The aim of the present study was to perform a longitudinal cohort study to evaluate plasma levels of sRAGE and HMGB1 in non-smokers, smokers without COPD, and smokers with COPD, and to estimate the predictive value of sRAGE and HMGB1 levels for decline of lung function over time. This evidence concerns the gene HMGB1 and chronic obstructive pulmonary disease.