title: Differentiating asthma phenotypes in young adults through polyclonal cytokine profiles.
abstract: 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 (TH) 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).
  
  
  CONCLUSIONS
  As expected, young adults with a history of an allergic asthma phenotype exhibited a TH2-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.
authors.affiliation: Division of Allergy and Immunology, Department of Internal Medicine, Henry Ford Hospital, Detroit, Michigan. Electronic address: ezoratt1@hfhs.org.
authors.forename: Edward
authors.initials: E
authors.lastname: Zoratti
authors.affiliation: Department of Public Health Sciences, Henry Ford Hospital, Detroit, Michigan.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Havstad
authors.affiliation: Department of Public Health Sciences, Henry Ford Hospital, Detroit, Michigan.
authors.forename: Ganesa
authors.initials: G
authors.lastname: Wegienka
authors.affiliation: Department of Public Health Sciences, Henry Ford Hospital, Detroit, Michigan.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Nicholas
authors.affiliation: Department of Public Health Sciences, Henry Ford Hospital, Detroit, Michigan.
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Bobbitt
authors.affiliation: Department of Public Health Sciences, Henry Ford Hospital, Detroit, Michigan.
authors.forename: Kimberley J
authors.initials: KJ
authors.lastname: Woodcroft
authors.affiliation: Division of Allergy and Immunology, Department of Pediatrics, Georgia Regents University, Augusta, Georgia.
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Ownby
authors.affiliation: Department of Public Health Sciences, Henry Ford Hospital, Detroit, Michigan.
authors.forename: Christine Cole
authors.initials: CC
authors.lastname: Johnson
mesh_terms: D000293:Adolescent; D001249:Asthma / Q000145:classification* / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology; D016022:Case-Control Studies; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology*; D005260:Female; D006801:Humans; D008297:Male; D016017:Odds Ratio; D061251:Primary Cell Culture; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D058408:Th1-Th2 Balance / Q000187:drug effects; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D055815:Young Adult
chemical_list: D016207:Cytokines; D013755:Tetradecanoylphorbol Acetate