Endotypes of Difficult-to-Control Asthma in Inner City Children Differ By Race

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Rationale

Blood neutrophils, eosinophils, and serum cytokine levels were assessed in an inner-city pediatric asthmatic population to identify endotypes of childhood asthma severity. We hypothesized that in addition to blood neutrophils and eosinophils, serum cytokines would significantly contribute to the definition of Difficult-to-Control asthma endotypes in African American and non-African American patients.

Methods

Blood neutrophils, blood eosinophils, and 38 serum cytokine levels determined by luminex assay were measured in a sample of 365 asthmatic children (6-17 years) enrolled in the Asthma Phenotypes in the Inner City study. Patients were classified as Easy-to-Control or Difficult-to-Control based on their dose of controller medication over one year. A multivariate variable selection procedure, stratified by race, was used to select cytokines associated with Difficult-to-Control versus

Results

In African Americans, 11 cytokines contributed to asthma severity (n=235), while only IL-5 was significant in non-African Americans (n=130). In African Americans, GRO, IL-8, and IL-17A were positively associated with Difficult-to-Control asthma, while IL-4 and IL-13 were positively associated with Easy-to-Control asthma.

Conclusions

In an inner city pediatric population, serum cytokines significantly contributed to the definition of Difficult-to-Control asthma endotypes in African Americans, and to a lesser extent in non-African Americans, suggesting that inflammatory responses may differ by race. Mixed responses characterized by Th2 and Th17 cytokines were most associated with asthma severity in African Americans. Accordingly, treatment regimens that specifically target inflammatory pathways characteristic of asthma

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