Asthma affects approximately 1 in 10 children and the prevalence of asthma has dramatically increased within a generation, strongly implicating lifestyle and/or environmental causes, explain the authors of a recent study. Black and Hispanic children growing up in disadvantaged urban neighborhoods, they add, have the highest rates of asthma and related morbidity in the United States.

“While medications and environmental and lifestyle modifications can help to control asthma, a cure for asthma remains elusive,” they write. “Several birth cohorts have identified different phenotypes of childhood asthma, but incomplete understanding of the molecular mechanisms underpinning these phenotypes and corresponding risk factors has hampered efforts towards asthma prevention.”

For a paper published in the Journal of Allergy and Clinical Immunology, the researchers aimed 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. “Clinical observations in urban children can be used to identify respiratory allergy and asthma phenotypes,” they write. “These phenotypes can be linked to environmental exposures in early life, and molecular pathways through analysis of nasal epithelial cells.”

The study consisted of 442 high-risk urban children who had repeated wheezing, allergen-specific IgE, and lung through the age of 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.

High Exposure to Ergosterol in House Dust

Of the six identified respiratory phenotypes, a high-wheeze, high-atopy, low-lung function (HW-HA-LF) group had the greatest respiratory morbidity, the researchers found.  “In early life, this group had low exposure to common allergens and high exposure to ergosterol in house dust,” they write. “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 closed with impaired lung function, and MUC5AC (a gene that has been linked to mucus hypersecretion in the respiratory tract).” In contrast, they note, 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,” the authors write. “Moreover, unique patterns of airway gene expression demonstrate how specific molecular pathways underlie distinct respiratory phenotypes, including allergic and non-allergic asthma.”

 Children at Risk Could Be Recognized Early in Life

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. In addition, the results of this study suggest pathways that could be targeted in studies to prevent specific asthma endotypes.

“Most notably, children developing a HW-HA-LF (T2-high) endotype that can be identified early in life would be excellent candidates for interventions to interrupt mucus secretion pathways or to boost mucosal immune responses in the airway in order to preserve lung function development,” the authors note. “Alternatively, the MW-LA (T2-low) endotype might be prevented by treatments (to be developed) aimed at improving airway epithelial cell barrier function and/or the response to oxidative stress.”