Dataset Information

Relationship between cytokine expression patterns and clinical outcomes: two population-based birth cohorts.

ABSTRACT:

Background

Models that incorporate patterns of multiple cytokine responses to allergens, rather than individual cytokine production, may better predict sensitization and asthma.

Objective

To characterize the patterns of peripheral blood mononuclear cells' (PBMCs) cytokine responses to house dust mite (HDM) allergens among children from two population-based birth cohorts using machine learning techniques.

Methods

PBMCs collected at 8 years of age from the UK Manchester Asthma and Allergy Study (n = 268) and at 14 years of age from the Australian Raine Study (n = 1374) were cultured with HDM extract (10 ?g/ml). Cytokine expression (IL-13, IL-5, IFN-?, and IL10) was measured in the supernatant. Cytokine patterns were identified using a Gaussian mixture model clustering, and classification stability was assessed by bootstrapping.

Results

A six-class model indicated complex latent structure of cytokine expression. Based on the characteristics of each class, we designated them as follows: 'Nonresponders' (n = 905, 55%); 'IL-10 responders' (n = 49, 3%); 'IFN-? and IL-13 medium responders' (n = 56, 3.4%); 'IL-13 medium responders' (n = 351, 21.4%); 'IL-5 and IL-13 medium responders' (n = 77, 4.7%); and 'IL-13 and IL-5 high responders' (n = 204, 12.4%). 'IL-13 and IL-5 high responders' were at much higher risk of HDM sensitization and asthma compared to all other classes, with 88% of children assigned to this class being sensitized and 28.5% having asthma.

Conclusion

Using model-based clustering, we identified several distinct patterns of cytokine response to HDM and observed interplay between cytokine expression level, cytokine patterns (especially IL-13 and IL-5), and clinical outcomes. 'IL-13 and IL-5 high responders' class was strongly associated with HDM sensitization. However, among HDM-sensitized children, one-third showed no PBMC response to HDM, and the majority of HDM-sensitized children did not have asthma or wheeze. Our findings suggest that positive HDM 'allergy tests' and asthma are associated with a broad range of immunophenotypes, which may have important implications for the use of cytokine-targeted treatment approaches.

SUBMITTER: Wu J

PROVIDER: S-EPMC4950290 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Relationship between cytokine expression patterns and clinical outcomes: two population-based birth cohorts.

Wu J J Prosperi M C F MC Simpson A A Hollams E M EM Sly P D PD Custovic A A Holt P G PG

Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 20151201 12

<h4>Background</h4>Models that incorporate patterns of multiple cytokine responses to allergens, rather than individual cytokine production, may better predict sensitization and asthma.<h4>Objective</h4>To characterize the patterns of peripheral blood mononuclear cells' (PBMCs) cytokine responses to house dust mite (HDM) allergens among children from two population-based birth cohorts using machine learning techniques.<h4>Methods</h4>PBMCs collected at 8 years of age from the UK Manchester Asthm ...[more]

PMID: 26061524

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Project description:Our objective was twofold: to estimate the prevalence of underweight, overweight, and obesity in two birth cohorts (1999-2000 and 2007-2008) from Castilla-La Mancha, Spain; and to examine the association between parental socioeconomic status (SES) and weight status in these two cohorts.Cross-sectional analysis of baseline measurements was utilised in two cluster randomised trials. Using population-based samples of children from Castilla-La Mancha, Spain, 1158 children with a mean age of 9.5 years, born in the years 1999-2000 and 1588 children with a mean age of 5.3 years born in the years 2007-2008 participated. Children were classified according to the body mass index cut-offs proposed by the International Obesity Task Force criteria. An index of SES was calculated using questions regarding parental education and occupation levels.Prevalence of underweight was higher in the 2007-2008 birth cohort (20.5%, 95 % CI: 18.5, 22.5) than in the 1999-2000 birth cohort (8.1%, 95% CI: 6.5, 9.7), and the overweight/obesity prevalence was 20.4% (95% CI: 18.4, 22.5) and 35.5% (95% CI: 32.7, 38.3) respectively. In the lower SES stratum, in the 2007-2008 birth cohort, the prevalence of underweight and overweight/obesity was 36.7% (95% CI: 22.2, 51.2) and 16.3% (95% CI: 4.9, 27.7) respectively, and 22.2% (95% CI: 2.8, 60.0) and 55.5% (95% CI: 21.2, 86.3) in the 1999-2000 cohort. The ratio between underweight:overweight/obesity showed higher values for all SES categories in 2007-2008 cohort, but particularly in the lower SES group (0.4 in the 1999-2000 cohort and 2.2 in the 2007-2008 cohort).Underweight prevalence was lower in the cohort of children born in 1999-2000, and the prevalence of overweight and obesity was lower in the cohort of children born in 2007-2008. Furthermore, while in the 1999-2000 children's cohort underweight was more frequent amongst children from high SES families and overweight/obesity was more frequent in children from low SES families, in the 2008-2009 children's cohort the opposite was true.

Project description:ObjectiveTo determine survival and neonatal morbidity for babies born between 22 and 26 weeks' gestation in England during 2006, and to evaluate changes in outcome since 1995 for babies born between 22 and 25 weeks' gestation.DesignProspective national cohort studies.SettingMaternity and neonatal units in England.Participants3133 births between 22 and 26 weeks' gestation in 2006; 666 admissions to neonatal units in 1995 and 1115 in 2006 of babies born between 22 and 25 weeks' gestation.Main outcome measuresSurvival to discharge from hospital, pregnancy and delivery outcomes, infant morbidity until discharge.ResultsIn 2006, survival of live born babies was 2% (n=3) for those born at 22 weeks' gestation, 19% (n=66) at 23 weeks, 40% (n=178) at 24 weeks, 66% (n=346) at 25 weeks, and 77% (n=448) at 26 weeks (P<0.001). At discharge from hospital, 68% (n=705) of survivors had bronchopulmonary dysplasia (receiving supplemental oxygen at 36 weeks postmenstrual age), 13% (n=135) had evidence of serious abnormality on cerebral ultrasonography, and 16% (n=166) had laser treatment for retinopathy of prematurity. For babies born between 22 and 25 weeks' gestation from March to December, the number of admissions for neonatal care increased by 44%, from 666 in 1995 to 959 in 2006. By 2006 adherence to evidence based practice associated with improved outcome had significantly increased. Survival increased from 40% to 53% (P<0.001) overall and at each week of gestation: by 9.5% (confidence interval -0.1% to 19%) at 23 weeks, 12% (4% to 20%) at 24 weeks, and 16% (9% to 23%) at 25 weeks. The proportions of babies surviving in 2006 with bronchopulmonary dysplasia, major cerebral scan abnormality, or weight and/or head circumference <-2 SD were similar to those in 1995, but the proportion treated for retinopathy of prematurity had increased from 13% to 22% (P=0.006). Predictors of mortality and morbidity were similar in both cohorts.ConclusionSurvival of babies born between 22 and 25 weeks' gestation has increased since 1995 but the pattern of major neonatal morbidity and the proportion of survivors affected are unchanged. These observations reflect an important increase in the number of preterm survivors at risk of later health problems.

Dataset Information

Relationship between cytokine expression patterns and clinical outcomes: two population-based birth cohorts.

Background

Objective

Methods

Results

Conclusion

Publications

Relationship between cytokine expression patterns and clinical outcomes: two population-based birth cohorts.

Similar Datasets

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