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. 2015 Apr;135(4):877-83.e1.
doi: 10.1016/j.jaci.2014.10.026. Epub 2014 Dec 6.

Biomarker-based Asthma Phenotypes of Corticosteroid Response

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Free PMC article

Biomarker-based Asthma Phenotypes of Corticosteroid Response

Douglas C Cowan et al. J Allergy Clin Immunol. .
Free PMC article

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.

Figures

Figure 1
Figure 1. Changes in biomarkers in asthmatics treated with ICS
The percent of asthmatics that decrease biomarkers with ICS treatment for 28 days proportionately shown by size of colored circles [blue, FENO; green, sputum eosinophils; red, urinary BrTyr], and percent of asthmatics that do not have decrease in either of the two biomarkers in each panel is shown by the black circles.
Figure 2
Figure 2
ROC analysis describes ability of each biomarker i.e FENO, sputum eosinophils and urinary BrTyr to classify asthmatics who respond to inhaled corticosteroid as measured by 2 out of 3 clinical outcomes (≥12% increase in FEV1 and/or ≥0.5 point decrease in ACQ and/or ≥2 doubling dose increase in PC20AMP).
Figure 3
Figure 3
ORs and 95% Cl for the association between a high level of biomarker (FENO ≥ 35ppm; sputum eosinophils ≥ 3%, BrTyr ≥ 0.45 ng/mg Cr) or biomarker combination [FENO AND BrTyr] and two positive clinical outcomes in response to ICS. Results shown represent the ORs (filled circles) and 95% Cl (lines) of having a steroid response versus having no steroid response. Asterisk indicates P<0.05 as determined by likelihood-ratio χ2 test.

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