Biomarker-based asthma phenotypes of corticosteroid response

Abstract

Background: Asthma is a heterogeneous disease with different phenotypes. Inhaled corticosteroid (ICS) therapy is a mainstay of treatment for asthma, but the clinical response to ICSs is variable.

Objective: We hypothesized that a panel of inflammatory biomarkers (ie, fraction of exhaled nitric oxide [Feno], sputum eosinophil count, and urinary bromotyrosine [BrTyr] level) might predict steroid responsiveness.

Methods: The original study from which this analysis originates comprised 2 phases: a steroid-naive phase 1 and a 28-day trial of ICSs (phase 2) during which Feno values, sputum eosinophil counts, and urinary BrTyr levels were measured. The response to ICSs was based on clinical improvements, including a 12% or greater increase in FEV1, a 0.5-point or greater decrease in Asthma Control Questionnaire score, and 2 doubling dose or greater increase in provocative concentration of adenosine 5'-monophosphate causing a 20% decrease in FEV1 (PC20AMP). Healthy control subjects were also evaluated in this study for comparison of biomarkers with those seen in asthmatic patients.

Results: Asthmatic patients had higher than normal Feno values, sputum eosinophil counts, and urinary BrTyr levels during the steroid-naive phase and after ICS therapy. After 28-day trial of ICSs, Feno values decreased in 82% of asthmatic patients, sputum eosinophil counts decreased in 60%, and urinary BrTyr levels decreased in 58%. Each of the biomarkers at the steroid-naive phase had utility for predicting steroid responsiveness, but the combination of high Feno values and high urinary BrTyr levels had the best power (13.3-fold, P < .01) to predict a favorable response to ICS therapy. However, the magnitude of the decrease in biomarker levels was unrelated to the magnitude of clinical response to ICS therapy.

Conclusion: A noninvasive panel of biomarkers in steroid-naive asthmatic patients predicts clinical responsiveness to ICS therapy.

Keywords: Asthma; biomarker; clinical outcome; fraction of exhaled nitric oxide; inhaled corticosteroids; sputum eosinophils; urinary bromotyrosine.