HMGB1 and chronic obstructive pulmonary disease: The nature of HMGB1 involvement in COPD is unclear49, and the reduced expression of the HMGB1 gene in our COPD lung tissue study, in contrast to the increased protein levels in sputum and BAL in these previous studies, and in a study of plasma levels in COPD patients50, requires further investigation; differences in smoking status, disease severity and tissue of origin may explain the differing results.