An update and systematic review on drug therapies for the treatment of refractory chronic cough

ABSTRACT

Introduction: Chronic Cough (CC) is common and often associated with significant comorbidity and decreased quality of life. In up to 50% of cases, the cough is refractory despite extensive investigation and treatment trials. It is likely that the key abnormality in refractory CC is dysfunctional, hypersensitive sensory nerves, similar to conditions such as laryngeal hypersensitivity and neuropathic pain.

Areas covered: The aim of this systematic review is to assess drug therapies for refractory CC. The authors review the current management of CC and provide discussion of the similarities between neuropathic pain and refractory CC. They review repurposed and new pharmacological treatments. Several meta-analyses were performed to compare the efficacy of treatments where possible.

Expert opinion: Repurposed pain medications such as gabapentin and pregabalin reduce the frequency of cough and improve quality of life. Along with speech pathology, they are important and alternate treatments for refractory CC. However, more treatments are needed and the P2X3 ion channel receptor antagonists show the most promise. With a better understanding of neuronal activation and sensitisation and their signal processing in the brain, improved animal models of cough, and the use of validated cough measurement tools, more effective treatments will develop.

KEYWORDS:

• Antitussives
• cough hypersensitivity syndrome
• ion channel receptor antagonists
• neuromodulating drugs
• refractory chronic cough

Article highlights

• Refractory chronic cough is common and difficult to treat.

• Increased understanding of the similarities in refractory chronic cough and neuropathic pain have resulted in more treatments being available but they do not work for everyone.

• Gabapentin and speech pathology have recently been incorporated into treatment guidelines for refractory chronic cough.

• Novel treatments that target peripheral and central neural receptors are being tested for refractory chronic cough with the P2X3 receptor anatgonists showing the most promise.

• Functional brain imaging, phenotypic cough animal models, and the use of appropriate cough measurement tools will facilitate the development of novel antitussive drugs.

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Declaration of interest

S Birring has received fees for scientific advisory work for the development of therapies for refractory cough from Patara, Merck & Co., and Bayer Healthcare. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

NM Ryan is supported by an NHMRC Early Career Fellowship Award ID 1072056.