with unclear diaphragm shadow. 4. Calcification of pulmonary parenchyma: Calcified nodules may occur in the lungs of patients with rheumatic heart disease, scattered in the lower lung field, with large volume, low density and irregular shape, which is different from the calcification with smooth round edge. 5. Silicosis nodule calcification: It is more common in the middle and lower lung fields of both lungs, often accompanied by eggshell-like irregular calcification of hilar lymph nodes. Combined with the occupational disease history of dust exposure, it is not difficult to diagnose.

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7.4.6 Research Status and Progress Granulomas caused by pulmonary infectious lesions are often manifested as indeterminate pulmonary nodules (IPN) on imaging. 18F-FDG PET/CT can be used to evaluate moderate risk nodules, but its specificity for benign granulomatous nodules caused by fungal infection is significantly reduced, with false-positive results. In this case, pathological diagnosis evidence is usually necessary in clinic, and patients may have the risk of complications due to biopsy. Measuring biomarkers of fungal infection by serological test is a method with good application prospect. Some studies have used a new serum enzyme immunoassay (EIA) for histoplasmosis to evaluate such nodules, and compared it with metabolic diagnostic imaging of 18F-FDG PET/CT. 18 F-FDG PET/CT shows poor diagnostic results, with a sensitivity of 76% and a specificity of 39%. EIA positive results of histoplasmosis provide clinicians with effective information for diagnosis. The positive test of IgG and IgM antibodies suggests the active stage of pulmonary histoplasmosis, and then is used to differentiate this disease from lung cancer [51].

7.5 Coccidioides Immitis Bailu LiuZhehao Lyu, and Tingting Chen

7.5.1 Overview Coccidioidomycosis is a mycosis of lung or other organs caused by Coccidioides immitis. The lung is the most frequently involved organ. Coccidioidomycosis can be primary and progressive clinically. The primary manifestation is acute and self-limited respiratory tract infection. The progressive manifestation is chronic and fatal systemic infection. Sixty percent of coccidioidomycosis patients show asymptomatic subclinical course, which can only be found during Coccidioides Immitis skin test; 40% of the patients have different clinical manifestations, mainly including the following types: (1) Primary pulmonary coccidioidomycosis shows flu-like symptoms, dry cough, occasional bloodshot sputum and chest pain after 10–16 days of infection. Twenty percent of patients have conjunctivitis and allergic skin lesions such as erythema multiforme and erythema nodosum, which may be accompanied by multiple serositis (pleurisy, pericarditis and arthritis). The course of the disease was self-limited, and the symptoms may subside in 6–8 weeks. Fungemia is easy to occur in the early stage of infection, but there is little extrapulmonary damage, which is mainly found in skin, joints, bones and meninges. (2) Chronic progressive

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Coccidioides immitis pneumonia shows persisted and gradually deteriorated lung lesions 8  weeks after the primary infection, manifested as persistent low fever, cough, anorexia, weight loss, and hemoptysis in some patients. This stage is slow and lasts for a long period, which may be months to years. (3) Miliary pulmonary coccidioidomycosis is a serious complication of primary pulmonary coccidioidomycosis, and the pathogenic bacteria spread to the whole lung and other organs outside the lung through blood. This type often occurs in the early stage of the disease course, and can also be a complication of chronic progressive Coccidioides immitis pneumonia in the later stage. If it occurs in patients with immunosuppression and severe underlying diseases, its clinical manifestations are similar to hematogenous disseminated pulmonary tuberculosis, which can rapidly progress to respiratory failure. Hematogenous dissemination can involve skin, joints, lymph nodes, meninges, liver, spleen, etc. [52]. In patients with pulmonary coccidioidomycosis, the total number of leukocytes in peripheral blood increases. In patients with primary pulmonary coccidioidomycosis, the number of eosinophils in blood increases, especially in the second to third weeks after the onset. The skin test reaction of patients can be positive 4 weeks after the primary infection, but the previous infected patients may continue to be positive. Patients with hematogenous dissemination may be negative. Positive culture of Coccidioides immitis has special significance for diagnosis. The positive rate of sputum culture is 40%–60%, and the positive rate of fiberoptic bronchoscopy specimens is higher. The serological method for detecting Coccidioides immitis antibodies rarely has false-­ positive results, and the sensitivity of latex agglutination test is 90%, which is often used for primary screening. Antibody titer is related to disease severity [53].

7.5.2 Pathological Manifestations After invading the body, spores first cause suppurative inflammation and then form granuloma. The granuloma is composed of proliferation of various cellular components, which can cause caseous necrosis. Calcification is rare. Microscopic examination shows a large number of Coccidioides immitis, multinucleated giant cells, lymphocytes, plasmocytes and neutrophils infiltration, thereby forming giant cell granuloma lesions.

7.5.3 Imaging Manifestations 1. Normal or increased lung markings (nonspecific). 2. Lobular alveolar and interstitial infiltration of both lungs is manifested as irregular reticular opacities or reticular nodular opacities and/or ground-glass opacities. Nodules

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are often located in reticular opacities or ground-glass opacities. Reticular nodular opacities are distributed along the center of lobules. 3. Bronchopneumonia-like patchy opacities or consolidation in central segment and lobe, with clear edges. 4. Chronic infection can cause single or multiple nodules, rarely with calcification. Nodules and consolidation center necrosis can form cavities, with thick or thin cavity wall, but single thin-walled cavities are the most common. The cavity can develop into pleural cavity and cause pneumothorax, empyema or bronchopleural fistula. 5. Miliary nodule is a manifestation of disseminated pulmonary coccidioidomycosis, which is similar to miliary tuberculosis or reticular nodule opacities similar to those of cancerous lymphangitis. In such case, the lesion can involve pericardium and cause pericardial effusion, cardiac tamponade or constrictive pericarditis. 6. Pleura adjacent to the lesion is thickened, but pleural effusion is rare. 7. Hilar or mediastinal lymphadenectasis is rare, and mostly occurs unilaterally, with or without pulmonary parenchyma exudation [54, 55].

7.5.4 Diagnostic Key Points 1. Respiratory infections in epidemic areas may suggest the diagnosis of this disease. 2. Flu-like symptoms, dry cough, occasional bloodshot sputum and chest pain. 3. Lobular alveolar and interstitial infiltration of both lungs, bronchopneumonia-like patchy opacities or central segmental and lobar consolidation. 4. The specific spheroids of Coccidioides immitis found by smear or culture can be used to make a definite diagnosis [56, 57].

7.5.5 Differential Diagnosis 1. Pulmonary tuberculoma: It has clinical symptoms of tuberculosis poisoning, and most of the related indicators of tuberculosis in laboratory examination are positive. It usually occurs in the posterior segment of the upper lobe apex and the dorsal segment of the lower lobe of both lungs, showing large cavities with thin and irregular wall. Most are dry cavities without liquid or gas–liquid plane, and the spherical contents in the cavities can be caseous necrotic masses with uneven density and irregular edges, showing no mobility. Periphery satellite lesions can be

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found. The lesions progress slowly with little change in a short period. 2. Lung cancer: The outer edge is lobulated, irregular in shape, sometimes showing cavities with uneven thickness. The shape of spherical nodules on the cavity wall is irregular. Finding cancer cells in sputum is helpful for the diagnosis of this disease.

7.5.6 Research Status and Progress Pulmonary coccidioidomycosis often develops into pulmonary nodular lesions. At present, there is no reliable noninvasive method to identify this disease, and the invasive method of biopsy is usually used for diagnosis. The latest studies have adopted the time points of PET/CT scanning to differentiate pulmonary coccidioidomycosis nodules from pulmonary malignant tumors [58]. The activity of glucose6-phosphatase (G6PD) in inflammatory lesions is quite different from that in malignant lesions, and the enzyme activity in malignant cells is low, so 18F-FDG will continue to be accumulated over time. If 18F-FDG uptake is high, dual time point imaging (DTPI) of FDG has a good clinical application prospect in differentiating benign lesions and malignant lesions [59]. Bone involvement in disseminated coccidioidomycosis mainly causes osteolytic changes. Soft tissue evaluation by PET/CT can find more clinical occult soft tissue infections or abscesses that need surgical treatment. Therefore, 18F-FDG PET/CT can provide comprehensive systemic evaluation and guide biopsy [60].

