How should cough be treated in patients with IPF?
Dry, nonproductive cough is a very common symptom of IPF.1 At least 70%-85% of patients with IPF have a dry cough, which often gets worse on exertion.1 Many patients with IPF can have a cough that is caused by other pathologies.2,3 However, cough in IPF is usually refractory to medical therapy and can dramatically affect patients’ quality of life.4,5
Causes of Cough in IPF
The IPF disease process itself can increase patients’ sensitivity to cough triggers, although up to 50% of cases of cough may be caused by comorbidities, including postnasal drip, gastroesophageal reflux (GERD), cough-variant asthma, and certain medications.2,3,6
Mechanisms of Cough in IPF
The mechanism(s) causing cough in IPF are not fully known. In general, coughing is mediated by specific types of sensory neurons that can be activated through mechanical and/or chemical stimuli.7-9 In IPF, one potential explanation for this cough is that increased mechanical stress on the lungs caused by fibrosis may cause increased sensitivity to cough triggers.6 Another hypothesis is that fibrosed tissue may be more sensitive to chemical triggers.10,11 Finally, changes in mucus production and clearance may also affect patients’ susceptibility to cough, based on the observation that patients with IPF who have mutations in MUC5B tend to have more severe cough.12
Treating Cough in IPF
Nothing is approved to treat cough in IPF. Further, many of the standard treatments for acute cough do not alleviate this symptom in patients with IPF.1 Standard cough suppressants that target the cough reflex are generally ineffective, although a few have recently shown effects in treating idiopathic chronic cough.13-16 Therapies that directly target the mechanism(s) of IPF may reduce or stabilize the severity of cough, although neither approved agent has shown direct effects on reducing cough severity.1 A few alternative therapies have been tested in IPF. The only one tested in a placebo-controlled trial improved both the cough-related and respiratory-related quality of life scores.17 A small non-placebo-controlled study showed that a different agent was able to alleviate cough in patients with IPF and chronic cough.18 Finally, there are conflicting data about whether using steroids can reduce cough severity.4,11
What It Means
The presence of cough in IPF correlates with disease severity and predicts progression, as well as directly impacts patients’ quality of life and emotional well-being. Understanding the current options for treating cough in patients with IPF can help providers better manage these patients.
Link to abstract: https://www.ncbi.nlm.nih.gov/pubmed/28137504
- Vigeland CL, Hughes AH, Horton MR. Etiology and treatment of cough in idiopathic pulmonary fibrosis. Respir Med. 2017;123:98-104.
- Kilduff CE, Counter MJ, Thomas GA, Harrison NK, Hope-Gill BD. Effect of acid suppression therapy on gastroesophageal reflux and cough in idiopathic pulmonary fibrosis: an intervention study. Cough. 2014;10:4.
- Madison JM, Irwin RS. Chronic cough in adults with interstitial lung disease. Curr Opin Pulm Med. 2005;11(5):412-416.
- Key AL, Holt K, Hamilton A, Smith JA, Earis JE. Objective cough frequency in idiopathic pulmonary fibrosis. Cough. 2010;6:4.
- Swigris JJ, Kuschner WG, Jacobs SS, Wilson SR, Gould MK. Health-related quality of life in patients with idiopathic pulmonary fibrosis: a systematic review. Thorax. 2005;60(7):588-594.
- Harrison NK. Idiopathic pulmonary fibrosis: a nervous cough? Pulm Pharmacol Ther. 2004;17(6):347-350.
- Fox AJ, Barnes PJ, Urban L, Dray A. An in vitro study of the properties of single vagal afferents innervating guinea-pig airways. J Physiol. 1993;469:21-35.
- Mazzone SB. An overview of the sensory receptors regulating cough. Cough. 2005;1:2.
- Widdicombe J. Functional morphology and physiology of pulmonary rapidly adapting receptors (rars). Anat Rec A Discov Mol Cell Evol Biol. 2003;270(1):2-10.
- Doherty MJ, Mister R, Pearson MG, Calverley PM. Capsaicin induced cough in cryptogenic fibrosing alveolitis. Thorax. 2000;55(12):1028-1032.
- Hope-Gill BD, Hilldrup S, Davies C, Newton RP, Harrison NK. A study of the cough reflex in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2003;168(8):995-1002.
- Scholand MB, Wolff R, Crossno PF, et al. Severity of cough in idiopathic pulmonary fibrosis is otalassociated with MUC5 B genotype. Cough. 2014;10:3.
- Abdulqawi R, Dockry R, Holt K, et al. P2X3 receptor antagonist (AF-219) in refractory chronic cough: a randomised, double-blind, placebo-controlled phase 2 study. Lancet. 2015;385(9974):1198-1205.
- Bastian RW, Vaidya AM, Delsupehe KG. Sensory neuropathic cough: a common and treatable cause of chronic cough. Otolaryngol Head Neck Surg. 2006;135(1):17-21.
- Morice AH, Fontana GA, Belvisi MG, et al. ERS guidelines on the assessment of cough. Eur Respir J. 2007;29(6):1256-1276.
- Ryan NM, Birring SS, Gibson PG. Gabapentin for refractory chronic cough: a randomised, double-blind, placebo-controlled trial. Lancet. 2012;380(9853):1583-1589.
- Horton MR, Santopietro V, Mathew L, et al. Thalidomide for the treatment of cough in idiopathic pulmonary fibrosis: a randomized trial. Ann Intern Med. 2012;157(6):398-406.
- Lutherer LO, Nugent KM, Schoettle BW, et al. Low-dose oral interferon alpha possibly retards the progression of idiopathic pulmonary fibrosis and alleviates associated cough in some patients. Thorax. 2011;66(5):446-447.