Looking ahead to novel therapies for chronic cough. Part 1 – peripheral sensory nerve targeted treatments

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Abstract
Due to a relatively high prevalence and negative impact on quality of life chronic cough (CC) is a challenge for both patients and clinicians. Our approach to CC management has changed significantly over the recent years. There is ongoing research to address the unmet need and develop more effective antitussive treatment options. This is the first part of a series of two reviews of new antitussive medications. Medical databases (Medline, Embase and SCOPUS) and trial registries (ClinicalTrials.gov and EudraCT) were searched for studies on antitussive drugs targeting peripheral sensory nerves. This review presents current knowledge of peripheral receptors, that are not only involved in evoking the cough reflex, but are also potentially responsible for more sustained neural alterations. Blockage of the receptors and ion channels is discussed in terms of its potential antitussive effect. A better understanding of CC mechanisms has facilitated the development of novel treatments including the expected imminent launch of one of the first antitussive drugs acting peripherally, gefapixant, a P2X2/3 receptor inhibitor. There remain several gaps in the knowledge about the mechanisms and treatment of CC. These include the lack of tests to diagnose cough hypersensitivity syndrome and predictors of response to specific treatments. Also, the mechanism and site of the cough hypersensitivity remains unknown. Further research into cough phenotypes and endotypes will yield important insights and a personalized approach to cough management.

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