- •Preface to the First Edition
- •Preface to the Second Edition
- •Contents
- •Diagnostic Challenges
- •Expert Centers
- •Patient Organizations
- •Clinical Trials
- •Research in Orphan Lung Diseases
- •Orphan Drugs
- •Orphanet
- •Empowerment of Patients
- •Conclusions
- •References
- •Introduction
- •Challenges to Overcome in Order to Undertake Quality Clinical Research
- •Lack of Reliable Data on Prevalence
- •Small Number of Patients
- •Identifying Causation/Disease Pathogenesis
- •Disease Complexity
- •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
- •Concluding Remarks
- •References
- •3: Chronic Bronchiolitis in Adults
- •Introduction
- •Cellular Bronchiolitis
- •Follicular Bronchiolitis
- •Respiratory Bronchiolitis
- •Airway-Centered Interstitial Fibrosis
- •Proliferative Bronchiolitis
- •Diagnosis
- •Chest Imaging Studies
- •Pulmonary Function Testing
- •Lung Biopsy
- •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
- •Treatment
- •Constrictive Bronchiolitis
- •Follicular Bronchiolitis
- •Airway-Centered Interstitial Fibrosis
- •Proliferative Bronchiolitis
- •References
- •Background and Epidemiology
- •Pathophysiology
- •Host Characteristics
- •Clinical Manifestations
- •Symptoms
- •Laboratory Evaluation
- •Skin Testing
- •Serum Precipitins
- •Eosinophil Count
- •Total Serum Immunoglobulin E Levels
- •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
- •General Diagnostic Recommendations
- •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
- •Clinical Features
- •Pulmonary Function Studies
- •Imaging Studies
- •Bronchoscopy
- •Treatment
- •Introduction and Clinical Presentation
- •Clinical Features
- •Pulmonary Function Studies
- •Imaging Studies
- •Bronchoscopy
- •Treatment
- •Tracheomalacia
- •Introduction
- •Clinical Features
- •Pulmonary Function Studies
- •Imaging Studies
- •Bronchoscopy
- •Treatment
- •Tracheobronchomegaly
- •Introduction
- •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
- •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
- •6: Amyloidosis and the Lungs and Airways
- •Introduction
- •Diagnosis and Evaluation of Amyloidosis
- •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
- •Conclusions
- •References
- •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
- •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
- •Pediatric GPA
- •Diagnosis
- •Diagnostic Approach
- •Laboratory Investigations
- •Biology
- •Immunology
- •Pathology
- •Treatment
- •Glucocorticoids
- •Cyclophosphamide
- •Rituximab
- •Other Current Induction Approaches
- •Other Treatments in GPA
- •Intravenous Immunoglobulins
- •Plasma Exchange
- •CTLA4-Ig (Abatacept)
- •Cotrimoxazole
- •Other Agents
- •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
- •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
- •Pulmonary Capillary Hemangiomatosis
- •Treatment
- •Conclusions
- •References
- •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
- •Therapeutic Management
- •Treatment of PAA
- •Treatment of PAT
- •Prognosis
- •References
- •Introduction
- •Portopulmonary Hypertension (PoPH)
- •Epidemiology and Risk Factors
- •Molecular Pathogenesis
- •PoPH Treatment
- •Hepatopulmonary Syndrome (HPS)
- •Epidemiology and Risk Factors
- •Molecular Pathogenesis
- •HPS Treatment
- •Conclusion
- •References
- •12: Systemic Sclerosis and the Lung
- •Introduction
- •Risk factors for SSc-ILD
- •Genetic Associations
- •Clinical Presentation of SSc-ILD
- •Pulmonary Function Tests (PFTs)
- •Imaging
- •Management
- •References
- •13: Rheumatoid Arthritis and the Lungs
- •Introduction
- •Epidemiology
- •Risk Factors for ILD (Table 13.3)
- •Pathogenesis
- •Clinical Features and Diagnosis
- •Treatments
