title: Validity of HMGB1 measurement in epithelial lining fluid in patients with COPD.
abstract: BACKGROUND
  It has been known that high-mobility group box 1 (HMGB1) plays an important role in the pathogenesis of various inflammatory disorders in the lung. We attempted to determine the validity of measurement of HMGB1 levels in epithelial lining fluid (ELF) from patients with chronic obstructive pulmonary disease (COPD).
  
  
  METHODS
  We measured HMGB1 levels in ELF separately obtained from central or peripheral airways using a bronchoscopic microsampling technique in 14 non-smokers, 13 smokers without COPD and 30 smokers with COPD. We also evaluated whether those levels were correlated with the indexes of pulmonary function and grade of low-attenuation area (LAA) on high-resolution computed tomographic scans.
  
  
  RESULTS
  HMGB1 levels in ELF from central airways did not significantly differ among the three groups. However, HMGB1 levels in peripheral airways were significantly higher in COPD patients than in non-smokers and smokers without COPD. Both the concentrations of interleukin-8 and human polymorphonuclear elastase in peripheral airways were also significantly higher in COPD patients. Moreover, those levels were significantly correlated with HMGB1 level. In addition, HMGB1 level in peripheral airways was closely correlated with the degree of airflow obstruction and grade of LAA in COPD patients.
  
  
  CONCLUSIONS
  HMGB1 levels in peripheral airways were elevated in smokers without COPD, as compared with non-smokers, and those levels were further augmented in COPD patients. Those levels were associated with the severity of COPD. Therefore, HMGB1 in peripheral airways may be a potentially interesting target for new pharmacological treatments in COPD patients.
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, Osaka, Japan. kanazawa-h@med.osaka-cu.ac.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kanazawa
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Tochino
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Asai
authors.forename: Yukikazu
authors.initials: Y
authors.lastname: Ichimaru
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Watanabe
authors.forename: Kazuto
authors.initials: K
authors.lastname: Hirata
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D001999:Bronchoscopy / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D024243:HMGB1 Protein / Q000378:metabolism*; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D019272:Leukocyte Elastase / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism* / Q000503:physiopathology; D015203:Reproducibility of Results; D012129:Respiratory Function Tests / Q000379:methods; D020545:Respiratory Mucosa / Q000378:metabolism; D012907:Smoking / Q000378:metabolism; D013223:Statistics as Topic; D014057:Tomography, X-Ray Computed / Q000379:methods
chemical_list: D015415:Biomarkers; D024243:HMGB1 Protein; D016209:Interleukin-8; D019272:Leukocyte Elastase