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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:We sought to determine whether environmental exposures in early life influence cytokine responses that 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 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-? and IL-10 responses to certain stimulants and responses to phytohemagglutinin. Regarding the clinical outcomes, reduced LPS-induced IL-10 responses at birth were associated with recurrent wheeze. In contrast, reduced respiratory syncytial virus-induced IL-8 responses and increased 5'-cytosine-phosphate-guanine-3' (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.

SUBMITTER: Gern JE

PROVIDER: S-EPMC5509531 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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

Gern James E JE Calatroni Agustin A Jaffee Katy F KF Lynn Henry H Dresen Amy A Cruikshank William W WW Lederman Howard M HM Sampson Hugh A HA Shreffler Wayne W Bacharier Leonard B LB Gergen Peter J PJ Gold Diane R DR Kattan Meyer M O'Connor George T GT Sandel Megan T MT Wood Robert A RA Bloomberg Gordon R GR

The Journal of allergy and clinical immunology 20170113 3

<h4>Background</h4>Disadvantaged urban children have high rates of allergic diseases and wheezing, which are diseases associated with type 2-biased immunity.<h4>Objective</h4>We sought to determine whether environmental exposures in early life influence cytokine responses that affect the development of recurrent wheezing illnesses and allergic sensitization.<h4>Methods</h4>A birth cohort of 560 urban families was recruited from neighborhoods with high rates of poverty, and 467 (83%) children wer ...[more]

PMID: 28089873

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Project description:ImportanceRhinovirus infection in early life, particularly with allergic sensitization, is associated with higher risks of developing recurrent wheeze and asthma. While emerging evidence links different rhinovirus species (eg, rhinovirus C) to a higher severity of infection and asthma exacerbation, to our knowledge, little is known about longitudinal associations of rhinovirus C infection during infancy with subsequent morbidities.ObjectiveTo examine the association of different viruses (respiratory syncytial virus [RSV], rhinovirus species) in bronchiolitis with risks of developing recurrent wheeze.Design, setting, and participantsThis multicenter prospective cohort study of infants younger than 1 year who were hospitalized for bronchiolitis was conducted at 17 hospitals across 14 US states during 3 consecutive fall to winter seasons (2011-2014).ExposuresMajor causative viruses of bronchiolitis, including RSV (reference group) and 3 rhinovirus species (rhinovirus A, B, and C).Main outcomes and measuresDevelopment of recurrent wheeze (as defined in national asthma guidelines) by age 3 years.ResultsThis analytic cohort comprised 716 infants who were hospitalized for RSV-only or rhinovirus bronchiolitis. The median age was 2.9 months (interquartile range, 1.6-3.8 months), 541 (76%) had bronchiolitis with RSV only, 85 (12%) had rhinovirus A, 12 (2%) had rhinovirus B, and 78 (11%) had rhinovirus C infection. Overall, 231 (32%) developed recurrent wheeze by age 3 years. In the multivariable Cox model, compared with infants with RSV-only infection, the risk of recurrent wheeze was not significantly different in those with rhinovirus A or B (rhinovirus A: hazard ratio [HR], 1.27; 95% CI, 0.86-1.88; rhinovirus B: HR, 1.39; 95% CI, 0.51-3.77; both P > .10). By contrast, infants with rhinovirus C had a significantly higher risk (HR, 1.58; 95% CI, 1.08-2.32). There was a significant interaction between virus groups and IgE sensitization on the risk of recurrent wheeze (P for interaction < .01). Only infants with both rhinovirus C infection and IgE sensitization (to food or aeroallergens) during infancy had significantly higher risks of recurrent wheeze (HR, 3.03; 95% CI, 1.20-7.61). Furthermore, compared with RSV-only, rhinovirus C infection with IgE sensitization was associated with significantly higher risks of recurrent wheeze with subsequent development of asthma at age 4 years (HR, 4.06; 95% CI, 1.17-14.1).Conclusions and relevanceThis multicenter cohort study of infants hospitalized for bronchiolitis demonstrated between-virus differences in the risk of developing recurrent wheeze. Infants with rhinovirus C infection, along with IgE sensitization, had the highest risk. This finding was driven by the association with a subtype of recurrent wheeze: children with subsequent development of asthma.

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

Publications

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

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