- •Prognosis
- •Epidemiology
- •Risk Factors
- •Clinical Features, Diagnosis, and Outcome
- •Subtypes or RA-AD
- •Obliterative Bronchiolitis
- •Bronchiectasis
- •COPD
- •Cricoarytenoid Involvement
- •Pleural Disease
- •Conclusion
- •References
- •Introduction
- •Systemic Lupus Erythematosus
- •Epidemiology
- •Pathophysiology
- •Pulmonary Manifestations
- •Pleural Disease
- •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
- •Lung Transplantation
- •Conclusion
- •References
- •Introduction
- •Diagnostic Criteria
- •Controversies in the Diagnostic Criteria
- •Typical Clinical Features
- •Disease Progression and Prognosis
- •Summary
- •References
- •Introduction
- •Histiocytes and Dendritic Cells
- •Introduction
- •Cellular and Molecular Pathogenesis
- •Pathology
- •Clinical Presentation
- •Treatment and Prognosis
- •Erdheim-Chester Disease
- •Epidemiology
- •Cellular and Molecular Pathogenesis
- •Histopathology and Immunohistochemistry
- •Clinical Presentation
- •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
- •Epidemiology
- •Etiology/Pathophysiology
- •Histopathology and Immunohistochemistry
- •Clinical Presentation
- •Investigation/Diagnosis
- •Management/Treatment
- •Prognosis
- •Conclusions
- •Diagnostic Criteria for Primary Histiocytic Disorders of the Lung
- •References
- •17: Eosinophilic Pneumonia
- •Introduction
- •Eosinophil Biology
- •Physiologic and Immunologic Role of Eosinophils
- •Release of Mediators
- •Targeting the Eosinophil Cell Lineage
- •Historical Perspective
- •Clinical Presentation
- •Pathology
- •Diagnosis
- •Eosinophilic Lung Disease of Undetermined Cause
- •Idiopathic Chronic Eosinophilic Pneumonia
- •Clinical Features
- •Imaging
- •Laboratory Studies
- •Bronchoalveolar Lavage
- •Lung Function Tests
- •Treatment
- •Outcome and Perspectives
- •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
- •Treatment and Prognosis
- •Long-Term Outcome
- •Hypereosinophilic Syndrome
- •Pathogenesis
- •Clinical and Imaging Features
- •Laboratory Studies
- •Treatment and Prognosis
- •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
- •Miscellaneous Lung Diseases with Associated Eosinophilia
- •References
- •Introduction
- •Pulmonary Langerhans’ Cell Histiocytosis
- •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
- •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
- •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
- •Lymphangioleiomyomatosis
- •Pathogenesis
- •Pathologic and Radiographic Characteristics
- •Diagnostic Approach
- •Pulmonary Langerhans Cell Histiocytosis (PLCH)
- •Pathogenesis
- •Pathological and Radiographic Characteristics
- •Diagnostic Approach
- •Birt-Hogg-Dubé Syndrome (BHD)
- •Pathogenesis
- •Pathological and Radiographic Characteristics
- •Diagnostic Approach
- •Lymphoproliferative Disorders
- •Pathogenesis
- •Pathological and Radiographic Characteristics
- •Diagnostic Approach
- •Amyloidosis
- •Light Chain Deposition Disease (LCDD)
- •Conclusion
- •References
- •Introduction
- •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
- •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
- •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
- •Introduction
- •Epidemiology
- •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)
- •GER and Acute Exacerbations of IPF
- •Suggested Approach
- •Summary and Future Directions
- •References
- •Introduction
- •Familial Interstitial Pneumonia
- •Telomere Related Genes
- •Genetic
- •Telomere Length
- •Pulmonary Involvement
- •Interstitial Lung Disease
- •Other Lung Disease
- •Hepatopulmonary Syndrome
- •Emphysema
- •Extrapulmonary Manifestations
- •Mucocutaneous Involvement
- •Hematological Involvement
- •Liver Involvement
