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

Clair D Lake; Keith K H Wong; Clare P Perry; Heikki O Koskela; John D Brannan

doi:10.3389/falgy.2022.864890

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

Front Allergy. 2022 May 31:3:864890. doi: 10.3389/falgy.2022.864890. eCollection 2022.

Authors

Clair D Lake^{1

2}, Keith K H Wong^{1

2

3}, Clare P Perry⁴, Heikki O Koskela^{5

6}, John D Brannan^{7

8}

Affiliations

¹ Department of Respiratory and Sleep Medicine, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
² Faculty of Medicine and Health, University of Sydney, Camperdown, NSW, Australia.
³ Woolcock Institute of Medical Research, Glebe, NSW, Australia.
⁴ Department of Respiratory and Sleep Medicine, Westmead Hospital, Westmead, NSW, Australia.
⁵ Unit for Medicine and Clinical Research, Pulmonary Division, Kuopio University Hospital, Kuopio, Finland.
⁶ Faculty of Health Sciences, School of Medicine, Institute of Clinical Sciences, University of Eastern Finland, Kuopio, Finland.
⁷ Department of Respiratory and Sleep Medicine, John Hunter Hospital, New Lambton, NSW, Australia.
⁸ School of Medicine and Public Health, University of Newcastle, Callaghan, NSW, Australia.

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 caused by 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: Airway hyperresponsiveness was abolished in the majority (84%, n = 130) over the treatment period (mean ± SD 143 ± 72days), and it was defined as the provoking dose of mannitol to cause a 15% fall in FEV1 (cumulative inhaled dose of mannitol to cause 15% fall in FEV₁, PD₁₅) improved from (GeoMean) 183 to 521 mg. 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 635 mg), in those where AHR remained (16%, n = 25), baseline AHR was more severe (PD15: 85 mg vs. 213 mg, 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), FEF_25-75% (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: Airway hyperresponsiveness 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. Thus, those with a slower response to daily ICS on AHR can potentially be identified at the commencement of monitoring ICS using inhaled mannitol.

Keywords: airway hyperresponsiveness (AHR); asthma; indirect bronchial challenge test; inhaled corticosteroids; occupational assessment.