Respiratory phenotypes in at-risk urban youth – risk factors and mechanisms

Published: March 10, 2021

Asthma affects approximately one in ten children and the prevalence of asthma has dramatically increased within a generation. While recent advances in biological interventions have helped to control asthma, a cure for asthma remains elusive. Several birth cohorts have identified different varieties (“phenotypes”) of childhood asthma, but not knowing the risk factors and causes for these phenotypes has hampered efforts towards asthma prevention. The close relationships between respiratory allergies and viral wheezing illnesses in early life with the development of asthma suggest that impaired immune development in the airway mucosa, at the site of allergic inflammation, may be closely related to pathogenic mechanisms of childhood asthma.

In a recently published study in The Journal of Allergy and Clinical Immunology (JACI), Altman et al. used 10 years of longitudinal information to identify respiratory phenotypes of minority children growing up in disadvantaged urban neighborhoods in the Urban Environment and Childhood Asthma (URECA) birth cohort study. Small samples obtained by brushing the lining of the nose were analyzed to determine gene expression profiles and then compare them to the respiratory phenotypes and early-life environmental exposure data.

Six distinct respiratory phenotypes were identified among 442 children based on patterns of wheezing, allergy, and lung function in the first 10 years of life. A high-wheeze, high-allergy, low-lung-function (HW-HA-LF) group was the most affected by asthma. In early life, this group had low exposure to common allergens and high exposure to fungi as measured in house dust. A set of genes related to mucus hypersecretion was uniquely upregulated in this HW-HA-LF group compared to all others, and another set of genes indicative of an epithelium response to the cytokine IL-13 was associated with the degree of impaired lung function among highly allergic children. In contrast, a medium-wheeze, low-allergy (MW-LA) group had an altered expression of genes related to epithelial integrity, epithelial injury, and antioxidant pathways.

In summary, following children from birth through early school-age enabled identification of different forms of asthma, each with a unique set of corresponding early life environmental exposures and patterns of nasal cell gene expression. These findings suggest that urban children who are in the process of developing asthma could be identified early in life from clinical information and patterns of nasal cell gene expression. In addition, the results suggest strategies to prevent specific varieties of childhood asthma.

The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.

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