Journal article
Soluble receptor for advanced glycation end products (sRAGE) as a biomarker of COPD
Respiratory research, Vol.22(1), pp.127-127
04/27/2021
DOI: 10.1186/s12931-021-01686-z
PMCID: PMC8076883
PMID: 33906653
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 FEV1 and 4.14 +/- 0.55 g/L lower adjusted lung density. After adjusting for covariates, lower sRAGE at baseline was associated with greater FEV1 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.
Details
- Title: Subtitle
- Soluble receptor for advanced glycation end products (sRAGE) as a biomarker of COPD
- Creators
- Katherine A. Pratte - National Jewish HealthJeffrey L. Curtis - University of Michigan–Ann ArborKaterina Kechris - Colorado School of Public HealthDavid Couper - University of North Carolina at Chapel HillMichael H. Cho - Brigham and Women's HospitalEdwin K. Silverman - Brigham and Women's HospitalDawn L. DeMeo - Brigham and Women's HospitalFrank C. Sciurba - University of PittsburghYingze Zhang - University of PittsburghVictor E. Ortega - Wake Forest UniversityWanda K. O'Neal - University of North Carolina at Chapel HillLucas A. Gillenwater - University of Colorado Anschutz Medical CampusDavid A. Lynch - National Jewish HealthEric A. Hoffman - University of IowaJohn D. Newell - University of IowaAlejandro P. Comellas - University of IowaPeter J. Castaldi - Brigham and Women's HospitalBruce E. Miller - COPD Fdn, Miami, FL USASimon D. Pouwels - University Medical Center GroningenNick H. T. ten Hacken - Univ Groningen, Dept Pathol & Med Biol, Groningen, NetherlandsRainer Bischoff - AnalyticaFrank Klont - AnalyticaPrescott G. Woodruff - University of California, San FranciscoRobert Paine - University of UtahR. Graham Barr - Columbia UniversityJohn Hoidal - University of UtahClaire M. Doerschuk - University of North Carolina at Chapel HillJean-Paul Charbonnier - Thirona, LungQ, Nijmegen, NetherlandsRuby Sung - Research and Development, GlaxoSmithKline, Collegeville, USANicholas Locantore - Research and Development, GlaxoSmithKline, Collegeville, USAJohn G. Yonchuk - Research and Development, GlaxoSmithKline, Collegeville, USASean Jacobson - National Jewish HealthRuth Tal-singer - COPD FoundationDebbie Merrill - COPD FoundationRussell P. Bowler - National Jewish Health
- Resource Type
- Journal article
- Publication Details
- Respiratory research, Vol.22(1), pp.127-127
- DOI
- 10.1186/s12931-021-01686-z
- PMID
- 33906653
- PMCID
- PMC8076883
- NLM abbreviation
- Respir Res
- ISSN
- 1465-9921
- eISSN
- 1465-993X
- Publisher
- Springer Nature
- Number of pages
- 13
- Grant note
- Regeneron Pharmaceuticals, Inc.; Regeneron Takeda Pharmaceutical Company; Takeda Pharmaceutical Company Ltd 4100062224 / Pennsylvania CURE SAP NCT00608764 / COPD Foundation Grifols Therapeutics, Inc. Foundation for the NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA ProterixBio HHSN268200900013C; HHSN268200900014C; HHSN268200900015C; HHSN268200900016C; HHSN268200900017C; HHSN268200900018C; HHSN268200900019C; HHSN268200900020C; U01 HL137880; U24 HL141762 / NIH/NHLBI; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) Theravance Biopharma BoehringerIngelheim Pharmaceuticals, Inc.; Boehringer Ingelheim U01 HL089897; U01 HL089856; R01 HL137995; R01 HL129937; P50HL084948; R21HL129917 / National Heart, Lung, and Blood Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) Mylan Bellerophon Therapeutics GlaxoSmithKline Bayer; Bayer AG Chiesi Farmaceutici S.p.A.; Chiesi Pharmaceuticals Inc Novartis Pharmaceuticals Corporation; Novartis Sunovion Sanofi COPD Foundation from AstraZeneca/MedImmune Ikaria, Inc. Nycomed GmbH Forest Research Institute, Inc.
- Language
- English
- Date published
- 04/27/2021
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiology; Pulmonary, Critical Care, and Occupational Medicine; Psychiatry; ICTS; Internal Medicine
- Record Identifier
- 9984318806502771
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