Orphan Lung Diseases: A Clinical Guide to Rare Lung Disease

Preface to the First Edition
Preface to the Second Edition
Contents
Part I: Introduction
1: Orphan Lung Diseases: From Definition to Organization of Care
Definitions
The Wide Spectrum of Rare Pulmonary Diseases
Diagnostic Challenges
Expert Centers
Patient Organizations
Clinical Trials
Research in Orphan Lung Diseases
Orphan Drugs
Orphanet
Empowerment of Patients
Conclusions
References
2: Challenges of Clinical Research in Orphan Diseases
Introduction
Challenges to Overcome in Order to Undertake Quality Clinical Research
Lack of Reliable Data on Prevalence
Small Number of Patients
Genetic Component, Variable Degree of Penetrance, and Environmental Interactions
Identifying Causation/Disease Pathogenesis
Unclear/Imprecise Definitions
Disease Complexity
Several Forms of Disease: The Paradigm of Pulmonary Alveolar Proteinosis (PAP)
Lack of Access to a Correct Diagnosis
Delay in Diagnosis
Challenges But Not Negativity
Some Success Stories
The Means to Overcome the Challenges of Clinical Research: Get Bigger Numbers of Well-Characterized Patients
The Importance of Patient Organizations
National and International Networks
End Points for Trials: Getting Them Right When Numbers Are Small and Change Is Modest
Orphan Drug Development
Importance of Referral Centers
Looking at the Future
The Arguments for Progress
The Goal of Clinical Research in Rare Diseases
Concluding Remarks
References
Part II: Orphan Diseases of the Airways
3: Chronic Bronchiolitis in Adults
Introduction
Classification
Cellular Bronchiolitis
Follicular Bronchiolitis
Respiratory Bronchiolitis
Airway-Centered Interstitial Fibrosis
Diffuse Panbronchiolitis
Proliferative Bronchiolitis
Diagnosis
Chest Imaging Studies
Pulmonary Function Testing
Lung Biopsy
Clinical Syndromes Associated with Bronchiolitis
Bronchiolitis Secondary to Inhalational Lung Injury
Mineral Dusts
Organic Dusts
Volatile Flavoring Agents
Infectious Causes of Bronchiolitis
Idiopathic Forms of Bronchiolitis
Connective Tissue Diseases
Organ Transplantation
Hematopoietic Stem Cell Transplantation
Drug-Induced Bronchiolitis
Diffuse Panbronchiolitis
Treatment
Constrictive Bronchiolitis
Diffuse Panbronchiolitis
Follicular Bronchiolitis
Airway-Centered Interstitial Fibrosis
Proliferative Bronchiolitis
References
4: Allergic Bronchopulmonary Aspergillosis
Background and Epidemiology
Pathophysiology
Host Characteristics
Clinical Manifestations
Symptoms
Laboratory Evaluation
Skin Testing
Serum Precipitins
Eosinophil Count
Total Serum Immunoglobulin E Levels
Serum Antibodies Specific to Aspergillus fumigatus
Recombinant Antigens
Radiographic Imaging
Pulmonary Function Testing
Histology
Diagnostic Criteria
Historical Diagnostic Criteria
Rosenberg and Patterson Diagnostic Criteria
ISHAM Diagnostic Criteria
Cystic Fibrosis Foundation Diagnostic Criteria
Baxter ABPA in Cystic Fibrosis Diagnostic Criteria
General Diagnostic Recommendations
Differential Diagnosis
Allergic Aspergillus Sinusitis (AAS)
Natural History
Treatment
Corticosteroids
Antifungal Therapy
Monoclonal Antibodies
Monitoring for Treatment Response
Conclusions
References
5: Orphan Tracheopathies
Introduction
Anatomical Considerations
Clinical Presentation
Etiological Considerations
Idiopathic Subglottic Stenosis
Introduction
Etiology and Pathogenesis
Clinical Features
Pulmonary Function Studies
Imaging Studies
Bronchoscopy
Treatment
Tracheobronchopathia Osteochondroplastica
Introduction and Clinical Presentation
Etiology and Pathogenesis
Clinical Features
Pulmonary Function Studies
Imaging Studies
Bronchoscopy
Treatment
Tracheomalacia
Introduction
Etiology and Pathogenesis
Clinical Features
Pulmonary Function Studies
Imaging Studies
Bronchoscopy
Treatment
Tracheobronchomegaly
Introduction
Etiology and Pathogenesis
Clinical Features
Pathophysiology
Pulmonary Function Studies
Imaging Studies
Treatment
Tracheopathies Associated with Systemic Diseases
