What is the recommended treatment for interstitial lung disease?

Treatment for Interstitial Lung Disease

Treatment of ILD must be tailored to the specific underlying etiology: mycophenolate is the preferred first-line therapy for connective tissue disease-associated ILD, while antifibrotic agents (nintedanib or pirfenidone) are first-line for idiopathic pulmonary fibrosis and progressive fibrosing ILD. 1, 2, 3

Critical First Step: Establish the Specific ILD Subtype

The treatment approach fundamentally differs based on whether the ILD is inflammatory (requiring immunosuppression) versus fibrotic (requiring antifibrotic therapy), making accurate diagnosis essential before initiating treatment. 1, 4

For systemic autoimmune rheumatic disease-associated ILD (SARD-ILD):

• Screen for connective tissue disease markers including rheumatoid factor, anti-CCP antibodies, ANA, anti-Scl-70, and anti-Jo-1 antibodies 2
• Evaluate for systemic sclerosis, rheumatoid arthritis, idiopathic inflammatory myopathies, mixed connective tissue disease, and Sjögren disease 1

For other ILD subtypes:

• Assess for environmental/occupational exposures including organic antigens, silica, asbestos, and drug toxicity 2
• Consider hypersensitivity pneumonitis (15% of ILD cases) and sarcoidosis 3

First-Line Treatment for SARD-ILD

Mycophenolate is the preferred first-line immunosuppressive therapy across all SARD-ILD subtypes, including those with UIP pattern. 1, 2

Additional first-line options include:

• Nintedanib for systemic sclerosis-ILD specifically 2
• Rituximab as a conditionally recommended alternative 2
• Tocilizumab for connective tissue disease-associated ILD 3

Conditionally recommended alternatives:

• Cyclophosphamide (typically not combined with other agents) 2
• Azathioprine for most SARD-ILD except systemic sclerosis 2

Critical caveat for systemic sclerosis-ILD: Glucocorticoids are strongly recommended AGAINST as first-line therapy and after ILD progression in systemic sclerosis. 1 For all other SARDs, glucocorticoids are only conditionally recommended. 1

First-Line Treatment for Idiopathic Pulmonary Fibrosis

Antifibrotic therapy with either pirfenidone or nintedanib is first-line for IPF, as these agents slow annual FVC decline by approximately 44% to 57%. 2, 3

Critical pitfall: Avoid systemic corticosteroids in IPF for disease management, as they are associated with increased mortality and should be limited only to IPF exacerbations or co-existing asthma/eosinophilic bronchitis. 5

Both pirfenidone and nintedanib have similar efficacy in slowing disease progression in IPF. 2 Immunosuppressive therapy is not effective in IPF and may be harmful. 2

Treatment for Progressive Pulmonary Fibrosis (PPF)

Monitor for PPF phenotype development, defined as ≥10% decline in FVC, worsening respiratory symptoms, and/or radiographic progression within the past year despite treatment. 2

When PPF develops in SARD-ILD:

• Consider adding nintedanib to ongoing immunosuppressive therapy 2
• Antifibrotic therapy (nintedanib or pirfenidone) is indicated for progressive pulmonary fibrosis of any cause 3

A 5% decline in FVC over 12 months is associated with an approximately 2-fold increase in mortality compared with no change in FVC, making early recognition of progression critical. 3

Management of ILD-Associated Cough

Systematically evaluate and treat alternative causes of cough before attributing it to ILD itself. 5

Evaluate for:

• Gastroesophageal reflux disease (GERD) 1, 5
• Asthma or nonasthmatic eosinophilic bronchitis 5
• Upper airway cough syndrome 5
• Medication side effects 5
• Pulmonary infections 5

For refractory ILD-associated cough:

• Gabapentin is first-line treatment for refractory cough, following dosing protocols for unexplained chronic cough 5
• Multimodality speech pathology therapy (cough suppression techniques and breathing exercises) is also first-line 5
• Low-dose controlled-release morphine is second-line therapy 5

Critical pitfall for sarcoidosis: Do not routinely prescribe inhaled corticosteroids for chronic cough in sarcoidosis, as three trials demonstrated no significant reduction in cough. 5

Supportive and Advanced Therapies

Structured exercise therapy:

• Reduces symptoms and improves 6-minute walk test distance in individuals with dyspnea 3
• Improves quality of life 3

Oxygen therapy:

• Reduces symptoms and improves quality of life in individuals who desaturate below 88% on 6-minute walk test 3

Pulmonary hypertension management:

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

Lung transplantation:

• Should be considered for patients with advanced ILD 3
• Median survival after lung transplant is 5.2 to 6.7 years compared with less than 2 years in patients with advanced ILD who do not undergo transplant 3

Palliative Care Considerations

For patients with chronic cough adversely affecting quality of life when alternative treatments have failed, opiates should be used for symptom control in a palliative care setting, with reassessment of benefits and risks at 1 week, then monthly before continuing. 5