Hyaluronic acid (HA) is a key component of the extracellular matrix. HA and its metabolism are suggested to be altered in the lungs of patients with chronic obstructive pulmonary disease (COPD). The present study explored systemic HA, and its metabolic regulators, in patients with clinically stable COPD and smoking and non-smoking controls. Furthermore, associations of HA with acute exacerbations (AECOPD), airway-related hospitalizations, systemic inflammation and cardiovascular risk were studied. In total, 192 patients with moderate to very severe COPD [aged 62.3 y (± SD 7.0)], 84 smoking controls [aged 61.8 y (± 5.7)], and 107 non-smoking controls [aged 60.1 y (± 7.0)] were included. Plasma HA was reduced in patients with COPD compared to non-smoking controls (p = 0.033), but was comparable after adjusting for age and sex. Expression of HAS-3 did not differ between groups, but was substantially less detectable in more patients with COPD than (non)smoking controls (p < 0.001). Expression of HYAL-2 was enhanced in patients with COPD versus smoking (p = 0.019) and non-smoking (p < 0.001) controls, also in the age- and sex- adjusted model (p < 0.001). Plasma HA was not associated with AECOPD, airway-related hospitalizations in the previous year, or systemic inflammation in COPD. Arterial pulse wave velocity explained some of the variance (< 10%) in plasma HA (p = 0.006). Overall, these results indicate that expression of HYAL-2, but not plasma HA nor HAS-3, is enhanced in patients with COPD compared to (non)smoking controls. Furthermore, HA was not associated with clinical outcomes, yet, cardiovascular risk might play a role in its systemic regulation in stable COPD.
© 2021. The Author(s).