Validity of HMGB1 measurement in epithelial lining fluid in patients with COPD

Abstract

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). 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. 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. 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.