- •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
39 Lymphoproliferative Lung Disorders |
703 |
|
|
References
1.\Poletti V, Colella S, Piciucchi S, et al. Haematological disorders and bone marrow transplant recipients. In: Wuyts WA, Cottin V, Spagnolo P, Wells AU, editors. Pulmonary manifesations of systemic diseases. (ERS monograph); 2019. p. 333–58.
2.\Swerdlow SH, Campo E, Harris NL, et al. WHO classifcation of tumours of haematopoietic and lymphoid tissues. Lyon: IARC; 2017.
3.\Fishback N, Koss M. Update on lymphoid interstitial pneumonitis. Curr Opin Pulm Med. 1996;2:429–533.
4.\Escalon JG, Richards JC, Koelsch T, Downey GP, Lynch DA. Isolated cystic lung disease: an algorithmic approach to distinguishing Birt-Hogg-Dubè syndrome, lymphangioleiomyomatosis and lymphocytic interstitial pneumonia. AJR. 2019;212:1260–4.
5.\Shimakage M, Sakamoto H, Harada S, et al. Expression of the Epstein-Barr virus in lymphoproliferative diseases of the lung. Oncol Rep. 2007;17:1347–52.
6.\Bhoopat L, Rangkakulnuwat S, Ya-In C, et al. Relationship of cell bearing EBER and p24 antigens in biopsy-proven lymphocytic interstitial pneumonia in HIV-1 subtype E infected children. Appl Immunohistochem Mol Morphol. 2011;19:547–51.
7.\Yousem SA, Colby TV, Carrington CB. Follicular bronchitis/bronchiolitis. Hum Pathol. 1985;16:700–6.
8.\Castleman B, Iverson L, Menendez VP. Localized mediastinal lymphnode hyperplasia resembling thymoma. Cancer. 1956;9:822–30.
9.\Wu D, Lim MS, Jaffe ES. Pathology of Castleman disease. Hematol Oncol Clin N Am. 2018;32:37–52.
10.\Igawa T, SatoY. TAFRO syndrome. Hematol Oncol Clin North Am. 2018;32:107–18.
11.\Oksenhendler E. Maladies de Castleman. In: Guillevin L, Meyer O, Hachulla E, et al., editors. Traité de Maladies et syndromes systematiques. 6th ed. Paris: Lavoisier Medicine Sciences; 2015. p. 1064–76.
12.\Terasaki Y, Ikushima S, Matsui S, et al. Comparison of clinical and pathological features of lung lesions of systemic IgG4- related disease and idiopathic multicentric Castleman’s disease. Histopathology. 2017;70:1114–24.
13.\Borie R, Cadranel J, Guihot A, et al. Pulmonary manifestations of human herpesvirus-8 during HIV infection. Eur Respir J. 2013;42:1105–18.
14.\Fajgenbaum DC. Novel insights and therapeutic approaches in idiopathic multicentric Castleman disease. Blood. 2018;132:2323–30.
15.\Van Rhee F, Voorhees P, Dispenzieri A, et al. International, evidence-based consensus treatment guidelines for idiopathic multicentric Castleman disease. Blood. 2018;132:2115–24.
16.\Ahmed S, Kussick SJ, Siddiqui AK, et al. Bronchial-associated lymphoid tissue lymphoma: a clinical study of a rare disease. Eur J Cancer. 2004;40:1320–6.
17.\Adam P, Czapiewski P, Colak S, et al. Prevalence of Achromobacter xyloxidans in pulmonary mucosa associated lymphoid tissue lymphoma in different regions of Europe. Br J Haematol. 2014;164:804–10.
18.\Cordier J, Chailleux E, Lauque D, et al. Primary pulmonary lymphomas. A clinical study of 70 cases in non immunocompromised patients. Chest. 1993;103:201–8.
19.\Borie R, Wislez M, Thabut G, et al. Clinical characteristics and prognostic factors of pulmonary MALT lymphoma. Eur Respir J. 2009;34:1408–16.
20.\Isaacson PG, Du MQ. MALT lymphoma: from morphology to molecules. Nat Rev Cancer. 2004;4:644–453.
21.\Zucca E, Bertoni F. The spectrum of MALT lymphoma at different sites. Biological and therapeutic relevance. Blood. 2016;127:2082–92.
