Patterns of immune development in urban preschoolers with recurrent wheeze and/or atopy

Abstract

Background Disadvantaged urban children have high rates of allergic diseases and wheezing, which are diseases associated with Type 2-biased immunity. Objective To determine whether environmental exposures in early life influence cytokine responses which affect the development of recurrent wheezing illnesses and allergic sensitization. Methods A birth cohort of 560 urban families was recruited from neighborhoods with high rates of poverty, and 467 (83%) children were followed until 3 years of age. Cytokine responses were measured in blood cell samples obtained at birth (cord blood) and ages 1 and 3 years. Cytokine responses were examined in relation to personal characteristics and environmental exposures to allergens and endotoxin, and also to the development of allergic sensitization and recurrent wheeze assessed at age 3 years. Results Cytokine responses generally increased with age, but responses at birth were poorly predictive for those at ages 1 and 3 years. Exposure to certain allergens (cockroach, mouse, dust mite) was significantly associated with enhanced cytokine responses at age 3 years, including IFN-α and IL-10 responses to certain stimulants, and responses to phytohemagglutinin. Regarding the clinical outcomes, reduced LPS-induced IL-10 responses at birth was associated with recurrent wheeze. In contrast, reduced RSV-induced IL-8 responses, and increased CpG-induced IL-12p40 and allergen-induced IL-4 responses were associated with atopy. Conclusions These findings suggest that diverse biologic exposures, including allergens and endotoxin, in urban homes stimulate the development of cytokine responses in early life, and that cytokine responses to specific microbial and viral stimuli are associated with the development of allergic sensitization and recurrent wheeze.

Advances in asthma in 2017: Mechanisms, biologics, and genetics

“…, and this past year, several studies expanded our knowledge of the influence of early-life allergen exposure on asthma risk and demonstrated interactions between these indoor allergens and genetic polymorphisms. 49,[53][54][55][56] These gene-environment interactions could act through epigenetic or nonepigenetic mechanisms. In addition, studies demonstrated links between genetic signatures and asthma phenotypes related to steroid responsiveness, adult-onset asthma, and total IgE levels.…”

“…The role played by the environment in shaping the development and exacerbation of asthma is examined as well (Fig 3). [40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56] We conclude with a section on health literacy, a critical component for successfully treating asthma, and other related advances.…”

Lessons learned from birth cohort studies conducted in diverse environments

“…3 A number of factors affect early-life immune responses, including season of birth, 5–7 sex, 8 maternal stress, 9 and allergen and microbial exposures (farms, dog, cockroach, and endotoxin) during pregnancy and early life. 7,10 Reduced IFN-γ responses in cord blood and early infancy have been linked to the risk of LRTIs and recurrent wheezing in multiple cohorts. 11–14 Interestingly, early-life LRTIs are associated with a significant increase in mononuclear cell T H 1 and T H 2 responses in early life.…”

“…11–14 Interestingly, early-life LRTIs are associated with a significant increase in mononuclear cell T H 1 and T H 2 responses in early life. 7,14 An exaggerated response of PBMCs to bacterial pathogens in infancy has also been associated with an increased risk of subsequent wheezing and asthma in the Copenhagen Prospective Studies on Asthma in Childhood (COPSAC) study. 15 Furthermore, a diminished regulatory T-cell response at birth has been identified as a risk factor for allergic sensitization and wheezing.…”

Development of allergic immunity in early life

“…In comparison, allergic children show enhanced cytokine production at birth but this decreased over time so that by age 5, this hyper‐responsiveness to stimuli had declined and cytokine responses were reduced in comparison to similar aged non‐allergic children. A comprehensive study of immune development in urban preschool children determined that early life environmental exposures are vital in the stimulation of cytokine responses . Importantly, although cytokine production increased with age, these responses at birth were poorly predictive for later responses at aged 1 or 3.…”