An improved bronchial provocation test with dry powder adenosine instead of nebulised adenosine monophosphate (AMP)

Background: Airway hyperresponsiveness to AMP, a precursor of adenosine, is a marker for eosinophilic airway inflammation in asthma and can be used to monitor disease activity and therapeutic effectiveness of inhaled corticosteroids. However, the highest AMP concentration that can be nebulised often fails to cause sufficient bronchoconstriction in asthma patients, limiting its clinical usefulness. Aim: To study if bronchial provocation with adenosine can be improved by using dry powder (DP) adenosine instead of nebulised AMP. Methods: 60 subjects with asthma underwent provocations with doubling doses of AMP and adenosine, with an interval of 14±7 days. AMP was administered by nebulisation (0.04–320 mg/mL, equivalent to 0.003–28 mg adenosine), whereas DP adenosine (0.04–80 mg) was administered with an investigational inhaler. We determined the provocative concentration (PC20) of AMP and dose (PD20) of adenosine that caused a drop of 20% in FEV1 and assessed associations with clinical characteristics. Results: PC20 AMP and PD20 adenosine were strongly correlated (r = 0.799) and had a moderate agreement (κ = 0.42), with more subjects responding to adenosine (85%) than to AMP (70%). Age, blood eosinophils, FEV1 and residual volume predicted around 30% of the variation found in both PC20 AMP and PD20 adenosine in our subjects. Conclusions: More subjects reached a 20% drop in FEV1 in response to DP adenosine compared to nebulised AMP. The strong correlation between the tests and comparable baseline predictors suggest that bronchial provocation with DP adenosine is a suitable alternative to nebulised AMP, yet with a higher sensitivity for less hyperresponsive subjects with asthma.