Defining Molecular Endotypes of Respiratory Allergy, Asthma in Urban Children

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Boy-asthma-inhaler_G_85775459
High-risk children living in urban neighborhoods in the United States develop specific phenotypes of respiratory health vs disease, which may link environmental exposures in early life to childhood allergic sensitization and asthma.

High-risk children living in urban neighborhoods in the United States develop specific phenotypes of respiratory health vs disease, which may link environmental exposures in early life to childhood allergic sensitization and asthma, according to study results published in The Journal of Allergy and Clinical Immunology. In addition, certain airway gene expression patterns highlight how specific molecular pathways affect respiratory phenotypes, such as allergic and nonallergic asthma. 

In a previous analysis, a team of investigators identified a number of phenotypes of wheezing, atopy, and respiratory health in children who participated in the Urban Environment and Childhood Asthma (URECA) birth cohort study. In the current analysis, the investigators further extended phenotype definitions to include wheeze, allergen-specific immunoglobulin E (IgE), and lung function data for children from birth to 10 years of age.

The study authors aimed to characterize specific respiratory phenotypes related to health and disease in this demographic, and to determine the correlation with early-life exposures, as well as molecular patterns of gene expressions in nasal epithelial cells that affect clinical disease.

A total of 442 children the URECA cohort were included in the analysis. Children were predominantly from minority groups (72% Black, 20% Hispanic) with high poverty rates. At age 10, the overall prevalence of asthma as 29.7%, which was significantly linked to a history of maternal asthma and response to bronchodilator.  

A total of 6 respiratory phenotypes were identified: low wheeze-low atopy (LW-LA; n=95), transient wheeze-low atopy (TW-LA; n=75), medium wheeze-low atopy (MW-LA; n=76), low wheeze-high atopy (LW-HA; n=86), medium wheeze-high atopy (MW-HA; n=54), high wheeze-high atopy-low lung function (HW-HA-LF; n=56).

Of the phenotypes, children in the HW-HA-LF group had the greatest respiratory morbidity, and the highest prevalence of asthma at age 10. In addition, members of this group had lower exposure to common allergens in early life but had high exposures to ergosterol in house dust.

Serum IgE was most elevated in the 3 phenotypes with high atopy. In addition, there was an increase in the expression of type 2 inflammation gene module in nasal epithelial samples of all groups with high atopy; however, an epithelium IL-13 response module was impaired lung function was closely related to impaired lung function, and the MUC5AC hypersecretion module was distinctly upregulated in children in the HW-HA-LF group. Lastly, altered expression of modules of epithelial integrity, epithelial injury, and antioxidant pathways were present in the MW-LA group.

“These findings suggest how the children at risk for persistent asthma endotypes, even among a population already with significant risk of asthma based on demographics, could be recognized early in life from clinical and molecular data,” the authors noted. “In addition, the results of this study suggest pathways that could be targeted in studies to prevent specific asthma endotypes.”

Disclosure: Several authors declared affiliations with the pharmaceutical industry. Please refer to the original article for a full list of authors’ disclosures.

Reference

Altman MC, Calatroni A, Ramratnam S, et al; for the Inner City Asthma Consortium. Endotype of allergic asthma with airway obstruction in urban children. J Allergy Clin Immunol. Published online March 10, 2021. doi:10.1016/j.jaci.2021.02.040