Interstitial Lung Disease (ILD): Management

Overview of ILD Categories

General Principles

Initial Evaluation

• HRCT is cornerstone: defines pattern (UIP, NSIP, OP, DIP, LIP), distribution, extent
• PFTs: restrictive pattern with reduced DLCO; tracks progression and response
• Serologic workup: ANA, RF, anti-CCP, anti-Scl-70, anti-Jo-1, anti-MDA5, myositis panel — mandatory to distinguish CTD-ILD from idiopathic ILD (different prognosis and management implications)
• BAL: lymphocytosis suggests HP/NSIP/sarcoid; neutrophilia/eosinophilia suggests IPF or fibrotic disease
• SLB or TBLC: when HRCT pattern is non-diagnostic or atypical

Distinguishing CTD-ILD from idiopathic ILD is essential and has major implications for prognosis and management. Serologic testing — and repeat testing if needed — is recommended. — Murray & Nadel's Textbook of Respiratory Medicine

Disease-Specific Management

1. Idiopathic Pulmonary Fibrosis (IPF)

• Nintedanib (tyrosine kinase inhibitor — VEGFR, FGFR, PDGFR, FGFR): slows FVC decline ~50%; GI side effects common (diarrhea)
• Pirfenidone: anti-fibrotic/anti-inflammatory; also slows FVC decline; side effects include photosensitivity, nausea

• Corticosteroids (no benefit, potential harm in pure IPF)
• Azathioprine + N-acetylcysteine + prednisone combination (PANTHER-IPF trial: increased mortality)
• Anticoagulation (COMET trial: harmful)

• Supplemental O₂ for hypoxemia
• Pulmonary rehabilitation
• Treat comorbidities (GERD — microaspiration is a recurrent epithelial injury trigger; OSA; PH)
• Lung transplantation: definitive treatment; bilateral preferred; refer early

2. CTD-ILD (General)

• Corticosteroids (prednisolone 0.5–1 mg/kg/day tapered over months) — cornerstone for inflammatory CTD-ILD (NSIP, OP patterns)

• Mycophenolate mofetil (MMF): preferred in SSc-ILD (SLS II trial) and widely used across CTD-ILD; better tolerated than azathioprine
• Azathioprine: alternative steroid-sparing agent
• Cyclophosphamide (CYC): IV or oral; used for rapidly progressive or severe SSc-ILD (SLS I); significant toxicity (hemorrhagic cystitis, malignancy risk)
• Rituximab (anti-CD20): emerging evidence in RA-ILD and refractory CTD-ILD; anecdotal benefit in Sjögren-associated LIP

• Nintedanib is now approved for progressive fibrosing ILD beyond IPF (INBUILD trial) — including SSc-ILD, RA-ILD, NSIP, CHP; slows FVC decline regardless of underlying diagnosis

3. SSc-ILD (Scleroderma)

4. RA-ILD

• Patterns: UIP (worse prognosis, similar to IPF) and NSIP (better prognosis)
• RA-UIP with classical HRCT: average outcomes similar to IPF in short-term, though ~25% have better long-term trajectories
• Treatment: MMF or azathioprine + corticosteroids for NSIP pattern
• Nintedanib: evidence from INBUILD supports use in progressive RA-ILD
• Caution: methotrexate and leflunomide (used for RA itself) can cause drug-induced ILD
• Rituximab: increasingly used for refractory RA-ILD

5. PM/DM-ILD

• Anti-synthetase syndrome (anti-Jo-1, anti-MDA5, etc.) — high risk of ILD
• Pattern: NSIP most common; OP component often present early; diffuse alveolar damage (DAD) in acute/subacute cases
• Rapidly progressive ILD (especially anti-MDA5): high mortality, often resistant to treatment
• Treatment: high-dose corticosteroids + early combination immunosuppression (MMF, azathioprine, tacrolimus, or CYC)
• Anti-MDA5 rapidly progressive ILD: combination triple therapy (corticosteroids + calcineurin inhibitor + CYC or rituximab) increasingly used

6. Hypersensitivity Pneumonitis (HP)

• Acute/subacute: antigen avoidance is the most critical intervention; corticosteroids for acute disease
• Chronic fibrotic HP (cHP): behaves like progressive fibrosing ILD; antigen avoidance + corticosteroids; nintedanib may have role (INBUILD included cHP)
• Prognosis worsens with UIP pattern on HRCT

7. Sarcoidosis

• Stage I–II: many patients remit spontaneously; treatment not always required
• Indications for treatment: symptomatic, worsening PFTs, cardiac/neurologic/ocular involvement
• First-line: Oral prednisone (20–40 mg/day, taper over 6–24 months)
• Steroid-sparing: Methotrexate, azathioprine, hydroxychloroquine
• Refractory: Infliximab (anti-TNF) — evidence from RCTs for pulmonary and extra-pulmonary sarcoidosis

8. Organizing Pneumonia (COP/OP)

• Highly corticosteroid-responsive
• Prednisone 0.75–1 mg/kg/day for 4–8 weeks, then slow taper over 6–12 months
• Relapse common on tapering — requires prolonged low-dose maintenance in many patients
• Excellent prognosis if treated

Non-Pharmacological / Supportive Management (All ILDs)

Monitoring

• PFTs (FVC, DLCO) every 3–6 months: ≥10% decline in FVC or ≥15% decline in DLCO = significant progression
• HRCT: annually or with clinical change (avoid excess radiation)
• 6-minute walk test: functional capacity and O₂ desaturation
• Echocardiography: screen for pulmonary hypertension (common complication of fibrotic ILD)

Summary Algorithm

ILD diagnosed on HRCT
        │
        ├─ Serologic panel → CTD identified?
        │       Yes → CTD-ILD management (immunosuppression ± antifibrotics)
        │       No  → IIP workup (BAL ± biopsy)
        │
        ├─ Pattern UIP + no CTD → IPF
        │       → Antifibrotics (nintedanib or pirfenidone)
        │       → No corticosteroids
        │
        ├─ Pattern NSIP/OP → likely CTD or HP
        │       → Corticosteroids ± immunosuppressants
        │
        └─ Progressive fibrosing ILD (any cause)
                → Nintedanib (INBUILD evidence)
                → Lung transplant evaluation

Common drugs used in the treatment of CTD may result in major pulmonary complications — always consider drug-induced ILD in the differential. — Murray & Nadel's Textbook of Respiratory Medicine