Serologically assessed collagen remodeling appears to play a key role in the severity of chronic obstructive pulmonary disease (COPD), as determined by airflow limitation and dyspnea, as well as in disease outcomes—that is, time to exacerbation and prognosis, as evaluated by the BODE (body mass index [BMI], airflow obstruction, dyspnea, and exercise capacity) index. A prospective, observational, multicenter study was conducted in patients with COPD GOLD (Global Initiative for Chronic Obstructive Lung Disease) stage 2 to 4, in which extracellular matrix (ECM) biomarkers were evaluated in serum at stable state, at disease exacerbation, and at follow-up 4 weeks after exacerbation. Results of the Predicting Outcome Using Systemic Markers in Severe Exacerbations of Chronic Obstructive Pulmonary Disease (PROMISE-COPD) study were published in Chest.
A total of 498 patients were enrolled in the study. Overall, 72% of the participants were men, and the mean age was 67 years. At stable state, a significant inverse association was reported between forced expiratory volume in 1 second (FEV1)% predicted and degradation fragments of type 1 (C1M), and type IV (C4Ma3) collagen biomarkers, as well as the proform of collagen type V (Pro-C5). Moreover, C1M, C4M2, C4Ma3, and Pro-C5 were all associated with the BODE index, as well as with the modified medical research council (MMRC) score.
C1M, C4M2, C4Ma3, and Pro-C5 all increased significantly from stable state to COPD exacerbation and then decreased at follow-up. Additionally, the biomarkers were significantly higher during severe exacerbations compared with moderate exacerbations. Multivariate analysis adjusted for BMI, MMRC score, unadjusted Charlson score, and FEV1% predicted demonstrated a significant impact of C1M, C4Ma3, and C4M2 on time to disease exacerbation. In fact, all of the collagen biomarkers that were investigated demonstrated a significant association with FEV1/forced vital capacity (FVC)%. None of the biomarkers that were assessed were predictors of mortality.
A major limitation of the current study was the fact that the researchers did not measure changes in ECM biomarkers in stable COPD longitudinally. The investigators concluded that collagen degradation and formation may play a critical role in COPD severity and disease outcomes.
Schumann DM, Leeming D, Papakonstantinou E, et al. Collagen degradation and formation are elevated in exacerbated COPD compared to stable disease [published online June 29, 2018]. Chest. pii: S0012-3692(18)30980-2. doi: 10.1016/j.chest.2018.06.028.