Airway responsiveness to mannitol 24h after allergen challenge in atopic asthmatics

BackgroundAirway responsiveness to indirect stimuli correlates positively with airway inflammation. In atopic asthmatics, allergen inhalation is associated with an influx of inflammatory cells and increased responsiveness to the direct-acting stimuli methacholine at 3 and 24h after exposure. We have shown mannitol responsiveness decreases 3h after allergen inhalation. The current investigation assessed mannitol responsiveness 24h after allergen challenge. MethodsEleven mild atopic asthmatics completed allergen challenges on two separate occasions. In random order, methacholine or mannitol challenges were performed 24h pre- and post-allergen challenge. Levels of fractional exhaled nitric oxide were also measured. ResultsAllergen challenge increased airway responsiveness to methacholine 24h postchallenge; the geometric mean (95% CI) methacholine PC20 decreased from 5.9mg/ml (1.8-19.4) to 2.2mg/ml (0.81-5.89); P=0.01. This coincided with a significant increase (P=0.02) in FeNO levels. Conversely, allergen challenge decreased airway responsiveness to mannitol; geometric mean (95% CI) dose-response ratio was significantly higher after allergen exposure (57mg/% FEV1 fall [27-121] to 147mg/% FEV1 fall [57-379]; P=0.03), and FeNO levels were not significantly increased (P=0.054). ConclusionAllergen-induced changes in airway responsiveness to direct and indirect stimuli are markedly different. The loss in responsiveness to mannitol is likely not explainable by a refractory state. The effect(s) of allergen exposure on airway responsiveness to indirect-acting stimuli require further investigation.