ILD Flashcards
Describe Interstitial Lung Diseases (ILD)
• Disorders of the interstitial space of the lung
o Primarily affects lung parenchyma (alveolar/capillary units)
• Diverse group of disorders
• Range from acute to chronic pulmonary disorders
Common features: o Clinical presentation o Interstitial changes on chest x-rays o Injury and/or inflammation in parenchyma of lung with variable interstitial fibrosis o Architectural distortion o Restrictive pattern of ventilation
Types of ILD
Idiopathic forms of ILD
• Idiopathic pulmonary fibrosis IPF)
Dysregulated inflammatory response • Granulomatous Disorders (Ex: sarcoidosis) • CT disorders • Eosinophilic pneumonias • Alveolar hemorrhage syndromes
Exogenous injurious exposures
• Occupational/environmental/inhalational (ex. Asbestosis)
• Iatrogenic pneumonitis/fibrosis
• Drugs: amiodarone (atrial fibrillation), nitrofurantoin (UTI antibiotic) and methotrexate & bleomycin (anti-neoplastic agent)
Inherited disorders
Miscellaneous ILDs
common pathophysiology of ILD
o Inflammation and/or scarring of alveolar interstitial spaces
Results:
• Accumulation of inflammatory cells and T cells within alveolar interstitium → remodeling of lung parenchyma
• Parenchymal cells (epithelial, endothelial, or mesenchymal) release cytokines and mediators = contribute to inflammation
• Matrix components (collagen) = enhance inflammatory process
• Fibrosis
• Increased elasticity of lung (less able to inflate due to decreased lung compliance) → restrictive lung physiology
• Low TLC, FRC, RV
• Increases work of breathing
• Destruction of alveolar/capillary gas exchanging surfaces → low DLCO, high A-a gradient
• Thickening of alveolar/capillary interface → diffusion limitation with exercise
• Exercise-induced hypoxemia
Progression of ILDs
- Increased PaCO2
- Decreased PaO2
- Severe pulmonary hypertension → cor pulmonale over time
- Most commonly occurs in patients with IPF or scleroderma
Pulmonary fibrosis
o Decreased lung compliance → Restrictive ventilatory defect (decreased FVC, RV, TLC)
o Decreased compliance and increased dead space → increased respiratory rate
o Decreased alveolar-capillary membrane surface area; diffusion impairment → decreased DLCO
o Low V/Q → increased A-a O2 gradient
o Decreased V/Q, loss of pulmonary vascular bed, diffusion limitation, low mixed venous O2 tension, +/- shunt → exertional oxyhemoglobin desaturation
Pulmonary function testing in IPF
FEV1: decreased FVC: decreased FEV1/FVC: normal or increased TLC: decreased RV: decreased DLCO: very decreased
Change in FVC% = best validated marker of disease progression; correlates with survival
ILD: common symptoms
o Dyspnea on exertion (from increased work of breathing)
o Non-productive (paroxysmal) cough
o Abnormal breath sounds to auscultation
• Crackles or rales
• Most prominent over lower lobes
o Fatigue or malaise
ILD: helpful physical exam findings
Crackles/rales –> Idiopathic pulmonary fibrosis; Asbestosis»_space; other ILD
Mid-inspiratory squeaks –> Hypersensitivity pneumonitis; Bronchiolitis
Digital clubbing –> Idiopathic pulmonary fibrosis; Asbestosis; Chronic hypersensitivity pneumonitis; Desquamative interstitial pneumonia
Anterior uveitis –> Sarcoidosis; Wegener
Skin lesions/rashes –> Sarcoid; Collagen vascular disease; TS/NF
Joint disease –> Collagen vascular disease
Muscle weakness –> Polymyositis
Laboratory evaluation of ILD patient
o Serologic testing to evaluate for CTD
o Chest x-ray or CT (interstitial opacities)
• Use previous x-rays = time of onset/chronicity, rate of progression
• Patterns: interstitial, nodular, etc.
