INDIRECT AIRWAY CHALLENGES
Mannitol Inhalation Challenge
Mannitol is a sugar alcohol that is inhaled orally from a dry powder inhaler device. Inhaled mannitol induces acute bronchoconstriction and can be used as a measure of AHR.
The precise mechanisms through which inhaled mannitol causes bronchocon- striction are not well characterized. Mannitol is known to induce bronchoconstric- tion by a hypertonic mechanism, that is, drawing water out of cells and into the airways, which is similar to the actions of hypertonic saline that is also used as an indirect airway challenge (Jones et al. 2001). While this mechanism of action may assist in the clearance of mucus from airways, mannitol also activates local inflammatory cells, causing the release of inflammatory mediators from mast cells and basophils (Brannan et al. 2003) (Figure 10.2).
Mannitol doses are administered as doubling doses, starting with 5 mg, then 10 mg, followed by 20, 40, 80, and 160 mg, and then two more inhalations of 160 mg. The FEVj is measured 1 min after each dose and the challenge is stopped when the FEVj falls by 15% or if the cumulative dose of 635 mg is reached. A positive test occurs when a 15% fall in FEVj is reached at a dose of <635 mg mannitol (Spector et al. 2009) and the response to inhaled mannitol is reported as the PD15, the provocative dose causing a 15% reduction in FEV1.