title: Biomarker Profiles in Asthma With High vs Low Airway Reversibility and Poor Disease Control.
abstract: BACKGROUND
  High bronchodilator reversibility in adult asthma is associated with distinct clinical characteristics. This analysis compares lung function, biomarker profiles, and disease control in patients with high reversibility (HR) and low reversibility (LR) asthma.
  
  
  METHODS
  A retrospective analysis was performed with data from two completed clinical trials of similar design. Patients were divided into HR and LR subgroups based on their response to bronchodilators (HR = ΔFEV1 postbronchodilator ≥ 20%). Blood eosinophil count, serum IgE level, and fraction of exhaled nitric oxide concentration, biomarkers commonly used to stratify patients into T-helper (Th)-2-high vs Th2-low phenotypes, were measured in patients with not well controlled (1.5 ≤ Asthma Control Questionnaire [ACQ] ≤ 2.143) and very poorly controlled (ACQ > 2.143) disease.
  
  
  RESULTS
  The majority of patients in the HR and LR subgroups displayed Th2-low biomarker profiles and very poor disease control. HR was more frequently associated with Th2-high biomarker profiles (40.1% vs 29.4%, P = .006), lower lung function (FEV1, 63.5 ± 7.7% predicted vs 67.9 ± 8.4% predicted; P < .001), and atopy (93.7% vs 86.5%, P = .005).
  
  
  CONCLUSIONS
  HR is a physiologic indicator of reduced lung function and is more often associated with elevations in Th2 biomarkers than LR in moderate to severe asthma. However, the majority of patients with HR and LR asthma in this analysis had a Th2-low biomarker profile. Moreover, a Th2-high biomarker profile was not associated with worse disease control.
authors.affiliation: University of Wisconsin, Madison, WI.
authors.forename: William W
authors.initials: WW
authors.lastname: Busse
authors.affiliation: Clinical and Experimental Sciences, Facility of Medicine, University of Southhampton, Highfield, Southhampton, England.
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Holgate
authors.affiliation: University of Pittsburgh Medical Center, Pittsburgh, PA.
authors.forename: Sally W
authors.initials: SW
authors.lastname: Wenzel
authors.affiliation: Amgen Inc, Thousand Oaks, CA.
authors.forename: Paul
authors.initials: P
authors.lastname: Klekotka
authors.affiliation: Amgen Inc, Thousand Oaks, CA.
authors.forename: Yun
authors.initials: Y
authors.lastname: Chon
authors.affiliation: Amgen Inc, Thousand Oaks, CA.
authors.forename: JingYuan
authors.initials: J
authors.lastname: Feng
authors.affiliation: Amgen Inc, Thousand Oaks, CA. Electronic address: ingenito@amgen.com.
authors.forename: Edward P
authors.initials: EP
authors.lastname: Ingenito
authors.affiliation: Amgen Inc, Thousand Oaks, CA.
authors.forename: Ajay
authors.initials: A
authors.lastname: Nirula
mesh_terms: D000328:Adult; D001249:Asthma / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D001944:Breath Tests / Q000379:methods; D001993:Bronchodilator Agents / Q000494:pharmacology*; D016903:Drug Monitoring / Q000379:methods; D004804:Eosinophils / Q000276:immunology*; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood*; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000032:analysis*; D015230:Prostaglandin D2 / Q000037:antagonists & inhibitors; D012129:Respiratory Function Tests / Q000379:methods; D012137:Respiratory System / Q000187:drug effects / Q000276:immunology; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013223:Statistics as Topic; D018418:Th2 Cells / Q000276:immunology*; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D001993:Bronchodilator Agents; D005938:Glucocorticoids; D009569:Nitric Oxide; D007073:Immunoglobulin E; D015230:Prostaglandin D2