• Adenopathy
• Pleural disease (plaques, effusions)
• Regional prominence (upper vs. lower)
ILD: diagnostic tests
• Exercise with O2 saturation or PaO2 (6-MWT)
Bronchoscopy (in selected patients)
• Ex. Sarcoidosis, hypersensitivity pneumonia
1) Bronchoalveolar Lavage (BAL)
• Usually not diagnose, but can support a diagnose
2) Transbronchial biopsy (TBLB)
• Less invasive
• Less risky
• Limited use because ILD can be patchy so may not get representative tissue sample
Surgical lung biopsy in selected patients
• Gold standard
• When unable to establish a diagnosis from above studies
• Greater risk to patient
Sarcoidosis: definition
o Diffuse inflammatory disorder
o Characterized by granulomatous inflammation
o Most often affects lungs and lymphatics, but variable multi-organ effects
Sarcoidosis: epidemiology
o Worldwide prevalence o Can occur at any age • Young adults more frequently affected • Peaks in 20’s; smaller peak in 50’s o Higher prevalence in females and certain ethnic groups (African-American, northern European)
Sarcoidosis: clinical features
o Usually subacute symptom onset (but can be acute)
o Often asymptomatic (30-60%)
• Instead = incidental finding on routine chest x-ray
• See bilateral hilar hymphadenopathy
o Most common affected organs = lungs > nodes > skin > eyes
o Can affect any organ
Symptoms
• Fatigue, lethargy, malaise
• Cough
• Fever, arthralgias, weight loss
Physical exam: Lungs usually clear to auscultation May have skin involvement o Erythema nodosum (vasculitis with red, raised lesions affecting lower extremities) o Sarcoid plaques May have eye involvement o Uveitis o Retinitis Extrapulmonary diseases may be present o Cardiac rhythm disturbance o Transaminitis (eleveated ALT, AST) o Hypercalcemia o Nephrolithiasis o Neurologic complications Course: can be relapsing, remitting, or chronic
Sarcoidosis: pathogenesis
o T-cell driven immune response
o Inciting event = antigen processing and presentation by macrophage (APC)
o Classic TH1 response with granuloma formation
o Release of IL-2, IL-12, IFN-gamma, TNF-alpha
o Consequences of granulomas and tissue inflammation in lung:
• Volume of inflammatory cells → distorts lung architecture → alters gas exchange
• Granulomatous inflammation → tissue damage and fibrosis → pulmonary dysfunction
• Can develop pulmonary HT (even without extensive fibrosis)
Sarcoidosis: pathology
o Tightly formed, non-caseating granulomas
o Often in clusters in intersitium and bronchovascular bundle
Sarcoidosis: Radiography
o Classify into stages (showing pulmonary involvement)
o see nodules on CT
Stages of Sarcoidosis
1) Bi-hilar LAD (likelihood of spontaneous remission >80%)
2) Bi-hilar LAD + pulmonary infiltrates (65%)
3) Pulmonary infiltrates, no LAD (30%)
4) Fibrosis (usually on upper lobes); no LAD (0%)
Sarcoidosis: therapy
Therapy of Sarcoidosis o No treatment if minimal disease or no evidence of progression Immunosuppressive therapies • Corticosteroids • Cytotoxic agents (ex: methotrexate) • Hydroxychloroquine Immunomodulatory agents • Anti-TNF antibodies • Thalidomide Lung transplantation
Lofgren’s Syndrome
• Acute onset of o Hilar lymphadenopathy o Erythema nodosum (usually on shins) o Fever o Arthritis • Usually spontaneous remission within 2 years
Idiopathic Pulmonary Fibrosis (IPF): defintions
o Most common form of idiopathic interstitial pneumonia
o Lung injury/fibrosis cannot be linked to CT disease, drug exposure, or inhaled pro-fibrotic dust (asbestos)
Idiopathic Pulmonary Fibrosis (IPF): epidemiology
o Increasing incidence and prevalence
o Usually occurs after 5th decade (highest in elderly)
o Affects males slightly more than females
o Poor prognosis: median survival is 2-3 years post-diagnosis
Idiopathic Pulmonary Fibrosis (IPF): associated risk factors
Environmental • Smoking • Dusts (metal, wood) • Farming • Hair dressing • Stone cutting or polishing
Genes
• Telomerase
• MUC5B
Chronic viral infection
• EBV
Associations with other conditions
• Gastroesophageal reflux +/- HH → microaspiration
• Diabetes mellitus
• advanced age
Idiopathic Pulmonary Fibrosis (IPF): pathology
o Architectural distortion of lung
o Areas of intense fibrosis
o Intervening areas of normal lung (heterogeneity)
o Fibroblastic foci
• At junction of normal lung and fibrotic change
• With fibroblasts and collagen
o Peripheral zones of chronic scar and honeycombing (small peripheral cysts)
o Interstitial inflammatory change = usually only mild and focal
Idiopathic Pulmonary Fibrosis (IPF): pathogenesis
o Recurrent alveolar epithelial cell injury
• Exposure + susceptibility
o Loss of homeostatic function
o Release of profibrotic mediators
Result: formation of serum rich “wound clot”
• Activation of coagulation cascade
• Influx of resident mesenchymal cells and circulating fibrocytes
• Local epithelial-mesenchymal transition
o Myofibroblast differentiation and reorganization of wound clot → fibroblastic focus
o Cycle repeats = can’t resolve wound-healing response; progressive tissue remodeling and architectural distortion