7.6 Candida Bailu LiuZhehao Lyu, and Tingting Chen

7.6.1 Overview Pulmonary candidiasis is an acute, subacute or chronic bronchial and pulmonary infection caused by candida. Pulmonary fungal infections are common, most of which are nosocomial infections, especially in intensive care unit, burn department and oncology department. Clinically, pulmonary candidiasis can be divided into three types. (1) Bronchitis type: The patients are generally in good condition, with mild symptoms, cough, white mucus sputum or milky white sputum, occasionally bloodshot, but no fever. (2) Pneumonia type: It is more common in patients with immunosuppression or extremely weak general

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c­ ondition, showing acute pneumonia or septicemia, chills, fever, cough with white mucus jelly-like sputum or purulent sputum, often with bloodshot or necrotic tissue, showing yeast odor, even hemoptysis, dyspnea, etc. Dry and moist rales can be heard in the lungs. In addition to the above symptoms, blood-borne pneumonia can be accompanied by skin lesions, myocarditis, candida bacteremia and shock. Chronic cases are characterized by diffuse fibrosis and emphysema, which can be diagnosed by Candida cultured in sputum or bronchoalveolar lavage fluid. (3) Allergic type: It is manifested as bronchial asthma or allergic rhinitis. Histopathological examination includes fiberoptic bronchoscopic biopsy or percutaneous lung biopsy. Histopathological examination with evidence of candida hyphae invasion can confirm the diagnosis.

7.6.2 Pathological Manifestations Candida transforms into hyphal type and proliferates after invading tissues. Candida hyphae has antiphagocytic ability, causing acute inflammatory reaction mainly showing leukocyte infiltration, which can be manifested as the infiltration of inflammatory cells such as monocytes, lymphocytes and neutrophils, thereby forming ulcers, multiple microabscesses and tissue necrosis, manifested as necrotic foci of different sizes, with relatively less inflammatory cells inside. Chronic infection is mainly granulomatous lesions and fibrous tissue hyperplasia, which are relatively rare. Besides general inflammatory cell infiltration, nodular granuloma formed by multinucleated giant cells and epithelioid cells can also be found. Hematogenous dissemination type is the diffuse damage to both lungs caused by hyphae and yeast invading blood vessels, which is typically manifested as hemorrhagic nodules composed of necrotic lung tissue and proliferating candida.

7.6.3 Imaging Manifestations 1. Bronchopneumonia type: The lesions mainly involve bronchus and its surrounding tissues, but do not invade lung parenchyma. The lung markings are thickened and blurred, mixed with dotted opacities, which can be accompanied by lymphadenovarix, especially in bilateral lower lungs. 2. Pneumonia type: It is mostly manifested as consolidation of lung lobes and segments, namely single large patchy lesion with blurred edge, uneven density and irregular shape (Fig.  7.6), which are also common in bilateral

Fig. 7.6  Pulmonary candidiasis (I). The patient, a 57-year-old female, with a history of anaphylactoid purpura and impaired glucose tolerance. CT lung window showed multiple small patchy and large patchy consolidation in both lungs, with blurred edge, mainly distributed under pleura and in lower lobe of both lungs, with air bronchogram in consolidation

lower fields (Fig. 7.7). It can also be manifested as small patchy opacities, which can fuse into large patchy opacities. Necrosis, cavities with thick wall can be found in large inflammatory areas. The local thickness of cavity wall is uneven. There are no obvious wall nodules (Fig.  7.8). The lesion can finally develop into lung abscess. In the early stage, it is not accompanied by pulmonary interstitial changes. In the later stage, thickened pulmonary interlobular septa and thickened bronchovascular bundle can be found, sometimes with a small amount of pleural effusion or thickened pleura (Fig. 7.9). 3. Dissemination type: If fungi spread through blood, the manifestations often show miliary and patchy nodular opacities distributed diffusely in both lungs (Fig.  7.10), which are more common in both lower lungs and can involve the whole body. Cotton-shaped opacities are scattered in lung lesions in the early stage, with blurred edges, which can further develop into multiple lung abscesses, mixed by solid nodules, cavity nodules and cystic lesions. The fungal ball is a quasi-round solid mass, parasitic in the cavity, V-shaped or Y-shaped from the hilum to the outside. It may also show “grape cluster” opacities, which can disappear within a few weeks and reappear later. It can also be migratory, accompanied by thickened pleura and a small amount of pleural effusion (Fig.  7.11). In addition, some underlying lesions can be found, such as emphysema, pulmonary arterial hypertension and right ventricular enlargement. CT examinations show that the

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a

Fig. 7.7  Pulmonary candidiasis (II). The same patient as that in Fig. 7.6. (a) Bedside radiographs showed patchy hyperdensities in both lungs, with blurred edges and slightly enhanced lung markings, and the hyperdense area was mainly in the lower field of both lungs; (b) CT

a

Fig. 7.8  Pulmonary candidiasis (III). The same patient as that in Fig. 7.6. (a) CT lung window showed multiple patchy opacities in both lungs with blurred edges; (b) After 10  days of treatment, there were cavity-like changes in the same position, the local thickness of the cav-

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b

lung window showed that the lesion scope of both lungs was further enlarged, and the consolidation was mainly distributed in the lower lobe of both lungs

b

ity wall was uneven, the inner wall was smooth and sharp, with no obvious wall nodule, and the lesions of both lower lungs were significantly absorbed

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Fig. 7.9 Pulmonary candidiasis (IV). The patient, a 32-year-old female, had intermittent fever with cough and expectoration for 1 week. CT mediastinal window showed bilateral thickened pleura locally (arrow)

Fig. 7.10  Pulmonary candidiasis (V). The same patient as that in Fig. 7.9. CT lung window showed multiple small nodular hyperdensities in the upper lobe of the right lung with blurred edges (arrow)

nodules are mostly located on the interlobular septa and pleura, with blurred edges, larger and sparser than those of hematogenous disseminated pulmonary tuberculosis, mostly not involving the apex of the lung. Thin-slice CT scan is recognized as the most sensitive method to detect the early pulmonary changes in immunocompromised patients with acute lung disease [61]. CT scan is a supplement method to detect the lesions not shown on chest radiograph, and can show some characteristic manifestations of lesions, while helping guide biopsy [62]. However, even though thin-slice CT scan may show some findings about candida pneumonia, the information is very limited, which are generally found after transplantation, and most of

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Fig. 7.11  Pulmonary candidiasis (VI). The same patient as that in Fig.  7.9. CT mediastinal window showed a small amount of curved liquid opacities in the right thoracic cavity and slightly enlarged lymph nodes in the anterior mediastinum

Fig. 7.12  Pulmonary candidiasis (VII). The same patient as that in Fig. 7.9. CT lung window showed multiple scattered nodules of different sizes in both lungs, with blurred edges. Lumpy opacities were found in the upper lobe of the left lung, with ground-glass opacities inside, which is the common “reversed halo” sign of pulmonary fungal infection (arrow)

them are solitary lesions. Multiple nodular lesions are still the main CT manifestations of this disease, with a diameter of 3–30 mm and clear edges. Sometimes air inflation sign, “tree-in-bud” sign and surrounding ground-glass opacities (“halo” sign) can be found (Fig. 7.12). Histologically, the dense core of the nodule is a coagulative necrosis area caused by candida, and the “halo” sign ­corresponds to a mixture of edema and hemorrhage around the infarction. Another characteristic CT manifestation is that multiple small bubble signs can be seen in irregular consolidation,

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7.6.5 Differential Diagnosis

Fig. 7.13  Pulmonary candidiasis (VIII). After 1  month of treatment for the patient of Fig.  7.9, the lung window of thin-slice chest CT showed that the slightly dilated distal end of bronchus in the middle lobe of right lung, the thickened wall of bronchus, the lesions absorbed significantly, and the lesions transforming from lobar and segmental consolidation to bronchiolar pneumonia-like changes

and the consolidation area shows bronchopneumonia, alveolar hemorrhage and exudation; cavity-like lesions are rare and usually complicated with other bacterial lesions. Involvement of small airways can lead to inflammation of bronchiolar wall, which is characterized by thickened and dilated bronchiolar wall (Fig.  7.13); Thin-slice CT may show tree bud-like centrilobular nodules, mostly in peripheral zone of lung, showing small “Y” shape and “V” shape. Rare CT findings of candida pneumonia also include pleural effusion [63].

7.6.4 Diagnostic Key Points 1. Cough with mucus sputum or purulent sputum, hemoptysis, shortness of breath, etc. 2. The examination of the oral cavity and pharynx can show the covered punctate white membrane, and dry and moist rales can be heard in the lungs. 3. Chest X-ray radiographs show small patchy or dotted opacities, and some of them can be fused. 4. The same strain of candida in sputum can be cultured for three times or a large number of pseudohyphae or hyphae and spore groups can be found by direct microscopic examination. 5. Cricothyroid membrane puncture suction or fiberoptic bronchoscope can reach respiratory tract secretions, lung tissue, pleural effusion, or take cerebrospinal fluid to culture candida or directly smear to find a large number of spores and pseudohyphae.

Pulmonary candidiasis usually occurs if the body’s resistance is reduced, so the diagnosis should be closely combined with clinical conditions, and attention should be paid to the primary disease and inducement. Because its clinical symptoms and imaging manifestations are nonspecific, it needs to be differentiated from lobular pneumonia and hypersensitivity pneumonia, which is generally not difficult to distinguish according to the medical history. Diffuse miliary lesions need to be differentiated from hematogenous disseminated pulmonary tuberculosis. The former nodules are thicker and sparse than the latter, and rarely involve the apex of the lung. Because hormones have nonspecific inhibitory effect on inflammation, symptoms can be improved after using hormones, but the lesions are not absorbed on imaging, and may continue to develop.

