Identification of Pathways to Asthma Severity in Inner-City Children

Rationale: Pathways describing how host and environmental factors lead to asthma severity have not been well defined in inner-city children.

Methods: Nine sites in the NIAID-funded Inner City Asthma Consortium enrolled 717 children aged 6-17 years with asthma. Subjects were evaluated every two months for one year, with adjustments in asthma and rhinitis management made at each visit. An overall measure of asthma severity was defined using longitudinal measures of asthma symptoms, exacerbations and treatment. Twenty-two other variables measured at baseline or longitudinally were used to define 8 domains: allergic sensitization, blood eosinophils and exhaled nitric oxide (Eos/FeNO), lung function, Vitamin D, stress, obesity, exposure to tobacco smoke (ETS), and rhinitis severity. A conceptual model of how these domains act through different pathways to explain asthma severity was tested using structural equation models.

Results: This analysis included 579 participants with rhinitis who completed at least 4 follow-up visits. In an allergy pathway to asthma severity, allergic sensitization strongly affected Eos/FeNO (p<0.001); and Eos/FeNO was indirectly associated with asthma severity via lung function and rhinitis severity (p<0.001). Additionally, ETS, lung function and rhinitis severity were directly associated with asthma severity (p<0.004). ETS was also indirectly associated with asthma severity via lung function (p<0.001). Our complete pathways model accounted for 50.9% of the variance in asthma severity.

Conclusions: This is the first study to identify specific pathways and their relative contributions to asthma severity in inner-city children with asthma and rhinitis, providing a strategic blueprint of pathogenesis and prioritized targets for preventive interventions.