학술논문
Soluble receptor for advanced glycation end products (sRAGE) as a biomarker of COPD.
Document Type
Academic Journal
Author
Pratte KA; Department of Biostatistics, National Jewish Health, Denver, CO, USA.; Curtis JL; Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI, USA.; Medical Service, Ann Arbor Healthcare System, Ann Arbor, MI, USA.; Kechris K; Department of Biostatistics and Informatics, School of Public Health, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA.; Couper D; Department of Biostatistics, Collaborative Studies Coordinating Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Cho MH; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA.; Silverman EK; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.; DeMeo DL; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA.; Sciurba FC; Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.; Zhang Y; Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.; Ortega VE; Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC, USA.; O'Neal WK; Marsico Lung Institute (CF Research Center), University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Gillenwater LA; Division of Pulmonary Medicine, Department of Medicine, National Jewish Health, 1400 Jackson Street, Denver, CO, 80206, USA.; Computational Bioscience Program, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA.; Lynch DA; Department of Radiology, National Jewish Health, Denver, CO, USA.; Hoffman EA; Department of Radiology and Biomedical Engineering, University of Iowa, Iowa City, IA, USA.; Newell JD Jr; Department of Radiology and Biomedical Engineering, University of Iowa, Iowa City, IA, USA.; Comellas AP; Department of Internal Medicine, College of Medicine, University of Iowa Carver, Iowa City, IA, USA.; Castaldi PJ; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.; Miller BE; COPD Foundation, Miami, FL, USA.; Pouwels SD; Department of Pathology and Medical Biology, University of Groningen, Groningen, Netherlands.; Hacken NHTT; Department of Pathology and Medical Biology, University of Groningen, Groningen, Netherlands.; Bischoff R; Department of Analytical Biochemistry, University of Groningen, Groningen, Netherlands.; Klont F; Department of Analytical Biochemistry, University of Groningen, Groningen, Netherlands.; Woodruff PG; Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of California-San Francisco, San Francisco, CA, USA.; Cardiovascular Research Institute, University of California-San Francisco, San Francisco, CA, USA.; Paine R; Division of Pulmonary and Critical Care, University of Utah, Salt Lake City, UT, USA.; Barr RG; Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Columbia University, New York, NY, USA.; Hoidal J; Division of Pulmonary and Critical Care, University of Utah, Salt Lake City, UT, USA.; Doerschuk CM; Marsico Lung Institute (CF Research Center), University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Charbonnier JP; Thirona, LungQ, Nijmegen, Netherlands.; Sung R; Research and Development, GlaxoSmithKline, Collegeville, PA, USA.; Locantore N; Research and Development, GlaxoSmithKline, Collegeville, PA, USA.; Yonchuk JG; Research and Development, GlaxoSmithKline, Collegeville, PA, USA.; Jacobson S; Department of Genetics, National Jewish Health, Denver, CO, USA.; Tal-Singer R; COPD Foundation, Miami, FL, USA.; Merrill D; COPD Foundation, Miami, FL, USA.; Bowler RP; Division of Pulmonary Medicine, Department of Medicine, National Jewish Health, 1400 Jackson Street, Denver, CO, 80206, USA. BowlerR@NJHealth.org.
Source
Publisher: BioMed Central Ltd Country of Publication: England NLM ID: 101090633 Publication Model: Electronic Cited Medium: Internet ISSN: 1465-993X (Electronic) Linking ISSN: 14659921 NLM ISO Abbreviation: Respir Res Subsets: MEDLINE
Subject
Language
English
Abstract
Background: Soluble receptor for advanced glycation end products (sRAGE) is a proposed emphysema and airflow obstruction biomarker; however, previous publications have shown inconsistent associations and only one study has investigate the association between sRAGE and emphysema. No cohorts have examined the association between sRAGE and progressive decline of lung function. There have also been no evaluation of assay compatibility, receiver operating characteristics, and little examination of the effect of genetic variability in non-white population. This manuscript addresses these deficiencies and introduces novel data from Pittsburgh COPD SCCOR and as well as novel work on airflow obstruction. A meta-analysis is used to quantify sRAGE associations with clinical phenotypes.
Methods: sRAGE was measured in four independent longitudinal cohorts on different analytic assays: COPDGene (n = 1443); SPIROMICS (n = 1623); ECLIPSE (n = 2349); Pittsburgh COPD SCCOR (n = 399). We constructed adjusted linear mixed models to determine associations of sRAGE with baseline and follow up forced expiratory volume at one second (FEV1 ) and emphysema by quantitative high-resolution CT lung density at the 15th percentile (adjusted for total lung capacity).
Results: Lower plasma or serum sRAGE values were associated with a COPD diagnosis (P < 0.001), reduced FEV1 (P < 0.001), and emphysema severity (P < 0.001). In an inverse-variance weighted meta-analysis, one SD lower log 10 -transformed sRAGE was associated with 105 ± 22 mL lower FEV 1 and 4.14 ± 0.55 g/L lower adjusted lung density. After adjusting for covariates, lower sRAGE at baseline was associated with greater FEV 1 decline and emphysema progression only in the ECLIPSE cohort. Non-Hispanic white subjects carrying the rs2070600 minor allele (A) and non-Hispanic African Americans carrying the rs2071288 minor allele (A) had lower sRAGE measurements compare to those with the major allele, but their emphysema-sRAGE regression slopes were similar.
Conclusions: Lower blood sRAGE is associated with more severe airflow obstruction and emphysema, but associations with progression are inconsistent in the cohorts analyzed. In these cohorts, genotype influenced sRAGE measurements and strengthened variance modelling. Thus, genotype should be included in sRAGE evaluations.
Methods: sRAGE was measured in four independent longitudinal cohorts on different analytic assays: COPDGene (n = 1443); SPIROMICS (n = 1623); ECLIPSE (n = 2349); Pittsburgh COPD SCCOR (n = 399). We constructed adjusted linear mixed models to determine associations of sRAGE with baseline and follow up forced expiratory volume at one second (FEV
Results: Lower plasma or serum sRAGE values were associated with a COPD diagnosis (P < 0.001), reduced FEV
Conclusions: Lower blood sRAGE is associated with more severe airflow obstruction and emphysema, but associations with progression are inconsistent in the cohorts analyzed. In these cohorts, genotype influenced sRAGE measurements and strengthened variance modelling. Thus, genotype should be included in sRAGE evaluations.