Airway responsiveness to mannitol 24 h after allergen challenge in atopic asthmatics.
BACKGROUND
Airway 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 24 h after exposure. We have shown mannitol responsiveness decreases 3 h after allergen inhalation. The current investigation assessed mannitol responsiveness 24 h after allergen challenge.


METHODS
Eleven mild atopic asthmatics completed allergen challenges on two separate occasions. In random order, methacholine or mannitol challenges were performed 24 h pre- and post-allergen challenge. Levels of fractional exhaled nitric oxide were also measured.


RESULTS
Allergen challenge increased airway responsiveness to methacholine 24 h postchallenge; the geometric mean (95% CI) methacholine PC20 decreased from 5.9 mg/ml (1.8-19.4) to 2.2 mg/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 (57 mg/% FEV1 fall [27-121] to 147 mg/% FEV1 fall [57-379]; P = 0.03), and FeNO levels were not significantly increased (P = 0.054).


CONCLUSIONS
Allergen-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.
Division of Respirology, Critical Care and Sleep Medicine, Department of Medicine, University of Saskatchewan, Saskatoon, SK, Canada.|Department of Physiology, College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada.
B E
BE
Davis
Department of Physiology, College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada.
D O
DO
Amakye
Division of Respirology, Critical Care and Sleep Medicine, Department of Medicine, University of Saskatchewan, Saskatoon, SK, Canada.|Department of Physiology, College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada.
D W
DW
Cockcroft
D000280:Administration, Inhalation; D000328:Adult; D000485:Allergens / Q000494:pharmacology*; D001249:Asthma / Q000503:physiopathology*; D001944:Breath Tests; D001980:Bronchi / Q000187:drug effects*; D001985:Bronchial Provocation Tests; D016085:Bronchoconstrictor Agents / Q000494:pharmacology*; D018592:Cross-Over Studies; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects*; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000503:physiopathology*; D008297:Male; D008353:Mannitol / Q000494:pharmacology*; D016210:Methacholine Chloride / Q000494:pharmacology*; D009569:Nitric Oxide; D055815:Young Adult
D000485:Allergens; D016085:Bronchoconstrictor Agents; D016210:Methacholine Chloride; D009569:Nitric Oxide; D008353:Mannitol
allergen; asthma; mannitol; refractoriness