Abstract

Small airways are an important site of inflammation and obstruction in asthma, which contributes to the severity of airway hyperresponsiveness (AHR) that is usually measured by nebulisation of large-particle stimuli. We investigated whether small and large particle sizes of aerosolized adenosine-'5-monophospate (AMP) provide similar severity of AHR. Additionally, effects of small-particle ICS ciclesonide and large-particle ICS fluticasone on AHR to large- and small-particle size AMP were assessed.

After a 4-week run-in period using open-label fluticasone 100 μg b.i.d., 37 mild-to-moderate asthmatics underwent provocations with standard size (3.7 micron), large-particle (9.9 micron) and small-particle (1.06 micron) AMP. Subjects received 4-week ciclesonide 160 μg s.i.d. or fluticasone 100 μg b.i.d. (double-blind, double-dummy) followed by large- and small-particle AMP provocation.

Small-particle AMP induced a 20% fall in FEV1 (PC20) at a significantly higher dose than large-particle AMP. Ciclesonide and fluticasone had comparable effects on AMP provocations. Not all subjects reached a PC20 at the highest AMP dose. In those who did, ciclesonide improved small-particle PC20AMP by 1.74 doubling doses (DD) (p=0.03), whereas fluticasone did not. Conversely, fluticasone improved large-particle PC20AMP significantly (1.32DD, p=0.03), whereas ciclesonide did not.

Small-particle AMP provocation appears a promising tool to assess changes in small airways inflammation. Future adjustments are necessary taking into account the very small-particle size used, with large exhaled fractions. In asthmatics reaching a PC20 with small- and large-particle AMP provocations, ciclesonide improves hyperresponsiveness with small-particle size AMP, and fluticasone with large-particle size. This warrants further research to target provocations and treatment to specific airway sizes.