Chronic cough and refractory chronic cough: An important distinction

Abstract

Cough is the most common concern for which patients in the United States seek medical attention. Cough is typically classified according to its duration: acute cough (<3 weeks), subacute cough (3‐8 weeks), and chronic cough (>8 weeks). The vast majority of cases of acute cough in patients are due to an acute viral upper respiratory tract infection (common cold) and are self limited. Subacute cough is often due to a prolonged postviral cough. Once a cough meets the definition of chronic, it becomes likely that the cough is due to one or more treatable underlying etiologies: upper airway cough syndrome (formerly, postnasal drip syndrome), asthma and non-asthmatic eosinophilic bronchitis, and gastroesophageal reflux disease. Refractory chronic cough (RCC) refers to chronic cough that persists despite adequate therapeutic trials aimed at the known causes of chronic cough. The term cough hypersensitivity syndrome has recently been introduced to stress the concept that RCC is a distinct disease entity due to vagal hyperactivity causing hypersensitivity of the cough reflex. No medications have ever been approved for chronic cough or RCC in the United States and most of the world. Thus, physicians are limited to the use of off-label medications for their patients with this chronic and often debilitating condition. However, recent insights into the mechanisms of cough have resulted in multiple molecules currently being evaluated as potential antitussives. Among these, furthest along in the drug development pipeline are the P2X3-antagonists, of which, gefapixant has completed phase III trials, and camlipixant is currently in phase III studies.