7.6.6 Research Status and Progress Currently, the diagnosis of pulmonary candidiasis in clinical laboratories depends on fungal culture, but the culture or molecular test of respiratory specimens cannot distinguish the sources of the disease (pollution, colonization and invasive diseases). Culture-independent techniques have made progress in identifying other respiratory pathogens, but fungal culture is still the “gold standard” for candida identification, which has the disadvantages of lack of sensitivity and long growth duration of fungi. Studies of respiratory specimens included prior exposure to antimicrobial therapy and technical factors such as sample size, medium used, culture duration and temperature. Another method is to observe bronchoalveolar lavage fluid directly by microscope, which is more sensitive than fungal culture. However, its clinical application is limited because it needs professional knowledge to explain and has little difference among fungi with similar morphology. The 1,3-β-D-glucan assay, which detects soluble fungal wall components released during fungal growth and division, has been proved to be useful as a screening test for invasive fungal infections in blood, but its effectiveness in bronchoalveolar lavage fluid has not been demonstrated. However, the 1,3-β-Dglucan assay cannot distinguish candida from other fungi, which limits its clinical diagnostic efficacy [64–66]. In addition, studies have proved that latex agglutination can be used to detect candida antigen in bronchoalveolar lavage fluid, and PCR technology can be used to analyze and identify candida isolates with mixed infection [67]. Having been proven by enough researches, these methods can be used in clinical practice.

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8

Parasitic Infections Jianghong Chen

8.1 Pulmonary Schistosoma Jianghong Chen Schistosoma which is harmful to human health mainly includes Schistosoma japonicum, Schistosoma mansoni, and Schistosoma haematobium, of which Schistosoma japonicum is the main epidemic species in China, with the main epidemic areas in Hunan, Hubei, Jiangxi, Anhui, Sichuan, Yunnan, and other provinces, which are the main habitats where the intermediate host Oncomelania lives.

8.1.1 Overview Patients infected with schistosomiasis are the main source of infection, and their feces containing live eggs are discharged into water, which is an important link in the transmission of schistosomiasis. Cattle, sheep, horses, pigs, and other domestic animals infected with schistosomiasis are also the main sources of infection. After people or animals being infected with schistosomiasis discharge feces containing eggs into water, the eggs hatch into miracidia in water. Miracidia infect the intermediate host Oncomelania snails, grow, and multiply in their bodies and finally develop into cercariae, which enter the water again. If people come into contact with contaminated water, cercariae quickly attach to human skin and quickly shed their tails and invade the body through the skin to become schistosomula. Another route of infection is that people drink water containing cercariae, which can enter the human body through oral mucosa. After infection, most patients have occult onset without obvious symptoms and the most common respiratory symptoms are cough, expectoration, and fever. The symptoms such as night fever, dry cough, shortness of breath, myalgia, J. Chen (*) Beijing Friendship Hospital, Capital Medical University, Beijing, China

headache, and abdominal tenderness occur after primary infection or 14–84  days after severe reinfection, which is called Katayama syndrome [1].

8.1.2 Pathological Manifestations Cercariae become schistosomula, enter the human body, and flow back into pulmonary capillaries through vein. Schistosomula enter the systemic circulation through the pulmonary circulation, partially enter the mesenteric vein, enter the portal vein branch in liver with blood flow, and develop into adults to lay eggs after maturity. The eggs are deposited in intestinal tract and liver, often causing inflammation of colon and rectum and schistosomiasis cirrhosis. Therefore, inflammatory lesions caused by eggs are the main reason of body damage, and the resulted egg granuloma and fibrosis are the most important pathological changes, while the damage caused by schistosomiasis in other developmental stages is relatively minor. Ectopic damage caused by schistosomiasis mainly involves lung and brain. When migrating along the blood flow, schistosomula can cause organ damage. Lung lesions are obvious, which can penetrate the capillaries of alveolar wall and involve lung tissue. Hemorrhage, leukocyte, and eosinophil infiltration can be found locally, and then patients will have clinical symptoms such as cough and fever, which are related to allergic reactions caused by metabolites or disintegrating products of schistosomiasis. Laboratory examinations show the increased total number of leukocytes and eosinophil count. There are also a small number of schistosomula staying in the pulmonary veins and develop into adults and lay eggs there. A large number of eosinophils and a small number of leukocytes will gather around the eggs, forming eosinophilic granuloma. Adults in portal vein lay eggs into blood, which can reach the lungs and cause the manifestations of miliary nodules, namely eosinophilic egg nodules. Eventually, eggs rupture or calcify, surrounded by

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tuberculosis-­like nodules of lymphocytes and macrophages, which are called “pseudo-tuberculosis nodules”, and such nodules will be gradually absorbed or develop into fibrosis. After several years of persistent infection in human body, eggs can block small pulmonary artery branches and cause pulmonary arterial hypertension changes, which is an important pulmonary manifestation.

8.1.3 Imaging Manifestations 1. X-ray: The more severe the infection of schistosomiasis in patients, the more likely they are to have pulmonary symptoms and related imaging manifestations. The pulmonary lesions in the early stage of acute infection are mainly caused by mechanical injury caused by cercariae passing through lung tissue and allergic reaction caused by metabolites. Most patients’ chest radiographs only show increased and thickened lung markings, while a small number of patients show patchy opacities in different scopes, mainly in bilateral lower lungs, which can be manifested as transient and migratory lesions. Large patchy consolidation lesions may be caused by secondary infection, which is difficult to distinguish from ordinary lung infection and easy to be misdiagnosed. In addition, nodular opacities with blurred edges can be found. Nodules are common manifestations in chronic stage. In addition, pulmonary arterial hypertension is characterized by distension of pulmonary artery segment, “residual root” changes of pulmonary artery in hilum, and even cardiac enlargement. 2. CT: In the acute phase, patchy consolidation and ground-­ glass opacity foci can be found mainly under the pleura. The ground-glass opacity foci may be located around the

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consolidation to form the “halo” sign, or the consolidation foci may be located around the ground-glass opacity foci to form the “reversed halo” sign. In the acute stage, eggs enter lung tissue along blood flow to form miliary nodules (Fig. 8.1). CT can show the distribution, shape, and density of nodules more clearly, which is similar to the manifestations of hematogenous disseminated pulmonary tuberculosis and viral infection [2]. In the subacute stage, due to the deposition of immune complexes around eggs and the infiltration of eosinophils, multiple large nodules can be formed with “halo” sign [3]. In the chronic stage, nodules are typical manifestations, with high density in the center of nodules surrounded by “halo” sign formed by ground glass-like opacity lesions. Pathological results suggest tissue necrosis and fibrous tissue hyperplasia [4]. Long-term large amount of eggs can block small pulmonary arteries, resulting in vascular injury, pulmonary arterial hypertension, and thickened pulmonary arteries [5].

8.1.4 Diagnostic Key Points 1. Epidemiological history and contact history with contaminated water. 2. Pulmonary lesions are often atypical. In the acute stage, patchy consolidation and ground-glass opacity foci distributed under pleura are the main manifestations. In acute and chronic stages, multiple nodules with “halo” sign are the main manifestations. Long-term infection causes pulmonary arterial hypertension. 3. Diagnosis should be confirmed in combination with laboratory examination. Feces examination by hatching, egg

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Fig. 8.1  Pulmonary schistosomiasis. (a, b) CT lung window showed random distribution of small nodules in both lungs with blurred edges

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examination, and microscopic examination of rectal mucosa often show positive results. If eggs or hatched miracidia are found in feces examination, it suggests that there are live adult parasitic in the body. However, due to intestinal wall fibrosis in chronic or advanced stages, eggs cannot be easily discharged from intestinal wall, so the positive rate of patients is very low. In such case, rectoscopy should be performed for mucosal biopsy. There are false positives and false negatives in immunological methods, which may have cross reaction with other trematodiasis. Combined detection of circulating antigen, IgG antibody and egg antibody of schistosomiasis can improve the sensitivity and specificity of diagnosis.

8.1.5 Differential Diagnosis 1. Hematogenous disseminated pulmonary tuberculosis: Patients often have a history of underlying diseases with impaired immunity. Clinically, there are symptoms of tuberculosis infection poisoning such as low fever, night sweat, and fatigue. The nodules of acute hematogenous disseminated pulmonary tuberculosis are typically uniform in size, distribution, and density, while the lesions of subacute and chronic hematogenous disseminated pulmonary tuberculosis are more common and larger in the upper lung field, generally with clear nodule edges. The inflammatory exudation of nodules formed by schistosomiasis eggs entering the lung is blurred. 2. Hematogenous metastases: Patients often have a history of malignant tumors, and nodules are more common in the peripheral zone of lower lungs, with different sizes and clear edges. 3. Hematogenous lung abscess: Patients have obvious infection symptoms such as high fever and chills. Blood routine examination shows the significant increase of the total number of leukocytes and the proportion of neutrophils. In the early stage, multiple patchy consolidations are distributed in the inner and outer peripheral zones of lung, followed by the occurrence of multiple cavities and gas–liquid planes.

