Towards understanding and managing chronic cough

Abstract

Chronic cough is a common and troublesome condition affecting approximately 12% of the general population. It is associated with poor quality of life with psychological, social and physical consequences. Patients typically complain of a dry irritating cough, driven by a strong urge to cough associated with a sensation or irritation located in the throat. Treatment of potential 'causes', ie asthma, gastro-oesophageal reflux disease and rhino-sinusitis, may produce a complete or partial response, but the response of some patients to opiates and alpha-2-delta ligand antagonists (gabapentin and pregabalin) supports the concept that this is primarily a neurological disorder, characterised by hyper-responsiveness of the nerves. Novel and highly effective neuronal treatments are in development and offer hope of better symptom control with fewer side effects within a few years. This review focuses on understanding the mechanism of chronic cough, current management approaches and research that may lead to novel therapies.

Keywords: Capsaicin; P2X3; chronic cough; cough hypersensitivity syndrome; vagus nerve.

Fig 1.

Structure of human airway nerves. A – thin unmyelinated c-fibres located near the ­epithelial membrane; B – sub-epithelial ­myelinated Aδ fibres. Reprinted with permission of the American Thoracic Society. Copyright © 2016 American Thoracic Society.

Fig 2.

Schematic diagram representing the cough reflex. Vagal afferents transmit stimuli from the airways to the nucleus tractus solitarius (nTS) and paratrigeminal nucleus (Para V) in the brainstem. Neuronal signals are then transmitted to the somatosensory cortex via the thalamus causing throat irritation and urge to cough. These sensations, if great enough, lead to cough via activation of spinal motor neurons.

Fig 3.

Schematic diagram representing cough hyper-responsiveness to airway stimuli displayed by chronic cough patients. Compared with healthy volunteers, patients with chronic cough predominantly exhibit heightened cough responses to airway stimuli, such as inhaled capsaicin and citric acid, in cough challenge test and report coughing triggered by changes in temperature, perfumes, aerosols, smoke and to small volumes of mucus.