Relapsing Polychondritis
Introduction
Clinical Features
Laboratory Findings
Pulmonary Function and Imaging Studies
Treatment
Granulomatosis with Polyangiitis
Introduction
Clinical Features
Pulmonary Function Studies
Imaging Studies
Bronchoscopy
Treatment
Tracheobronchial Amyloidosis
Introduction
Clinical Features
Pulmonary Function Studies
Imaging Studies
Bronchoscopy
Treatment
Sarcoidosis
Introduction
Pulmonary Function Studies
Imaging Studies
Bronchoscopy
Treatment
Orphan Tracheopathies: Conclusions
References
Part III: Systemic Disorders with Lung Involvement
6: Amyloidosis and the Lungs and Airways
Introduction
Diagnosis and Evaluation of Amyloidosis
Systemic Amyloidosis Complicating Respiratory Diseases
Systemic AA Amyloidosis
Systemic AL Amyloidosis
Amyloidosis Localised to the Respiratory Tract
Laryngeal Amyloidosis
Tracheobronchial Amyloidosis
Parenchymal Pulmonary Amyloidosis
Pulmonary Amyloidosis Associated with Sjögren’s Disease
Mediastinal and Hilar Amyloid Lymphadenopathy
Conclusions
References
7: Eosinophilic Granulomatosis with Polyangiitis
Introduction
Pathophysiology
Genetic Predisposition
Immune Dysregulation
Epidemiology
Incidence and Prevalence
Triggering Factors
Clinical Manifestations
General Symptoms
Pulmonary Manifestations
Ear, Nose, and Throat (ENT) Manifestations
Neurological Manifestations
Skin Manifestations
Cardiac Manifestations
Gastrointestinal Involvement
Renal Manifestations
Ophthalmological Manifestations
Complementary Investigations
Diagnosis
Diagnostic Criteria
Differential Diagnosis
Prognosis and Outcomes
Phenotypes According to the ANCA Status
Treatment
Therapeutic Strategies
Remission Induction
Maintenance Therapy
Other Treatments
Prevention of AEs
Conclusions
References
8: Granulomatosis with Polyangiitis
A Brief Historical Overview
Epidemiology
Pathogenesis
Clinical Manifestations
Constitutional Symptoms
Ear, Nose, and Throat (ENT) Manifestations
Pulmonary Manifestations
Kidney and Urological Manifestations
Kidney Manifestations
Urological Manifestations
Neurological Manifestations
Peripheral Nervous System (PNS) Manifestations
Central Nervous System (CNS) Manifestations
Spinal Cord and Cranial Nerve Involvement
Skin and Oral Mucosal Manifestations
Eye Manifestations
Cardiac Involvement
Gastrointestinal Manifestations
Gynecological and Obstetric Manifestations
Venous Thrombosis and Other Vascular Events
Other Manifestations
Limited/Localized Versus Severe/Diffuse/Systemic Forms
Pediatric GPA
Diagnosis
Diagnostic Approach
Laboratory Investigations
Biology
Immunology
Radiology, Endoscopy, and Other Nonbiological Investigations
Pathology
Differential Diagnosis
Disease Activity, Prognosis, and Damage Scores
Treatment
Induction Treatment for Systemic/Severe/Generalized Forms
Glucocorticoids
Cyclophosphamide
Rituximab
Other Current Induction Approaches
Maintenance Therapy for Systemic/Severe/Generalized Forms
Treatment of Localized/Limited/Early Systemic GPA
Other Treatments in GPA
Intravenous Immunoglobulins
Plasma Exchange
Avacopan (and Other Complement Inhibitors/Blockers): A Major Upcoming Change in the Treatment of GPA
CTLA4-Ig (Abatacept)
Cotrimoxazole
Other Agents
Specific Treatments for Certain Manifestations of GPA
Adjuvant Measures and Prevention of Treatment Adverse Effects
Principles of Treatment for Relapsing and Refractory GPA
Outcomes and Prognostic Factors
Survival and Causes of Deaths
Relapse
Damage and Disease Burden on Quality of Life
Conclusions
References
9: Alveolar Hemorrhage
Introduction
Clinical Presentation
Diagnosis (Table 9.1, Fig. 9.3)
Pulmonary Capillaritis
Histology (Fig. 9.4)
Etiologies
ANCA-Associated Small Vessel Vasculitis: Granulomatosis with Polyangiitis (GPA)
ANCA-Associated Small Vessel Vasculitis: Microscopic Polyangiitis
Isolated Pulmonary Capillaritis
Systemic Lupus Erythematosus
Antiphospholipid Antibody Syndrome
Anti-Basement Membrane Antibody Disease (Goodpasture Syndrome)