8.2 Paragonimus Jianghong Chen Paragonimus is mainly distributed in Asia, Africa, and South America. In China, it is mainly distributed in in southwest region. There are mainly two species of paragonimus: paragonimus westermani and paragonimus skrjabini in China. Paragonimus infection in human body is usually caused by eating raw or uncooked freshwater crabs and crayfish con-

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taining metacercaria. WHO ranks more than 20 kinds of parasites causing food-borne infections, and Paragonimus ranks 14th [6], which is significantly harmful to human body.

8.2.1 Overview The disease goes through acute stage and chronic stage. In the acute stage, metacercaria enter the body and become schistosomula migrating in the body, which often causes fever, abdominal pain, diarrhea, and other manifestations. In the chronic stage, the paragonimus invades the lungs, which is mainly characterized by cough, hemoptysis, and other symptoms. If other organs are involved, related symptoms will occur. Sometimes, the manifestation is occult infection, and only eosinophils are increased clinically. Pulmonary infection with paragonimus westermani is easy to cause multiple serous effusions, which is manifested as pleural effusion and pericardial effusion, and is easy to be misdiagnosed as tuberculosis infection. Once it is diagnosed as moderate to large amount of pericardial effusion caused by parasites, surgical treatment is required [7]. According to different affected sites, paragonimiasis may be thoracopulmonary type, abdominal type, cerebrospinal type, cutaneous type, and mixed type [8]. 1. Thoracopulmonary type: Paragonimus invades the lungs, which can cause cough, expectoration, chest pain, and other symptoms. Pleural and pericardial inflammation causes pleural effusion and pericardial effusion. 2. Abdominal type: Paragonimus can cause abdominal pain, diarrhea, indigestion, and other symptoms in the process of abdominal migration. It can also invade the liver and peritoneum to cause ascites. 3. Cerebrospinal type: It can cause headache, dizziness, convulsion, disturbance of consciousness, and other symptoms. Spinal cord invasion can cause sensory and motor disorders and even paralysis, which is the most harmful extrapulmonary manifestation. 4. Cutaneous type: Migratory masses occur under the skin of chest, back, waist, and limbs, mostly without redness and tenderness in local areas. Laboratory examination: Blood routine examination shows the increased total number of leukocytes, the increased proportion, and absolute value of eosinophils, but not specific for diagnosis. The increased eosinophils can also be found in other allergic immune diseases. If there is serous cavity effusion, effusion examination can show the increased eosinophils and decreased glucose. Immunological examination includes antigen detection and antibody detection. Direct detection of specific antigen can confirm paragonimus infection. Antibody detection

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includes paragonimus antigen intradermal test and postcercariae membrane reaction, all of which have good sensitivity and specificity. Enzyme-linked immunosorbent assay (ELISA) has been used to diagnose paragonimiasis in China since the early 1980s, and the positive rate can reach 100%. Compared with ELISA, dot immune filtration assay (DIGFA) is more suitable for clinical detection and its advantages include simple equipment requirements, easy operation, and rapid detection [8].

8.2.2 Pathological Manifestations The eggs of paragonimus develop into miracidia in water which invades the first intermediate host. Oncomelania snails are the first intermediate host and miracidia develops into cercaria in their bodies. Cercariae enter the water and invade the second intermediate host, mostly freshwater crabs and crayfish, forming metacercariae. When people eat raw or undercooked freshwater crabs and crayfish, they are infected with paragonimus. Metacercariae dissolve in human intestine, while schistosomulae penetrate intestinal wall into abdominal cavity, chest cavity, lung, skin, and even brain, causing local inflammatory reaction or hemorrhage, and other different clinical symptoms. Paragonimus skrjabini mainly invades extrapulmonary tissues, while Paragonimus westermani mainly invades lung tissues.

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Fig. 8.2  Paragonimiasis. (a) CT lung window showed irregular subpleural nodules in the posterior segment of the upper apex of the left lung, with gas-filled translucent area inside. Pleural effusion occurred

J. Chen

8.2.3 Imaging Manifestations 1. X-ray: It is difficult to show the imaging features of paragonimus on chest X-ray radiograph, which is manifested as patchy consolidation, ground-glass opacity foci, cystic foci, cavities, or characterized by nonspecific manifestations such as pleural effusion, pneumothorax, pericardial effusion, and localized diaphragm eminence, so it is difficult to be diagnosed and often misdiagnosed as other inflammatory lesions. 2. CT: Chest CT can accurately evaluate the shape, density, and scope of lesions. CT manifestations depend on the stage of infection. In the migratory stage of schistosomulae, local manifestations are inflammation, hemorrhage, patchy consolidation, ground-glass opacity foci, pleural effusion, etc., which are difficult to distinguish from those of ordinary inflammation and sometimes show stripe-like consolidation extending from subpleural site to the lung, suggesting the migratory track of schistosomulae. Cystic foci, nodules, cavities, etc. can be formed in the later stage, and sometimes “halo” signs occur around the nodules, which is related to hemorrhage. When migrating in lung tissue, paragonimus can cause mechanical damage to lung tissue. The death and absorption of paragonimus lead to the formation of typical “tunnel” sign, manifested as stripe-like lucency shadows in patchy consolidation lesions, which is an important imaging manifestation for the diagnosis of paragonimiasis (Fig. 8.2) [9]. About 30%

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in the left side and (b) translucent area was in the upper part of the left lobe, showing typical “tunnel” sign

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of patients has pleural effusion or hydropneumothorax, and some patients also have multiple serous cavity effusions such as ascites and pericardial effusion. The pleura can be thickened and calcified [10]. Hilar or mediastinal lymphadenectasis occur in 10% of patients.

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losus and Echinococcus multilocularis in the genus Echinococcus of Taenia. China is one of the countries with high incidence of echinococcosis, mainly cystic echinococcosis.

8.3.1 Overview 8.2.4 Diagnostic Key Points

Echinococcosis mainly occurs in Xinjiang, Qinghai, Gansu, 1. Epidemiological history includes eating raw freshwater Ningxia, Tibet, Inner Mongolia, and other places where animal husbandry is relatively developed in China. The lesions crabs, crayfish, etc. 2. Laboratory tests can show positive paragonimus antigen mainly involve the liver. 65–80% of CE occur in the liver, and 98% of AE occurs in the liver, followed by lung and and antibody. bone [11]. 3. CT shows typical “tunnel” sign. Clinical symptoms depend on the parasitic site, the size of lesions, and the presence or absence of complications. Sometimes it can be parasitic on human body for several 8.2.5 Differential Diagnosis years or more than 10 years without obvious symptoms. If If the imaging manifestations of paragonimiasis have no the hydatid cyst grows rapidly in lung tissue and becomes typical “tunnel” sign, it is difficult to diagnose the disease larger, it produces compression symptoms and may cause only from the imaging manifestations. The patient’s history dry cough, hemoptysis and other symptoms. Laboratory tests include enzyme-linked immunosorbent of eating raw freshwater crabs and crayfish, and the increased assay (ELISA), indirect haemagglutination test (IHA), rapid blood eosinophil in laboratory examination, suggests the ELISA using PVC film, Western blot (WB), and other immupossibility of paragonimus infection. nological tests. If specific antibodies or circulating antigens 1. Community-acquired pneumonia: Bacterial infection is or immune complexes related to echinococcosis are found, more common, and the typical consolidation is distrib- the diagnosis can be confirmed. Among them, ELISA is senuted according to anatomical structures such as lung sitive and the most commonly used. Echinococcus cyst wall, lobes and segments, rather than subpleural stripe-like ascus, protoscolex, or cephalic hooklet found in surgical consolidation manifested in paragonimiasis. The anti-­ biopsy materials, excised lesions, or effluents can be used for infective treatment generally has good effect, with less etiological diagnosis [12]. amount of serous effusion than that of parasitic diseases. 2. Pulmonary tuberculosis: The typical onset sites are the posterior segment of upper lobe apex and the dorsal seg- 8.3.2 Pathological Manifestations ment of lower lobe, which are characterized by polymorphic lesions, such as consolidation, nodule, stripe-like Echinococcosis is mainly transmitted through fecal-oral opacities, “tree-in-bud” sign, cavity, etc. There are clini- route. The intermediate hosts are human and ungulates (cattle, horses, pigs, sheep, etc.), and the final hosts are canines cal symptoms of tuberculosis infection and poisoning. 3. Bronchiectasis: If paragonimiasis shows “tunnel” sign, it and felines. The final hosts discharge echinococcus eggs, should be distinguished from bronchiectasis which often which pollute the soil, water source, grassland, etc., while involves multiple branches and occurs in its route site, the intermediate hosts are infected by the eggs. Echinococcus accompanied by pulmonary artery. However, the “tunnel” eggs enter the duodenum of the intermediate hosts, and under sign of paragonimiasis is generally solitary in non-­ the action of digestive juice, the oncospheres emerge from the eggs, then penetrate into the intestinal wall, and enter the bronchus anatomical site and route site. portal vein system along blood circulation. Most larvae develop into echinococci in the liver, and only a few reaches the lungs or reaches other organs through systemic circula8.3 Pulmonary Echinococcus tion to develop into echinococci. Jianghong Chen Echinococcosis, also known as hydatid disease, is a zoonotic parasitic disease caused by Echinococcus larvae parasitizing human body. Cystic echinococcosis (CE) and alveolar echinococcosis (AE) are the main parasite diseases in human body, which are caused by Echinococcus granu-

8.3.3 Imaging Manifestations The imaging manifestations of echinococcosis mainly depend on the solid matter, vesicles, and calcification degree of nodules or cysts [13].