22.\Habermann TM, Ryu JH, Inwards DJ, et al. Primary pulmonary lymphoma. Semin Oncol. 1999;26:307–15.
23.\Borie R, Wislez M, Antoine M, Cadranel J. Lymphoproliferative disorders of the lung. Respiration. 2017;94:157–75.
24.\King LJ, Padley SP, Wotherspoon AC, Nicholson AG. Pulmonary MALT lymphoma: imaging fndings in 24 cases. Eur Radiol. 2000;10:1932–8.
25.\Kurtin PJ, Myers JL, Adlakha H, et al. Pathologic and clinical features of primary pulmonary extranodal marginal zone B-cell lymphoma of MALT type. Am J Surg Pathol. 2001;25:997–1008.
26.\Nicholson AG, Wotherspoon AC, Diss TC, et al. Pulmonary B-cell non-Hodgkin’s lymphomas. The value of immunohistochemistry and gene analysis in diagnosis. Histopathology. 1995;26:395–403.
27.\Shaikh G, Sehgal R, Mehrishi A, Karnik A. Primary pulmonary plasmacytoma. J Clin Oncol. 2008;26:3089–91.
28.\Shah BK, Shrestha A. Pulmonary plasmacytoma. J Thorac Oncol. 2012;7:923.
29.\Horiuchi T, Hirokawa M, Oyama Y, Kitabayashi A, Satoh K, Shindoh T, et al. Diffuse pulmonary infltrates as a roentgeno— graphic manifestation of primary pulmonary plasmacytoma. Am J Med. 1998;105:72–4.
30.\Cheah CY, Lingaratnam S, Seymour JF. Rituximab for the treatment of follicular lymphoma. Future Oncol. 2013;9:1283–98.
31.\Morice WG, Colby TV. Lymphoproliferative lung diseases. In: Tomashefski Jr JF, editor. Dail and Hammar’s pulmonary pathology. 3rd ed. Berlin: Springer; 2015. p. 1–46.
32.\Chilosi M, Zinzani PL, Poletti V. Lymphoproliferative lung disorders. Semin Respir Crit Care Med. 2005;26:490–501.
33.\Li G, Hansmann ML, Zwingers T, Lennert K. Primary lymphomas of the lung: morphological, immunohistochemical and clinical features. Histopathology. 1990;16:519–31.
34.\Poletti V, Gurioli C, Piciucchi S, Rossi A, Ravaglia C, Dubini A, Asioli CGL. Intravascular large B cell lymphoma presenting in the lung:the diagnostic value of transbronchial cryobiopsy. Sarcoidosis Vasc Diffuse Lung Dis. 2015;31:354–8.
35.\Lee JS, Tuder R, Lynch DA. Lymphomatoid granulomatosis: radiologic, features and pathologic correlations. Am J Roentgenol. 2000;175:1335–133.
36.\Sukswai N, Lyapichev K, Khoury JD, Medeiros LJ. Diffuse large B-cell lymphoma variants:an update. Pathology. 2020;52:53–67.
37.\Travis WD, Brambilla E, Műller-Hermelink HK, Harris CC. WHO: pathology and genetics of tumours of the lung, pleura, thymus and heart. Lyon: IARC Press; 2004.
38.\Bolaman Z, Kadikoylu G, Polatli M, Barutca S, Culhaci N, Senturk T. Migratory nodules in the lung: lymphomatoi granulomatosis. Leuk Lymphoma. 2003;44:197–200.
39.\Siegloch K, Schmitz N, Wu HS, et al. Hematopoietic stem cell transplantation in patients with lymphomatoid granulomatosis: a European group for blood and marrow transplantation report. Biol Blood Marrow Transplant. 2013;19:1522–5.
40.\Aoki T, Harada Y, Matsubara E, et al. Long-term remission after multiple relapses in an elderly patient with lymphomatoid granulomatosis after rituximab and high-dose cytarabine chemotherapy without stem-cell transplantation. J Clin Oncol. 2013;31:e390.
41.\Shet T, Suryawanshi P, Epari S, et al. Extranodal natural killer/T cell lymphomas with extranasal disease in non-endemic regions are disseminated or have nasal primary: a study of 84 cases from India. Leuk Lymphoma. 2014;55:2748–53.