Lung Allograft Rejection
Others
Bland Pulmonary Hemorrhage (Fig. 9.5)
Histology
Etiologies
Idiopathic Pulmonary Hemosiderosis
Drugs and Medications
Coagulopathy
Valvular Heart Disease and Left Ventricular Dysfunction
Other
Diffuse Alveolar Damage
Histology
Etiologies
Hematopoietic Stem Cell Transplantation (HSCT)
Cocaine Inhalation
Acute Exacerbation of Interstitial Lung Disease
Acute Interstitial Pneumonia
Acute Respiratory Distress Syndrome
Miscellaneous Causes
Etiologies
Human Immunodeficiency Virus (HIV)
Pulmonary Capillary Hemangiomatosis
Treatment
Conclusions
References
10: Pulmonary Involvement in Takayasu Arteritis and Behçet Disease
Takayasu Arteritis
Epidemiology
Pathologic Features
Pathogenesis
Clinical Features
Laboratory Findings
Imaging Studies
Therapeutic Management
Prognosis
Behçet’s Disease
Epidemiology
Pathologic Features
Pathogenesis
Diagnostic Criteria
Clinical Features
Pulmonary Artery Aneurysm
Pulmonary Artery Thrombosis
Pulmonary Parenchymal Involvement
Laboratory Findings
Imaging Studies
Differential Diagnosis
Therapeutic Management
Treatment of PAA
Treatment of PAT
Prognosis
References
11: Portopulmonary Hypertension and Hepatopulmonary Syndrome
Introduction
Portopulmonary Hypertension (PoPH)
Epidemiology and Risk Factors
Molecular Pathogenesis
Screening and Diagnosis
PoPH Treatment
Hepatopulmonary Syndrome (HPS)
Epidemiology and Risk Factors
Molecular Pathogenesis
Screening and Diagnosis
HPS Treatment
Conclusion
References
12: Systemic Sclerosis and the Lung
Introduction
Epidemiology of SSc-ILD
Risk factors for SSc-ILD
Genetic Associations
Clinical Presentation of SSc-ILD
Pulmonary Function Tests (PFTs)
Imaging
Prognostic Evaluation of SSc-ILD: When Should Treatment Be Instituted?
Management
References
13: Rheumatoid Arthritis and the Lungs
Introduction
Rheumatoid Arthritis-Associated Interstitial Lung Disease
Epidemiology
Risk Factors for ILD (Table 13.3)
Pathogenesis
Clinical Features and Diagnosis
Treatments
Prognosis
Rheumatoid Arthritis-Associated Airways Disease
Epidemiology
Risk Factors
Clinical Features, Diagnosis, and Outcome
Subtypes or RA-AD
Obliterative Bronchiolitis
Bronchiectasis
COPD
Cricoarytenoid Involvement
Pleural Disease
Conclusion
References
14: Lung Disease in Systemic Lupus Erythematosus, Myositis, Sjögren’s Disease, and Mixed Connective Tissue Disease
Introduction
Systemic Lupus Erythematosus
Epidemiology
Pathophysiology
Pulmonary Manifestations
Pleural Disease
Acute Lupus Pneumonitis and Diffuse Alveolar Hemorrhage
Shrinking Lung Syndrome
Thrombotic Manifestations
Interstitial Lung Disease
Other Pulmonary Manifestations
Prognosis
Sjögren’s Syndrome
Epidemiology
Pathophysiology
Pulmonary Manifestations
Airway Disorders
Lymphoproliferative Disease
Interstitial Lung Disease
Prognosis
Mixed Connective Tissue Disease
Epidemiology
Pathophysiology
Pulmonary Manifestations
Pulmonary Hypertension
Interstitial Lung Disease
Prognosis
Myositis
Epidemiology
Pathophysiology
Pulmonary Manifestations and Treatments
Interstitial Lung Disease
Respiratory Muscle Weakness
Other Pulmonary Manifestations
Prognosis
Other Therapeutic Options in CTD-ILD
Antifibrotic Therapy
Lung Transplantation
Conclusion
References
15: Interstitial Pneumonia with Autoimmune Features
Introduction
Diagnostic Criteria
Controversies in the Diagnostic Criteria
Typical Clinical Features
Disease Progression and Prognosis
Management Considerations and Future Studies
Summary
References
16: Primary Histiocytic Disorders of the Lung
Introduction
Histiocytes and Dendritic Cells
PLCH: The Prototypical Adult Pulmonary Histiocytic Disorder
Introduction
Cellular and Molecular Pathogenesis
Pathology
Clinical Presentation
Treatment and Prognosis
Erdheim-Chester Disease
Definition
Epidemiology
Cellular and Molecular Pathogenesis
Histopathology and Immunohistochemistry
Clinical Presentation
Clinical Presentation-Extrapulmonary/Extraskeletal Involvement
Investigation/Diagnosis
Chest Studies
