What is the recommended treatment approach for interstitial lung disease?

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Last updated: February 25, 2026 • View editorial policy

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Treatment of Interstitial Lung Disease

Critical First Step: Determine ILD Subtype Before Treatment

The treatment of ILD depends entirely on whether the disease is inflammatory (requiring immunosuppression), fibrotic (requiring antifibrotic therapy), or associated with systemic autoimmune rheumatic disease (SARD), making accurate classification mandatory before initiating any therapy. 1

Diagnostic Classification Required

  • Screen all patients for underlying connective tissue diseases including systemic sclerosis, rheumatoid arthritis, inflammatory myopathies, mixed connective tissue disease, and Sjögren syndrome using rheumatoid factor, anti-CCP antibodies, ANA, anti-Scl-70, and anti-Jo-1 antibodies. 1
  • High-resolution CT (HRCT) is the gold standard with 91% sensitivity and 71% specificity for diagnosing ILD subtypes and determining usual interstitial pneumonia (UIP) pattern. 2, 3
  • Evaluate for environmental/occupational exposures (organic antigens, silica, asbestos) and drug toxicity to exclude secondary causes. 1

Treatment for SARD-Associated ILD (Including UIP Pattern)

First-Line Immunosuppressive Therapy

Mycophenolate is the preferred first-line immunosuppressive agent for all SARD-ILD subtypes, regardless of radiologic pattern including UIP. 4, 1, 2

  • Mycophenolate achieved outcomes comparable to cyclophosphamide in systemic sclerosis-ILD but with superior tolerability. 1
  • This preference is based on substantial clinical experience and favorable efficacy-to-toxicity ratio. 1

Alternative First-Line Options (Ranked by Preference)

Rituximab is conditionally recommended as an alternative first-line agent, particularly for RA-ILD with active inflammatory arthritis given potential benefits for both joint disease and ILD. 4, 1

Cyclophosphamide is conditionally recommended as monotherapy (not combined with other agents) for SARD-ILD. 4, 1

Azathioprine is conditionally recommended for most SARD-ILD with UIP pattern, except systemic sclerosis where it serves only as an adjunct. 1

Disease-Specific Considerations for Systemic Sclerosis-ILD

Glucocorticoids are strongly recommended AGAINST in systemic sclerosis-ILD due to risk of scleroderma renal crisis. 4, 1

  • If glucocorticoids are unavoidable, use the lowest effective dose with close monitoring for renal complications. 1
  • Nintedanib is conditionally recommended as an additional first-line option specifically for systemic sclerosis-ILD. 1, 2
  • Tocilizumab may be considered in early progressive SSc-ILD with diffuse skin involvement and elevated acute phase reactants. 4

Glucocorticoid Use in Other SARD-ILD

  • Short-term glucocorticoids (≤3 months) are conditionally recommended for SARD-ILD other than systemic sclerosis, useful during flares or as a bridge when switching immunosuppressive agents. 1
  • Long-term glucocorticoid monotherapy should be avoided; limit to short courses or combine with steroid-sparing immunosuppressants. 1

Agents to AVOID in SARD-ILD

Methotrexate, leflunomide, TNF-inhibitors, and abatacept should NOT be used as first-line ILD treatments due to insufficient efficacy data and potential harm, though they may be appropriate for extrapulmonary manifestations. 4, 1

Treatment for Idiopathic Pulmonary Fibrosis (IPF) with UIP Pattern

Antifibrotic therapy with either pirfenidone or nintedanib is recommended for IPF with definite UIP pattern, as immunosuppressive therapy is not effective and may be harmful. 1, 5, 3

  • Both pirfenidone and nintedanib have similar efficacy in slowing disease progression, reducing annual FVC decline by approximately 44-57%. 1, 3
  • Pirfenidone is administered as 801 mg three times daily with food (total 2,403 mg/day). 5
  • The choice between pirfenidone and nintedanib should consider individual patient tolerability profiles and comorbidities. 1

Management of Progressive Pulmonary Fibrosis (PPF) Despite First-Line Treatment

Monitoring for PPF

Monitor for PPF phenotype including: 1

  • ≥10% decline in FVC
  • Worsening respiratory symptoms
  • Radiographic progression within the past year despite treatment