42.\Au WY, Weisenburger DD, Intragumtornchai T, Nakamura S, Kim WS, Sng I, et al. Clinical differences between nasal and extranasal natural killer/T-cell lymphoma: a study of 136 cases from the international peripheral T-cell lymphoma project. Blood. 2009;113:3931–7.
43.\Tse E, Kwong YL. NK/T cell lymphomas. Best Pract Res Clin Haematol. 2019;32:253–61.
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
704 |
V. Poletti et al. |
|
|
44.\Sverzellati N, Poletti V, Chilosi M, Casoni GL, Hansell DM, Zompatori M. The crazy-paving pattern in granulomatous mycosis fungoides: HRTC-pathologic correlation. J Comput Assist Tomogr. 2006;30:843–5.
45.\Yousen SA, Weiss LM, Colby TV. Primary pulmonary Hodgkin’s disease. Cancer. 1986;57:1217–724.
46.\Radin AI. Primary pulmonary Hodgkin’s disease. Cancer. 1990;65:550–63.
47.\Cartier Y, Johkoh T, Honda O, Müller NL. Primary pulmonary Hodgkin’s disease: CT fndings in three patients. Clin Radiol. 1999;54:182–4.
48.\Romero S, Montoro J, Guinot M, et al. Post-transplant lymphoproliferative disorders after solid organ and hematopoietic stem cell transplantation. Leuk Lymphoma. 2019;60:142–50.
49.\Yoon GY, Kim MY, Shim TS. Posttransplant lymphoproliferative disorder of the thorax: CT and FDG-PET features in a single tertiary referral center. Medicine (Baltimore). 2015;94:e1274.
50.\Poletti V, Chilosi M, Olivieri D. Diagnostic invasive procedures in diffuse infltrative lung diseases. Respiration. 2004;71:107–19.
51.\Poletti V, editor. Transbronchial cryobiopsy in diffuse parenchymal lung diseases. Berlin: Springer; 2019.
52.\Iqbal S, Depew ZS, Kurtin PJ, et al. Endobronchial ultrasound and lymphoproliferative disorders: a retrospective study. Ann Thorac Surg. 2012;94:1830–4.
53.\Poletti V, Romagna M, Gasponi A, Baruzzi G, Allen KA. Bronchoalveolar lavage in the diagnosis of low-grade, MALT type, B-cell lymphoma in the lung. Monaldi Arch Chest Dis. 1995;50:191–4.
54.\Zoie S, Couderc LJ, Cadranel J, Antoine MA, Epardeau B, Fleury- Feith J, Popa N, Santoli F, Farcet JP, Delfau-Larue MH. Clonality analysis of alveolar B lymphocytes contributes to the diagnostic strategy in clinical suspicion of pulmonary lymphoma. Blood. 2004;103:3208–15.
55.\Oh SY, Kim WS, Kim JS, et al. Multiple mucosa-associated lymphoid tissue organs involving marginal zone B cell lymphoma: organ-specif c relationships and the prognostic factors. Consortiumfor improving survival of lymphoma study. Int J Hematol. 2010;92:510–7.
56.\de Boer JP, Hiddink RF, Raderer M, et al. Dissemination patterns in non-gastric MALT lymphoma. Haematologica. 2008;93:201–16.
57.\Lenz G, Pasqualucci L, editors. Malignant lymphomas: biology and molecular pathogenesis. Berlin: De Gruyter; 2016.
58.\Zinzani PL, Casadei B, Derenzini E, et al. Extranodal marginal zone B-cell lymphoma of the lung: experience with udarabine and mitoxantrone-containing regimens. Hematol Oncol. 2013;31:183–8.
59.\ZinzaniPL,TuraS,CavoM,LewisRE.Hematology:pathophysiology, diagnosis and treatment. Bologna: Esculapio; 2018.
