Cough response to isocapnic hyperpnoea of dry air and hypertonic saline are interrelated

BACKGROUND: Mechanisms behind asthmatic cough are largely unknown. It is known that hyperosmolar challenges provoke cough in asthmatic but not in the healthy subjects. It has been postulated that isocapnic hyperpnea of dry air (IHDA) and hypertonic aerosols act via similar mechanisms in asthma to cause bronchoconstriction. We investigated whether there is an association between cough response induced by IHDA and hypertonic saline (HS) challenges. METHODS: Thirty-six asthmatic and 14 healthy subjects inhaled HS solutions with increasing osmolalities administered via ultrasonic nebuliser until 15 cumulative coughs were recorded. The IHDA consisted of three three-minute ventilation steps: 30%, 60% and 100% of maximal voluntary ventilation with an end-point of 30 cumulative coughs. The challenges were performed on separate days at least 48 hours between them and within one week. Inhaled salbutamol (400 mcg) was administered before the challenges to prevent bronchoconstriction. The cough response was expressed as the cough-to-dose ratio (CDR) which is the total number of coughs divided by the maximal osmolality inhaled or the maximal ventilation achieved. RESULTS: Cough response to IHDA correlated with the HS challenge (Rs = 0.59, p < 0.001). Cough response to IHDA was at its strongest during the first minute after the challenge. IHDA induced more cough among asthmatic than healthy subjects CDR being (mean ± SD) 0.464 ± 0.514 and 0.011 ± 0.024 coughs/MVV%, p < 0.001, respectively. Salbutamol effectively prevented bronchoconstriction to both challenges. CONCLUSIONS: Asthmatic patients are hypersensitive to the cough-provoking effect of hyperpnoea, as they are to hypertonicity. Cough response induced by IHDA and HS correlated well suggesting similar mechanisms behind the responses.