Treatment Adjustment for SARD-ILD with PPF

When PPF develops despite first-line immunosuppression, adding nintedanib to the existing immunosuppressive regimen is conditionally recommended rather than switching immunosuppressive agents. 1

  • The decision to add nintedanib versus changing immunosuppression should consider speed of progression, extent of fibrotic involvement, and presence of UIP pattern on CT. 1

Second-Line Options for IIM-ILD Progression

For inflammatory myopathy-ILD (IIM-ILD) with progression despite first-line treatment: 4

  • Calcineurin inhibitors (CNIs) are conditionally recommended, particularly for anti-synthetase syndrome or MDA-5-ILD
  • JAK inhibitors are conditionally recommended as emerging treatment options
  • IVIG is conditionally recommended, especially when rapid onset of action is needed (e.g., severe respiratory muscle weakness)

For SARD-ILD other than IIM-ILD, CNIs are conditionally recommended AGAINST. 4

Treatment of Rapidly Progressive ILD (RP-ILD)

First-Line RP-ILD Treatment

Pulse intravenous methylprednisolone is conditionally recommended as first-line RP-ILD treatment due to rapid onset of action. 4

  • Typically followed by high-dose oral prednisone, administered with other immunosuppressive agents. 4
  • In the rare occurrence of RP-ILD in systemic sclerosis, an individualized approach is suggested given the life-threatening nature despite scleroderma renal crisis risk. 4

Additional First-Line RP-ILD Options

Rituximab, cyclophosphamide, IVIG, mycophenolate, CNIs, and JAK inhibitors are all conditionally recommended as first-line RP-ILD treatment options in combination with glucocorticoids. 4

Management of ILD-Associated Cough

Systematic Evaluation Required

Before attributing cough to ILD itself, systematically evaluate for alternative causes including gastroesophageal reflux disease (GERD), asthma, nonasthmatic eosinophilic bronchitis, and upper airway cough syndrome. 4, 1

  • ILD is likely the cause when there is evidence of disease progression, temporal association between cough onset and disease progression, and favorable response to ILD therapy. 4
  • GERD is a common reversible contributor that must be assessed, particularly in systemic sclerosis with esophageal dysmotility. 4, 1

Treatment of Refractory ILD-Associated Cough

When alternative treatments have failed and cough adversely affects quality of life: 4

  • Consider gabapentin or multimodality speech pathology therapy
  • Low-dose opiates (e.g., slow-release morphine 5 mg twice daily) are suggested for symptom control in a palliative care setting, with reassessment of benefits and risks at 1 week and then monthly before continuing

Supportive Care and Advanced Therapies

Oxygen Therapy

Oxygen reduces symptoms and improves quality of life in individuals with ILD who desaturate below 88% on a 6-minute walk test. 3

Exercise Therapy

Structured exercise therapy reduces symptoms and improves 6-minute walk test distance in individuals with dyspnea. 3

Pulmonary Hypertension Management

Up to 85% of individuals with end-stage fibrotic ILD develop pulmonary hypertension; in these patients, inhaled treprostinil improves walking distance and respiratory symptoms. 3

Lung Transplantation

For systemic sclerosis-ILD with progression despite first-line treatment, referral for stem cell transplantation and/or lung transplantation is conditionally recommended. 4

  • Lung transplant may improve symptoms and resolve respiratory failure in end-stage ILD, with median survival of 5.2-6.7 years post-transplant versus less than 2 years without transplant. 3
  • Referral should occur before deterioration renders patients ineligible. 4

Critical Pitfalls to Avoid

  • Never use immunosuppression for IPF—it is ineffective and potentially harmful; antifibrotics are the only evidence-based therapy. 1
  • Never use high-dose glucocorticoids in systemic sclerosis-ILD due to scleroderma renal crisis risk. 4, 1
  • Never attribute cough to ILD without excluding GERD and other common causes first. 4, 1
  • A 5% decline in FVC over 12 months is associated with approximately 2-fold increased mortality, requiring prompt treatment escalation. 2, 3
  • Co-management with pulmonologists is advised for initiation of ILD treatment, particularly to determine need for treatment in asymptomatic patients with stable and mild ILD. 4

References

1
Guideline

Initial Treatment for ILD with UIP Pattern

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

2
Guideline

Interstitial Lung Disease Diagnosis and Management

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

4
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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