Pulmonary Manifestations |
40 |
of Hematological Malignancies |
Focus on Pulmonary Chronic Graft-Versus-Host
Disease
Laïla Samy, Louise Bondeelle, and Anne Bergeron
Introduction
Hematological malignancies, such as lymphoma or leukemia, can lead to various pulmonary complications related to the disease itself or its treatment. Although there has been signi cant advancement in the management of these patients over the past two decades, more than half will develop pulmonary complications. Among those cases, one-quarter will be of noninfectious etiology [1]. Hematopoietic stem cell transplantation (HSCT) has become a mainstay of treatment in various hematological diseases, including aplastic anemia, high-risk acute leukemia, myelodysplastic syndrome, and myelo brosis. Despite major advances in HSCT, patients must often manage multiple infectious and noninfectious complications, such as graft-versus-host disease (GVHD), which can involve the lungs in a variety of ways. Thus, pulmonologists should be aware of the potential pulmonary complications that can occur and their treatment. In this chapter, we briefy review nontransplantand transplant- related noninfectious pulmonary complications of hematological malignancies with a particular focus on late noninfectious pulmonary complications occurring after allogeneic HSCT, including bronchiolitis obliterans syndrome.
L. Samy
Service de Pneumologie, Hôpitaux Universitaires de Genève, Genève, Switzerland
Service de Pneumologie, Hôpital Royal-Victoria, Centre Universitaire de Santé McGill, Montréal, QC, Canada e-mail: laila.samy@mcgill.ca
L. Bondeelle · A. Bergeron (*)
Service de Pneumologie, Hôpitaux Universitaires de Genève, Genève, Switzerland
e-mail: louise.bondeelle@aphp.fr; Anne.Bergeron@hcuge.ch
Noninfectious Pulmonary Complications
of Hematological Malignancies: Non-HSCT
Related
When evaluating a patient with a hematological malignancy, pulmonary involvement can be approached according to its pathophysiological process as follows: direct invasion from the malignancy and indirect reactions that can be immunological or treatment related (Table 40.1). First, direct invasion will depend on the underlying malignancy. Lymphoma, for example, can arise in the lung parenchyma. When presenting as a mediastinal mass, compression of airways or neurovascular structures, such as the vena cava, can occur and should be promptly recognized [2]. Chronic lymphocytic leukemia typically in ltrates the lung parenchyma and airways in 26–41% of cases and can be identi ed via monoclonal proliferation in lymphocytic bronchoalveolar lavage fuid or lung or endobronchial biopsy [3–5]. Plasmacytoma in multiple myeloma can manifest as a lung mass and be mistaken for primary lung cancer [6]. Second, there can be a variety of malignancy-related indirect manifestations [7, 8]. For example, acquired pulmonary alveolar proteinosis, characterized by a crazy paving pattern on chest CT and positive PAS staining on bronchoalveolar lavage, has been associated with various hematological malignancies, especially myeloid disorders [8–10]. Third, treatment-related pulmonary complications can occur from direct parenchymal toxicity via drugs or radiation or indirectly from cardiogenic or noncardiogenic pulmonary edema. Many drugs used to treat hematological diseases can cause lung damage. Certain drugs have been associated with different lung involvement, such as pulmonary brosis or diffuse alveolar hemorrhage. Pneumotox.com is a useful French website that collects data on drug-induced lung diseases. Bleomycin, commonly used in Hodgkin’s lymphoma, is a classic example of a drug that can induce lung toxicity. It can induce severe interstitial lung disease that can manifest in various manners from diffuse alveolar damage to interstitial brosis [11–13]. The most frequent drugs associated with lung toxicity are listed in
© Springer Nature Switzerland AG 2023 |
705 |
V. Cottin et al. (eds.), Orphan Lung Diseases, https://doi.org/10.1007/978-3-031-12950-6_40 |
|
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
706 |
L. Samy et al. |
|
|
Table 40.1 Nonspeci c noninfectious pulmonary complications reported in hematological malignancies
Hematological malignancies |
Pulmonary complications |
Acute leukemia |
Organizing pneumonia |
|
Sweet syndrome |
|
Alveolar proteinosis |
|
|
Lymphoma/chronic |
Sarcoid-like granulomatosis |
lymphocytic leukemia |
Langerhans histiocytosis |
|
Lung cancer |
|
|
Myeloma |
