Biomarkers of type 2 airway inflammation as predictors of loss of asthma control during step-down therapy for well-controlled disease: The Long Acting Beta Agonist Step-down Study (LASST)
2020
ABSTRACT Background Biomarkers that can predict loss of asthma control among patients being considered for step-down therapy in well-controlled disease are lacking. Objective To evaluate if baseline biomarkers of type 2 airway inflammation and/or serial measurement of fractional exhaled nitric oxide (FeNO) predict loss of asthma control as therapy is stepped down. Methods In sub-analyses of a multi-center randomized, double-blind, parallel 3-arm trial comparing strategies for step-down therapy in well-controlled asthma (LASST), we assessed whether baseline atopy as determined by serum aeroallergen allergy screening test (Phadiatop), baseline serum eosinophil peroxidase (EpX), or baseline or serial FeNO measurements during follow-up, predicted the time to loss of asthma control among participants. Loss of asthma control was defined in the study protocol. We analyzed these associations in adjusted models including all participants, after testing for interactions with assignment to each of the three treatment groups (continuation of stable dose of combination ICS-LABA, step-down of inhaled corticosteroid (ICS), or discontinuation of long acting bronchodilator (LABA)). Results Four hundred and forty-seven of the 553 LASST participants who were randomized to one of 3 treatment arms and had at least one biomarker measurement were included in this analysis. At baseline, higher levels of FeNO were significantly associated with greater levels of multi-allergen IgE levels (P 50 ppb) levels did not have significantly increased likelihood of subsequent treatment failure (hazard ratios (95% confidence interval) 1.03 (0.59, 1.78) and 1.29 (0.65, 2.54), respectively. There were no significant interactions of treatment group and baseline biomarkers. Conclusions In patients with well-controlled asthma, neither baseline levels of type 2 airway inflammatory biomarkers nor serial measures of FeNO are strong predictors of treatment failure.
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