- •Other Manifestations
- •Treatment
- •Telomerase Complex Agonists
- •Lung Transplantation
- •Surfactant Pathway
- •Surfactant Protein Genes
- •Pulmonary Involvement
- •Treatment
- •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
- •Introduction
- •Pathophysiology
- •Clinical Presentation
- •Epidemiology
- •Genetic Causes of Bronchiectasis
- •Disorders of Mucociliary Clearance
- •Cystic Fibrosis
- •Primary Ciliary Dyskinesia
- •Other Ciliopathies
- •X-Linked Agammaglobulinemia
- •Chronic Granulomatous Disease and Other Disorders of Neutrophil Function
- •Other Genetic Disorders Predisposing to Bronchiectasis
- •Idiopathic Bronchiectasis
- •Diagnosis of Bronchiectasis
- •Management of Patients with Bronchiectasis
- •Airway Clearance Therapy (ACT)
- •Management of Infections
- •Immune Therapy
- •Surgery
- •Novel Therapies for Managing Cystic Fibrosis
- •Summary
- •References
- •Pulmonary Arteriovenous Malformations
- •Background Pulmonary AVMs
- •Anatomy Pulmonary AVMs
- •Clinical Presentation of Pulmonary AVMs
- •Screening Pulmonary AVMs
- •Treatment Pulmonary AVMs
- •Children with Hereditary Hemorrhagic Telangiectasia
- •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
- •Introduction
- •Hermansky-Pudlak Syndrome
- •Telomerase-Associated Pulmonary Fibrosis
- •Lysosomal Storage Diseases
- •Lysinuric Protein Intolerance
- •Familial Hypocalciuric Hypercalcemia
- •Surfactant Dysfunction Disorders
- •Concluding Remarks
- •References
- •Introduction
- •Background
- •Image Acquisition
- •Key Features of Fibrosis
- •Ancillary Features of Fibrosis
- •Other Imaging Findings in FLD
- •Probable UIP-IPF
- •Indeterminate
- •Alternative Diagnosis
- •UIP in Other Fibrosing Lung Diseases
- •Pleuroparenchymal Fibroelastosis (PPFE)
- •Combined Pulmonary Fibrosis and Emphysema
- •Chronic Hypersensitivity Pneumonitis
- •Other Fibrosing Lung Diseases
- •Fibrosing Sarcoidosis
- •CTD-ILD and Drug-Induced FLD
- •Complications
- •Prognosis
- •Computer Analysis of CT Imaging
- •The Progressive Fibrotic Phenotype
- •Other Imaging Techniques
- •Conclusion
- •References
- •Introduction
- •Bronchoalveolar Lavage (BAL)
- •Technique
- •Interpretation
- •Transbronchial Biopsy (TBB)
- •Transbronchial Lung Cryobiopsy (TLCB)
- •References
- •Introduction
- •Overview of ILD Diagnosis
- •Clinical Assessment
- •Radiological Assessment
- •Laboratory Assessment
- •Integration of Individual Features
- •Multidisciplinary Discussion
- •Diagnostic Ontology
- •Conclusions
- •References
- •Introduction
- •Idiopathic Pulmonary Fibrosis
- •Chronic Hypersensitivity Pneumonitis
- •Connective Tissue Disease
- •Drug-Induced Lung Diseases
- •Radiation Pneumonitis
- •Asbestosis
- •Hermansky-Pudlak Syndrome
- •Risk Factors for Progression
- •Diagnosis
- •Pharmacological Management
- •Conclusions
- •References
- •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
- •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
- •Acute Interstitial Pneumonia (AIP)
- •Epidemiology
- •Presentation
- •Diagnostic Evaluation
- •Radiology
- •Histopathology
- •Clinical Course
- •Treatment
- •Epidemiology
- •Presentation
- •Diagnostic Evaluation
- •Radiology
- •Histopathology
- •Clinical Course
- •Desquamative Interstitial Pneumonia (DIP)
- •Presentation
- •Diagnostic Evaluation
- •Radiology
- •Histopathology
- •Clinical Course
- •Treatment
- •Epidemiology
- •Presentation
- •Diagnostic Evaluation
- •Radiology
- •Histopathology
- •Clinical Course
- •Treatment
- •References
- •Organizing Pneumonias
- •Epidemiology
- •Pathogenesis
- •Clinical Features
- •Imaging
- •Multifocal Form
- •Isolated Nodular Form
- •Other Imaging Patterns
- •Histopathological Diagnosis of OP Pattern
