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J Allergy Clin Immunol. 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.

Author information

1
Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
2
Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.
3
Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio; Respiratory Institute, Cleveland Clinic, Cleveland, Ohio.
4
Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.
5
Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio. Electronic address: comhais@ccf.org.

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

Comment in

PMID:
25488689
PMCID:
PMC4388771
DOI:
10.1016/j.jaci.2014.10.026
[Indexed for MEDLINE]
Free PMC Article

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