Abstract
Cough affects all individuals at different times, and its economic burden is substantial. Despite these widespread adverse effects, cough research relies on animal models, which hampers our understanding of the fundamental cause of cough. Postnasal drip is speculated to be one of the most frequent causes of chronic cough; however, this is a matter of debate. Here we show that mechanical stimuli by postnasal drip cause chronic cough. We distinguished human cough from sneezes and expiration reflexes by airflow patterns. Cough and sneeze exhibited one-peak and two-peak patterns, respectively, in expiratory airflow, which were also confirmed by animal models of cough and sneeze. Transgenic mice with ciliary dyskinesia coughed substantially and showed postnasal drip in the pharynx; furthermore, their cough was completely inhibited by nasal airway blockade of postnasal drip. We successfully reproduced cough observed in these mice by injecting artificial postnasal drip in wild-type mice. These results demonstrated that mechanical stimulation by postnasal drip evoked cough. The findings of our study can therefore be used to develop new antitussive drugs that prevent the root cause of cough.
Highlights
Cough is a protective reflex that eliminates foreign materials and sputum from the airway
We used a spirometer to measure airflow through the nose and mouth during respiratory reflexes; cough and the expiration reflex were evoked by inhaled capsaicin while sneeze was evoked by rubbing the nasal cavity
We experimentally demonstrated that cough was evoked by mechanical stimuli due to postnasal drip from rhinosinusitis
Summary
Cough is a protective reflex that eliminates foreign materials and sputum from the airway. This important reflex prevents aspiration of foreign material and cleans the lower airway in cooperation with ciliary movement. Absence of the normal cough reflex increases the risk of developing pneumonia. Many individuals are prone to excessive and intolerable cough, and acute and chronic cough impairs quality of life [1, 2]. Uncontrolled cough often causes adverse events such as syncope, urinary incontinence, bone fracture, muscle ache, and sleep disturbance. The most frequent reason for seeking medical help is cough [3], and the economic burden of cough in the United Kingdom is estimated to be at least £104 million [4].
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