Introduction Recent studies have suggested a role for adenosine triphosphate (ATP) activated P2×3 receptors in the pathophysiology of chronic cough. ATP has previously been used as an inhalational challenge substance in asthmatics and COPD patients, with the main focus being on bronchospasm. We have considered whether chronic cough patients are hypersensitive to inhaled ATP compared to healthy volunteers.
Method The recognised ERS standardised cough challenge using the Ko-Ko digidoser was performed with ATP and AMP as substrates. 20 Healthy volunteers and 20 chronic cough patients were randomised to the order of challenges. C5 (the concentration of substrate causing at least 5 coughs) was compared for ATP and AMP. Average cough response to ATP was compared between the 2 groups.
Results 6 male and 14 female volunteers in each group were randomised to receive cough challenges. Hull Airways Reflux Questionnaire score range was 0–8 in healthy volunteers and 21–52 in chronic cough patients. 1 healthy volunteer had a mild hypersensitivity reaction to ATP with urticaria. 1 patient withdrew after their first challenge due to worsening cough. No other side effects were reported. 2/19 healthy volunteers coughed with AMP, neither achieved C5. 8/20 chronic cough patients coughed with AMP, 2 achieved C5. 18/20 healthy volunteers coughed with ATP with 15 achieving C5. 19/19 chronic cough patients coughed with ATP, 18 achieved C5. The chronic cough patients had a greater cough response at lower concentrations of ATP as demonstrated in Figure 1.
Discussion Previous human ATP challenges have documented cough as a symptom but none have objectively measured the cough response in chronic cough patients. We present here the first results demonstrating that chronic cough patients have increased sensitivity to ATP compared to healthy volunteers. This supports a role for ATP driven receptors in the cough reflex arc and supports further research in this area as a target for treatments in chronic cough.