Diffuse parenchymal lung disease Flashcards
Definiton of interstitial lung disease
Affect parenchyma distal to small airways
Too much of something in the interstitial space
- increased collagen, matrix proteins
- increased chronic inflammatory cells
- granulomas
Common interstitial lung diseases
Usual interstitial pneumonia (UIP) - NOT INFECTIOUS ( = idiopathic pulmonary fibrosis, IPF) Sarcoidosis Hypersensitivity pneumonitis (HP) - NOT INFECTIOUS Pneumoconioses such as asbestosis
Clinical features of interstitial lung diseases
SOB
dry cough
systemic symptoms (fever, weight loss) - sometimes
clubbing with severe disease
“velcro rales” heard on inspiration
interstitial markings on plain film
restrictive pulmonary function abnormality
Conditions associated with UIP
IPF (most common)
UIP associated with collagen vascular disease (lupus, RA)
Drug-induced UIP
Familial UIP
Pneumoconioses, mainly asbestosis (not exact mimics)
Collagen vascular diseases associated with UIP
Scleroderma (high freq) Rheumatoid arthritis (common) Lupus erythematosus (uncommon)
Drugs associated with UIP
Most chemotherapeutic agents
Nitrofurantoin (also associated with other types of interstitial disease)
Amiodarone (as above)
Clinical features of UIP
Disease of middle-age and elderly
Typically presents with insidious onset of SOB
SOB increases over a period of months - yrs
Velcro rales on inspiration
Clubbing in ~50% cases
ANA, RF, cryoglobulins may be elevated even in those without collagen vascular disease
Restrictive functional abnormality
Radiographic features of UIP
Plain chest films: reticulonodular (“interstitial”) markers, usually more severe in lower zones
Honeycombing in advanced cases
HRCT: subpleural reticular pattern with predominantly subpleural honeycombing
Evidence of cor pulmonale may be seen in severe cases
Gross features of UIP
Predominantly lower zone fibrosis + honeycombing
Worse in periphery of lung, lobule
Microscopic features of UIP
Patchy patterns of interstitial inflammation & fibrosis mixed with normal parenchyma
Tends to be worse in periphery of lobule
Scattered fibroblast foci (small tufts of granulation tissue applied to alveolar walls)
Interstitial inflammation minimal except in honeycombed foci
Airspace macrophages minimal except in honeycombed foci
Honeycombed areas usually present by the time of biopsy
Temporal and morphologic heterogeneity
Morphogenesis of granulation tissue in UIP
- repairative pattern of proliferative fibroblasts, often acocmpanied by capillary channels & chronic inflammatory cells
- most organs: granulation tissue undergoes organization, gradually transformed into dense collagen
Focal epithelial injury –> local fibrin deposition, overgrowth of fibroblasts from interstitium to organize the fibrin (“fibroblast foci”) into granulation tissue
- fibrinolytic mechanism impaired in UIP
- overproduction of plasminogen activator inhibitor leads to lack of plasminogen & persisting fibrin
Epithelium grows over to incorporate the new granulation tissue into interstitium
Granulation tissue foci (fibroblast foci) –> interstitial fibrous tissue
Alveolar collapse with organization and eventual fibrosis –> loss of alveoli
End as old scar tissue with reorganization of parenchyma
UIP - granulation tissue response to steroids
Normal granulation tissue very sensitive to steroids (scar does not form, undergoes apoptosis)
Granulation tissue of UIP are not sensitive to steroids at all
Causes of restrictive lung disease
Interstitial lung disease
Densely fibrotic pleura (fibrothorax)
Chest wall muscle weakness
Chest wall deformity/obesity
Findings of restrictive lung disease
FVC, FEV1 small TLC small FEV1/FVC preserved or increased compliance decrease typically diffusing capacity decreased
Unproven hypotheses - pathogenesis of UIP
Triggering injury: environmental agents (smoke, metal/wood dust), viral infections (Hep C, EBV
Immunologic factors: ongoing immunologic rxn, autoantibiodies against alveolar epithelium, TH2 lymphocytes –> IL-4, IL-5 (IL-4 stimulates fibroblast proliferation), Absence of IFNgamma (inhibitor of collagen synthesis)
Cytokines: increased levels of profibrotic cytokines:
TGFbeta, TGFalpha, PDGF, IGF, endothelin-1
Fibroblast abnormalities: increased motility, increased rate of proliferation, anchorage independent growth, resistance to apoptosis, Hypermethylation of promoter of Thy-1 (makes fibroblasts insensitive to TGFbeta and decrease matrix production)
