In order to avoid excessive declines in FEV
1, a test with mannitol can be used to identify the potential for EIB that is provoked by an increase in airway osmolarity and mediator release. The mannitol dry powder challenge requires the participant to inhale increasing doses of a dry powder of mannitol to a cumulative dose of 635 mg, with FEV
1 measured 60 seconds after each dose.
49,50 The mannitol test kit includes prepacked capsules and an inhaler device (Aridol; Pharmaxis Inc, Exton, Pennsylvania). A positive response to mannitol is indicated by a 15% decrease in FEV
1, a value that represents the 95% confidence interval observed in healthy individuals without asthma.
49 The target of a 15% decrease from baseline FEV
1 results in fewer FEV
1 falls of more than 30% compared with exercise and EVH.
50
The index used to assess sensitivity to mannitol is the provoking dose to cause a 15% decline in FEV
1 (ie, PD
15). The index used to express reactivity or rate of change is the response dose ratio (RDR). The RDR is calculated by dividing the final percentage decline in FEV
1 by the dose of mannitol (in mg) that provoked that decline.
49 The PD
15 and RDR values to mannitol have been compared with patient responses to exercise and to EVH.
The repeatability of the PD
15 measure of bronchial responsiveness to mannitol was found to be 1.1 doubling doses in a cohort of children with asthma.
51 Although a positive response to the mannitol challenge is more likely in patients who are atopic, there have been many positive test results recorded in individuals without atopy to common allergens.
A positive response to the mannitol challenge reveals the potential for EIB, and in individuals with a clinical diagnosis of asthma, the PD
15 and RDR values are indirect indices of EIB severity.
52,53 A 10% decrease in FEV
1 has been used by some investigators to compare patient response to mannitol with responses to EVH and exercise.
53-56 In a study of patients with symptoms of asthma but no definitive diagnosis who had EIB identified on at least 1 of 2 identical exercise tests, a mannitol challenge performed in fewer than 35 minutes showed sensitivities of 64%, 75%, and 83% to identify exercise-related FEV
1 decreases of 10%, 15%, and 20%, respectively.
50 However, in the same study population, the frequency of a 15% decrease in FEV
1 in response to mannitol was 1.65 times that of a 15% decrease in FEV
1 from exercise (when only the first of 2 identical exercise tests was considered).
50