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Exploration of early-life candidate biomarkers for childhood asthma using antibody arrays.

ABSTRACT: Proteomic approaches identifying biomarkers have been applied to asthma to only a very limited extent.With an antibody array (RayBiotech, Norcross, GA, USA), the relative intensity and rank differences of 444 proteins were compared in 24 plasma samples obtained at age 3, 11 from children with and 12 without asthma diagnoses at ages 5 and 9. Protein candidates identified by antibody array were quantitated by ELISA in an enlarged sample. Proteins found to differentiate children with and without asthma were also examined for association with known Year 1 asthma risk factors, eczema, and wheeze.In the antibody array, four proteins had rank differences between asthma and non-asthma groups (FDR <0.1). By ELISA, mean log (±s.e.m.) erythropoietin (EPO) level (IU/l) was lower (0.750 ± 0.048 vs. 0.898 ± 0.035; p = 0.006) and mean (±s.e.m.) soluble GP130 (sGP130) level (ng/ml) was higher in the asthma vs. the non-asthma group (302 ± 13 vs. 270 ± 8; p = 0.041). The other 2 array proteins (galactin-3 and eotaxin-3) did not differ by ELISA by asthma. EPO related to the asthma risk factor, first year eczema, whereas sGP130 related to first year wheeze.Through two independent assessments, age 3 plasma levels of EPO and sGP130 were found related to childhood asthma.

SUBMITTER: Xu H

PROVIDER: S-EPMC5526199 | biostudies-other | 2016 Nov

REPOSITORIES: biostudies-other

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Exploration of early-life candidate biomarkers for childhood asthma using antibody arrays.

Xu Haili H Radabaugh Timothy T Lu Zhenqiang Z Galligan Michael M Billheimer Dean D Vercelli Donata D Wright Anne L AL Monks Terrence J TJ Halonen Marilyn M Lau Serrine S SS

Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology 20160912 7

<h4>Background</h4>Proteomic approaches identifying biomarkers have been applied to asthma to only a very limited extent.<h4>Methods</h4>With an antibody array (RayBiotech, Norcross, GA, USA), the relative intensity and rank differences of 444 proteins were compared in 24 plasma samples obtained at age 3, 11 from children with and 12 without asthma diagnoses at ages 5 and 9. Protein candidates identified by antibody array were quantitated by ELISA in an enlarged sample. Proteins found to differe ...[more]

PMID: 27434124

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Project description:RationaleThe prevalence of childhood asthma has been increasing worldwide in parallel with childhood obesity.ObjectivesWe investigated whether there is a temporal relationship between early life weight gain (reflecting growth velocity) and early life body mass index (BMI) attained status (reflecting accumulative weight) with future risk of asthma in the Boston Birth Cohort.MethodsThis report includes 1,928 children from the Boston Birth Cohort with a mean age of 7.8 years (standard deviation, 3.3 yr), enrolled at birth and followed prospectively. Asthma was defined using physician diagnosis code (International Classification of Diseases, Ninth Revision, Clinical Modification code 493.xx) in children 2 years and older. We categorized the children by their weight gain trajectory on the basis of changes in z-scores: slow (less than -0.67), on track (-0.67 to 0.67), rapid (0.67-1.28), and extremely rapid (>1.28); and by their BMI attained status (underweight, normal weight, and overweight) during the first 4, 12, and 24 months. Poisson regression models with robust variance estimation were applied to examine the relationship between early life weight gain/attained BMI and asthma.ResultsDuring the first 4 months of life, 37% had on-track weight grain, 22% had slow weight gain, 15% had rapid weight gain, and 26% had extremely rapid weight gain. At 4 months, 61% were normal weight, 7% were underweight, and 32% were overweight. In adjusted analyses, extremely rapid early life weight gain during the first 4 and 24 months of life were each associated with increased risks of asthma (risk ratio, 1.34 for extremely rapid weight gain at 4 months; 95% confidence interval [CI], 1.06-1.70; risk ratio, 1.32 for extremely rapid weight gain at 24 months; 95% CI, 1.00-1.75) Similarly, overweight at 4, 12, and 24 months were each associated with an increased risk of asthma. Analyses that further adjusted for birthweight or preterm birth showed similar findings.ConclusionsIn this predominantly urban U.S. low-income minority birth cohort, excessive early life weight gain and overweight status were both associated with an increased risk of asthma in childhood.

Project description:ImportanceExposure to particulate matter (PM) has been associated with childhood asthma and wheeze. However, the specific associations between asthma and PM with an aerodynamic equivalent diameter of 1 μm or less (ie, PM1), which is a contributor to PM2.5 and potentially more toxic than PM2.5, remain unclear.ObjectiveTo investigate the association of early-life (prenatal and first year) exposure to size-segregated PM, including PM1, PM1-2.5, PM2.5, PM2.5-10, and PM10, with childhood asthma and wheeze.Design, setting, and participantsThis cross-sectional study was based on a questionnaire administered between June 2019 and June 2020 to caregivers of children aged 3 to 6 years in 7 Chinese cities (Wuhan, Changsha, Taiyuan, Nanjing, Shanghai, Chongqing, and Urumqi) as the second phase of the China, Children, Homes, Health study.ExposuresExposure to PM1, PM1-2.5, PM2.5, PM2.5-10, and PM10 during the prenatal period and first year of life.Main outcomes and measuresThe main outcomes were caregiver-reported childhood asthma and wheeze. A machine learning-based space-time model was applied to estimate early-life PM1, PM2.5, and PM10 exposure at 1 × 1-km resolution. Concentrations of PM1-2.5 and PM2.5-10 were calculated by subtracting PM1 from PM2.5 and PM2.5 from PM10, respectively. Multilevel (city and child) logistic regression models were applied to assess associations.ResultsOf 29 418 children whose caregivers completed the survey (15 320 boys [52.1%]; mean [SD] age, 4.9 [0.9] years), 2524 (8.6%) ever had wheeze and 1161 (3.9%) were diagnosed with asthma. Among all children, 18 514 (62.9%) were breastfed for more than 6 months and 787 (2.7%) had parental history of atopy. A total of 22 250 children (75.6%) had a mother with an educational level of university or above. Of the 25 422 children for whom information about cigarette smoking exposure was collected, 576 (2.3%) had a mother who was a current or former smoker during pregnancy and 7525 (29.7%) had passive household cigarette smoke exposure in early life. Early-life PM1, PM2.5, and PM10 exposure were significantly associated with increased risk of childhood asthma, with higher estimates per 10-μg/m3 increase in PM1 (OR, 1.55; 95% CI, 1.27-1.89) than in PM2.5 (OR, 1.14; 95% CI, 1.03-1.26) and PM10 (OR, 1.11; 95% CI, 1.02-1.20). No association was observed between asthma and PM1-2.5 exposure, suggesting that PM1 rather than PM1-2.5 contributed to the association between PM2.5 and childhood asthma. There were significant associations between childhood wheeze and early-life PM1 exposure (OR, 1.23; 95% CI, 1.07-1.41) and PM2.5 exposure (OR, 1.08; 95% CI, 1.01-1.16) per 10-μg/m3 increase in PM1 and PM2.5, respectively.Conclusions and relevanceIn this cross-sectional study, higher estimates were observed for the association between PM with smaller particles, such as PM1, vs PM with larger particles and childhood asthma. The results suggest that the association between PM2.5 and childhood asthma was mainly attributable to PM1.

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Exploration of early-life candidate biomarkers for childhood asthma using antibody arrays.

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Exploration of early-life candidate biomarkers for childhood asthma using antibody arrays.

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