title: Sputum hyaluronan and versican in severe eosinophilic asthma.
abstract: BACKGROUND
  We 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.
  
  
  METHODS
  Patients 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.
  
  
  RESULTS
  After 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).
  
  
  CONCLUSIONS
  Sputum 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.
authors.affiliation: Division of Allergy and Infectious Diseases, University of Washington, Seattle, Wash., USA. dayars@u.washington.edu
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Ayars
authors.forename: Leonard C
authors.initials: LC
authors.lastname: Altman
authors.forename: Sue
authors.initials: S
authors.lastname: Potter-Perigo
authors.forename: Katherine
authors.initials: K
authors.lastname: Radford
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Wight
authors.forename: Parameswaran
authors.initials: P
authors.lastname: Nair
mesh_terms: D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D006820:Hyaluronic Acid / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D011657:Pulmonary Eosinophilia / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D013183:Sputum / Q000737:chemistry*; D018709:Statistics, Nonparametric; D011795:Surveys and Questionnaires; D053675:Versicans / Q000032:analysis*
chemical_list: D018927:Anti-Asthmatic Agents; D061067:Antibodies, Monoclonal, Humanized; D053675:Versicans; D006820:Hyaluronic Acid; C434107:mepolizumab