The search for the hypersensitivity in chronic cough.

Chronic cough is a common disorder that affects an estimated 10% of the general population [1]. Adverse symptoms such as urinary incontinence, chest pains, headaches and syncope are frequently associated with cough and lead to poor health-related quality of life [2, 3]. Chronic cough has long been viewed as a symptom of other chronic disorders, hence the current approach to assessing and treating patients focuses on identifying an underlying condition, such as asthma and gastro-oesophageal reflux disease [4]. A significant number of cases of chronic cough, as many as 50%, remain unexplained following detailed assessment. They are often referred to as idiopathic, unexplained or refractory chronic cough [5, 6]. Recently, there has been consensus that chronic cough is a disorder of dysregulated sensory nerves and the associated central processing [7]. In this model, an important symptom reported by patients is an exaggerated sensation of the urge to cough, reflecting a disorder of the primary ascending neurons that innervate the airways and lungs [8]. Cough nerve endings are part of a larger visceral sensory nervous system that communicates information about the local environment via the vagus nerve to the central nervous system [8]. The trigger for cough is often a peripheral stimulation of the airways. Chemical and mechanical stimuli can activate the airway afferent nerves, for example changes in osmolarity, temperature, pH and environmental irritants in the air that we breathe [8]. Patients with chronic cough, compared to healthy subjects are hypersensitive to a wide range of inhaled tussive agents. Examples include capsaicin, citric acid and fog, and their use to induce cough is the basis of the cough challenge test, widely used in research [9]. The peripheral stimulus can activate a brain stem mediated reflex-cough or, more often, a sensation associated with airway irritation (urge to cough) that promotes a behavioural or voluntary cough to relieve this [8].