A novel method for studying airway hyperresponsiveness in allergic guinea pigs in vivo using the PreciseInhale system for delivery of dry powder aerosols

Abstract

Inhaled adenosine receptor agonists induce bronchoconstriction and inflammation in asthma and are used as bronchial challenge agents for the diagnosis of asthma and in respiratory drug development. Recently developed dry powder aerosols of adenosine have several advantages over nebulised adenosine 5′-monophosphate (AMP) as bronchial challenge agents. However, reverse translation of this bronchial challenge technique to pre-clinical drug development is limited by the difficulty of administering powder aerosols to animals. The aim of the current study was to develop methods for delivering powder aerosols of adenosine receptor agonists to sensitised guinea pigs (as a model of allergic asthma) and evaluate their effect as challenge agents for the measurement of airway responsiveness. The PreciseInhale system delivered micronised AMP and adenosine powders, with mass median aerodynamic diameters of 1.81 and 3.21 μm and deposition fractions of 31 and 48% in the lungs, respectively. Bronchoconstrictor responses in passively sensitised, anaesthetised, spontaneously breathing guinea pigs were compared to responses to nebulised and intravenously administered AMP and adenosine. AMP- and adenosine-induced bronchoconstriction following all routes of administration with the magnitude of response ranking intravenous > dry powder > nebulisation, probably reflecting differences in exposure to the adenosine agonists delivered by the different routes. In conclusion, the PreciseInhale system delivered AMP and adenosine dry powder aerosols accurately into the lungs, suggesting this method can be used to investigate drug effects on airway responsiveness.