Associations of AMP and adenosine induced dyspnea sensation to large and small airways dysfunction in asthma

BACKGROUND: Bronchial provocation is often used to confirm asthma. Dyspnea sensation, however, associates poorly with the evoked drop in FEV(1). Provocation tests only use the large airways parameter FEV(1), although dyspnea is associated with both large- and small airways dysfunction. Aim of this study was to explore if adenosine 5′-monophosphate (AMP) and adenosine evoke an equal dyspnea sensation and if dyspnea associates better with large or small airways dysfunction. METHODS: We targeted large airways with AMP and small airways with dry powder adenosine in 59 asthmatic (ex)-smokers with ≥5 packyears, 14 ± 7 days apart. All subjects performed spirometry, impulse oscillometry (IOS), and Borg dyspnea score. In 36 subjects multiple breath nitrogen washout (MBNW) was additionally performed. We analyzed the association of the change (Δ) in Borg score with the change in large and small airways parameters, using univariate and multivariate linear regression analyses. MBNW was analyzed separately. RESULTS: Provocation with AMP and adenosine evoked similar levels of dyspnea. ΔFEV(1) was not significantly associated with ΔBorg after either AMP or adenosine provocation, in both univariate and multivariate analyses. In multivariate linear regression, a decrease in FEF(25–75) during adenosine provocation was independently associated with an increase in Borg. In the multivariate analyses for AMP provocation, no significant associations were found between ΔBorg and any large or small airways parameters. CONCLUSION: AMP and adenosine induce equally severe dyspnea sensations. Our results suggest that dyspnea induced with dry powder adenosine is related to small airways involvement, while neither large nor small airways dysfunction was associated with AMP-induced dyspnea. TRAIL REGISTRATION: NCT01741285 at www.clinicaltrials.gov, first registered Dec 4th, 2012. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12890-019-0783-0) contains supplementary material, which is available to authorized users.