Title | Soluble receptor for advanced glycation end products (sRAGE) as a biomarker of COPD. |
Publication Type | Publication |
Year | 2021 |
Authors | Pratte KA, Curtis JL, Kechris K, Couper D, Cho MH, Silverman EK, DeMeo DL, Sciurba FC, Zhang Y, Ortega VE, O'Neal WK, Gillenwater LA, Lynch DA, Hoffman EA, Newell JD, Comellas AP, Castaldi PJ, Miller BE, Pouwels SD, Hacken NHTTen, Bischoff R, Klont F, Woodruff PG, Paine R, R Barr G, Hoidal J, Doerschuk CM, Charbonnier J-P, Sung R, Locantore N, Yonchuk JG, Jacobson S, Tal-Singer R, Merrill D, Bowler RP |
Journal | Respir Res |
Volume | 22 |
Issue | 1 |
Pagination | 127 |
Date Published | 2021 Apr 27 |
ISSN | 1465-993X |
Keywords | Aged, biomarkers, Female, Forced Expiratory Volume, Humans, Longitudinal Studies, Lung, Male, Middle Aged, phenotype, Pulmonary Disease, Chronic Obstructive, Pulmonary Emphysema, Receptor for Advanced Glycation End Products, Severity of Illness Index, Spirometry, Tomography, X-Ray Computed, Vital Capacity |
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 (FEV) 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 FEV (P < 0.001), and emphysema severity (P < 0.001). In an inverse-variance weighted meta-analysis, one SD lower log-transformed sRAGE was associated with 105 ± 22 mL lower FEV and 4.14 ± 0.55 g/L lower adjusted lung density. After adjusting for covariates, lower sRAGE at baseline was associated with greater FEV 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. |
DOI | 10.1186/s12931-021-01686-z |
Alternate Journal | Respir Res |
PubMed ID | 33906653 |
PubMed Central ID | PMC8076883 |
Grant List | HHSN268200900017C / HL / NHLBI NIH HHS / United States HHSN268200900018C / HL / NHLBI NIH HHS / United States HHSN268200900014C / HL / NHLBI NIH HHS / United States HHSN268200900020C / HL / NHLBI NIH HHS / United States R21HL129917 / HL / NHLBI NIH HHS / United States HHSN268200900016C / HL / NHLBI NIH HHS / United States HHSN268200900019C / HL / NHLBI NIH HHS / United States Number U01 HL089856 / HL / NHLBI NIH HHS / United States U01 HL137880 / HL / NHLBI NIH HHS / United States R01 HL137995 / HL / NHLBI NIH HHS / United States U01 HL089897 / HL / NHLBI NIH HHS / United States U24 HL141762 / HL / NHLBI NIH HHS / United States HHSN268200900013C / HL / NHLBI NIH HHS / United States P50HL084948 / HL / NHLBI NIH HHS / United States P30 ES005605 / ES / NIEHS NIH HHS / United States HHSN268200900015C / HL / NHLBI NIH HHS / United States P30 DK054759 / DK / NIDDK NIH HHS / United States R01 HL129937 / HL / NHLBI NIH HHS / United States |
Soluble receptor for advanced glycation end products (sRAGE) as a biomarker of COPD.
MS#:
MS055
Manuscript Full Title:
Soluble receptor for advanced glycation end products (sRAGE) as a biomarker of COPD.
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Manuscript Status:
Published and Public