Interstitial Lung Disease (ILD)

Spencer Scott, Jacob Lee

Background

  • Parenchymal lung diseases characterized by fibrosis of the lung parenchyma, particularly the interstitium
  • Pathophysiology: Repetitive cycles of inflammation leading to scarring with associated loss of lung volume and compliance and impaired gas exchange

Etiologies

  • ILD can be broadly divided into idiopathic (primary) causes and secondary causes 
  • Pattern = What the lung looks like (radiographic on CT vs histologic)

Pattern

Radiologic Findings

Idiopathic

Secondary
Interstitial Filling Pattern
Usual interstitial pneumonia (UIP) Subpleural and usually lower lung predominance. Fibrotic changes including reticulation, peripheral traction bronchiectasis, and honeycombing IPF CTD-ILD, fibrotic hypersensitivity pneumonitis, asbestosis
Non-specific interstitial pneumonia (NSIP) Lower-lobe predominance, commonly with subpleural sparing, GGOs, fine reticulation, and traction bronchiectasis, without honeycombing iNSIP Connective tissue disease (CTD) most common, drug toxicity
Bronchiolocentric interstitial pneumonia (BIP)

*new overarching term that now includes HP 		Non-fibrotic BIP: centrilobular ground-glass nodules, mosaic attenuation, and/or lobular air trapping

Fibrotic BIP: peribronchovascular ground-glass, traction bronchiectasis, mosaic attenuation, lobular air trapping, and three-density sign 		iBIP Hypersensitivity pneumonitis most common but aspiration, CTD, inhalational exposures, medication
Diffuse alveolar damage (DAD) Patchy or diffuse GGOs that may progress to fibrosis over time iDAD (replaces acute interstitial pneumonia) Many; infections, drugs, inhalational injuries, CTDs
Pleuroparenchymal fibroelastosis (PPFE) Biapical pleural thickening, dense subpleural confluent fibrosis and traction bronchiectasis with volume loss and upward hilar retraction iPPFE Transplant related, chemotherapy, radiation, recurrent infections
Lymphoid interstitial pneumonia (LIP) Mid- to lower-lobe predominant thin-walled lung cysts with reticulation, GGOs, bronchovascular thickening and perilymphatic interstitial thickening iLIP CTD (esp Sjögren's, SLE, RA), immunodeficiency, chronic infection
Alveolar Filling Pattern
Organizing Pneumonia Patchy consolidation with air bronchograms, patchy GGOs, focal nodules, and/or mass-like lesions COP Post-infectious, meds, aspiration, CTD
Respiratory bronchiolitis ILD (RB-ILD) Upper-lobe-predominant centrilobular ground-glass nodularity IRB-ILD Smoking most common
Alveolar macrophage pneumonia (AMP)

*replaces desquamative interstitial pneumonia (DIP) 		Primarily patchy and confluent ground-glass opacities with smooth reticulation. Cystic spaces may be present within the ground-glass; emphysema and traction bronchiectasis may also be seen iAMP Smoking most common

*Over 150 medications are linked to ILD (www.pneumotox.com is the best reference for drugs associated with specific ILD patterns)

Evaluation 

  • Symptoms: progressive, dry cough, dyspnea, and fatigue. Other symptoms are usually related to the underlying secondary cause 
  • History: 
    • PMHx: AI disease (Raynaud’s), vasculitis, arthritis, lung disease 
    • Occupational/environmental exposures: pets (birds), allergens, mold/stagnant water, asbestos, silica, coal, beryllium, heavy metals 
    • Medications/Therapeutics: amiodarone, nitrofurantoin, chemotherapy, immunotherapy, radiation 
    • Smoking and smoke exposure 
  • Physical Exam: 
    • Respiratory: fine crackles not clearing with cough, wheezing 
  • Cardio: JVD, loud P2, TR murmur suggest pulmonary HTN 
    • MSK: clubbing, joint swelling/tenderness/deformities 
    • Skin: Raynaud’s, sclerosis, rash

Diagnostics

  • Imaging: 
    • CXR 
    • CT non-contrast 
    • Gold standard: HRCT protocol (inspiratory and expiratory films in the supine and prone position) 
  • Labs without Pulmonology consult: 
    • CBC with diff (eosinophilia or cytopenias cf autoimmune disease) 
    • CMP, CK, aldolase 
    • RPP, sputum culture 
    • ESR, CRP, ANA w/ reflex ENA, RF, CCP, C3, C4 
  • Labs in conjunction with Pulmonology: 
    • Myositis panel, anti-Scl-70 and anti-RNP 
    • Hypersensitivity pneumonitis panel 
    • Histo, blasto, aspergillus, 1-3-β-D-glucan, sputum GMS; consider NTM and HIV 
  • PFTs: usually restrictive lung disease +/- low DLCO 
  • Bronchoscopy and biopsy (if stable enough) 
  • BAL to r/o infection and assess cell counts 
    • Cryo bx for histopath (if too sick for surgical lung biopsy), transbronchial lung biopsy can dx sarcoidosis or HP
  • Consider SLP if cf aspiration 
  • 6-minute walk for prognosis 
  • TTE for pHTN

Management

  • Acute exacerbation (AE-ILD) - clinical decline within 1 mo, CT evidence of new/worsening bilateral GGO and/or consolidation superimposed on a background pattern consistent with the ILD, NOT due to another cause 
    • Rule out infection, HF, PE, drug toxicity 
    • Empiric antibiotics; consider PJP coverage if risk factors 
    • Pulse-dose steroids -> prolonged taper (subtype dependent) 
    • Don't make changes to IS without pulm/rheum input 
  • Chronic therapy 
    • Antifibrotics (Nintedanib, Pirfenidone, nerandomilast) 
    • Mainly for IPF; can be used for progressive fibrosis due to any etiology 
    • Immunosuppression (mycophenolate, azathioprine; also cyclophosphamide, rituximab, and calcineurin inhibitors
    • MUST rule out infection prior to use 
    • Often responsive: COP, NSIP, CT-ILD, HP, sarcoidosis, vasculitis-associated 
    • Not usually steroid responsive: IPF, fibrotic HP 
    • Other considerations: 
      • Smoking cessation and exposure elimination 
      • Drug removal: consider discontinuing amiodarone, checkpoint inhibitor, etc. 
      • Hypersensitivity pneumonitis: antigen exposure elimination 
      • Eosinophilic pneumonia: steroids; biologics can be used (send to Allergy clinic) 
      • Consider lung transplant eval for progressive or rapidly decompensating fibrotic lung disease 
      • Pulmonary rehabilitation is crucial (trend towards mortality benefit)
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