Treatment of Cough in Interstitial Lung Disease
First, systematically evaluate and treat alternative causes of cough before attributing it to ILD itself, then proceed with disease-specific ILD treatment when indicated, and finally consider neuromodulators (gabapentin) or speech pathology therapy for refractory cases. 1, 2
Initial Diagnostic Approach
The critical first step is recognizing that cough in ILD patients is frequently caused by conditions other than the ILD itself. 1
Evaluate for these common alternative causes: 1
- Gastroesophageal reflux disease (GERD) - particularly important in systemic sclerosis-associated ILD 1
- Asthma or nonasthmatic eosinophilic bronchitis 1
- Upper airway cough syndrome (rhinosinus conditions) 1
- Medication side effects from ILD treatments 1
- Pulmonary infections - especially in immunosuppressed patients 1
Assess for ILD progression as a cause of cough: 1
- Evidence of disease progression on imaging or pulmonary function tests 1
- Temporal association between cough onset and disease worsening 1
- Favorable response to ILD-directed therapy 1
Disease-Specific ILD Treatment
For Idiopathic Pulmonary Fibrosis (IPF)
Antifibrotic therapy (pirfenidone or nintedanib) should be prescribed according to standard guidelines, not specifically for cough control. 1 These medications may reduce cough severity as a secondary benefit, but this requires confirmation in larger trials. 1
Avoid systemic corticosteroids in IPF for cough management. 1 The combination of corticosteroids with azathioprine and N-acetyl-cysteine ("triple therapy") has been associated with increased mortality compared to placebo. 1 Corticosteroids should be limited to IPF exacerbations or co-existing asthma/eosinophilic bronchitis. 1
For Sarcoidosis
Do not routinely prescribe inhaled corticosteroids for chronic cough in pulmonary sarcoidosis. 3 Three trials demonstrated no significant reduction in cough with inhaled corticosteroids. 1
For Other ILDs
Treatment should target the underlying disease when progression is evident, using immunomodulatory therapy as appropriate for connective tissue disease-associated ILD. 1
Treatment for Refractory ILD-Associated Cough
When alternative causes have been excluded and ILD-directed therapy is insufficient:
First-Line Options for Refractory Cough
Gabapentin therapy is recommended as first-line treatment, following dosing protocols for unexplained chronic cough. 2 This addresses the cough hypersensitivity syndrome that occurs in ILD patients, particularly IPF, where increased cough reflex sensitivity to capsaicin and substance P has been documented. 1
Multimodality speech pathology therapy (cough suppression techniques and breathing exercises) is also recommended as first-line. 2, 3
Emerging Therapies
Inhaled cromolyn sodium (PA101) shows promise with a >30% reduction in objective cough frequency in a pilot study, though it requires larger trials with longer treatment periods. 1 The drug was well-tolerated. 1
Second-Line Options
Low-dose controlled-release morphine is recommended as second-line therapy, with regular reassessment of benefits and risks. 2 The European Respiratory Society recommends low-dose morphine derivatives (<30 mg oral morphine equivalents daily) with careful monitoring. 3
Codeine is recommended by the European Respiratory Society as first-line therapy for dry cough in pulmonary fibrosis. 3
Palliative Care Setting
For patients with chronic cough adversely affecting quality of life when alternative treatments have failed, opiates should be recommended for symptom control in a palliative care setting. 1, 2, 3 Reassess benefits and risks at 1 week, then monthly before continuing. 1, 2
Important Caveats and Pitfalls
Do not prescribe proton pump inhibitor therapy for cough if GERD workup is negative. 2, 3 This is a common error that exposes patients to unnecessary medication.
Thalidomide is not suggested for routine use despite showing quality of life improvements in a small trial, due to significant side effects (77% vs 22% in placebo; P = .001). 1, 4 However, it may be considered as a later-line option after gabapentin, speech therapy, and morphine have failed. 4
High-dose corticosteroids are poorly tolerated and inadvisable for long-term management. 3
Clinical Significance
Up to 80% of IPF patients experience chronic cough, which significantly impairs quality of life. 2 Cough has prognostic significance and is associated with disease progression independent of disease severity. 2 More than 50% of ILD patients referred for cough evaluation have cough caused by alternative diagnoses rather than the ILD itself. 5