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Fig. 8.3  Pulmonary echinococcosis (I). (a) CT lung window showed huge spherical lesions in the right lung with clear, smooth and regular edges; (b) the mediastinal window showed that the liquid density in the cyst was uniform, the thickness of the cyst wall was uniform and regu-

lar, and the surrounding lung tissue was compressed; and (c and d) enhanced scan showed arterial phase and venous phase had no enhancement of lesions (case images by courtesy of Wenya Liu and Tieliang Zhang of the First Affiliated Hospital of Xinjiang Medical University)

1. X-ray: In the diagnosis of simple pulmonary echinococcosis, the lesions can be clearly displayed, usually manifested as single or multiple round and quasi-round opacities in the lungs, with clear and smooth edges. The lesions vary in size, with diameters ranging from several centimeters to more than 10  cm [14]. If the cyst ruptures and connects with bronchus, gas entering the cyst can form a crescentshaped translucent area. Combined with clinical epidemiology, a more definite diagnosis can be made, but cyst rupture or complication with other diseases brings some difficulties to diagnosis, and the diagnosis cannot be easily made only by chest X-ray radiograph. 2. CT: It has obvious advantages in diagnosing pulmonary echinococcosis. Common manifestations include single or multiple cystic lesions in the lung. Single cyst is common, with smooth cyst wall, mostly located in the outer zone of the middle and lower lungs. The lesions vary in size, ranging from small sacs about 1  cm to large sacs

over 10 cm (Fig. 8.3), which are easy to adhere to pleura. The external capsule of hydatid cyst is a fibrous capsule formed by the reaction of adjacent lung tissue to hydatid cyst, and the internal capsule is the inherent cyst wall of hydatid cyst. The germinal layer of the internal capsule can give birth to small spores and gradually grow into ascus, so CT shows that there is ascus in the cyst, which is a specific change (Fig.  8.4), but such manifestation only accounts for about 10%, which is significantly lower than the probability of ascus in hepatic hydatid. The large cyst contains more asci, forming the manifestation of “mulberry” or “honeycomb”. If the external capsule ruptures and connects with bronchus, gas enters between the internal and external capsules, forming a “crescent” sign. The internal and external capsules rupture, the contents of the cyst are partially discharged, and the air enters the internal and external capsules at the same time. There is a gas–liquid plane,

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Fig. 8.4  Pulmonary Echinococcosis (II). (a) CT lung window showed spherical lesions in the right upper lung with smooth and clear edges; (b) the mediastinal window showed multiple cysts of different sizes in the cystic lesions of the upper lobe of the right lung, and the cystic walls

were uniform and smooth; and (c) enhanced scan showed no obvious enhancement of lesions (case images by courtesy of Wenya Liu and Tieliang Zhang of the First Affiliated Hospital of Xinjiang Medical University)

with two layers of arc-shaped translucent bands above, forming a “double bow” sign. If both the internal and external capsules rupture, after the contents are discharged, the internal capsule collapses and floats on the liquid surface, thereby forming a diagnostic “ribbon” sign or “floating lotus” sign (Fig. 8.5). The surrounding area may be accompanied by signs of bronchial vascular compression and displacement, and pleural effusion can be found if the cyst ruptures and connects with the thorax [15–17]. After infection, hydatid cysts often lose sharp edges, manifested as vague, irregular or spinous protuberance, with uneven density in the cyst. CT findings are similar to those of Lung abscess.

8.3.4 Diagnostic Key Points 1. Epidemiological history includes previous living in the epidemic area and contact with dogs, sheep, and other animals. 2. Imaging manifestations include cystic masses in the lung, manifested as typical signs such as ascus in the cyst, “ribbon” sign, and “crescent” sign. 3. Immunological examination can detect specific antibodies or circulating antigens or immune complexes associated with echinococcosis or obtain etiological diagnosis results.

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Fig. 8.5  Pulmonary Echinococcosis (III). (a) CT lung window showed the increased density of the lower lobe of the right lung, with a gas–liquid plane inside; (b) the mediastinal window showed cystic opacity foci in the lower lobe of the right lung, with irregular stripe-like hyperdensities in cystic fluid, and patchy solid lung tissue was found around the

cystic opacity foci; and (c) enhanced scan showed no obvious enhancement of cyst wall and stripe-like hyperdensities in cyst fluid (case images by courtesy of Wenya Liu and Tieliang Zhang of the First Affiliated Hospital of Xinjiang Medical University)

8.3.5 Differential Diagnosis

bronchus, surrounded by “satellite foci” or bronchial disseminated lesions manifested as “tree-in-bud” sign. 3. Cancerous cavity: The outer edge of the cavity is clear, with typical manifestations such as lobulation sign and pleural depression sign. The inner wall is uneven, with wall nodules. If there are enlarged lymph nodes in the ipsilateral hilum and mediastinum, it is more helpful for diagnosis.

1. Lung abscess: The clinical symptoms of patients are significant, such as high fever and chills. Blood routine examination shows the significantly increased total number of leukocytes. The outer wall of acute lung abscess cavity is blurred with exudate, and the inner wall is smooth with a gas–liquid plane. In chronic lung abscess, the outer edge of the cave wall is relatively clear, with irregular shape. However, obvious “lobulation” sign is rare, and the inner wall is relatively smooth. 2. Pulmonary tuberculosis cavity: The lesions are generally located in the posterior segment of the upper apex and the dorsal segment of the lower lobe, where tuberculosis is common. Thick-walled or thin-walled cavities can be found, but the gas–liquid plane is rare. There is drainage

8.3.6 Research Status and Progress 1. MRI: The external capsule of hydatid was a layer of fibrous connective tissue, which is manifested as continuous, uniform, and smooth circular hypointense signal on T1WI and T2WI, and enhanced scan shows

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delayed enhancement. Its good resolution of tissue structure is helpful for displaying cyst wall and ascus, judging the nature of cyst fluid and confirming the changes after infection, by which MRI is superior to CT. In addition, MRI can accurately judge the relationship between the lesion and the surrounding large blood vessels and the heart, thereby providing reliable help for the operation. 2. PET/CT: The advantage is to show the metabolic activity of lesions. It is mainly for the study of hepatic hydatid lesions. PET/CT shows the uptake of lesions and the active lesion areas at the edge, thereby reflecting the development trend of lesions, which is of great value in judging whether there is infiltration. PET/CT can also be used to follow up and observe the response of lesions to drug therapy [18]. PET/CT has obvious diagnostic value for the diagnosis of hydatid infection with multiple organ involvement.

8.4 Pneumocystis Jianghong Chen

8.4.1 Overview Taenia solium is a common zoonotic disease in China, which often involves subcutaneous, muscle, and brain tissues, while lung infection is rare. Parasitic on the small intestine, taenia solium absorbs nutrients ingested by human body and continuously releases metabolites, mainly causing digestive system symptoms such as abdominal pain and diarrhea. Cysticercus is the larva of taenia solium, which can cause different clinical symptoms in terms of parasitic site, larva number, survival, and body reaction. Parasitic in the brain can cause cerebral cysticercosis, manifested as epilepsy, intracranial hypertension, and other symptoms. Parasitic in the lung can cause pulmonary cysticercosis, mainly manifested as respiratory symptoms such as cough and expectoration or insignificant symptoms. Laboratory examination includes checking eggs and gravid proglottid in feces. Subcutaneous nodule biopsy can be performed for subcutaneous muscular cysticercosis, ophthalmoscopy can be performed for ocular cysticercosis, and typical imaging manifestations and serological examinations can be performed for cerebral cysticercosis, such as enzyme immunotransfer blotting (EITB), with the specificity of 100% in detecting serum antibodies to taenia solium.

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8.4.2 Pathological Manifestations People can be infected by eating raw or half-cooked pork containing cysticercus cellulosae. Cysticercus enters the intestinal tract and extends scolex to be attached on the intestinal wall under the action of digestive juice, causing intestinal wall damage. Cysticercus gradually develops on the intestinal wall, growing somite, developing into adults. Cysticercus can parasitize human body for several years or decades, constantly expelling gravid proglottid, and becoming the main source of infection. After people have accidentally taken in taenia solium eggs or gravid proglottid, oncospheres emerge from the eggs in duodenum and penetrate into intestinal wall, enter blood circulation, and reach all parts of the body, forming cysticercus. If it stays in the lungs, pneumocystis will occur. Therefore, humans are not only the final hosts of taenia solium but also the intermediate hosts.

