Divergent transcriptional profiles in pediatric asthma patients of low and high socioeconomic status

Miller, Gregory E.; Chen, Eric; Shalowitz, Madeleine U.; Story, Rachel E.; Leigh, Adam K.K.; Ham, Paula J.; Arevalo, Jesusa M.G.; Cole, Steve W.

doi:10.1002/ppul.23983

Cited by 30 publications

(25 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…More importantly, differential transcription factor usage is primordial in immune cell differentiation and activation. There is now preliminary data published during the writing and revising of this manuscript associating low SES with gene expression profiles that suggest the peripheral immune system is biased towards a Th activity, and furthermore, towards a Th2/Th17 profile, and away from Th1 that was thought to further decrease asthma symptom control amongst low SES children (Miller et al 2018. There is also a growing literature on the role of adipose tissues linking ELA to both depressive symptoms and increased inflammation.…”

Section: Discussionmentioning

confidence: 88%

Glucocorticoid receptor signaling in leukocytes after early life adversity

et al. 2019

View full text Add to dashboard Cite

Early life adversity (ELA) has been associated with inflammation and immunosenescence, as well as hyporeactivity of the HPA axis. Because the immune system and the HPA axis are tightly intertwined around the glucocorticoid receptor (GR), we examined peripheral GR functionality in the EpiPath cohort among participants who either had been exposed to ELA (separation from parents and/or institutionalization followed by adoption; n = 40) or had been reared by their biological parents (n = 72). Expression of the strict GR target genes FKBP5 and GILZ as well as total and 1F and 1H GR transcripts were similar between groups. Furthermore, there were no differences in GR sensitivity, examined by the effects of dexamethasone on IL6 production in LPS-stimulated whole blood. Although we did not find differences in methylation at the GR 1F exon or promoter region, we identified a region of the GR 1H promoter (CpG 1-9) that showed lower methylation levels in ELA. Our results suggest that peripheral GR signaling was unperturbed in our cohort and the observed immune phenotype does not appear to be secondary to an altered GR response to the perturbed HPA axis and glucocorticoid (GC) profile, although we are limited in our measures of GR activity and time points.

show abstract

Section: Discussionmentioning

confidence: 88%

Glucocorticoid receptor signaling in leukocytes after early life adversity

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Potential Mechanisms There is conflicting evidence correlating SES with immune response; the type, timing, and duration of exposure to common environmental toxins (e.g., mold, dusts, pests, poor air quality) appear to delineate the direction of this association. In a cross-sectional study of SES and genome-wide mRNA expression in asthmatic children, downregulation of genes associated with a type I response and upregulation of those associated with a type II response were found in low SES children [38]. A second study supports this association between SES and type II response [39].…”

Section: Socioeconomic Positionmentioning

confidence: 86%

Structural and Social Determinants of Health in Asthma in Developed Economies: a Scoping Review of Literature Published Between 2014 and 2019

Sullivan

Thakur

2020

Curr Allergy Asthma Rep

127

View full text Add to dashboard Cite

Purpose of Review Using the WHO Conceptual Framework for Action on the Social Determinants of Health, this review provides a discussion of recent epidemiologic, mechanistic, and intervention studies of structural and social determinants of health and asthma outcomes covering the period from 2014 to 2019. Recent Findings A majority of studies and interventions to date focus on the intermediary determinants of health (e.g., housing), which as the name suggests, exist between the patient and the upstream structural determinants of health (e.g., housing policy). Race/ethnicity remains a profound social driver of asthma disparities with cumulative risk from many overlapping determinants. A growing number of studies on asthma are beginning to elucidate the underlying mechanisms that connect social determinants to human disease. Several effective interventions have been developed, though a need for large-scale policy research and innovation remains. Summary Strong evidence supports the key role of the structural determinants, which generate social stratification and inequity, in the development and progression of asthma; yet, interventions in this realm are challenging to develop and therefore infrequent. Proximal, intermediary determinants have provided a natural starting point for interventions, though structural interventions have the most potential for major impact on asthma outcomes. Further research to investigate the interactive effect of multiple determinants, as well as intervention studies, specifically those that are cross-sector and propose innovative strategies to target structural determinants, are needed to address asthma morbidities, and more importantly, close the asthma disparity gap.

show abstract

“…This mode of protection is typically lost when maternally derived antibodies are degraded, but the maturing offspring immune system's ability to generate its own effective adaptive immunity replaces it [56]. A wide body of research highlights the fundamental role early-life environment plays in determining the broad transcriptional identity of circulating lymphocytes and showing that the early-life environment has a very strong influence on T-cells [57][58][59][60][61][62].…”

Section: Maternal Pre-conception Environment and Long Lasting Influenmentioning

confidence: 99%

Environmental Impact on Health across Generations: Policy Meets Biology. A Review of Animal and Human Models

et al. 2018

View full text Add to dashboard Cite

Intrauterine and early life has been accepted as important susceptibility windows for environmental exposure and disease later in life. Emerging evidence suggests that exposure before conception may also influence health in future generations. There has been little research on human data to support this until now. This review gives evidence from epigenetic as well as immunologic research, and from animal as well as human models, supporting the hypothesis that there may be important susceptibility windows before conception in relation to exposure such as obesity, diet, smoking and infections. It is likely that we can identify vulnerability windows in men and women in which interventions may have an impact on several generations in addition to individual health. Establishing vulnerability windows affecting health over future generations, and not only in the now or the near future of the individual, may provide tremendous opportunities for health policy and practice.

show abstract

Divergent transcriptional profiles in pediatric asthma patients of low and high socioeconomic status

Abstract: Collectively, these patterns implicate pro-inflammatory monocytes and Type 2 cytokine activity as mechanisms contributing to worse asthma control among lower-SES children.

Cited by 30 publications

References 40 publications

Glucocorticoid receptor signaling in leukocytes after early life adversity

Glucocorticoid receptor signaling in leukocytes after early life adversity

Structural and Social Determinants of Health in Asthma in Developed Economies: a Scoping Review of Literature Published Between 2014 and 2019

Environmental Impact on Health across Generations: Policy Meets Biology. A Review of Animal and Human Models

Contact Info

Product

Resources

About