Safety of ATP inhalation in healthy volunteers

<bold>Background:</bold> P2X3 antagonists can reduce cough frequency in refractory/unexplained chronic cough (RUCC) patients, implying that adenosine triphosphate (ATP) is a key mediator in RUCC. Inhaled ATP has been used to experimentally evoke cough in healthy volunteers (HVs) and RCC patients (1), but can cause bronchoconstriction in asthmatics (2). <bold>Aims:</bold> To assess the influence of different dosimeters in ATP cough challenge, however the study highlighted previously unreported safety issues. <bold>Methods:</bold> 13 HVs (54% female) underwent 2 ATP cough challenges, inhaling doubling doses of ATP (0.125–512 mg/ml) 2-7 days apart using either the provo-x or koko dosimeters. Spirometry was measured pre and post challenge. HVs had no history of respiratory disease; 12/13 were never smokers. <bold>Results:</bold> Participants had a median (IQR) age 36(33-50) years, FEV1 3.34(2.83–4.35), % predicted 104 (92.5–110.3), FVC 4.49 (3.38–5.28), % predicted 108 (101.9–115.8). ATP challenge dropped FEV1 by a median of 10% (range 0–36%). 8/13 (62%) of HVs experienced AEs including drop in FEV1 >20% (3/13). Additional safety measures were introduced in the final 7 HVs including; continuous oxygen saturation monitoring and auscultation of the chest after each incremental dose of ATP. Additional AEs included audible wheeze (3/7, 43%), tight chest (4/7, 57%) and desaturation below 94% (2/7, 29%). AEs occurred in 13/24 (54%) of cough challenges unrelated to the nebuliser used. <bold>Conclusion:</bold> Despite providing mechanistic insights into RCC, inhaled ATP is a potent bronchoconstrictor even in HVs. Spirometry and additional safety measures must be considered when performing ATP cough challenge to mitigate this risk.1. Fowles et al. ERJ. 2017;49(2); 2. Bagsolu et al. Chest. 2005 Oct;128(4):1905-9