Cardiovascular Imaging
CNS Imaging
Bone Radiography
Other Imaging Findings and Considerations
Disease Monitoring
Pathology
Management/Treatment
Prognosis
Rosai-Dorfman Destombes Disease
Definition
Epidemiology
Etiology/Pathophysiology
Histopathology and Immunohistochemistry
Clinical Presentation
Investigation/Diagnosis
Management/Treatment
Prognosis
Conclusions
Diagnostic Criteria for Primary Histiocytic Disorders of the Lung
References
Part IV: Lung-Dominant or -Limited Orphan Diseases
17: Eosinophilic Pneumonia
Introduction
Eosinophil Biology
Eosinophil Differentiation and Recruitment
Physiologic and Immunologic Role of Eosinophils
Release of Mediators
Targeting the Eosinophil Cell Lineage
General Features of Eosinophilic Pneumonias
Historical Perspective
Clinical Presentation
Pathology
Diagnosis
Eosinophilic Lung Disease of Undetermined Cause
Idiopathic Chronic Eosinophilic Pneumonia
Clinical Features
Imaging
Laboratory Studies
Bronchoalveolar Lavage
Differential Diagnosis
Lung Function Tests
Treatment
Outcome and Perspectives
Idiopathic and Smoking-Related Acute Eosinophilic Pneumonia
Clinical Features
Imaging
Laboratory Studies
Bronchoalveolar Lavage
Lung Function Tests
Lung Biopsy
Treatment and Prognosis
Eosinophilic Granulomatosis with Polyangiitis
History and Nomenclature
Pathology
Clinical Features
Imaging
Laboratory Studies
Pathogenesis
Diagnosis
Differential Diagnosis
Treatment and Prognosis
Long-Term Outcome
Hypereosinophilic Syndrome
Definition
Pathogenesis
Clinical and Imaging Features
Laboratory Studies
Treatment and Prognosis
Idiopathic Hypereosinophilic Obliterative Bronchiolitis
Eosinophilic Lung Disease of Determined Cause
Eosinophilic Pneumonias of Parasitic Origin
Tropical Eosinophilia [191]
Ascaris Pneumonia
Eosinophilic Pneumonia in Larva Migrans Syndrome
Strongyloides Stercoralis Infection
Eosinophilic Pneumonias in Other Infections
Allergic Bronchopulmonary Aspergillosis
Pathogenesis
Diagnostic Criteria
Biology
Imaging
Treatment
Bronchocentric Granulomatosis
Drug, Toxic Agents, and Radiation-Induced Eosinophilic Pneumonias
Miscellaneous Lung Diseases with Associated Eosinophilia
References
18: Langerhans Cell Granulomatosis and Smoking-Related Interstitial Lung Diseases
Introduction
Pulmonary Langerhans’ Cell Histiocytosis
History and Classification
Epidemiology
Pathogenesis
Diagnosis
Clinical Features
Extrathoracic Lesions
Pulmonary Function Tests
Chest Radiography
High-Resolution Computed Tomography (HRCT)
Bronchoscopy and Bronchoalveolar Lavage (BAL)
Lung Biopsy
Pathology
Treatment
Course and Prognosis
Case Report I
Respiratory Bronchiolitis-associated Interstitial Lung Disease (RB-ILD)
Introduction
Epidemiology
Clinical Features
Histopathological Findings
Radiologic Findings
Prognosis and Therapy
Desquamative Interstitial Pneumonia
Epidemiologic and Clinical Features
Histopathological Findings
Radiological Findings
Prognosis and Therapy
Conclusion
References
19: Lymphangioleiomyomatosis
Introduction
Pathogenesis
Presentation
Diagnosis and Workup
Prognosis
Management
General Measures
Parenchymal Lung Disease
Pleural Disease
Renal Angiomyolipoma
Abdominopelvic Lymphatic Disease
Pregnancy
Tuberous Sclerosis
Drug Treatment
Bronchodilators
mTOR Inhibitors
Anti-Oestrogen Therapy
Experimental Therapies
Interventions for Advanced Disease
Oxygen Therapy
Pulmonary Hypertension
References
20: Diffuse Cystic Lung Disease
Introduction
Common Diffuse Cystic Lung Diseases
Lymphangioleiomyomatosis
Pathogenesis
Pathologic and Radiographic Characteristics
Diagnostic Approach
Prognosis and Management
Pulmonary Langerhans Cell Histiocytosis (PLCH)
Pathogenesis
Pathological and Radiographic Characteristics
Diagnostic Approach
Prognosis and Management
Birt-Hogg-Dubé Syndrome (BHD)
Pathogenesis
Pathological and Radiographic Characteristics
Diagnostic Approach
Prognosis and Management
Lymphoproliferative Disorders
Lymphocytic Interstitial Pneumonia/Follicular Bronchiolitis
