BACKGROUND AND OBJECTIVE: Prediction of idiopathic pulmonary fibrosis (IPF) progression is vital for the choice and timing of treatment and patient follow-up. This could potentially be achieved by prognostic blood biomarkers of extracellular matrix (ECM) remodelling. METHODS: Neoepitope biomarkers of types III and VI collagen turnover (C3M, C6M, PRO-C3 and PRO-C6) were measured in 185 patients with newly diagnosed IPF. Disease severity at baseline and progression over 6 months was assessed by lung function tests and 6-min walk tests. All-cause mortality was assessed over a 3-year follow-up period. RESULTS: High baseline levels of C3M, C6M, PRO-C3 and PRO-C6 were associated with more advanced disease at the time of diagnosis. Baseline levels of C6M and PRO-C3 were also associated with mortality over 3 years of follow-up (hazard ratio [HR]: 2.3, 95% CI: 1.3-3.9, p = 0.002 and HR: 1.8, 95% CI: 1.1-3.0, p = 0.03). Patients with several increased biomarkers at baseline, representing a high ECM remodelling phenotype, had more advanced disease at baseline, higher risk of progression or death at 6 months (OR: 1.4, 95% CI: 1.1-1.8, p = 0.002) and higher mortality over 3 years of follow-up (HR: 2.4, 95% CI: 1.3-4.5, p = 0.007). CONCLUSION: Blood biomarkers of types III and VI collagen turnover, assessed at the time of diagnosis, are associated with several indices of disease severity, short-term progression and long-term mortality. These biomarkers can help to identify patients with a high ECM remodelling phenotype at high risk of disease progression and death.
BACKGROUND AND OBJECTIVE: Prediction of idiopathic pulmonary fibrosis (IPF) progression is vital for the choice and timing of treatment and patient follow-up. This could potentially be achieved by prognostic blood biomarkers of extracellular matrix (ECM) remodelling. METHODS: Neoepitope biomarkers of types III and VI collagen turnover (C3M, C6M, PRO-C3 and PRO-C6) were measured in 185 patients with newly diagnosed IPF. Disease severity at baseline and progression over 6 months was assessed by lung function tests and 6-min walk tests. All-cause mortality was assessed over a 3-year follow-up period. RESULTS: High baseline levels of C3M, C6M, PRO-C3 and PRO-C6 were associated with more advanced disease at the time of diagnosis. Baseline levels of C6M and PRO-C3 were also associated with mortality over 3 years of follow-up (hazard ratio [HR]: 2.3, 95% CI: 1.3-3.9, p = 0.002 and HR: 1.8, 95% CI: 1.1-3.0, p = 0.03). Patients with several increased biomarkers at baseline, representing a high ECM remodelling phenotype, had more advanced disease at baseline, higher risk of progression or death at 6 months (OR: 1.4, 95% CI: 1.1-1.8, p = 0.002) and higher mortality over 3 years of follow-up (HR: 2.4, 95% CI: 1.3-4.5, p = 0.007). CONCLUSION: Blood biomarkers of types III and VI collagen turnover, assessed at the time of diagnosis, are associated with several indices of disease severity, short-term progression and long-term mortality. These biomarkers can help to identify patients with a high ECM remodelling phenotype at high risk of disease progression and death.
Authors: Benjamin E Decato; Diana Julie Leeming; Jannie Marie Bülow Sand; Aryeh Fischer; Shuyan Du; Scott M Palmer; Morten Karsdal; Yi Luo; Anne Minnich Journal: Respir Res Date: 2022-03-18
Authors: H Jessen; N Hoyer; T S Prior; P Frederiksen; M A Karsdal; D J Leeming; E Bendstrup; J M B Sand; S B Shaker Journal: Respir Res Date: 2021-07-15