COPD Exacerbations Are Associated With Proinflammatory Degradation of Hyaluronic Acid

BACKGROUND: COPD is characterized by chronic airway inflammation and remodeling, with serious modifications of the extracellular matrix (ECM). Hyaluronic acid (HA) is an abundant ECM molecule in the lung with various biologic functions that depend on its molecular weight (MW). High-MW HA exhibits antiinflammatory and immunosuppressive effects, whereas low-MW HA is proinflammatory. In this study, we investigated whether acute exacerbations of COPD (AECOPDs), which affect patient quality of life and survival, are associated with altered HA turnover in BAL. METHODS: We used BAL from patients with stable COPD (n = 53) or during AECOPD (n = 44) matched for demographics and clinical characteristics and BAL from control subjects (n = 15). HA, HA synthase-1 (HAS-1), and hyaluronidase (HYAL) values were determined by enzyme-linked immunosorbent assay, and HYAL activity was determined by HA zymography. The MW of HA was analyzed by agarose electrophoresis. RESULTS: Levels of HA, HAS-1, and HYAL were significantly increased in BAL of patients with stable COPD and during exacerbations compared with control subjects. HYAL activity was significantly increased in BAL of patients with AECOPD, resulting in an increase of low-MW HA during exacerbations. In patients with AECOPD, we also observed a significant negative correlation of HA and HYAL levels with FEV1 % predicted but not with diffusing capacity of lung for carbon monoxide % predicted, indicating that increased HA degradation may be more associated with airway obstruction than with emphysema. CONCLUSIONS: AECOPDs are associated with increased HYAL activity in BAL and subsequent degradation of HA, which may contribute to airway inflammation and subsequent lung function decline during exacerbations.