Pathogenesis
Pathological and Radiographic Characteristics
Diagnostic Approach
Prognosis and Management
Amyloidosis
Light Chain Deposition Disease (LCDD)
Smoking-Related Diffuse Cystic Lung Disease
Conclusion
References
21: Complex Thoracic Lymphatic Disorders of Adults
Introduction
The Pulmonary Lymphatic System: Structure and Function
Lymphatic Development
Clinical Presentation of Lymphatic Disorders
Approaches to Diagnosis and Management of Congenital Lymphatic Anomalies
Generalized Lymphatic Anomaly
Etiopathogenesis
Clinical Presentation and Diagnosis
Course/Prognosis
Management
Kaposiform Lymphangiomatosis
Etiopathogenesis
Clinical Presentation and Diagnosis
Management
Course/Prognosis
Gorham Stout Disease
Etiopathogenesis
Clinical Presentation and Diagnosis
Management
Course/Prognosis
Channel-Type LM/Central Conducting LM
Etiopathogenesis
Clinical Presentation and Diagnosis
Management
Course/Prognosis
Yellow Nail Syndrome
Etiopathogenesis
Clinical Presentation and Diagnosis
Management
Course/Prognosis
Summary
References
22: Pulmonary Alveolar Proteinosis Syndrome
Introduction
Historical Note
Epidemiology
Pathogenesis
Surfactant Homeostasis in PAP
GM-CSF Signaling Disruption
Myeloid Cell Dysfunction
GM-CSF Autoantibodies
Lymphocytosis
Clinical Manifestations
Clinical Presentation
Secondary Infections
Pulmonary Fibrosis
Diagnosis
Pulmonary Function Testing
Radiographic Assessment
Bronchoscopy and Bronchoalveolar Lavage
Laboratory Studies and Biomarkers
GM-CSF Autoantibodies
GM-CSF Signaling Deficiency Test
Genetic Testing
Lung Pathology
Diagnostic Approach to the Patient with PAP
Natural History and Prognosis
Treatment
Whole-Lung Lavage
Subcutaneous GM-CSF
Inhaled GM-CSF
Other Approaches
Conclusions and Future Directions
References
23: Gastroesophageal Reflux: Idiopathic Pulmonary Fibrosis and Lung Transplantation
Introduction
Definitions (GER/GERD/Microaspiration)
Epidemiology/Anatomy and Physiology/Pathobiology
Epidemiology
Anatomy/Embryogenesis of the Upper GI and Respiratory Tracts
Gastric Contents
Pathobiology of GER/Microaspirate in the Lungs of Patients with IPF
GER and the Microbiome
Diagnosis
Clinical History/Physical Exam
Investigations
Esophageal Physiology
Upper Esophageal Sphincter
Esophagus and Peristalsis
Lower Esophageal Sphincter and Diaphragm
Esophageal pH and Impedance Testing
High Resolution Esophageal Manometry
Esophagram/Barium Swallow
Bronchoalveolar Lavage/Sputum: Biomarkers
Treatment
Anti-Acid Therapy (PPI/H2 Blocker)
Other Effects of PPI Therapy (Pleiotropic)
Laparoscopic Anti-Reflux Surgery (LARS)
GER and Acute Exacerbations of IPF
Reflux/GER/Microaspiration in Lung Transplant
Suggested Approach
Summary and Future Directions
References
Part V: Genetic Rare Lung Diseases
24: Genetic and Familial Pulmonary Fibrosis Related to Monogenic Diseases
Introduction
Familial Interstitial Pneumonia
Telomere Related Genes
Genetic
Telomere Length
Pulmonary Involvement
Interstitial Lung Disease
Other Lung Disease
Hepatopulmonary Syndrome
Emphysema
Immunodeficiency
Extrapulmonary Manifestations
Mucocutaneous Involvement
Hematological Involvement
Liver Involvement
Other Manifestations
Treatment
Antifibrotic Therapy
Telomerase Complex Agonists
Lung Transplantation
Surfactant Pathway
Surfactant Protein Genes
Pulmonary Involvement
Treatment
Other Genetic Diseases That Can Cause Fibrosing ILD
Heritable Forms of Pulmonary Fibrosis with Autoimmune Features
TMEM173
COPA
Pulmonary Alveolar Proteinosis
GMCSF Receptor Mutations
GATA2
MARS
Lysinuric Protein Intolerance
Lysosomal Diseases
Hermansky-Pudlak Syndrome
Lysosomal Storage Disorders
FAM111B, NDUFAF6, PEPD
Conclusion
References
25: Diffuse Bronchiectasis of Genetic or Idiopathic Origin
Introduction
Pathophysiology
Clinical Presentation
Epidemiology
Genetic Causes of Bronchiectasis
Disorders of Mucociliary Clearance
Cystic Fibrosis
Primary Ciliary Dyskinesia
Other Ciliopathies
Primary Immunodeficiency Disorders
