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

Allergy. 2015 Jun;70(6):682-8. doi: 10.1111/all.12601. Epub 2015 Mar 17.


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).

Conclusion: 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.

Keywords: allergen; asthma; mannitol; refractoriness.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Administration, Inhalation
  • Adult
  • Allergens / pharmacology*
  • Asthma / physiopathology*
  • Breath Tests
  • Bronchi / drug effects*
  • Bronchial Provocation Tests
  • Bronchoconstrictor Agents / pharmacology*
  • Cross-Over Studies
  • Female
  • Forced Expiratory Volume / drug effects*
  • Humans
  • Hypersensitivity, Immediate / physiopathology*
  • Male
  • Mannitol / pharmacology*
  • Methacholine Chloride / pharmacology*
  • Nitric Oxide
  • Young Adult


  • Allergens
  • Bronchoconstrictor Agents
  • Methacholine Chloride
  • Nitric Oxide
  • Mannitol