- •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
- •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
- •Introduction
- •Acute Berylliosis
- •Chronic Beryllium Disease
- •Exposure
- •Epidemiology
- •Immunopathogenesis and Pathology
- •Genetics
- •Clinical Description and Natural History
- •Treatment and Monitoring
- •Indium–Tin Oxide-Lung Disease
- •Hard Metal Lung
- •Flock Worker’s Disease
- •Asbestosis
- •Nanoparticle Induced ILD
- •Flavoring-Induced Lung Disease
- •Silica-Induced Interstitial Lung Disease
- •Chronic Silicosis
- •Acute and Accelerated Silicosis
- •Chronic Obstructive Disease in CMDLD
- •Simple CMDLD
- •Complicated CMDLD
- •Conclusion
- •References
- •38: Unclassifiable Interstitial Lung Disease
- •Introduction
- •Diagnostic Scenarios
- •Epidemiology
- •Clinical Presentation
- •Diagnosis
- •Clinical Features
- •Radiology
- •Laboratory Investigations
- •Pathology
- •Conclusion
- •References
- •39: Lymphoproliferative Lung Disorders
- •Introduction
- •Nodular Lymphoid Hyperplasia
- •Lymphocytic Interstitial Pneumonia (LIP)
- •Follicular Bronchitis/Bronchiolitis
- •Castleman Disease
- •Primary Pulmonary Lymphomas
- •Primary Pulmonary MALT B Cell Lymphoma
- •Pulmonary Plasmacytoma
- •Follicular Lymphoma
- •Lymphomatoid Granulomatosis
- •Primary Pulmonary Hodgkin Lymphoma (PPHL)
- •Treatment
- •References
- •Introduction
- •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
- •Introduction
- •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 Lymphangioleiomyomatosis (Group 3)
- •Hereditary Hemorrhagic Telangiectasia (Group 1.2)
- •Pulmonary Veno-Occlusive Disease (Group 1.5)
- •Small Patella Syndrome (Group 1.2)
- •Conclusion
- •References
- •Introduction
- •Epidemiology
- •Timing, Chronology, Delay Time
- •Route of Administration
- •Patterns of Involvement [3, 4]
- •Drugs and Agents Fallen Out of Favor
- •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 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
- •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
- •Cystic Tumors
- •Cavitating Tumors
- •Intrathoracic Pseudotumors
- •Respiratory Papillomatosis
- •Pulmonary Langerhans Cell Histiocytosis
- •References
- •Index
Vincent Cottin ·
Luca Richeldi · Kevin Brown ·
Francis X. McCormack Editors
Orphan Lung
Diseases
A Clinical Guide to Rare Lung Disease
Second Edition
123
Orphan Lung Diseases
Vincent Cottin • Luca Richeldi
Kevin Brown • Francis X. McCormack
Editors
Orphan Lung Diseases
A Clinical Guide to Rare Lung Disease
Second Edition
Editors |
|
Vincent Cottin |
Luca Richeldi |
Department of Respiratory Medicine, National |
Fondazione Policlinico A. Gemelli IRCCS |
Coordinating Reference Centre for Rare |
Università Cattolica del Sacro Cuore |
Pulmonary Diseases (OrphaLung) |
Roma, Italy |
Louis Pradel Hospital, University of Lyon |
|
Lyon, France |
Francis X. McCormack |
|
Division of Pulmonary, Critical Care, and |
Kevin Brown |
Sleep Medicine |
National Jewish Health |
Department of Internal Medicine |
Denver, CO, USA |
University of Cincinnati |
|
Cincinnati, OH, USA |
ISBN 978-3-031-12949-0 ISBN 978-3-031-12950-6 (eBook) https://doi.org/10.1007/978-3-031-12950-6
© The Editor(s) (if applicable) and TheAuthor(s), under exclusive license to Springer Nature SwitzerlandAG 2015, 2023 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifcally the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microflms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed.
The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specifc statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use.
The publisher, the authors, and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affliations.
