Black and Hispanic children growing up in disadvantaged urban neighborhoods have the highest rates of asthma and related morbidity in the United States.
To identify specific respiratory phenotypes of health and disease in this population, associations with early-life exposures, and molecular patterns of gene expression in nasal epithelial cells that underlie clinical disease.
The study population consisted of 442 high-risk urban children who had repeated assessments of wheezing, allergen-specific IgE, and lung function through age 10 years. Phenotypes were identified by developing temporal trajectories for these data, and then compared to early life exposures and patterns of nasal epithelial gene expression at age 11.
Of the 6 identified respiratory phenotypes, a high-wheeze high-atopy low-lung-function (HW-HA-LF) group had the greatest respiratory morbidity. In early life, this group had low exposure to common allergens and high exposure to ergosterol in house dust. While all high atopy groups were associated with increased expression of a type-2 inflammation gene module in nasal epithelial samples, an epithelium IL-13 response module tracked closely with impaired lung function, and a MUC5AC hypersecretion module was uniquely upregulated in HW-HA-LF. In contrast, a medium-wheeze low-atopy (MW-LA) group showed altered expression of modules of epithelial integrity, epithelial injury, and antioxidant pathways.
In the first decade of life, high-risk urban children develop distinct phenotypes of respiratory health versus disease that link early-life environmental exposures to childhood allergic sensitization and asthma. Moreover, unique patterns of airway gene expression demonstrate how specific molecular pathways underlie distinct respiratory phenotypes, including allergic and non-allergic asthma.

Copyright © 2021. Published by Elsevier Inc.

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