What is the prognosis and treatment for advanced Interstitial Lung Disease (ILD)?

Prognosis and Treatment for Advanced Interstitial Lung Disease (ILD)

Advanced ILD has a poor prognosis with median survival of less than 2 years without lung transplantation, requiring a combination of disease-modifying therapies and palliative approaches to manage symptoms and improve quality of life. 1

Prognosis Factors

• Advanced ILD is associated with high mortality rates, with significant variation based on ILD subtype - idiopathic pulmonary fibrosis (IPF) has worse outcomes than non-IPF ILDs 2
• Acute exacerbations of ILD are life-threatening events with 90-day mortality rates of 57% in IPF, 29% in non-IPF idiopathic interstitial pneumonias, and 33% in secondary ILD 2
• Disease progression is defined by decline in forced vital capacity (FVC) of ≥10% of predicted value, or decline of 5-10% with worsening respiratory symptoms or increased fibrosis on HRCT within 24 months 3
• A 5% decline in FVC over 12 months is associated with approximately 2-fold increase in mortality compared with no change in FVC 1
• Rapidly progressive ILD (RP-ILD) represents a particularly aggressive subtype with rapid progression from baseline oxygen requirement to high oxygen needs or intubation within days to weeks 3

Disease-Modifying Treatment Approaches

For IPF:

• Antifibrotic therapy with nintedanib or pirfenidone is first-line treatment, slowing annual FVC decline by approximately 44% to 57% 1
• Pirfenidone has demonstrated efficacy in reducing FVC decline in clinical trials (mean treatment difference 193 mL at Week 52 compared to placebo) 4

For Connective Tissue Disease-Associated ILD:

• Immunomodulatory therapy is first-line treatment, with options including mycophenolate, azathioprine, rituximab, and cyclophosphamide 3
• For systemic sclerosis-associated ILD, glucocorticoids are strongly recommended against as first-line treatment 3
• For other SARD-ILD (systemic autoimmune rheumatic disease-ILD), glucocorticoids are conditionally recommended as first-line treatment 3

Symptom Management

Cough Management:

• Chronic cough affects up to 80% of IPF patients and significantly impairs quality of life 5
• Treatment algorithm for refractory cough in advanced ILD:
  1. First evaluate for progression of underlying disease or complications from immunosuppressive treatment 5
  2. Assess for common comorbidities including GERD, obstructive sleep apnea, and pulmonary hypertension 5
  3. If GERD workup is negative, proton pump inhibitor therapy should not be prescribed 5
  4. First-line options include gabapentin therapy and multimodality speech pathology therapy (including cough suppression techniques) 3, 5
  5. For intractable cough with substantial impact on quality of life when alternative treatments have failed, opiates should be considered for symptom control in a palliative care setting 3

Other Supportive Measures:

• Structured exercise therapy reduces symptoms and improves 6-minute walk test distance in individuals with dyspnea 1
• Oxygen therapy reduces symptoms and improves quality of life in individuals who desaturate below 88% on a 6-minute walk test 1
• Up to 85% of individuals with end-stage fibrotic ILD develop pulmonary hypertension - in these patients, treatment with inhaled treprostinil improves walking distance and respiratory symptoms 1

Advanced Disease Management

• Lung transplantation should be considered for patients with advanced ILD, improving median survival from less than 2 years to 5.2-6.7 years 1
• For patients with chronic cough due to advanced ILD when alternative treatments have failed, opiates are recommended for symptom control with reassessment of benefits and risks at 1 week and then monthly 3
• Hospitalization risk might be reduced by improved management of comorbidities and optimized pharmacological and non-pharmacological ILD therapy 6

Monitoring Disease Progression

• Regular pulmonary function tests, including spirometry and diffusing capacity for carbon monoxide (DLCO), should be performed at least every 6 months in higher-risk patients and yearly in others 3
• High-resolution computed tomography (HRCT) is approximately 91% sensitive and 71% specific for diagnosing ILD subtypes 1
• Functional assessment should include 6-minute walk distance test, which is widely recognized, simple, non-invasive, and reproducible 3

Pitfalls and Caveats

• Delayed initiation of medical ILD treatment is associated with increased frequency and earlier hospitalizations 6
• Comorbidities significantly impact hospitalization patterns and should be actively managed 6
• Anti-MDA5 antibody positivity is an independent risk factor for mortality due to rapidly progressive ILD in inflammatory myopathies 7
• When using opiates for symptom control, regular reassessment of benefits versus risks is essential 5