Abstract
In clinical practice, we commonly face adversity when encountering dysfunction of the cough reflex. Similar to ancient Roman deity Janus, it often presents with one of two opposing “faces”. Continual aberrant activation of the cough reflex, also known as chronic cough, can cause great detriment to quality of life and many of these patients are left misdiagnosed and undertreated. In contrast, loss of normal functioning of the cough reflex is the cause of a significant proportion of mortality in the elderly, primarily through the development of aspiration pneumonia. In this review we discuss both hyper- and hypo-activation of the cough reflex and how airway reflux and chronic aspiration may be involved in the aetiology and sequalae of both disease states. We detail the physiological and pharmacological mechanisms involved in cough, and how the recent development of P2X3 receptor antagonists may lead to the first pharmaceutical agent licensed for chronic cough. The treatment and prevention of loss of the cough reflex, which has been largely neglected, is also discussed as novel low-cost interventions could help prevent a number of hospital and domiciliary deaths from both acute and chronic aspiration.
Highlights
The cough reflex is a vital defense mechanism that allows the body to expel inhaled foreign objects, potential pathogens, and endogenous secretions
This concept is based on the theory that there may be crosstalk at the nucleus tractus solitarius between the stimuli from esophageal and airway neurons converging in this area, which would allow refluxmediated irritation of the esophagus to produce a “referred” initiation of the cough reflex
Both of these terms are synonymous with airway reflux, “silent” reflux, whilst appropriate for voice change is inappropriate for the patient with chronic cough! The phenomena listed in the questionnaire were derived from interviews with patients with chronic cough, and are inextricably linked to the opening of the lower esophageal sphincter (Mittal and Balaban, 1997)
Summary
The cough reflex is a vital defense mechanism that allows the body to expel inhaled foreign objects, potential pathogens, and endogenous secretions. For the purposes of drug trials, patients with chronic cough have been stratified into one of two categories: Unexplained Chronic Cough (UCC), usually defined as cough with no obvious cause for > 1 years duration, and Refractory Chronic Cough (RCC), that being an unexplained chronic cough that persists despite rigorous investigation and treatment in accordance with bestpractice guidelines (Gibson et al, 2016; Dicpinigaitis, 2020) We suggest that these definitions may be further simplified, with RCC being the failure of the treatment to improve a patient’s cough and UCC being the failure of the physician to identify the cause of the patient’s cough. For the purposes of simplicity in this review, we will use the definition of CC as defined by the ERS and ACCP
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