Comparison of bronchoconstrictor responses to AMP and adenosine in sensitised guinea pigs using the PreciseInhale® system for generation and administration of dry powder aerosols

A.J. Lexmond, S. Keir, C.P. Page, B. Forbes

Inhaled adenosine induces bronchoconstriction and inflammation in asthma and can therefore be used for bronchial challenge testing. Bronchial challenge tests are sometimes performed with nebulised solutions of adenosine 5’-monophosphate (AMP). The nebulised AMP test has several disadvantages, including long administration times and a maximum concentration that does not induce sufficient bronchoconstriction in all patients. Using aerosolised dry powder adenosine instead of nebulised AMP may improve adenosine delivery to the lungs. However, it remains to be elucidated whether comparable effects are obtained when administering the challenge using a powder versus droplet presentation, and when using adenosine versus AMP. The aim of this study was to compare the bronchoconstrictor responses to the different delivery methods in an allergic guinea pig model.
The PreciseInhale® system was used to generate dry powder aerosols of AMP and adenosine for pulmonary administration, with an MMAD of 1.81 μm and 3.21 μm, respectively. In a small proof-of-principle study, bronchonconstrictor responses to these dry powder aerosols in passively sensitised guinea pigs were compared to the responses to nebulised and intravenously administered AMP and adenosine. Airway obstruction in response to the challenges was measured as an increase in total lung resistance (RL) and decrease in dynamic lung compliance (Cdyn). All six administrations successfully induced bronchoconstriction in this animal model. The time to maximal response was comparable for both inhaled administration methods and the bronchoconstriction produced by adenosine and AMP was similar, but the magnitude of response varied: iv > dry powder > nebulisation. The next step will be to investigate dose-response to the dry powder aerosols.

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