Plasma and bronchoalveolar lavage ATP in refractory/unexplained chronic cough

<bold>Background:</bold> The efficacy of P2X3 antagonists in refractory/unexplained chronic cough (RUCC) implicates extracellular ATP (eATP) in the disease. We aimed to compare plasma and bronchoalveolar lavage eATP levels between RUCC and healthy volunteers (HV) and correlate these with cough measures. <bold>Methods:</bold> Adult RUCC and HV underwent 24h cough monitoring, cough measures (LCQ/VAS), blood and bronchoalveolar lavage (BAL) sampling. Blood collected in EDTA bottles, was centrifuged and plasma transferred to cryotubes and stored at-80℃. BAL collected from the right middle lobe was transferred to EDTA bottles and centrifuged prior to aliquoting and storage (−80℃). Plasma and BAL relative light units (RLU) were measured using an ATP detection luminescence assay kit (Cayman chemical). <bold>Results:</bold> We compared RUCC (n=22) median (IQR) age 59 (55–65) y) with HV (n=14) 33 (25–44) y, p<0.01); sex, lung function and blood eosinophils were comparable. Mean (SEM) plasma eATP was higher in RUCC than HV, [3051(±195) nM vs. 1939 (±307) nM, p<0.01; 5 haemolysed RUCC samples excluded]. In contrast, mean (SEM) BAL eATP was lower in RUCC [582 (±38) nM vs. 727 (±47) nM, p=0.02]. Plasma eATP correlated with day VAS (R = 0.51, p = 0.02), and trended towards correlation with LCQ (r = -0.38, p=0.06) and 24hr cough frequency (r=0.40, p=0.06). BAL eATP also correlated with LCQ (r =–0.43, p=0.02), but not cough frequency or day VAS (both p >0.05). <bold>Conclusion:</bold> ATP levels in plasma support the hypothesis that increased eATP drives cough in RUCC. Reduced airway ATP levels were unexpected, but may reflect enhanced ATP breakdown by ectonucleotidases in the airways or after sampling.