Effects of Aerosolized Adenosine 5′-Triphosphate in Smokers and Patients With COPD

BACKGROUND Extracellular adenosine 5′-triphosphate (ATP) stimulates vagal C and Ad fibers in the lung, resulting in pronounced bronchoconstriction and cough mediated by P2X2/3 receptors located on vagal sensory nerve terminals. We investigated the effects of nebulized ATP on cough and symptoms in control subjects, healthy smokers, and patients with COPD and compared these responses to the effects of inhaled adenosine, the metabolite of ATP. METHODS We studied the effects of inhaled ATP and adenosine monophosphate (AMP) on airway caliber, perception of dyspnea assessed by the Borg score, cough sensitivity, and ATP in exhaled breath condensate in healthy nonsmokers (n = 10), healthy smokers (n = 14), and patients with COPD (n = 7). RESULTS In comparison with healthy subjects, ATP induced more dyspnea, cough, and throat irritation in smokers and patients with COPD, and the effects of ATP were more pronounced than those of AMP. The concentration of ATP in the exhaled breath condensate of patients with COPD was elevated compared with that of healthy subjects. CONCLUSIONS Smokers and patients with COPD manifest hypersensitivity to extracellular ATP, which may play a mechanistic role in COPD. CHEST 2015;148(2):430-435