Bronchial provocation testing with dry powder mannitol in children with cystic fibrosis

There has been recent interest in dry powder inhaled mannitol as a therapeutic agent in patients with cystic fibrosis (CF). It is has been shown to increase mucociliary clearance (MCC) by rehydrating the airway. To date there have been no studies exclusively in children with CF examining the effect of dry powder mannitol on the airways. The aim of this study was to determine acute tolerability of inhaled mannitol in children with CF.

Thirty-nine children (aged 8-18 years) with CF underwent a bronchial provocation challenge with incrementally increasing doses of dry powder mannitol (up to a maximum cumulative dose of 475 mg). A positive challenge was defined as a drop in FEV(1) of >or=15% from baseline.

Nine out of 38 subjects (24%; 95% confidence interval 10-38%) had a positive challenge. Only two of these nine subjects had a PD(15) (dose of mannitol required to cause a 15% reduction in FEV(1)) prior to the 315 mg dose, the remaining seven children dropping their FEV(1) by >or=15% on the 315 or 475 mg (final) cumulative dose. We found no association between patient characteristics and a positive challenge. Although cough was common during the challenge, other adverse events were infrequent.

We report that 24% of children with CF had a positive airway challenge with inhaled mannitol. This compares with a previously reported 12% of subjects in a study including both adults and children. We could not identify factors predictive of a positive mannitol challenge in our children.