Dataset Information

Serum soluble receptor for advanced glycation end-products (sRAGE) in infants with bronchiolitis: Associations with acute severity and recurrent wheeze.

ABSTRACT:

Background

Although bronchiolitis contributes to substantial acute (e.g., intensive care use) and chronic (e.g., recurrent wheeze and infections) morbidities in young children, the pathobiology remains uncertain. We examined relations of serum soluble receptor for advanced glycation end-products (sRAGE) with acute and chronic morbidities of bronchiolitis and whether the effect of serum sRAGE on development of recurrent wheeze is mediated through acute severity.

Methods

A multi-center, multi-year, prospective cohort study of infants hospitalized for bronchiolitis was analyzed. We measured serum sRAGE level at acute hospitalization and examined its association with intensive care use (use of mechanical ventilation and/or admission to intensive care unit) and development of recurrent wheeze by age 3 years. We performed causal mediation analysis to estimate indirect (mediation) and direct effects of sRAGE on recurrent wheeze.

Results

In 886 infants with bronchiolitis, median age was 2.9 months. Overall, 15% underwent intensive care and 32% developed recurrent wheeze by age 3 years. In the multivariable model adjusting for 11 confounders, higher presenting sRAGE level was associated with significantly lower risk of intensive care use (OR for each one-log increment, 0.39; 95%CI 0.16-0.91; P=0.03) and significantly lower rate of recurrent wheeze (HR 0.58; 95%CI 0.36-0.94; P=0.03). In mediation analysis, the direct effect was significant (HR 0.60; 95%CI 0.37-0.97; P=0.04) while the indirect effect was not (P=0.30).

Conclusions

Serum sRAGE levels were inversely associated with acute and chronic morbidities of bronchiolitis. Effect of sRAGE on development of recurrent wheeze is potentially driven through pathways other than acute severity of bronchiolitis.

SUBMITTER: Patregnani JT

PROVIDER: S-EPMC8563181 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Publications

Serum Soluble Receptor for Advanced Glycation End Products in Infants With Bronchiolitis: Associations With Acute Severity and Recurrent Wheeze.

Patregnani Jason T JT Fujiogi Michimasa M Camargo Carlos A CA Brooks Bonnie A BA Hoptay Claire E CE Mansbach Jonathan M JM Teach Stephen J SJ Freishtat Robert J RJ Hasegawa Kohei K

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20211101 9

<h4>Background</h4>Although bronchiolitis contributes to substantial acute (eg, intensive care use) and chronic (eg, recurrent wheeze) morbidities in young children, the pathobiology remains uncertain. We examined the associations of serum soluble receptor for advanced glycation end products (sRAGE) with acute and chronic morbidities of bronchiolitis including recurrent wheeze.<h4>Methods</h4>A multicenter, multiyear, cohort study of infants hospitalized for bronchiolitis was analyzed. We measur ...[more]

PMID: 33173945

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Project description:BackgroundSoluble 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.MethodssRAGE 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).ResultsLower 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 log10-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.ConclusionsLower 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.