Unraveling adenosine and AMP induced dyspnea sensation in asthma

Background: Bronchial provocation is often used to confirm asthma. Dyspnea sensation correlates poorly with the provocative dose that causes the FEV1 to drop ≥20% (PD20). Aim: To explore if dyspnea sensation associates better with small airways then large airways function. Methods: We induced dyspnea with dry powder adenosine and nebulized adenosine 5’‑monophosphate (AMP), targeting the small and large airways, respectively, 14±7 days apart. We obtained spirometry, impulse oscillometry (IOS), and Borg score in all subjects, but multiple breath nitrogen washout (MBNW) was only limited available. Subjects were asthmatic (ex‑)smokers with ≥5 packyears. We analyzed the correlation between the change (Δ) in large and small airways parameters to ΔBorg in univariate and multivariate linear regression analysis. MBNW was analyzed separately. Results: We included 61 subjects of which 36 performed MBNW. Provocation with adenosine and AMP evoked similar levels of dyspnea. The large airways parameter, ΔFEV1 was not significantly correlated with ΔBorg after either adenosine or AMP provocation, in both univariate and multivariate analyses. Multivariate linear regression models for ΔBorg included for adenosine: gender, smoking status, ΔFEV1, ΔFEF25-75, ΔR20, ΔR5‑R20, and ΔScond and for AMP: gender, smoking status, ΔFEV1, ΔFEF25-75, ΔR20, ΔX5, and ΔLCI5%. ΔFEF25-75 during adenosine provocation was independently associated with ΔBorg, but for ΔBorg during AMP provocation no significant associations were found. Conclusion: Our results suggest that dyspnea sensation induced with dry powder adenosine is related to small airways involvement, while neither large nor airways small airways dysfunction was associated with AMP induced dyspnea.