The Cough Response to Inhaled Mannitol in Healthy Subjects

Inhaled mannitol induces bronchoconstriction and cough. This study aimed to describe the cough response to mannitol among healthy adult subjects.

125 healthy subjects (aged 18-82 years, 52% females, 50% skin prick test positive) underwent a mannitol test. The coughs were recorded both simultaneously and afterwards from video recordings by two researchers. Three indices were evaluated: The cumulative number of coughs per cumulative dose of mannitol (CDR), cumulative provocative dose of mannitol to cause at least 5 coughs, and the maximal number of coughs provoked by any single mannitol dose. The test was repeated in 26 subjects after 3-7 days.

CDR showed the best repeatability with an intraclass correlation coefficient of 0.829. Gender was the only characteristics that associated with the cough response: The median CDR was 2.53 (interquartile range 0.45-7.01) coughs/100 mg among females and 0.787 (0.0-3.29) coughs/100 mg among males (p = 0.002). The interquartile range upper limits were defined as the cut-off limits for a normal response. The threshold for a statistically significant change in CDR was 6.26 coughs/100 mg. There was a close correlation between simultaneous- and video-assessed CDR (intraclass correlation coefficient 0.985).

Females cough more than males in response to mannitol. CDR is the most suitable index to describe the cough responsiveness. The repeatability of the response is good. Video recording of the coughs is not mandatory. The cut-off limits for a normal cough response to mannitol were provided.