Feasibility of Measuring Adenosine Triphosphate (ATP), CD39L1, and Adenosine in the Airways of Patients with Chronic Cough.

BACKGROUND: Extracellular adenosine triphosphate contributes to cough hypersensitivity through purinergic signalling, but airway purinergic biomarkers have not been well characterized in chronic cough. OBJECTIVE: To evaluate the feasibility of measuring sputum adenosine triphosphate, adenosine, and CD39L1 and their relationship with cough outcomes. METHODS: In a prospective observational study, 100 adults with chronic cough were classified as chronic cough secondary to asthma or non-asthmatic eosinophilic bronchitis (n=45) or refractory chronic cough (n=55) and received guideline-based treatment. Induced sputum was collected before and after treatment. Biomarkers were quantified using bioluminescence and enzyme-linked immunosorbent assays and compared with 24-hour cough frequency, cough-specific quality of life, and cough severity. RESULTS: Baseline biomarker concentrations were similar between groups. In refractory chronic cough, lower sputum adenosine triphosphate and higher CD39L1 were associated with worse patient-reported cough outcomes, whereas no associations were observed in chronic cough secondary to asthma or non-asthmatic eosinophilic bronchitis. Sputum adenosine triphosphate decreased following treatment in the overall cohort and in chronic cough secondary to asthma or non-asthmatic eosinophilic bronchitis, while adenosine and CD39L1 remained unchanged. Changes in biomarkers were not associated with clinical improvement. CONCLUSION: Purinergic biomarkers can be measured in induced sputum. Lower adenosine triphosphate and higher CD39L1 were associated with worse cough outcomes in refractory chronic cough. CLINICAL IMPLICATION: Measurement of airway purinergic biomarkers may help identify neuronal dysfunction and support the development of targeted therapies for refractory chronic cough. CLINICALTRIALS: GOV ID: NCT04758351 CAPSULE SUMMARY: Sputum purinergic biomarkers can be measured in chronic cough and may identify neuronal dysfunction, supporting their potential as treatable traits and biomarkers for targeted therapies.