BACKGROUND AND OBJECTIVE: We have previously shown that airway smooth muscle cells (ASMC) from COPD patients exhibit an abnormal metabolism of hyaluronic acid (HA) and that COPD exacerbations are associated with pro-inflammatory degradation of HA. In the present study, we investigated the effect of glucocorticoids and long-acting β-agonists (LABA) on the pathologic HA metabolism in COPD.METHODS: Primary cultures of ASMC, established from endo-bronchial biopsies of COPD patients, were treated with glucocorticoids and LABA. Secretion of HA was measured by ELISA and HA synthase-1 (HAS-1) and hyaluronidase-1 (HYAL-1) were assessed by RT-PCR and western blotting. Furthermore, from a cohort of 97 patients that underwent diagnostic bronchoscopy, we identified 11 treatment-naïve patients and 13 patients on inhaled corticosteroids (ICS) and LABA prior to bronchoscopy. HA, HAS-1 and HYAL-1 were measured in bronchoalveolar lavage (BAL) of these patients by ELISA and hyaluronidase activity by reverse zymography.RESULTS: The combination of glucocorticoids and LABA stimulated the secretion of HA with high molecular mass by ASMC from COPD patients. This effect was associated with increased expression of HAS-1 and reduced expression of HYAL-1. The effect of the drugs was mediated via their specific receptors since it was inhibited by specific receptor antagonists. Patients on ICS and LABA presented increased levels of HA and decreased levels of HYAL-1 and HYAL-1 activity in BAL.CONCLUSIONS: The combination of glucocorticoids with LABA counteracts the pathologic metabolism of HA in patients with COPD, suggesting an additional beneficial effect of the drugs when used for the treatment of COPD.