8.4.3 Imaging Manifestations The microcirculation in the subpleural area of the outer zone of the middle and lower lungs is relatively abundant and the blood flow is slow, which is beneficial to the retention of oncospheres, and local inflammatory reaction may occur, which will cause nonspecific inflammatory lesions or pleural effusion [19, 20]. These signs are not characteristic, and diagnosis cannot be easily confirmed only by lung imaging. If oncospheres stays in lung tissue and develop into cysticercus, it can stimulate the surrounding tissues to form fiber wrapping and eosinophil infiltration, manifested as circular foci with low central density and smooth edge. When calcification occurs in the scolex of cysticercus, small calcification points can be found in the small nodules [21], which is suggestive. Tuberculous granulation tissue can be formed around the necrotic tissue of cysticercus, followed by fibrous tissue hyperplasia, hyalinosis, and eosinophil infiltration, showing small nodules with uniform density and smooth edge. If cysticercosis occurs in other parts, especially intracranial or subcutaneous sites, pulmonary involvement should be considered.

8.4.4 Diagnostic Key Points 1. Epidemiological history includes eating raw or half-­ cooked pork. 2. Imaging examinations show diagnostic value if there are small central translucent nodules or calcified nodules in the lungs, and if there are cysticercosis infection lesions

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in subcutaneous site, muscle, or brain, it is more suggestive of the diagnosis of cysticercosis. 3. Laboratory serum tests show positive results of antibodies to taenia solium.

8.4.5 Differential Diagnosis 1. Hematogenous disseminated pulmonary tuberculosis: Patients have clinical symptoms of tuberculosis infection and poisoning such as low fever, night sweat, and fatigue. Subacute and chronic disseminated lesions are mainly distributed in the upper lung, while nodules in acute disseminated lesions show “three uniform” manifestations. Sometimes, cavities and other polymorphic lesions can be found in the posterior segment of upper lung apex or the dorsal segment of lower lung lobe where pulmonary tuberculosis is prone to occur. 2. Metastases: Patients generally have a history of tumor, and nodules are randomly distributed and vary in size, which are more common in the lower lungs, and punctate calcification in nodules is rare.

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J. Chen 5. Papamatheakis DG, Mocumbi AO, Kim NH, et al. Schistosomiasis-­ associated pulmonary hypertension. Pulm Circ. 2014;4(4):596–611. 6. Robertson LJ, van der Giessen JWB, Batz MB, et al. Have foodborne parasites finally become a global concern? Trends Parasitol. 2013;29(3):101–3. 7. Hu Y, Zhan X. Diagnosis and treatment progress of paragonimiasis. Chin J Clinicians (Electronic Edition). 2017;11(5):849–54. 8. Seon HJ, Kim YI, Lee JH, et al. Differential chest computed tomography findings of pulmonary parasite infestation between the paragonimiasis and nonparagonimiatic parasite infection. J Comput Assist Tomogr. 2015;39(6):956–61. 9. Sheng L, Kong X, Deng Y, et al. Clinical and imaging features of thirty cases of paragonimiasis westermani. Chin J Schist Cont. 2019;31(2):200–3. 10. Wu YH, Zhou YH, Jin X, et al. Diagnosis and surgical managenment of pericardial effusion due to paragonimiasis. Int Infect Dis. 2019;83:102–8. 11. Li D, Zhang L, Zhang Z, et al. Expert consensus of standard diagnosis and treatment technology on pulmonary echinococcosis. Chin J Clin Thorac Cardiovasc Surg. 2015;22(9):799–802. 12. National Committee on Standards for Endemic and Parasitic Diseases. Diagnostic criteria for echinococcosis (WS 257-2006). J Trop Dis Parasit. 2018;16(1):56–61. 13. Chu H, Wang Z, Zhang W. Clinical and pathological analysis of 668 cases of hydatid disease. J Xinjiang Med Univ. 2015;38(1):73–6. 14. Song Y.  Analysis of X-ray signs of pulmonary echinococcosis. World Health Digest. 2013;23:161–2. 15. Cao Y, Xiao J, He Y. Progress in imaging diagnosis of echinococcosis. J Pract Radiol. 2018;34(9):4. 16. Guan J, Jiang S, Zhu Z, et al. A case of ascus-type pulmonary echinococcosis. Chin J Tubercul Resp Dis. 2015;38(8):635–6. 17. Sun X. CT features of body echinococcosis at plateau of Qingbai. J Pract Radiol. 2008;24(8):1059–61. 18. Bulakçl M, Kartal MG, Yilmaz S, et al. Multimodality imaging in diagnosis and management of alveolar echinococcosis: an update. Diagn Interv Radiol. 2016;22(3):247–56. 19. Chen YF, Wang PL, Ding LR. Two cases of pulmonary cysticercosis manifesting as pleural effusion: case report and literature review. J Thorac Dis. 2017;9(8):E677–81. 20. Gupta N, Meena M, Harish S, et al. A rare case of pulmonary cysticercosis manifesting as lung cavity with pleural effusion. Lung India. 2015;32(5):515–7. 21. Pei Y, Deng D, Long L, et al. X-ray findings of pneumocystis disease. Chin J Radiol. 2002;36(5):468–9.

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Mycoplasma Pneumonia Bailu Liu, Zhehao Lyu, and Meiling Xu

9.1 Overview Mycoplasma pneumonia (MP) is an acute respiratory infection with pneumonia caused by mycoplasma pneumoniae, which can cause epidemic, accounting for about 10% of all pneumonia, and can also lead to death in severe cases. Mycoplasma pneumoniae can be found in respiratory secretions from 2 to 3 days before onset until several weeks after recovery. It grows between ciliated epithelium through contact infection and does not invade lung parenchyma. There are neuraminic acid receptors on its cell membrane, which can be attached to the surface of respiratory epithelial cells of the host, inhibit cilium activity, destroy epithelial cells, and produce hydrogen peroxide to further cause local tissue injury. Its pathogenicity may be related to the allergic reaction of patients to the pathogen or its metabolites. Humoral immunity can be caused after infection, and antibodies exist in serum of most adults, which leads to less incidence of disease. The incubation period of this disease lasts for 2–3 weeks, the onset of the disease is slow, and about 1/3 cases are asymptomatic. The disease is manifested as tracheobronchitis, pneumonia, and tympanitis. Pneumonia is the most serious disease. At the beginning of the disease, symptoms include fatigue, headache, sore throat, chills, fever, muscle soreness, loss of appetite, nausea, vomiting, and significant headache. The degree of fever varies and may be up to 39 °C. After 2–3 days, obvious respiratory symptoms occur, such as paroxysmal irritating cough, with a small amount of sticky sputum or mucopurulent sputum, sometimes with blood in sputum. Fever can last for 2–3  weeks. After the

body temperature returns to normal, there may still be cough with substernal pain, but no chest pain. The total number of leukocytes in patients with mycoplasma pneumonia is mostly in the normal range and occasionally increased. Neutrophils or eosinophils in leukocytes are slightly increased. Direct antiglobulin test may be positive, and erythrocyte sedimentation rate may increase in the early stage of the disease. Complement fixation test is a widely used serological diagnostic method for diagnosing mycoplasma pneumoniae infection. Indirect hemagglutination test mainly detects IgM antibodies. Enzyme-linked immunosorbent assay (ELISA) is used to detect IgM and IgG antibodies. This method is sensitive, specific, rapid, and economical, as a practical and reliable means to diagnose mycoplasma pneumoniae infection. ELISA kits are now available for sale. Cold agglutination test is a nonspecific test for diagnosing mycoplasma pneumoniae infection. Polymerase chain reaction (PCR) can examine clinical specimens of mycoplasma pneumoniae infection.

9.2 Pathological Manifestations Mycoplasma pneumonia is manifested as patchy or confluent bronchopneumonia or interstitial pneumonia with acute bronchitis. Alveoli may contain a small amount of exudate, sometimes accompanied by focal atelectasis, lung consolidation, and emphysema. Neutrophils and macromonocyte infiltration occurs in the alveolar wall and septum. Bronchial mucosal cells may have necrosis and exfoliation, with neutrophil infiltration. There may be fibrin exudation and a small amount of exudate in the pleura.

B. Liu (*) · M. Xu The 2nd Affiliated Hospital of Harbin Medical University, Harbin, China

9.3 Imaging Manifestations

Z. Lyu The First Affiliated Hospital of Harbin Medical University, Harbin, China

Without specificity, the imaging manifestations of mycoplasma pneumonia may be normal.

