Desiree M Schumann1, Diana Leeming2, Eleni Papakonstantinou1, Francesco Blasi3, Konstantinos Kostikas1, Wim Boersma4, Renaud Louis5, Branislava Milenkovic6, Joachim Aerts7, Jannie M B Sand2, Emiel F M Wouters8, Gernot Rohde8, Christina Prat9, Antoni Torres10, Tobias Welte11, Michael Tamm1, Morten Karsdal2, Daiana Stolz12. 1. Clinic of Pneumology and Pulmonary Cell Research, University Hospital Basel, Basel, Switzerland. 2. Nordic Bioscience, Fibrosis Biology and Biomarkers, Herlev, Denmark. 3. Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy; Internal Medicine Department, Respiratory Unit and Adult Cystic Fibrosis Center, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico Milan, Milan, Italy. 4. Department of Pneumology, Medisch Centrum Alkmaar, Alkmaar, The Netherlands. 5. Department of Pneumology, CHU Liege, University of Liege, GIGAI Research Group, Liege, Belgium. 6. Department of Pneumology, Institute for Pulmonary Diseases, Belgrade, Serbia. 7. Department of Pneumology, Amphia Hospital/Erasmus MC, Breda, The Netherlands. 8. Department of Respiratory Medicine, Maastricht University Medical Center, Maastricht the Netherlands. 9. Microbiology Department, Hospital Universitari Germans Trias I Pujol, Badalona Universitat Autonoma de Barcelona, CIBER Enfermedades Respiratorias (CIBERES) Instituto de Salud Carlos III, Barcelona Spain. 10. Pneumology, Hospital Clinic, Barcelona Spain. 11. Pneumology Medizinische Hochschule, Hannover Germany. 12. Clinic of Pneumology and Pulmonary Cell Research, University Hospital Basel, Basel, Switzerland. Electronic address: daiana.stolzl@usb.ch.
Abstract
BACKGROUND: The role of the extracellular matrix (ECM) structure and remodeling thereof in lung diseases is gaining importance. Pathology-related changes in ECM turnover may result in deleterious changes in lung architecture, leading to disease in the small airways. Here, degradation fragments of type I (C1M), type IV (α1 chain, C4M2), and type IV (α3 chain, C4Ma3) collagen, all degraded by metalloproteinases and the pro-form of collagen type V (PRO-C5) were investigated and associated with COPD severity and outcome. METHODS: In a prospective, observational, multicenter study including 498 patients with COPD Gold Initiative for Chronic Obstructive Lung Disease stage 2 to 4, ECM markers were assessed in serum at stable state, exacerbation, and at follow-up 4 weeks after exacerbation. RESULTS: At stable state, there was a significant inverse association between FEV1 % predicted and C1M, C4Ma3, and Pro-C5. C1M, C4M2, C4Ma3, and Pro-C5 were associated with BMI, airflow obstruction, dyspnea, and exercise capacity (BODE) index and the modified Medical Research Council (MMRC) score. C1M, C4M2, C4Ma3, and Pro-C5 were significantly increased from stable state to exacerbation and decreased at follow-up. Furthermore, the biomarkers were significantly higher during severe exacerbation compared with moderate exacerbation. Multivariate analysis adjusted for BMI, MMRC score, unadjusted Charlson score, and FEV1 %predicted showed a significant influence of C1M, C4Ma3, and C4M2 on time to exacerbation. None of the biomarkers were predictors for mortality. CONCLUSIONS: Serologically assessed collagen remodeling appears to play a significant role in COPD severity (airflow limitation, dyspnea) and disease outcome (time to exacerbation and prognosis as assessed by the BODE index).
BACKGROUND: The role of the extracellular matrix (ECM) structure and remodeling thereof in lung diseases is gaining importance. Pathology-related changes in ECM turnover may result in deleterious changes in lung architecture, leading to disease in the small airways. Here, degradation fragments of type I (C1M), type IV (α1 chain, C4M2), and type IV (α3 chain, C4Ma3) collagen, all degraded by metalloproteinases and the pro-form of collagen type V (PRO-C5) were investigated and associated with COPD severity and outcome. METHODS: In a prospective, observational, multicenter study including 498 patients with COPD Gold Initiative for Chronic Obstructive Lung Disease stage 2 to 4, ECM markers were assessed in serum at stable state, exacerbation, and at follow-up 4 weeks after exacerbation. RESULTS: At stable state, there was a significant inverse association between FEV1 % predicted and C1M, C4Ma3, and Pro-C5. C1M, C4M2, C4Ma3, and Pro-C5 were associated with BMI, airflow obstruction, dyspnea, and exercise capacity (BODE) index and the modified Medical Research Council (MMRC) score. C1M, C4M2, C4Ma3, and Pro-C5 were significantly increased from stable state to exacerbation and decreased at follow-up. Furthermore, the biomarkers were significantly higher during severe exacerbation compared with moderate exacerbation. Multivariate analysis adjusted for BMI, MMRC score, unadjusted Charlson score, and FEV1 %predicted showed a significant influence of C1M, C4Ma3, and C4M2 on time to exacerbation. None of the biomarkers were predictors for mortality. CONCLUSIONS: Serologically assessed collagen remodeling appears to play a significant role in COPD severity (airflow limitation, dyspnea) and disease outcome (time to exacerbation and prognosis as assessed by the BODE index).
Authors: Jannie M B Sand; Sarah R Rønnow; Lasse L Langholm; Morten A Karsdal; Tina Manon-Jensen; Ruth Tal-Singer; Bruce E Miller; Jørgen Vestbo; Diana J Leeming Journal: Respir Med Date: 2020-10-02 Impact factor: 3.415
Authors: Kiki Waeijen-Smit; Niki L Reynaert; Rosanne J H C G Beijers; Sarah Houben-Wilke; Sami O Simons; Martijn A Spruit; Frits M E Franssen Journal: Sci Rep Date: 2021-08-05 Impact factor: 4.379
Authors: Sarah R Rønnow; Lasse L Langholm; Morten A Karsdal; Tina Manon-Jensen; Ruth Tal-Singer; Bruce E Miller; Jørgen Vestbo; Diana J Leeming; Jannie M B Sand Journal: Respir Res Date: 2020-07-30