TY - JOUR
T1 - Differentiating asthma phenotypes in young adults through polyclonal cytokine profiles
AU - Zoratti, Edward
AU - Havstad, Suzanne
AU - Wegienka, Ganesa
AU - Nicholas, Charlotte
AU - Bobbitt, Kevin R.
AU - Woodcroft, Kimberley J.
AU - Ownby, Dennis R.
AU - Johnson, Christine Cole
N1 - Funding Information:
Funding: This work was funded by the Fund for Henry Ford Hospital and the National Institute of Allergy and Infectious Diseases (grant R01AI051598 ).
PY - 2014/7
Y1 - 2014/7
N2 - Background Recent research has emphasized the need to better discriminate asthma phenotypes and consider underlying mechanistic endotypes in epidemiologic and clinical studies. Although allergic asthma and nonallergic asthma are frequently combined into 1 disease category in observational research and clinical trials, few studies have investigated the extent to which these 2 separate phenotypes are associated with distinct cytokine immunologic profiles in a representative young adult population. Objective To investigate the cytokine production-based endotypes underlying the clinical phenotypes of allergic and nonallergic asthma in a population-based birth cohort evaluated as young adults. Methods Participants included 18- to 21-year-old members (n = 540) of a suburban Detroit birth cohort study, the Childhood Allergy Study. Phorbol myristate acetate-stimulated whole blood interleukin (IL)-4, IL-5, IL-10, IL-12, IL-13, IL-17A, IL-17F, IL-22, and interferon-γ secretory responses were analyzed for associations comparing participants with allergic vs nonallergic asthma phenotypes with those without asthma. Results T-helper cell type (T H) 2-polarized responses, measured as higher mean IL-5 and IL-13 secretions and lower ratios of interferon-γ and IL-12 to 3 TH2 cytokines (IL-4, IL-5, or IL-13), were observed only in participants with allergic asthma. Nonallergic asthma was associated with TH1-polarized responses, including higher adjusted interferon-γ secretion compared with participants with allergic asthma and, surprisingly, those without asthma (odds ratio 2.5, confidence interval 1.2-5.1, P <.01). Conclusion As expected, young adults with a history of an allergic asthma phenotype exhibited a T H2-polarized cytokine response after polyclonal stimulation. However, TH1 polarization was observed in patients with a history of nonallergic asthma. Allergic and nonallergic asthma are associated with etiologically distinct immune endotypes, underscoring the importance of discriminating these endotypes in research analyses and clinical management.
AB - Background Recent research has emphasized the need to better discriminate asthma phenotypes and consider underlying mechanistic endotypes in epidemiologic and clinical studies. Although allergic asthma and nonallergic asthma are frequently combined into 1 disease category in observational research and clinical trials, few studies have investigated the extent to which these 2 separate phenotypes are associated with distinct cytokine immunologic profiles in a representative young adult population. Objective To investigate the cytokine production-based endotypes underlying the clinical phenotypes of allergic and nonallergic asthma in a population-based birth cohort evaluated as young adults. Methods Participants included 18- to 21-year-old members (n = 540) of a suburban Detroit birth cohort study, the Childhood Allergy Study. Phorbol myristate acetate-stimulated whole blood interleukin (IL)-4, IL-5, IL-10, IL-12, IL-13, IL-17A, IL-17F, IL-22, and interferon-γ secretory responses were analyzed for associations comparing participants with allergic vs nonallergic asthma phenotypes with those without asthma. Results T-helper cell type (T H) 2-polarized responses, measured as higher mean IL-5 and IL-13 secretions and lower ratios of interferon-γ and IL-12 to 3 TH2 cytokines (IL-4, IL-5, or IL-13), were observed only in participants with allergic asthma. Nonallergic asthma was associated with TH1-polarized responses, including higher adjusted interferon-γ secretion compared with participants with allergic asthma and, surprisingly, those without asthma (odds ratio 2.5, confidence interval 1.2-5.1, P <.01). Conclusion As expected, young adults with a history of an allergic asthma phenotype exhibited a T H2-polarized cytokine response after polyclonal stimulation. However, TH1 polarization was observed in patients with a history of nonallergic asthma. Allergic and nonallergic asthma are associated with etiologically distinct immune endotypes, underscoring the importance of discriminating these endotypes in research analyses and clinical management.
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U2 - 10.1016/j.anai.2014.04.013
DO - 10.1016/j.anai.2014.04.013
M3 - Article
C2 - 24801891
AN - SCOPUS:84903149322
SN - 1081-1206
VL - 113
SP - 25
EP - 30
JO - Annals of Allergy, Asthma and Immunology
JF - Annals of Allergy, Asthma and Immunology
IS - 1
ER -