Childhood Asthma Risk Assessed Using Respiratory Phenotypes

In inner city children, patterns of wheezing, lung function, and allergic sensitization identified 5 respiratory phenotypes that can help to elucidate the contributions of environmental risk factors to distinct forms of childhood asthma, according to the findings from data collected prospectively from children in the Urban Environment and Childhood Asthma (URECA) birth cohort through 7 years of age. The results of the study were published in the American Journal of Respiratory and Critical Care Medicine.¹

Investigators sought to define respiratory phenotypes in inner city children and their relationships with early-life environmental exposures. They collected data prospectively from a total of 442 children in the URECA birth cohort. Maternal questionnaires were administered prenatally, and postnatal child health questionnaires were administered every 3 months until age 7 years. The data collected were reflective of such symptoms as wheezing, aeroallergen sensitization, pulmonary function, and body mass index.

Allergen-specific immunoglobulin E (IgE) levels for foods (milk, egg, and peanut) and German cockroach were measured at the ages of 1, 2, 3, 5, and 7 years; allergen-specific IgE levels for house dust mites, dog, cat, mouse, and Alternaria were measured at ages 2, 3, 5, and 7 years. Skin prick testing for 14 common aeroallergens was performed at ages 3, 5, and 7 years.^2,3 Positive tests were defined as the presence of a wheal ≥3 mm larger than the saline control on skin prick testing or specific IgE ≥0.35 kU/L.

Overall, 5 phenotypes were identified and differentiated mainly by patterns of wheezing and aeroallergen sensitization: low wheeze-low atopy, low wheeze-high atopy, transient wheeze-low atopy, high wheeze-low atopy, and high wheeze-high atopy. The presence of asthma was reported most often in the high-wheeze phenotypes, with the greatest respiratory morbidity observed in those children with frequent wheezing and allergic sensitization. Multiple early-life exposures, including maternal stress and depression, antenatal environmental tobacco smoke, and indoor allergens and house dust microbiomes, were differentially associated with specific phenotypes (P <.05 for all).

Prenatal smoke exposure, maternal stress, and depression were highest in the high wheeze-low atopy phenotype. In contrast, the high wheeze-high atopy phenotype was linked to low household microbial richness and diversity. Early-life aeroallergen exposure was lowest among high-wheeze phenotypes.

The investigators concluded that early-life exposure to stress, depression, tobacco smoke, and indoor allergens and microbes is differentially associated with specific phenotypes. The findings of the current study advance the identification of asthma endotypes, which may help to inform the development of mechanism-based strategies for the prevention of childhood asthma.

References

1. Bacharier LB, Beigelman A, Calatroni A, et al; NIAID sponsored Inner-City Asthma Consortium. Longitudinal phenotypes of respiratory health in a high-risk urban birth cohort [published online August 4, 2018]. Am J Respir Crit Care Med. doi:10.1164/rccm.201801-0190OC
2. O’Connor GT, Lynch SV, Bloomberg GR, et al. Early-life home environment and risk of asthma among inner-city children. J Allergy Clin Immunol. 2018;141(4):1468-1475.
3. Gern JE, Visness CM, Gergen PJ, et al. The Urban Environment and Childhood Asthma (URECA) birth cohort study: design, methods, and study population. BMC Pulm Med. 2009;9:17.