Common Variable Immunodeficiency
X-Linked Agammaglobulinemia
Chronic Granulomatous Disease and Other Disorders of Neutrophil Function
Other Immunodeficiency Diseases Associated with Bronchiectasis
Other Genetic Disorders Predisposing to Bronchiectasis
Idiopathic Bronchiectasis
Diagnosis of Bronchiectasis
Management of Patients with Bronchiectasis
Airway Clearance Therapy (ACT)
Management of Infections
Anti-Inflammatory Management
Immune Therapy
Surgery
Novel Therapies for Managing Cystic Fibrosis
Summary
References
26: Pulmonary Vascular Manifestations of Hereditary Hemorrhagic Telangiectasia
Pulmonary Arteriovenous Malformations
Background Pulmonary AVMs
Anatomy Pulmonary AVMs
Clinical Presentation of Pulmonary AVMs
Screening Pulmonary AVMs
Treatment Pulmonary AVMs
Pregnancy and Pulmonary Arteriovenous Malformations
Children with Hereditary Hemorrhagic Telangiectasia
Diffuse Pulmonary Arteriovenous Malformations
Pulmonary Hypertension
Pulmonary Hypertension Secondary to Liver Vascular Malformations
Pulmonary Arterial Hypertension
Background HHT
Pathogenesis
References
27: Pulmonary Alveolar Microlithiasis
Introduction
Epidemiology
Pathogenesis
Clinical Features
Diagnosis
Management
Summary
References
28: Rare Diffuse Lung Diseases of Genetic Origin
Introduction
Hermansky-Pudlak Syndrome
Telomerase-Associated Pulmonary Fibrosis
Lysosomal Storage Diseases
Lysinuric Protein Intolerance
Familial Hypocalciuric Hypercalcemia
Neurofibromatosis Type 1
Surfactant Dysfunction Disorders
Concluding Remarks
References
Part VI: Interstitial Lung Diseases, Non Systemic
29: Imaging Approach to Interstitial Lung Disease
Introduction
Background
Chest Radiographs and High-Resolution Computed Tomography
Image Acquisition
Key Features of Fibrosis
Ancillary Features of Fibrosis
Other Imaging Findings in FLD
UIP in IPF
Definite UIP-IPF
Probable UIP-IPF
Indeterminate
Alternative Diagnosis
UIP in Other Fibrosing Lung Diseases
Pleuroparenchymal Fibroelastosis (PPFE)
Combined Pulmonary Fibrosis and Emphysema
Chronic Hypersensitivity Pneumonitis
Unclassifiable Fibrosing Lung Disease
Other Fibrosing Lung Diseases
Non-specific Interstitial Pneumonia Pattern
Fibrosing Sarcoidosis
CTD-ILD and Drug-Induced FLD
Complications
Prognosis
Computer Analysis of CT Imaging
The Progressive Fibrotic Phenotype
Other Imaging Techniques
Conclusion
References
30: Bronchoscopic Approach to Interstitial Lung Disease
Introduction
Bronchoalveolar Lavage (BAL)
Technique
Interpretation
Transbronchial Biopsy (TBB)
Transbronchial Lung Cryobiopsy (TLCB)
Endobronchial Ultrasonographic Transbronchial Needle Aspiration (EBUS-TBNA) and Endo-esophageal Ultrasonographic Fine Needle Aspiration (EUS-FNA)
References
31: An Integrated Approach to Diagnosing Interstitial Lung Disease
Introduction
Overview of ILD Diagnosis
Clinical Assessment
Radiological Assessment
Laboratory Assessment
Bronchoscopic and Histopathological Assessment
Integration of Individual Features
Multidisciplinary Discussion
Diagnostic Ontology
Unclassifiable ILD
Conclusions
References
32: Idiopathic Pulmonary Fibrosis and the Many Faces of UIP
Introduction
Radiological and Pathological Definition of a UIP Pattern According to Current Guidelines
Clinical Differential Diagnosis of the UIP Pattern
Idiopathic Pulmonary Fibrosis
Chronic Hypersensitivity Pneumonitis
Connective Tissue Disease
Drug-Induced Lung Diseases
Radiation Pneumonitis
Asbestosis
Hermansky-Pudlak Syndrome
Non-IPF Progressive Fibrotic Interstitial Lung Diseases
Risk Factors for Progression
Diagnosis
Pharmacological Management
Conclusions
References
33: The Syndrome of Combined Pulmonary Fibrosis and Emphysema
Historical Perspective
Epidemiology and Etiologies
Tobacco Smoking and Male Sex
Genetic Predisposition
Systemic Diseases
Other Etiological Contexts
Clinical Manifestations
Pulmonary Function and Physiology
Imaging
Computed Tomography Characteristics and Patterns
Thick-Walled Large Cysts
