COPD Severity May Be Affected by Collagen Biomarker Remodeling

Collagen biomarkers were significantly higher at extreme exacerbations, and were also associated with circulating adrenomedullin.

Chronic obstructive pulmonary disease (COPD) may be significantly intensified by collagen biomarker degradation and formation according to a recent study published in CHEST.

This multicenter study examined patients (N=498) with moderate to severe, stable COPD every 6 months for 2 years through clinical exam, lung function tests, health-related questionnaires, exercise stress test, and biomarker evaluation. Researchers investigated the degradation fragments of collagen type 1 (C1M), collagen type 4 (alpha 1 chain, C4M2), collagen type 4 (alpha 3 chain, C4Ma3), and the pro-form of collagen type 5 (Pro-C5) and their associations with COPD.

All collagen biomarkers for were significantly higher at extreme exacerbations, and were also significantly associated with circulating adrenomedullin (a marker of poor outcome in COPD). In addition, C1M, C4Ma3, and Pro-C5 were significantly associated with forced expiratory volume in 1 second percent predicted (FEV1 %), even when adjusting for number of severe exacerbations, body mass index, smoking status, and unadjusted Charlson score. 

None of the biomarkers were associated with forced vital capacity percent predicted (FVC %). However, there was a significant association between the biomarkers and FEV1/FVC %. Collagen biomarkers were also associated with airflow limitations.

Researchers discovered that all collagen biomarkers increased from stable state to exacerbation and then returned to baseline levels at 4 weeks after the exacerbation (median C1M, 24.3 vs 41.2 vs 25.8 ng/mL; median C4M2, 54.6 vs 65.5 ng/mL vs 60.2 ng/mL; median C4Ma3, 5.7 vs 7.2 vs 5.8 ng/mL; median Pro-C5, 469.0 vs 560.1 vs 476.8 ng/mL). During severe exacerbations, there were significantly higher levels of collagen remodeling biomarkers compared with moderate exacerbations (median C1M, 70.9 vs 31.4 ng/mL; median C4M2, 75.6 vs 61.0 ng/mL; median C4Ma3, 9.3 vs 6.2 ng/mL; median Pro-C5, 643.2 vs 450.2 ng/mL).

Although only C1M was significantly associated with the unadjusted Charlson score (r=0.106; P =.032), all of the biomarkers were significantly associated with the dyspnea and exercise capacity (BODE) index. C4Ma3 and Pro-C5 were positively associated with pack years and negatively associated with the 6-minute walking test.

“Collagen degradation and formation may play a significant role in COPD severity (airflow limitation, dyspnea) and disease outcome (time to exacerbation and prognosis as assessed by the BODE index),” the researchers concluded.

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Disclosures: Drs Leeming, Kardal, and Sand are full-time employees of Nordic Bioscience; Dr Kostikas is an employee and shareholder of Novartis; and Dr Rohde has received personal fees from Pfizer, Boehringer Ingelheim, Solvay, and others.


Schumann DM, Leeming D, Papakonstantinou E, et al. Collagen degradation and formation are elevated in exacerbated COPD compared to stable disease [published online July 2, 2018]. CHEST. doi:10.1016/j.chest.2018.06.028