This Springer imprint is published by the registered company Springer Nature Switzerland AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland
This book is dedicated to Claudia, and to patients who suffer from rare pulmonary diseases and serve as a constant reminder of the importance of our commitment.
Vincent Cottin
Preface to the First Edition
So-called orphan diseases are those conditions that attract little interest by physicians and scientists, which are not widely researched, and where specifc treatments are lacking. Orphan diseases are nevertheless characterized by particularly high needs and expectations from patients, who feel abandoned in the world of health care and expect their treating physician to make every possible effort to help them by managing at best their disease. However, as one cannot expect physicians to be knowledgeable with each of the 6000–8000 orphan diseases, they generally lack experience of most orphan diseases and are left with insuffcient knowledge to manage these patients. Indeed, most orphan diseases are rare, at least in Europe and North America. Not all orphan diseases are rare, however, and especially neglected tropical infectious diseases are endemic in Africa, Asia, and the Americas, affecting one billion people worldwide and causing tremendous morbidity and mortality.
Rare diseases are defned numerically. In Europe, a disease is rare if it affects fewer than 1 person in 2000. In the USA, a rare disease is a disease that affects fewer than 200,000 people or that affects more than 200,000 but for which there is no reasonable expectation to be economically proftable, with the cost of drug development and availability for such a disease to be recovered from sales. Overall, given the plethora of different conditions, rare diseases are a major health-care burden worldwide. Regarding lung medicine alone, it is estimated that 1.5–3 million Europeans and 1.2–2.5 million Americans are affected by a rare lung disease.
Despite the many diffculties and obstacles, the new millennium witnessed an astonishing gain in the momentum to improve our understanding and the management of many rare diseases, some of which are, therefore, no longer orphan. Interest in rare diseases has increased greatly worldwide. Patients with orphan diseases have joined associations providing them with a previously unknown sense of community, unprecedented awareness, and strong advocacy for more research and better treatments. A steadily increasing number of international organizations and websites contribute to education, support, and research. Governments and agencies have introduced incentives to encourage the pharmaceutical industry to invest in research despite the small target populations. Specialized centers and clinical networks are now developing and have been identifed in many countries: This crucial step provides up-to-date management to patients, allows basic and clinical research, establishes registries, interacts with regulatory agencies, and supports patient associations. Novel conditions and syndromes are discovered. The genetic determinants of many diseases and their underlying pathophysiology are progressively better understood. An increasing number of drug candidates are identifed and may be granted an orphan drug designation with more clinical trials completed, thereby leading to the approval and licensing of drugs in diseases heretofore considered not treatable. Diseases such as pulmonary arterial hypertension and idiopathic pulmonary fbrosis, formerly devoid of any treatment, are now treatable although they are still deadly severe and not curable.
In this context, diagnosing and managing patients with orphan pulmonary diseases is an increasing challenge to pulmonologists and internal medicine specialists as it is increasingly diffcult to keep up to the current pace of growth of knowledge, especially in basic science. To witness the evolution of this feld is tremendously stimulating since progress made in pathophysiology, organization of care, and management rapidly translates into clinical practice for
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Preface to the First Edition |
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the beneft and better-being of patients. As progress continues, it is sure that additional diagnostic instruments and treatment options will soon be available. We, as doctors, should not let our patients miss any opportunity to get the correct diagnosis (avoiding unnecessary procedures) and the best management. Our goal in this book is to provide synthesized and easily accessible information about the main orphan lung diseases. Although some literature is available through original articles and review articles, it is often diffcult to fnd in a timely manner the answers to questions that clinicians caring for patients are facing. They will fnd here information oriented toward clinical practice, especially the diagnostic approach (including manifestations suggesting the disease, methods for diagnostic confrmation, diagnostic criteria, and differential diagnosis). The reader will understand that although comprehensive and covering most rare and orphan pulmonary diseases, this textbook is not fully exhaustive in an attempt to keep its size reasonable. Topics are divided into fve parts, respectively, on diseases affecting the airways, systemic disorders with lung involvement, orphan conditions limited to the lung, interstitial lung diseases, and miscellaneous conditions with lung involvement (for which information is not readily available elsewhere). We are very grateful to the authors, all leading experts experienced in the feld, who contributed time and effort to this endeavor and committed to provide clinically oriented manuscripts with a comprehensive overview, rich illustrations, real case examples, and guidance for the diagnostic process. They shared their expert opinion when evidence base was lacking, as it is often the case in this setting. We hope people will like this book and fnd it useful and look forward to hearing comments, suggestions, and feedback so that the next edition can be even better.