Imaging Phenotypes
Pitfalls
Quantification of Emphysema Extent
Pathology
Diagnosis
CPFE Is a Syndrome
Biology
Complications and Outcome
Mortality
Pulmonary Hypertension
Lung Cancer
Acute Exacerbation of Pulmonary Fibrosis
Other Comorbidities and Complications
Management
General Measures and Treatment of Emphysema
Treatment of Pulmonary Fibrosis
Management of Pulmonary Hypertension
References
34: Nonspecific, Unclassifiable, and Rare Idiopathic Interstitial Pneumonia: Acute Interstitial Pneumonia, Respiratory Bronchiolitis Interstitial Pneumonia, Desquamative Interstitial Pneumonia, Nonspecific Interstitial Pneumonia
Acute Interstitial Pneumonia (AIP)
History and Definition
Epidemiology
Presentation
Diagnostic Evaluation
Radiology
Histopathology
Clinical Course
Treatment
Smoking-Related Idiopathic Interstitial Pneumonias: Respiratory Bronchiolitis Interstitial Lung Disease (RB-ILD)/Desquamative Interstitial Pneumonia (DIP)
History and Definition
Epidemiology
Presentation
Diagnostic Evaluation
Radiology
Histopathology
Clinical Course
Treatment
Desquamative Interstitial Pneumonia (DIP)
History and Definition
Epidemiology
Presentation
Diagnostic Evaluation
Radiology
Histopathology
Clinical Course
Treatment
Nonspecific Interstitial Pneumonia (NSIP)
History and Definition
Epidemiology
Presentation
Diagnostic Evaluation
Radiology
Histopathology
Clinical Course
Treatment
Unclassifiable Interstitial Pneumonia
References
35: Organizing Pneumonias and Acute Interstitial Pneumonia
Organizing Pneumonias
Definition and Terminology
Epidemiology
Pathogenesis
Clinical Features
Imaging
Multifocal Form
Isolated Nodular Form
Diffuse Infiltrative Form
Other Imaging Patterns
Histopathological Diagnosis of OP Pattern
Clinico-Pathological Diagnosis of OP Syndrome
Differential Diagnosis
Etiological Diagnosis of OP
Treatment
Clinical Course and Outcome
Severe Forms of OP with Respiratory Failure
Acute Fibrinous and Organizing Pneumonia
Granulomatous Organizing Pneumonia
Acute Interstitial Pneumonia
Definition and Terminology
Epidemiology
Clinical Picture
Imaging
Histopathology
Diagnosis
Treatment
Outcome
References
36: Pleuroparenchymal Fibroelastosis
Introduction
Epidemiology
Clinical Manifestations
Laboratory Findings
Respiratory Function
Radiologic Features
Pathologic Features
Diagnosis
Treatment
Prognosis
Conclusions
References
37: Interstitial Lung Diseases of Occupational Origin
Introduction
Acute Berylliosis
Chronic Beryllium Disease
Definition
Exposure
Epidemiology
Immunopathogenesis and Pathology
Genetics
Clinical Description and Natural History
Diagnosis and Differential Diagnosis
Treatment and Monitoring
Prevention of Beryllium Sensitization and Chronic Beryllium Disease
Indium–Tin Oxide-Lung Disease
Hard Metal Lung
Flock Worker’s Disease
Asbestosis
Nanoparticle Induced ILD
Siderofibrosis
Flavoring-Induced Lung Disease
Silica-Induced Interstitial Lung Disease
Chronic Silicosis
Acute and Accelerated Silicosis
Coal Workers Disease—Coal Mine Dust Lung Disease (CMDLD)
Chronic Obstructive Disease in CMDLD
Simple CMDLD
Complicated CMDLD
Dust Diffuse Fibrosis (DDF) in CMDLD
Conclusion
References
38: Unclassifiable Interstitial Lung Disease
Introduction
Definition
Diagnostic Scenarios
Epidemiology
Clinical Presentation
Diagnosis
Clinical Features
Radiology
Laboratory Investigations
Pathology
Progression and Prognosis
Phenotyping Unclassifiable ILD
Management and Treatment
Conclusion
References
Part VII: Miscellaneous Orphan Lung Diseases
39: Lymphoproliferative Lung Disorders
Introduction
Reactive Pulmonary Lymphoproliferative Diseases
Nodular Lymphoid Hyperplasia
Lymphocytic Interstitial Pneumonia (LIP)
Follicular Bronchitis/Bronchiolitis
Castleman Disease
Primary Pulmonary Lymphomas
Primary Pulmonary B Cell Non-Hodgkin Lymphomas (PPBL)
Primary Pulmonary MALT B Cell Lymphoma
Pulmonary Plasmacytoma
Follicular Lymphoma
Diffuse Large B Cell Lymphoma
Lymphomatoid Granulomatosis
