The aim of this randomized crossover, placebo-controlled study (ClinicalTrials.gov Identifier:NCT03898466) was to assess the efficacy of a daily dose of fluticasone furoate (100 mcg) on methacholine-induced bronchoconstriction in patients with mild asthma over the course of a week. Patients were randomly assigned to receive once-daily fluticasone furoate 100 mcg or an identical-appearing placebo. All self-administered treatments occurred at approximately the same time each day for 1 week.
Methacholine challenge testing occurred at baseline, day 1, and day 3, using the volumetric method to determine the dose of inhaled methacholine that would lead to a 20% decrease in forced expiratory volume in 1 second (FEV₁). Fractional exhaled nitric oxide (FeNO) was measured at baseline and at day 7 by completing a full inhalation and exhalation cycle at a constant flow rate and measuring changes in FeNO levels. Sputum samples were collected during the first laboratory visit to measure eosinophil content.
Of the 11 patients who completed all visits, 64% were men, the mean age was 30 years, the mean baseline FEV₁ was 3.70 L, and the mean baseline dose of inhaled methacholine was 72.1 mcg. The methacholine challenge testing indicated a significant increase in the geometric mean dose of inhaled methacholine leading to a 20% decrease in FEV₁ at day 1 (P =.0014), day 3 (P =.0003), and day 7 (P=.0001), vs baseline measurement for the once-daily fluticasone furoate cohort.
Bronchoprotection differed between the 2 cohorts with doubling-dose shifts being 1.23 at day 1 (P=.0078), 1.17 at day 3 (P =.0009), and 1.44 at day 7 (P =.0017). FeNO was reduced by day 7 in the fluticasone furoate group (P =.005), with no change in the placebo group. Of the patients with a successful sputum collection (n=6), there was a significant positive relationship between baseline sputum eosinophils and the geometric mean for baseline FeNO (P =.03).
Limitations of this study included not measuring FeNO at day 1, the relatively poor sputum collection rate, and the small sample size.
The researchers concluded that “…bronchoprotection both within the active treatment and between [fluticasone furoate] and placebo was evident as early as 24 [hours] after a single 100 mcg dose.”
Okonkwo CS, Davis BE, Blais CM, Cockcroft DW. Short-term effect of once-daily fluticasone furoate on methacholine-induced bronchoconstriction in mild asthmatics. Respir Med. 2019;156:53-57.