Lancet Respir Medicine Published online 25 June, 2021 | https://www.sciencedirect.com/science/article/abs/pii/S2213260021001247
Digest author(s): Stylianos Loukides, e-Learning Director / 4 July, 2021
Fractional exhaled nitric oxide [FENO] has been used as a diagnostic and prognostic biomarker in patients with asthma. It potentially represents a biomarker closely related to eosinophilic inflammation at specific levels. In the current study, the authors used the statistical approach of the post hoc analysis. They used the cohort of the 2-week, double-blind, phase 3 LIBERTY ASTHMA QUEST study. The LIBERTY ASTHMA QUEST study was a Phase 3 Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate Dupilumab Efficacy/Safety in Patients with Uncontrolled, Moderate-to-Severe Asthma. Only patients treated with placebo were included.
620 patients were recruited. All patients had uncontrolled asthma treated with inhaled steroids plus up to two controllers. They had one or more exacerbations in the previous year, FEV1 % pred 40–80%, FEV1 reversibility of 12% or higher and 200 mL, Asthma Control Questionnaire (ACQ-5) score of 1·5 or higher and complete data on baseline type 2 biomarkers (FeNO, eosinophils, and total IgE). Annualised severe exacerbation rate was stratified according to baseline values of the different biomarkers by using specific cut off values and ranges.
Exacerbation rate was closely related to baseline FeNO values. Patients with baseline FeNO of 50 ppb or higher (n=144) had a 1·54-times higher exacerbation rate than patients with FeNO of less than 25 ppb (n=291; relative risk 1·54 [95% CI 1·11–2·14]; p=0·0097). Patients with baseline FeNO of 25 to <50 ppb (n=185) had a 1·33-times higher exacerbation rate than patients with FeNO of less than 25 ppb (1·33 [0·99–1·78]; p=0·0572). Combining patients with baseline FeNO of 25 ppb or higher, a blood eosinophil count of 150 cells per μL or higher, and two or more prior exacerbations (n=157) had an exacerbation rate 3·62-times higher than patients with FeNO of less than 25 ppb, a blood eosinophil count of less than 150 cells per μL, and one prior exacerbation (n=116; 3·62 [1·67–7·81]; p=0·0011). All the above data clearly indicates that a pronounced T2 status at baseline plus a frequent exacerbator phenotype potentially predict the possibility of future exacerbations.
Two major comments: The first one is addressing the fact of the independent role of FeNO in predicting future exacerbations. The results of this post hoc analysis strengthen this role irrespective of the baseline blood eosinophils AC. The second one is an indirect one. Considering the positive results of the initial study in terms of dupilumab we clearly identify a biomarker that could predict the response to treatment.