Chronic Cough in Interstitial Lung Disease: More Clinical Trials Needed

Evidence to support specific management approaches to chronic cough in interstitial lung disease (ILD) is lacking, but the neuromodulator gabapentin and speech pathology management may be of benefit, and opiates in a palliative care setting may be an option for cough that is refractory to other therapies and seriously impairs the patient’s quality of life, according to a CHEST guideline and expert panel report published in CHEST.

Surinder S. Birring, MD, from the Division of Asthma, Allergy & Lung Biology at the School of Transplantation, Immunology, Infection & Inflammation Sciences, Faculty of Life Sciences & Medicine at King’s College in London, United Kingdom, and colleagues performed a systematic review of the literature to determine whether there was evidence of clinically relevant treatment effects for therapies for cough in ILD. The investigators included studies of adults with a chronic cough that had lasted more than 2 months, and evaluated those studies for relevance and quality.

The investigators identified 8 randomized controlled trials and 2 case series with more than 10 participants with idiopathic pulmonary fibrosis (IPF), sarcoidosis, or scleroderma-related ILD who had received a number of interventions.

On the basis of this review, the expert panel came up with several suggestions. The first is that patients with ILD who present with a chronic cough should be evaluated for progression of their underlying disease or complications from immunosuppressive treatment, such as drug adverse effects or pulmonary infection. Patients should be considered for further investigation and treatment trials for their cough.

For cough in patients with IPF, the authors argued that the efficacy of thalidomide should be further investigated. Proton pump inhibitors (PPIs) are often used in IPF. However, the authors suggested that PPIs not be prescribed in patients with IPF, a chronic cough, and a negative workup for acid gastroesophageal reflux. The authors also suggested that inhaled corticosteroids not be routinely prescribed for chronic cough for patients with pulmonary sarcoidosis.

The expert panel suggested that patients with ILD and refractory chronic cough receive trials of therapies recommended for patients with unexplained chronic cough as per CHEST guidelines, with treatments such as gabapentin and speech pathology therapy. They also suggested enrollment in clinical trials when available.

When alternative therapies have failed and cough is impairing their quality of life, patients should receive opiates for symptom control in a palliative care setting. However, the benefits and risks should be reassessed at 1 week, and then monthly thereafter.

The authors noted the promising results from trials of thalidomide and inhaled cromolyn sodium (PA101) in IPF, but cautioned that further study is needed. They also argued that cough may be a biomarker in ILD, with the potential to assess disease severity and indicate prognosis. These points need to be evaluated in future studies.

Another promising therapy on the horizon is a P2X3 antagonist for IPF-associated cough. Potential anti-tussive targets include neurokinin-1, TRPV4, and alpha-7 nicotinic receptors. Noting the lack of trials involving chronic cough in ILD, the expert panel called for more research and clinical trials in this area.

Reference

Birring SS, Kavanagh JE, Irwin RS, Keogh K, Lim KG, Ryu JH. Treatment of interstitial lung disease associated cough: CHEST guideline and expert panel report [published online July 20, 2018]. CHEST. doi:10.1016/j.chest.2018.06.038