Collagen and elastin turnover increase at COPD exacerbation irrespectively its etiology

Abstract

Extracellular matrix (ECM) fragments serve as surrogate markers of disease activity in COPD. Respiratory infections have been implicated as the predominant risk factor for acute exacerbations of COPD (AECOPD).

We aimed to assess if serum levels of collagen and elastin turnover products are associated with the etiology of AECOPD.

Pro-forms of collagens III (PRO-C3), V (PRO-C5), VI (PRO-C6), degradation products of collagens I (C1M), III (C3M), IV (C4Ma3), VI (C6M) and neutrophil elastase-generated fragments of elastin (EL-NE) were measured in serum of the PREVENT study, an investigator-initiated and driven, controlled trial, with 450 COPD patients, GOLD II-IV, followed for 3 years. Out of 2833 visits, we included AECOPD visits without infection in the last stable visit (n=102) and categorised them according to etiology; no new infection (n=22); viral infections (n=23); bacterial infections (n=37); viral and bacterial infections (n=20). Multiplex PCR was used to monitor viral infections in laryngopharyngeal swabs and microbiological analysis was performed in sputum samples in all visits.

C1M, C3M, C4Ma3, C6M, EL-NE and PRO-C5 levels were significantly higher at AECOPD, as compared to previous stable visits (p<0.001 for all) and to follow-up visits (p<0.001 for all). Changes in serum levels of all biomarkers between last stable visit, AECOPD and follow-up were comparable and not associated with the presence or the type of infection. C1M, C3M, C4Ma3 and C6M were positively correlated with SGQ, CAT and MMRC scores and PRO-C6 and PRO-C3 with lung function.

These results indicate that systemic biomarkers of collagen and elastin turnover increase at AECOPD irrespectively the etiology of exacerbation.