TY - JOUR
T1 - Endotypes of difficult-to-control asthma in inner-city African American children
AU - Brown, K. R.
AU - Krouse, R. Z.
AU - Calatroni, A.
AU - Visness, C. M.
AU - Sivaprasad, U.
AU - Kercsmar, C. M.
AU - Matsui, E. C.
AU - West, J. B.
AU - Makhija, M. M.
AU - Gill, M. A.
AU - Kim, H.
AU - Kattan, M.
AU - Pillai, D.
AU - Gern, J. E.
AU - Busse, W. W.
AU - Togias, A.
AU - Liu, A. H.
AU - Hershey, G. K.Khurana
N1 - Funding Information:
This project has been funded with Federal funds from the National Institute of Allergy and Infectious Diseases (www.niaid.nih.gov), National Institutes of Health (www.nih.gov), Department of Health and Human Services (www.hhs.gov), under contract numbers HHSN272200900052C and HHSN272201000052I, 1UM1AI114271-01 and UM2AI117870. Additional support was provided by the National Center for Research Resources (www. ncrr.nih.gov), and National Center for Advancing Translational Sciences (https://ncats.nih.gov), National Institutes of Health, under grants NCRR/ NIH UL1TR000451, UL1RR025780, UL1TR000075, NCATS/NIH UL1TR001079, NCATS/NIH UL1TR000154, UL1TR001082, UL1TR000077-04, UL1TR000040, UL1TR000150, and UL1TR001105. Glaxo SmithKline (GSK) (www. gsk.com) provided Ventolin, Flovent, Advair and Flonase under a clinical trial agreement with NIH NIAID. This research was supported in part by the Cincinnati Children?s Research Foundation and the Cincinnati Biobank, as well as the Better Outcomes for Children Biorepository. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
PY - 2017/7
Y1 - 2017/7
N2 - African Americans have higher rates of asthma prevalence, morbidity, and mortality in comparison with other racial groups. We sought to characterize endotypes of childhood asthma severity in African American patients in an inner-city pediatric asthma population. Baseline blood neutrophils, blood eosinophils, and 38 serum cytokine levels were measured in a sample of 235 asthmatic children (6–17 years) enrolled in the NIAID (National Institute of Allergy and Infectious Diseases)-sponsored Asthma Phenotypes in the Inner City (APIC) study (ICAC (Inner City Asthma Consortium)-19). Cytokines were quantified using a MILLIPLEX panel and analyzed on a Luminex analyzer. Patients were classified as Easy-to-Control or Difficult-to-Control based on the required dose of controller medications over one year of prospective management. A multivariate variable selection procedure was used to select cytokines associated with Difficult-to-Control versus Easy-to-Control asthma, adjusting for age, sex, blood eosinophils, and blood neutrophils. In inner-city African American children, 12 cytokines were significant predictors of Difficult-to-Control asthma (n = 235). CXCL-1, IL-5, 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. Using likelihood ratio testing, it was observed that in addition to blood eosinophils and neutrophils, serum cytokines improved the fit of the model. In an inner-city pediatric population, serum cytokines significantly contributed to the definition of Difficult-to-Control asthma endotypes in African American children. Mixed responses characterized by TH2 (IL-5) and TH17-associated cytokines were associated with Difficult-to-Control asthma. Collectively, these data may contribute to risk stratification of Difficult-to-Control asthma in the African American population.
AB - African Americans have higher rates of asthma prevalence, morbidity, and mortality in comparison with other racial groups. We sought to characterize endotypes of childhood asthma severity in African American patients in an inner-city pediatric asthma population. Baseline blood neutrophils, blood eosinophils, and 38 serum cytokine levels were measured in a sample of 235 asthmatic children (6–17 years) enrolled in the NIAID (National Institute of Allergy and Infectious Diseases)-sponsored Asthma Phenotypes in the Inner City (APIC) study (ICAC (Inner City Asthma Consortium)-19). Cytokines were quantified using a MILLIPLEX panel and analyzed on a Luminex analyzer. Patients were classified as Easy-to-Control or Difficult-to-Control based on the required dose of controller medications over one year of prospective management. A multivariate variable selection procedure was used to select cytokines associated with Difficult-to-Control versus Easy-to-Control asthma, adjusting for age, sex, blood eosinophils, and blood neutrophils. In inner-city African American children, 12 cytokines were significant predictors of Difficult-to-Control asthma (n = 235). CXCL-1, IL-5, 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. Using likelihood ratio testing, it was observed that in addition to blood eosinophils and neutrophils, serum cytokines improved the fit of the model. In an inner-city pediatric population, serum cytokines significantly contributed to the definition of Difficult-to-Control asthma endotypes in African American children. Mixed responses characterized by TH2 (IL-5) and TH17-associated cytokines were associated with Difficult-to-Control asthma. Collectively, these data may contribute to risk stratification of Difficult-to-Control asthma in the African American population.
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U2 - 10.1371/journal.pone.0180778
DO - 10.1371/journal.pone.0180778
M3 - Article
C2 - 28686637
AN - SCOPUS:85022335990
VL - 12
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 7
M1 - e0180778
ER -