Treatment of Chronic Interstitial Lung Disease in Both Lower Lungs
The treatment of chronic ILD depends critically on the underlying etiology: for idiopathic pulmonary fibrosis (IPF), antifibrotic therapy with nintedanib or pirfenidone is first-line treatment, while for connective tissue disease-associated ILD (CTD-ILD), immunomodulatory therapy with mycophenolate, azathioprine, rituximab, or cyclophosphamide is recommended as first-line treatment. 1, 2
Treatment Algorithm Based on ILD Subtype
For Idiopathic Pulmonary Fibrosis (IPF)
Antifibrotic therapy with nintedanib or pirfenidone should be initiated, as these medications slow annual FVC decline by approximately 44% to 57% and reduce disease progression. 3, 2
Both medications have demonstrated efficacy in reducing the decline in forced vital capacity (FVC), with pirfenidone showing a mean treatment difference of 193 mL compared to placebo at 52 weeks. 3
Pirfenidone is administered at 2,403 mg/day divided into three doses with food, while monitoring for gastrointestinal side effects including nausea, diarrhea, and anorexia. 3, 4
For Connective Tissue Disease-Associated ILD (CTD-ILD)
Immunomodulatory therapy is first-line treatment, with mycophenolate, azathioprine, rituximab, and cyclophosphamide all conditionally recommended as first-line options. 1, 5
For systemic sclerosis-associated ILD (SSc-ILD), glucocorticoids are strongly recommended against as first-line treatment due to increased risk of scleroderma renal crisis. 1, 5
For other SARD-ILD (excluding SSc-ILD), glucocorticoids are conditionally recommended as first-line treatment in combination with other immunosuppressive agents. 1
For SSc-ILD specifically, nintedanib is conditionally recommended as a first-line option, and tocilizumab is conditionally recommended for both SSc-ILD and MCTD-ILD. 1
For Progressive ILD Despite First-Line Treatment
Disease progression is defined as: 5
- FVC decline ≥10% of predicted value, OR
- FVC decline 5-10% with worsening respiratory symptoms or increased fibrosis on HRCT, within 24 months
When progression occurs despite initial therapy: 1
- For SSc-ILD progression: mycophenolate, rituximab, cyclophosphamide, and nintedanib are conditionally recommended
- For RA-ILD progression: adding pirfenidone is conditionally recommended
- For IIM-ILD progression: calcineurin inhibitors (CNIs) and JAK inhibitors are conditionally recommended
- Referral for stem cell or lung transplantation should be considered for SSc-ILD with progression
Essential Supportive and Symptomatic Management
Pulmonary Rehabilitation and Oxygen Therapy
Structured exercise therapy and pulmonary rehabilitation should be implemented, as this reduces symptoms and improves 6-minute walk test distance in individuals with dyspnea. 2, 6
Oxygen therapy should be prescribed for patients who desaturate below 88% on 6-minute walk test, as it reduces symptoms and improves quality of life. 2, 6
Management of Chronic Cough
Chronic cough affects up to 80% of IPF patients and significantly impairs quality of life. 5
Initial assessment should include: 1
- Evaluation for ILD progression or complications from immunosuppressive treatment (drug side effects, pulmonary infection)
- Workup for gastroesophageal reflux, upper airway cough syndrome, and asthma
For refractory chronic cough in ILD: 1, 5
- Gabapentin (neuromodulator) and multimodality speech pathology therapy are suggested as first-line options for refractory cough
- Inhaled corticosteroids are NOT recommended for cough in sarcoidosis-associated ILD 1
- For IPF with chronic cough and negative GERD workup, proton pump inhibitors should NOT be prescribed 1
- Opiates should be considered for intractable cough with substantial impact on quality of life when alternative treatments have failed, with regular reassessment of benefits versus risks 1, 5
Monitoring Disease Progression
Pulmonary function tests (spirometry and DLCO) should be performed at least every 6 months in higher-risk patients and yearly in others. 5
A 5% decline in FVC over 12 months is associated with approximately 2-fold increase in mortality compared with no change in FVC. 2
Six-minute walk distance test should be included in functional assessment as it is simple, non-invasive, and reproducible. 5
Lung Transplantation Considerations
Lung transplant should be considered for patients with advanced ILD, as it improves symptoms and resolves respiratory failure. 2, 6
After lung transplant, patients with ILD have a median survival of 5.2 to 6.7 years compared with less than 2 years in patients with advanced ILD who do not undergo transplant. 2
Referral should occur before the patient deteriorates and is no longer eligible, given the limited number of transplant centers. 1
Critical Pitfalls to Avoid
Do not use glucocorticoids as first-line treatment in SSc-ILD due to risk of scleroderma renal crisis. 1, 5
Do not routinely prescribe inhaled corticosteroids for chronic cough in pulmonary sarcoidosis. 1
Do not add nintedanib or pirfenidone to mycophenolate in SARD-ILD patients without evidence of ILD progression. 1
Recognize that up to 85% of individuals with end-stage fibrotic ILD develop pulmonary hypertension, which may require specific treatment with inhaled treprostinil. 2