Successful examples have demonstrated that despite constraint resources, the concerted effort of dedicated patient organizations, clinicians, academic researchers, pharmaceutical companies, and health authorities can translate into major progress. We strongly hope that this book will contribute to the better sharing of knowledge on orphan lung diseases for the immediate beneft of our patients.
Lyon, France\ |
Vincent Cottin |
Roma, Italy\ |
Luca Richeldi |
Lyon, France\ |
Jean-François Cordier |
Preface to the Second Edition
The frst edition of Orphan Lung Diseases: A Clinical Guide to Rare Lung Disease was published in 2015. The book was very well received, as rare lung diseases are increasingly attracting attention, especially in the context of very active research on new treatments, with the milestone represented by the approval in 2014 of antifbrotic drugs to treat idiopathic pulmonary fbrosis. The book covers the feld of rare pulmonary diseases as a whole, and not just interstitial lung diseases, which of course represent the largest share. Due to the progress in the feld, the variably limited number of patients with each condition, and the number of conditions involved, it is very diffcult for clinicians to remain current in this feld. However, patients with rare pulmonary diseases collectively represent a signifcant fraction of the patients followed by practicing pulmonologists, as well as rheumatologists, internists, and other specialists. With the possible exception of idiopathic pulmonary fbrosis and progressive pulmonary fbrosis, rare pulmonary diseases typically receive less attention by clinicians, researchers, and industry than those more frequently seen in daily clinics. This textbook is oriented toward clinical practice and is accessible online, to provide busy practitioners with ready access to information needed in a timely manner.
The main change for the second edition is that the number of chapters has been increased from 36 in the previous edition to the current 43, now divided into seven parts. This enabled us to create new chapters on topics that have become increasingly relevant, such as pleuropulmonary fbroelastosis, unclassifable interstitial lung disease, complex thoracic lymphatic disorders of adults, and interstitial pneumonia with autoimmune features and overlap interstitial pneumonia. The parts on interstitial lung diseases and on systemic disorders with lung involvement have been expanded to better cover these important felds, and new chapters were created on diagnostic modalities, including separate chapters on imaging, bronchoscopic and integrated diagnostic approaches to interstitial lung diseases. A new part on rare lung diseases of genetic origin has been included: genetic and familial pulmonary fbrosis related to monogenic diseases, diffuse bronchiectasis of genetic or idiopathic origin, pulmonary vascular manifestations of hereditary hemorrhagic telangiectasia, pulmonary alveolar microlithiasis, and rare diffuse lung diseases of genetic origin. Although no book could hope to cover the immense and ever-growing area of rare pulmonary diseases, we welcome suggestions for the next edition.
The editorial board was joined by two new editors, Dr Kevin K. Brown and Dr Francis McCormack, who brought new ideas and expertise. As Prof. J.F. Cordier has now retired, this new edition was supervised by four editors. We also welcome new authors coming from a variety of countries and regions. As in the previous edition, our goal in this book was to synthesize and organize emerging clinical and research advances in an easily accessible format that is oriented toward the practicing clinician. We thank all authors who have dedicated time to this textbook, and have provided clinically oriented manuscripts, comprising numerous illustrations, representative case examples, and guidance for both the diagnostic process and the practical management, often without the luxury of offcial diagnostic criteria or guidelines.
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In rare diseases, expert opinion is key when evidence is lacking, and we are very grateful to the authors to have shared their experience to guide the clinicians in their practice. Our sincere wish is that this book may beneft the care of our patients.
Lyon, France\ |
Vincent Cottin |
Roma, Italy\ |
Luca Richeldi |
Denver, CO, USA\ |
Kevin Brown |
Cincinnati, OH, USA\ |
Francis X. McCormack |