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Int. Arch. Allergy Immunol. · Jan 2013
Randomized Controlled TrialSputum hyaluronan and versican in severe eosinophilic asthma.
- Andrew G Ayars, Leonard C Altman, Sue Potter-Perigo, Katherine Radford, Thomas N Wight, and Parameswaran Nair.
- Division of Allergy and Infectious Diseases, University of Washington, Seattle, Wash., USA. dayars@u.washington.edu
- Int. Arch. Allergy Immunol. 2013 Jan 1;161(1):65-73.
BackgroundWe examined levels of hyaluronan, a matrix glycosaminoglycan and versican, a matrix proteoglycan, in the sputum of asthmatics treated with mepolizumab (anti-IL-5 monoclonal antibody) versus placebo to evaluate the utility of these measurements as possible biomarkers of asthma control and airway remodeling.MethodsPatients with severe, prednisone-dependent asthma received either mepolizumab or placebo as described in a previously published randomized, double-blind, placebo-controlled study. We measured hyaluronan and versican levels by enzyme-linked immunosorbent assay in sputum collected before and after the 16-week treatment phase. Patients underwent a predefined prednisone tapering schedule if they remained exacerbation free, and sputum eosinophil percentage, asthma control questionnaire (ACQ) and spirometry were monitored.ResultsAfter 6 months of mepolizumab therapy and prednisone tapering, there was a significant increase in sputum hyaluronan in the placebo group compared with baseline (p = 0.003). In contrast, there was a significant decrease in sputum hyaluronan in the active treatment group compared with placebo (p = 0.007), which correlated with improvements in percent forced expiratory volume in 1 s (FEV1%) (p = 0.001) and ACQ scores (p = 0.009) as well as a decrease in sputum eosinophils (p = 0.02). There was a nonsignificant increase in sputum versican in the placebo group (p = 0.16), a decrease in the mepolizumab group (p = 0.13) and a significant inverse correlation between versican reduction and FEV1% improvement (p = 0.03).ConclusionsSputum hyaluronan values are reduced with mepolizumab therapy and correlate with improved clinical and spirometry values, suggesting this measurement may serve as a noninvasive biomarker of asthma control.Copyright © 2012 S. Karger AG, Basel.
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