AUTHOR=Lake Clair D. , Wong Keith K. H. , Perry Clare P. , Koskela Heikki O. , Brannan John D. 

TITLE=Daily Inhaled Corticosteroids Treatment Abolishes Airway Hyperresponsiveness to Mannitol in Defence and Police Recruits

JOURNAL=Frontiers in Allergy

VOLUME=Volume 3 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/allergy/articles/10.3389/falgy.2022.864890

DOI=10.3389/falgy.2022.864890

ISSN=2673-6101

ABSTRACT=Background: Airway hyperresponsiveness (AHR) is a key pathophysiological feature of asthma and causes exercise-induced bronchoconstriction (EIB). Indirect bronchial provocation tests (BPTs) (e.g. exercise, mannitol) aid to diagnose asthma and identify EIB. Daily inhaled corticosteroids (ICS) can abolish AHR to indirect stimuli. Where strenuous physical exertion is integral to an occupation, identification of those at risk of EIB is important and documentation of inhibition of AHR with ICS is required before recruitment.
Methods/Objectives: A retrospective analysis was performed on 155 potential recruits with AHR to mannitol who underwent follow-up assessment after daily ICS treatment to determine the proportion that can abolish AHR using ICS, and to determine any predictors of the persistence of AHR.
Results: AHR was abolished in the majority (84%, n=130) over the treatment period (mean±SD 143±72days) and AHR  defined as the provoking dose of mannitol to cause a 15% fall in FEV1 (PD15) improved from (GeoMean) 183mg to 521mg. Compared with recruits in whom AHR was abolished with daily ICS (i.e., no 15% fall in FEV1 to the maximum cumulative dose of mannitol of 635mg), in those where AHR remained (16%, n=25), baseline AHR was more severe (PD15: 85mg vs 213mg, P<0.001), baseline FEV1% was lower (89% vs 96%; 95%CI:2–12, P=0.004) and they had a longer follow-up duration (180 vs 136 days; 13–74, P=0.006). Baseline FEV1% (adjusted odds ratio 0.85; 95%CI:0.77–0.93), FEV1/FVC (0.78; 0.67–0.90), FEF25-75% (1.15; 1.06–1.25), and airway reactivity to mannitol (%Fall/cumulative dose of mannitol multiplied by 100) (1.07; 1.03–1.11) predicted AHR remaining after daily ICS.
Conclusion: AHR to mannitol can be abolished after 20-weeks of daily treatment with ICS. Inhibition of AHR is likely due to attenuation of airway inflammation in response to ICS treatment. Increased airway reactivity and lower spirometry variables predicted the persistence of AHR. If attenuation of indirect AHR or EIB is a desired clinical outcome of ICS treatment, those with a slower response to daily ICS on AHR can potentially be identified at the commencement of monitoring ICS using inhaled mannitol.