T/Natural Killer-Cell Primary Pulmonary Lymphomas (T/NK PPL)
Primary Pulmonary Hodgkin Lymphoma (PPHL)
Post-Transplantation Lymphoproliferative Disorders
Diagnosis and Staging
Treatment
References
40: Pulmonary Manifestations of Hematological Malignancies
Introduction
Noninfectious Pulmonary Complications of Hematological Malignancies: Non-HSCT Related
HSCT-Related Noninfectious Pulmonary Complications
Early Onset Pulmonary Complications Following HSCT
Late-Onset Pulmonary Complications
Bronchiolitis Obliterans (BO)
Pathophysiology
Diagnosis
Management of BOS
Post-HSCT Organizing Pneumonia
Other Late-Onset NonInfectious Pulmonary Complications (LONIPCs)
Conclusion
References
41: Pulmonary Hypertension in Orphan Lung Diseases
Introduction
Classification of Pulmonary Hypertension
Pulmonary Hypertension Associated with Sarcoidosis (Group 5.2)
PH Associated with Pulmonary Langerhans Cell Histiocytosis (Group 5.2)
PH in Combined Pulmonary Fibrosis and Emphysema (Group 3.3)
PH Associated with Neurofibromatosis Type 1 (Group 5.2)
PH Associated with Lymphangioleiomyomatosis (Group 3)
Hereditary Hemorrhagic Telangiectasia (Group 1.2)
Pulmonary Veno-Occlusive Disease (Group 1.5)
Small Patella Syndrome (Group 1.2)
Conclusion
References
42: Drug-Induced/Iatrogenic Respiratory Disease: With Emphasis on Unusual, Rare, and Emergent Drug-Induced Reactions
Introduction
Epidemiology
Timing, Chronology, Delay Time
Route of Administration
Patterns of Involvement [3, 4]
Diagnosing Drug-Induced Respiratory Disease (DIRD)
Uncommon and Rare Drug-Induced/Iatrogenic Respiratory Disease
Drugs and Agents Fallen Out of Favor
Potentially Life-Threatening Drug-Induced/Iatrogenic Emergencies (Table 42.6)
Acute Drug-Induced/Iatrogenic Emergencies with Diffuse Pulmonary Infiltrates and ARDS (Table 42.7)
Drug-Induced Noncardiac Pulmonary Edema
Drug-Induced Cardiogenic Pulmonary Edema
The “Chemotherapy Lung”
Drug-Induced/Iatrogenic Alveolar Hemorrhage
Drugs
Superwarfarin Rodenticides
Transfusion Reactions: TACO–TRALI
Acute Cellular Interstitial/Infiltrative Lung Diseases
Acute Cellular Nonspecific Interstitial Pneumonia Pattern
Acute Eosinophilic Pneumonia
Acute Granulomatous Interstitial Lung Disease
Acute Organizing Pneumonia (OP), Bronchiolitis Obliterans Organizing Pneumonia (BOOP), or Acute Fibrinous Organizing Pneumonia (AFOP) Patterns
Acute Amiodarone-Induced Pulmonary Toxicity (AIPT)
Accelerated Pulmonary Fibrosis
Acute Exacerbation of Previously Known (Idiopathic) Pulmonary Fibrosis
Anaphylaxis
Acute Vasculopathy
Drug-Induced/Iatrogenic Airway Emergencies
Airway Obstruction as a Manifestation of Anaphylaxis
Drug-Induced Angioedema
Hematoma Around the Upper Airway
The “Pill Aspiration Syndrome”
Catastrophic Drug-Induced Bronchospasm
Peri-operative Emergencies (Table 42.8)
Other Rare Presentations
Pulmonary Nodules and Masses
Pleuroparenchymal Fibroelastosis
Late Radiation-Induced Injury
Chest Pain
Rebound Phenomenon
Recall Pneumonitis
Thoracic Bezoars: Gossipybomas
Respiratory Diseases Considered Idiopathic That May Be Drug-Induced (Table 42.4)
Eye Catchers
Conclusion
References
43: Malignant Mimics of Orphan Lung Diseases
Cancer Mimicking Orphan Lung Disease at Imaging
Cancer Mimics of Organizing Pneumonia
Lung Adenocarcinoma/Bronchioloalveolar Carcinoma
Primary Pulmonary Lymphoma
Cancer Mimics of Interstitial Lung Diseases
Lymphangitic Carcinomatosis
Epithelioid Hemangio-Endothelioma
Lymphomatoid Granulomatosis
Cancer Mimics of Multiple Cystic/Cavitary Lung Disorders
Cystic Tumors
Cavitating Tumors
Cancer Mimics of Pulmonary Hypertension: Pulmonary Artery Sarcoma
Intrathoracic Pseudotumors
Inflammatory Myofibroblastic Tumor
Sclerosing Mediastinitis and Hyalinising Granuloma
Borderline Neoplastic-Non Neoplastic Disorders
Respiratory Papillomatosis
Amyloid and Non-amyloid Immunoglobulin Deposition Disorders
Pulmonary Langerhans Cell Histiocytosis
Lessons Learned: Rare Tumors Vs. Orphan Lung Diseases
References
Index