© Science Press 2023 H. Li et al. (eds.), Radiology of Infectious and Inflammatory Diseases - Volume 3, https://doi.org/10.1007/978-981-99-4614-3_9

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1. Segmental or lobar consolidation: The lesions can be mainly distributed in lobes or segments, manifested as large patchy consolidation. The density is high or uneven, and most are unilateral lesions, in more right lung than left lung, and more common in lower lobe than in upper lobe. The lesions are the most common in the lower lobe of right lung. 2. Small patchy or fan-shaped infiltration opacities: The lesions are mainly distributed in pulmonary lobules, manifested as bronchitis, which mostly occurs in the lower fields of both lungs, extending in a fan-shaped or radially outward from the hilum of the lung. The lesions can be manifested as patchy opacities of different sizes in the paracardiac area, with uneven density and blurred edges (Fig.  9.1). HRCT is more likely to detect centrilobular

Fig. 9.1  Mycoplasma pneumonia (I). The patient, a 6-year-old female. CT lung window showed multiple patchy opacities and small nodules in both lungs with blurred edges

a

B. Liu et al.

involvement and interstitial changes. As an interstitial pneumonia, mycoplasma pneumonia is pathologically manifested as mycoplasmas gathering on the surface of respiratory epithelium, destroying tracheal and bronchial epithelial cells, causing edema, ulcer of bronchial wall, interstitial congestion, edema and multinucleated cell infiltration around bronchus and blood vessels, and leading to bronchitis and interstitial pneumonia. In most cases, chest CT can show typical interstitial manifestations but simple interstitial manifestation is rare, and often exists together with lung parenchymal changes. 3. Perihilar localized interstitial inflammation: Perihilar interstitial infiltration and lymphadenovarix. Unilateral cases are more common than bilateral cases, manifested as enlarged hilar shadow with unclear structure, and the absorption time of lesions is more than 2–3 weeks. 4. Lung interstitial infiltration changes: The lesions are mostly distributed in the lower lung field, showing thickened and increased lung markings, reduced transparency of local lung field, blurred lung field, showing reticular and nodular opacities. 5. Atelectasis: It may occur during the absorption of large patchy opacity lesions. 6. Pleural effusion: The incidence is low, mostly with a small amount, distributed in the costophrenic angle area. The CT observation may need lateral horizontal projection. 7. Mycoplasma pneumonia in children: The lesion types include ground-glass opacities, reticular nodule opacities (Fig. 9.2), and consolidation. The main pathological features include air bronchogram, thickened bronchial wall, lymphadenovarix, and pleural changes. Children younger than 3  years old tend to have lesions in double lobes, while children older than 4 years old mostly have lesions confined to single lobe, and lesions are slightly more common in lower lobe than the upper lobe [1].

b

Fig. 9.2  Mycoplasma pneumonia (II). The patient, a 3-year-old male. (a and b) CT lung window showed multiple reticular nodular opacities in both lungs with blurred edges and partial consolidation in the middle lobe of the right lung

9  Mycoplasma Pneumonia

9.4 Diagnostic Key Points Imaging manifestations include large patchy consolidation, small patchy opacities, or fan-shaped infiltration opacities. Pulmonary interstitial changes can also be found. 1. Laboratory examination shows the normal or slightly increased total number of leukocytes, the increased erythrocyte sedimentation rate, and positive Coombs test. 2. The titers of serum lectin (IgM type) mostly increase to 1:32 or higher. The more severe the disease, the higher the positive rate. 3. Serum-specific antibody determination has a diagnostic value. Complement fixation test, indirect hemagglutination test, indirect immunofluorescence assay, and enzyme-linked immunosorbent assay are often used in clinical practice.

9.5 Differential Diagnosis 1. Primary pulmonary tuberculosis: It is common in children, which is similar to mild pneumonia, but primary pulmonary tuberculosis has a slow onset and may have systemic poisoning symptoms, such as low fever in the afternoon, night sweat, fatigue, weakness, etc. Imaging examination may have the characteristics of “dumbbell” sign. Secondary pulmonary tuberculosis: The cases with foci confined to the upper lung field sometimes need to be differentiated from secondary pulmonary tuberculosis mainly manifested as exudative infiltration. Mycoplasma pneumonia is generally absorbed significantly or ­completely in 1–2 weeks without special drug treatment, while tuberculosis is absorbed slowly without treatment, which can be distinguished by follow-up reexamination. 2. Acute lung abscess: The onset is acute, but it is characterized by coughing up a large amount of purulent smelly sputum with the progress of the disease, and sometimes cavity-like changes can be found by imaging examination. 3. Pneumococcal pneumonia: The onset is rapid, often caused by cold, being caught in the rain, upper respiratory tract infection, chills, with the symptoms of high fever, chest pain, cough with rust-colored sputum, obvious signs of lung consolidation. Blood routine examination shows significantly increased total number of leukocytes, mostly above 10 × 109/L. Pathogenic bacteria can be isolated from sputum and blood. 4. Hypersensitivity pneumonitis: Mycoplasma pneumonia has multiple lesions or lesion migration phenomenon, which should be differentiated from hypersensitivity pneumonitis. The eosinophil count in peripheral blood of

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most patients with mycoplasma pneumonia is not high, which can be used for identification. 5. Viral pneumonia: The imaging manifestations are similar, and the differentiation mainly depends on cold agglutination test or mycoplasma culture.

9.6 Research Status and Progress The studies of Gui et al. have shown that children with mycoplasma pneumonia have cellular immune disorder and humoral immune imbalance [2], and the more serious the disease is, the more obvious the disorder and imbalance are [3]. Vitamin D is a fat-soluble vitamin, which can regulate the metabolism of calcium and phosphorus, promote the growth and differentiation of cells, and also play an important role in immune regulation by regulating the local and systemic immune function of respiratory tract. Vitamin D receptor (VDR) exists in most immune cells. Vitamin D binds to VDR on immune cells, regulates the growth, differentiation and proliferation of various immune cells, and then affects the secretion of cytokines and antibacterial peptides, thus regulating innate immunity and adaptive immunity. The studies of Wang et  al. have shown that serum 25-(OH)-D3 level is related to mycoplasma pneumoniae pneumonia in children [4], suggesting that vitamin D deficiency may increase the risk of mycoplasma pneumonia and may be an independent predictor of its occurrence. The reason may be that vitamin D deficiency leads to the decreased immune regulation function and not being able to effectively regulate the immune disorder of mycoplasma pneumonia, thereby aggravating the severity of mycoplasma pneumonia. At present, the detection of mycoplasma pneumonia mainly depends on mycoplasma culture, serological detection, molecular detection, and other means. As the gold standard for the detection of mycoplasma pneumonia, mycoplasma culture is seriously limited in the early detection of mycoplasma pneumonia because of its time-­ consuming and low positive rate. The recently popular molecular detection has not been widely used because of the high requirements of instrument operation and cumbersome procedures, so serological detection is still widely used in clinical practice. Serological detection of mycoplasma pneumonia includes passive agglutination method, gold standard method, and indirect immunofluorescence method. Indirect immunofluorescence method has the highest sensitivity and specificity. Passive agglutination method has the lowest sensitivity and complicated operation. The sensitivity of the gold standard method is slightly lower, but the specificity is the same as that of indirect immunofluorescence method, and the detection is rapid, providing results in only 20 min, so the gold standard method has high potential value for rapid diagnosis. For the detection of mycoplasma pneumonia

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antibody, gold standard method combined with procalcitonin (PCT) and high-sensitivity C-reactive protein detection has significantly improved diagnostic efficiency of mycoplasma pneumonia infection and the detection duration is significantly shortened, which has good cost efficiency and practicability in clinical practice [5].

References 1. Lyu L, Lyu Z, Lyu Y, et  al. Chest CT imaging characteristics of mycoplasma pneumonia of 126 pediatric patients at different age groups. J Clin Pulm Med. 2017;22(2):294–8.

B. Liu et al. 2. Gui Y, Li X. Correlation between cough variant asthma and recurrent mycoplasma pneumoniae infection in children. J Clin Pulm Med. 2017;22(2):276–9. 3. Wittke A, Chang A, Froicu M. Vitamin D receptor expression by the lung micro-environment is required for maximal induction of lung inflammation. Arch Biochem Biophys. 2007;460(2):306–13. 4. Wang Z, Yan D, Wang H, et al. Correlation between serum 25-(OH)D3 level and mycoplasma pneumoniae pneumonia in children. Chin J Lab Diagn. 2019;23(7):1148–50. 5. Tu H, Han Z, Xu L, et  al. The application of combined tests of antibody-­coated colloid gold-based immunoassay, PCT and hs-CRP in fast diagnosis of mycoplasma pneumoniae pneumonia. Int J Lab Med. 2019;40(8):897–900, +904.

