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 aerosolised adenosine monophospate (AMP) provoke similar severity of AHR. Additionally, effects of the small-particle inhaled corticosteroid (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 μm), large-particle (9.9 μm) and small-particle (1.06 μm) AMP. Subjects received 4-week ciclesonide (160 μg s.i.d.) or fluticasone (100 μg b.i.d.) treatment (double-blind and double-dummy) followed by large- and small-particle AMP provocation.

Small-particle AMP induced a 20% decrease in forced expiratory volume in 1 s (FEV1) at a significantly higher dose than large-particle AMP. Ciclesonide and fluticasone had comparable effects on AMP provocations. Not all subjects reached the provocative concentration causing a 20% fall in FEV1 (PC20) at the highest AMP dose. In those who did, ciclesonide improved small-particle AMP PC20 by 1.74 doubling doses (DD) (p = 0.03), whereas fluticasone did not. Conversely, fluticasone improved large-particle AMP PC20 significantly (1.32 DD; p = 0.03), whereas ciclesonide did not.

Small-particle AMP provocation appears to be a promising tool to assess changes in small airway 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 to small particle size AMP, and fluticasone to large particle size. This warrants further research to target provocations and treatment to specific airway sizes.


  • Received December 29, 2009.
  • Accepted June 20, 2010.
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