14: Interstitial Lung Disease

Question 1

**Interstitial lung disease **general

Answer 1

• Presence of acquired cellular proliferation, cellular infiltration, and/or fibrosis of lung parenchyma not due to infection or neoplasia.
• A large number of conditions that involve the parenchyma of the lung (alveoli, the alveolar epithelium, the capillary endothelium, and the spaces between those structures).
• Newly-termed diffuse parenchymal lung disease (DPLD)
• Leads to restrictive ventilatory defect
  
  • ↓TLC
  • ↓FVC
  • ↓FEV1

Question 2

Gas exchange in ILD

Answer 2

• Hypoxemia common
  
  • Worsens as dz progresses
  • Worsens w/ exercise
  • Caused by:
    
    • V/Q mismatch
    • Diffusion abnormality (only during exercise/increased CO)

Question 3

Ventilation and vascular changes in ILD

Answer 3

• Alveolar hyperventilation (hypoxemia, abnormal mechanics and load)
• Vascular disease common (intimal hyperplasia, medial hypertrophy, pulmonary HTN)

Question 4

Similarities & differences between ILDs

Answer 4

• Similarities:
  
  • Dyspnea (progressive, exertional)
  • Cough (non-productive)
  • Bibasilar crackles
  • RVD
  • Impaired gas exchange
  • Abnormal lung imaging
• Differences:
  
  • Extrapulmonary findings (sarcoidosis, connective tissue dz)
  • Pattern on lung CT
  • Histology
  • Serologies

Question 5

Known causes of ILD

Answer 5

• Drugs (amiodarone, bleomycin, nitrofurantoin)
• Radiation-induced
• Connective tissue dz (rheumatoid arthritis, scleroderma, idiopathic inflammatory myopathies)
• Occupational/environmental
  
  • Inorganic antigens (asbestosis, coal worker’s pneumoconiosis, silicosis)
  • Organic antigens (birds, molds)

Question 6

Treatment of ILD

Answer 6

• Avoid lung injury
• Anti-inflammatory therapy
  
  • treat underlying dz
  • corticosteroids
  • steroid-sparing agents
• Anti-fibrotic therapy
  
  • pirfenidone
  • nintedanib
• Lung transplant

Question 7

**Usual interstitial pneumonia (UIP) **pattern

Answer 7

• HRCT: subpleural lower lobe predominant reticular changes, honeycombing, traction bronchiectasis
• Histopathology: peripheral lobular fibrosis, dense, small foci of fibroblastic proliferation; sparing of airways
• Gross pathology: fibrosis involving subpleural areas, leading to “honeycomb” pattern

Question 8

Idiopathic pulmonary fibrosis

Answer 8

• Most common idiopathic interstitial pneumonia
• Histopathology: usual interstitial pneumonia
• Risk factors: older age, male, cigarette smoker, FHx
• Pathology: fibrosis (IPF/UIP)
• Functional changes: ↓lung compliance, volume; ↑lung recoil (airways remain open); V/Q mismatch (ventilation unevenly affected); ↓diffusion (observed during exercise), restrictive dz
• Dx: 1) exclusion of known causes of ILD, 2) if no biopsy, UIP pattern on HRCT, 3) if biopsied, specific combo of HRCT + biopsy findings
• Management: risk factor reduction, O2 therapy, pulm rehab, vaccination, tx of resp infx, drug therapy, lung transplant

Question 9

Perfenidone

Answer 9

• Actions:
  
  • Inhibits release of pro-inflammatory cytokines
  • Attuenuates fibroblast proliferation
  • Inhibits release of TGF-B1
  • Inhibits collagen synthesis
• May slow dz progression in IPF

Question 10

Nintedanib

Answer 10

• Action: Growth factor/angiokinase inhibitor
• May have efficacy in IPF (slow progression)

Question 11

Sarcoidosis

Answer 11

• Systemic granulomatous dz that can affect any organ or body part; uknown cause
• Histopathology: non-necrotizing granulomas in hilar nodes and pulmonary interstitium
• Stages:
  
  • I: lymphadenopathy
  • II: lymphadenopathy + infiltrates
  • III: infiltrates only
  • IV: fibrosis
• Pathology: persistent antigen presenation leads to granuloma formation, fibrosis can result
• Treatment: if mild, just monitor; if symptomatic or extensive organ involvement or organ at risk, give corticosteroids (prednisone)

Question 12

Hypersensitivity pneumonitis

Answer 12

• Inflammatory and fibrotic ILD due to an immunologic response to inhaled organic antigens (animals, fungi, bacteria, chemicals)
• Genetic factors and other contributing causes largely unknown
  
  • HLA-linked
  • Antigen processing gene polymorphisms
  • TNF-a gene polymorphism
  • Association between HP and non-smoking!
• Inflammatory and immune response: humoral immunity plays role early on, CD4+ T-cell mediated airway and alveolar inflammatiom is major mechanism (Th1 type response)
• Dx: typical ILD presentation, Hx of exposure, precipitating Ab to Ag, RVD, radiologic picture of centrilobular nodules (early) and fibrotic pattern arround airways (late)
• Histopathology: expansion of peribronchial tissue with bronchiolitis, mild chronic interstitial pneumonitis, interstitial histocytic collections, poorly formed granulomas
• Treatment: antigen avoidance, immunosuppresion with corticosteroids, lung transplant (advanced fibrotic dz)