Sputum Hyaluronan as a Biomarker of Airway Remodeling in Severe Asthma

RATIONALE: We examined levels of hyaluronan, a matrix glycosaminoglycan involved in airway remodeling, in the sputum of asthmatics treated with mepolizumab (anti-IL5 mAb) vs. placebo to evaluate its role as a possible biomarker of airway remodeling. METHODS: Nineteen severe asthmatics with >3% sputum eosinophils despite >4 weeks of prednisone treatment received either 5 doses of mepolizumab (n=8) or placebo (n=11) in a randomized, double blind, placebo-controlled study. Patients underwent a pre-defined prednisone tapering schedule if they remained exacerbation free on follow-up visits. Spirometry was performed and hyaluronan levels were measured by ELISA in sputum supernatant before and after the 16-week treatment phase. RESULTS: There was no difference in baseline sputum hyaluronan levels between the two groups (mepolizumab= 119.5±25.22μg/ml vs. placebo= 83.86±15.78μg/ml; P=0.2). During the study there were 2 asthma exacerbations in the mepolizumab group and 12 in the placebo group, and after the 16 week treatment phase there was a significant increase in sputum hyaluronan levels in the placebo group (pre-treatment= 83.86±15.78μg/ml vs. post-treatment= 250.7±44.11μg/ml; P=0.002) and a significant difference in hyaluronan levels between the anti-IL5 and placebo groups (mepolizumab= 96.37±17.52μg/ml vs. placebo= 250.7±44.11μg/ml; P=0.01). Following treatment, the difference in sputum hyaluronan was inversely correlated with the change in FEV1% (P=0.0008). CONCLUSIONS: We examined levels of sputum hyaluronan in steroid-dependent asthmatics treated with mepolizumab or placebo and found a significant difference in post-treatment hyaluronan levels between the two groups and an inverse correlation between the change in hyaluronan and FEV1%. We conclude that sputum hyaluronan may serve as a non-invasive biomarker of airway remodeling.