Amyloidosis |
|
Venous thromboembolism |
Waldenstöm |
Intra-alveolar hemorrhage |
macroglobulinemia |
Pulmonary edema |
|
Amyloidosis |
|
Lung cancer |
Myelodysplastic/ |
Extramedullary hematopoiesis |
myeloproliferative disorders |
Sweet syndrome |
|
Diffuse in ltrative lung disease in |
|
the context of autoimmune disorders |
|
Eosinophilic pneumonia |
|
Alveolar proteinosis |
|
Organizing pneumonia |
|
Pulmonary hypertension |
|
|
Table 40.2 Main drugs used for the management of patients with hematological malignancies known to induce lung toxicities
Antibiotic |
Bleomycin, Mitomycin C |
chemotherapeutic |
|
agents |
|
|
|
Alkylating agents |
Busulfan, cyclophosphamide, |
|
chlorambucil, melphalan, ifosfamide, |
|
procarbazine |
Antimetabolites |
Methotrexate, 6-mercaptopurine, |
|
cytosine arabinoside, fudarabine |
|
|
Nitrosamines |
Bischloroethyl nitrosourea (BCNU), |
|
chloroethyl cyclohexyl nitrosourea |
|
(CCNU), methyl-CCNU |
|
|
Tubulin-acting agents |
Vinblastine, etoposide |
|
|
Other chemotherapeutic |
All-trans retinoic-acid (ATRA), Imatinib |
agents |
mesylate, dasatinib, bortezomib |
Immune checkpoint |
Ipilimumab, nivolumab, pembrolizumab, |
inhibitors |
atezolizumab |
|
|
Molecular targeted |
Ibrutinib, idelalisib, ruxolitinib, |
agents |
venetoclax |
Immunomodulatory |
Interferons, anti-interleukin-2, TNF |
agents |
alpha inhibitors |
|
|
mTOR inhibitors |
Sirolimus, temsirolimus, everolimus |
|
|
Monoclonal antibodies |
Brentuximab, rituximab, gemtuzumab |
|
ozogamicin, alemtuzumab |
Miscellaneous |
Blood transfusion, GM-CSF, G-CSF |
Table 40.2. Pulmonary cardiogenic or noncardiogenic edema is frequent and can be due to hyperhydration required before chemotherapy, cardiotoxicity secondary to the use of anthracyclines or increased capillary permeability from drugs, such as all-trans-retinoid acid, cytosine arabinoside, imatinib or dasatinib [14]. Hence, once an infectious process has been
excluded, the clinical presentation, CT scan imaging, and very often bronchoscopic examination (BAL +/− biopsies) are all crucial elements in identifying the correct diagnosis.
HSCT-Related Noninfectious Pulmonary
Complications
Hematopoietic stem cell transplantation (HSCT) has evolved signi cantly over the past two decades, now becoming a mainstay of treatment in many malignant and benign hematological disorders and in various congenital diseases, such as congenital dyskeratosis. It is now even being explored in autoimmune diseases, such as systemic sclerosis. There have been major advances in HSCT with regard to donor selection, conditioning and immunosuppressive regimens, and infectious prophylaxis. These factors have contributed to increased survival following HSCT and, by doing so, uncovered various pulmonary complications [15]. The goal of HSCT is to replace the patient’s bone marrow with healthy stem cells. First, the patient receives a conditioning regimen that can be myeloablative or nonmyeloablative. This aggressive chemotherapy induces moderate cytopenia to complete aplasia by destroying the patient’s stem cell production to the default of being unable to target diseased cells. Subsequently, donor stem cells are transplanted. They contain both immature CD34+ cells, which engraft in the receiver’s bone marrow and resume hematopoiesis, and donor T cells, which attack residual leukemic cells located in the patient’s tissues. This concept is called the “graft vs. leukemia/lymphoma” effect (GVL) and occurs at the expense of “graft vs host disease” (GVHD). Hence, depending on the reason for HSCT, the hematologist will juggle the immunosuppressive regimen to balance the GVL effect with GVHD. The most common and fatal complications of HSCT are infectious, but here, we focus on noninfectious pulmonary complications, which can be divided between early and late complications. A cutoff of 100 days post-HSCT is used to differentiate both. Currently, clinical presentation takes precedence to the timing of onset since acute and chronic GVHD manifestations, especially skin and gastrointestinal manifestations, have been found to occur at any time following transplantation. However, thisnding is less true for pulmonary complications, for which a time-based approach remains accurate [16].
Early Onset Pulmonary Complications
Following HSCT
Idiopathic pneumonia syndrome (IPS) is used as an umbrella term to group some of the early complications of HSCT. It is comprised of a very heterogeneous group of