Chlamydia Pneumonia

10

Bailu Liu, Zhehao Lyu, and Xianhe Zhang

10.1 Overview Chlamydia pneumonia is the pneumonia caused by chlamydia, which is divided into Chlamydia trachomatis, Chlamydia pneumoniae, Chlamydia psittaci, and Chlamydia pecorum. Chlamydia pneumoniae pneumonia is common, and Chlamydia psittaci pneumonia occasionally occurs. This disease is more common in school-age children, and most cases are mild, often with occult onset. There is no gender difference in the infection rate, and the disease can occur in all seasons. The infection route of Chlamydia pneumoniae is human-to-human transmission through respiratory secretions, and it can be prevalent in small semi-closed environments such as families, schools, military, and other densely populated work areas. Chlamydia pneumoniae infection may also be related to the onset of asthma, coronary heart disease and atherosclerosis, and acute attack and deterioration of chronic obstructive pulmonary disease. The onset of this disease is mostly occult, and the early manifestations are upper respiratory tract infection symptoms. Clinically, it is quite similar to mycoplasma pneumonia. Symptoms are usually mild, such as fever, chills, myalgia, dry cough, non-pleurisy chest pain, headache, malaise, and fatigue. Hemoptysis is rare. Patients with pharyngolaryngitis are characterized by sore throat and hoarseness, and some patients show two-stage course: pharyngitis at the beginning, showing improvement after symptomatic treatment; pneumonia or bronchitis after 1–3  weeks, showing aggravated cough. Chlamydia pneumoniae infection can also be accompanied by extrapulmonary manifestations, such as otitis media, arthritis, thyroiditis, encephalitis, Guillain–

B. Liu (*) · X. Zhang The 2nd Affiliated Hospital of Harbin Medical University, Harbin, China Z. Lyu The First Affiliated Hospital of Harbin Medical University, Harbin, China

Barré syndrome, and so on. Occasionally, moist rales can be heard in the lungs during physical examination. The total number and classification of leukocytes in patients with chlamydia pneumonia are mostly normal but often with increased erythrocyte sedimentation rate. Micro-­ immunofluorescence (MIF) test is currently the international standard and most commonly used serological diagnosis method of Chlamydia pneumoniae. Except for STD outpatients and other specific populations, the MIF serological diagnosis of Chlamydia pneumoniae pneumonia can be performed using a single antigen of Chlamydia pneumoniae, without the trouble to detect Chlamydia trachomatis and Chlamydia psittaci antibodies at the same time. Serological diagnostic criteria: If MIF test IgG  ≥  1:512 and/or IgM ≥ 1:32, recent infection can be diagnosed after excluding false positive result caused by rheumatoid factor (RF). Double serum antibody titer 4 times or more can also be used for the diagnosis of recent infection; 1:16  ≤  IgG  pulmonary tuberculoma = tuberculosis consolidation > tuberculosis cavity wall. The result shows that there are differences in water molecule dispersion strength among various lesions.

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(d) On T2WI, the order of signal value is as follows: tuberculosis consolidation / spinal cord > pneumonia consolidation/spinal cord. To sum up, MRI, especially DWI, can be used as an important auxiliary means to differentiate pulmonary tuberculosis from pneumonia consolidation, besides CT. 3. 18F-FDG PET/CT: Geadas et al. performed 18F-FDG PET/ CT study on 159 patients [18]. The study has shown that this examination can reflect the active foci of pulmonary tuberculosis, because symptom screening, sputum smear and Mycobacterium tuberculosis culture have limitations on judging the active stage of tuberculosis. However, in patients with unknown typical symptoms or recent tuberculosis, PET/CT manifestations of tuberculosis are similar to those of lung cancer, which is difficult to distinguish. In addition, PET/CT can also predict the recurrence and activity of tuberculosis and guide the treatment. 4. Acid-fast staining: Detection of Mycobacterium tuberculosis is still an important diagnostic method for tuberculosis. However, due to improper use of antibiotics, the emergence of drug-resistant Mycobacterium tuberculosis and HIV infection, the pathological features of pathological tissues in tuberculosis are very different, so the identification is difficult. Studies have shown that the positive rate of acid-fast staining in tuberculosis tissues is generally considered to be about 30%, and gender has no effect on it [19]. However, the positive rate of acid-fast staining of Mycobacterium tuberculosis in different parts is different. The positive rate of bronchial mucosa tuberculosis and intestinal tuberculosis is higher, but the positive rate of tuberculous pleurisy, spinal tuberculosis and joint tuberculosis is lower. Studies have shown that the age of patients with positive bacteria found by acid-fast staining has a bimodal change trend [20]. 5. PCR: This technique is a kind of nucleic acid amplification in vitro. In recent years, PCR has been widely used in the diagnosis of tuberculosis. According to the principle of DNA replication, the DNA of Mycobacterium tuberculosis in  vitro samples can be amplified, so that Mycobacterium tuberculosis can be detected more quickly and accurately. Ultrasound-guided pleural biopsy combined with pleural effusion TB-PCR and ADA detection has the highest detection rate of tuberculous pleurisy, and the combination of the three can basically confirm the diagnosis of tuberculous pleurisy.

16.6 Drug-Resistant Tuberculosis Li Li, Guiying Li, and Yiping Liu

B. Liu et al.

16.6.1 Overview The World Health Organization/International Tuberculosis and International Union Against Tuberculosis-Lung Diseases (WHO/IUATLD) have implemented a global antituberculosis drug resistance surveillance project. According to whether drug-resistant tuberculosis patients have received antituberculosis drugs, the situation includes new drug-resistant tuberculosis and retreatment drug-resistant tuberculosis [21, 22]. Drug-resistant tuberculosis (DR-TB) refers to tuberculosis caused by drug-resistant Mycobacterium tuberculosis. In China, drug-resistant tuberculosis is generally divided into five types, namely mono-resistant tuberculosis, poly-­resistant tuberculosis, multidrug-resistant tuberculosis, extensive drugresistant tuberculosis and rifampicin-resistant tuberculosis. 1. Mono-resistant tuberculosis (MR-TB): Mycobacterium tuberculosis in tuberculosis patients has been proved in  vitro to be resistant to one kind of antituberculosis drug. 2. Poly-resistant tuberculosis (PDR-TB): Mycobacterium tuberculosis in tuberculosis patients has been proved in vitro to be resistant to more than one kind of antituberculosis drug, but such case does not include the resistance to isoniazid (INH) and rifampicin (RFP) at the same time. 3. Multidrug-resistant tuberculosis (MDR-TB): Mycobacterium tuberculosis in tuberculosis patients has been proved in  vitro to be at least resistant to INH and RFP simultaneously. 4. Extensively drug-resistant tuberculosis (XDR-TB): Mycobacterium tuberculosis in tuberculosis patients has been proved in vitro to be at least resistant to any fluoroquinolones besides INH and RFP simultaneously, and at least resistant to one of three second-line antituberculosis injectable drugs [capreomycin (Cm), kanamycin (Km) and amikacin (AM)]. 5. Rifampicin-resistant tuberculosis (RR-TB): Mycobacterium tuberculosis has been proved in vitro to be resistant to rifampicin. It includes any rifampicinresistant tuberculosis, namely rifampicin mono-resistant tuberculosis (RMD-TB), rifampicin poly-resistant tuberculosis (RPR-­TB), MDR-TB and XDR-TB. This section mainly introduces drug-resistant tuberculosis. Risk factors of drug-resistant pulmonary tuberculosis: (1) patients have a history of antituberculosis drug administration; (2) the smear or culture is still positive after 3 months of antituberculosis treatment; (3) patients have a history of contact with drug-resistant TB patients; (4) those from regions with high incidence of drug-resistant tuberculosis; (5) treat-

16  Pulmonary Tuberculosis

ment with the first-line antituberculosis drugs for 2  weeks has poor effect. Among them, the failure of antituberculosis drug treatment is an independent predictor of XDR-TB [23]. Most patients with drug-resistant pulmonary tuberculosis have no special clinical manifestations, with mild or even absent symptoms. The presence/absence and the severity of symptoms are mainly related to the number of pulmonary lesions and airway function, and these manifestations are directly related to the duration of the disease. The longer the course of disease, the more lesions, the more significant the symptoms. Severe airway injury leads to significant symptoms. The main symptoms are cough, expectoration and hemoptysis, and some patients have shortness of breath, emaciation and even cachexia.

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Multiple pulmonary cavities are the main imaging manifestations of MDR-PTB.  Yeom et  al. reported a group of 39 cases of primary MDR-PTB [26]. The imaging findings were mainly multiple cavities, which well supported the conclusion of restriction fragment length polymorphism (RFLP). The incidence of acquired MDR-­ PTB cavities is about 70%, and the average number of cavities in patients with MDR-PTB cavities may be ≥3 [27, 28]. The main imaging manifestations are as follows: (a) Widely distributed lesions: The distribution of lesions reflects the severity of lesions to a certain extent. MDR-PTB lesions not only occur in the predilection sites of PTB (such as the posterior segment of the upper apex and the dorsal segment of the lower lobe of both lungs), but also often spread to the rare sites 16.6.2 Pathological Manifestations of PTB, involving more than three lobes or the whole lung [29]. Compared with drug-sensitive pulmonary The basic pathological changes of tuberculosis are exudatuberculosis group, the difference is statistically sigtion, hyperplasia and caseous necrosis. The pathological pronificant (P