In fact, our study is the first to compare circulatory HMGB1 levels between never-smokers, a control group of smokers without COPD, and smokers with early stage COPD and no comorbidities, and the inconsistencies of the HMGB1 levels in the COPD patients in the present study and those of the previous studies are probably related to the differences in the background characteristics of the study participants. Here, HMGB1 is linked to chronic obstructive pulmonary disease.