title: Clinical burden and predictors of asthma exacerbations in patients on guideline-based steps 4-6 asthma therapy in the TENOR cohort.
abstract: BACKGROUND
  Patients with severe or difficult-to-treat asthma on guideline-recommended Steps 4/5/6 therapy have not previously been described.
  
  
  OBJECTIVE
  To characterize patients with severe or difficult-to-treat asthma on Steps 4/5/6 therapy and assess predictors of future asthma exacerbations.
  
  
  METHODS
  Patients ages ≥12 years with baseline and month 12 medication data were assigned to Steps 4/5/6 care levels from the 2007 National Heart, Lung, and Blood Institute guidelines. Demographic, atopic, and clinical characteristics at baseline and month 12 were assessed by using descriptive statistics. Asthma-related quality of life was assessed by using the Mini Asthma Quality of Life Questionnaire, and work and activity impairment was assessed by the Work Productivity and Activity Impairment Questionnaire-Asthma. Odds ratios (OR) and 95% CI for asthma exacerbation risk at month 12 were generated by using multivariable logistic regression.
  
  
  RESULTS
  A total of 1186 patients were included. More than two-thirds of the patients (67.4%) were on ≥3 long-term controllers, and 55.1% were considered difficult to treat due to frequent exacerbations. Patients reported low asthma-related quality of life scores and considerable impairment in overall work and daily activity (21.4% and 32.1%, respectively). After adjustment for covariates, exacerbation history (hospitalization, OR 6.27 [95% CI, 3.61-10.88]; emergency department visit, OR 3.84 [95% CI, 2.50-5.91]; corticosteroid burst, OR 2.89 [95% CI, 2.18-3.82]) and very poorly controlled asthma (OR 1.95 [95% CI, 1.41-2.71] vs not well controlled) were independently associated with risk of a future exacerbation (all P < .001).
  
  
  CONCLUSIONS
  Despite multiple long-term controller medications, patients with severe or difficult-to-treat asthma on Steps 4/5/6 therapy present with significant clinical burden and risk of future asthma exacerbations.
authors.affiliation: Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas. Electronic address: wjcalhou@utmb.edu.
authors.forename: William J
authors.initials: WJ
authors.lastname: Calhoun
authors.affiliation: Genentech, Inc., South San Francisco, Calif.
authors.forename: Tmirah
authors.initials: T
authors.lastname: Haselkorn
authors.affiliation: ICON Clinical Research, San Francisco, Calif.
authors.forename: David R
authors.initials: DR
authors.lastname: Mink
authors.affiliation: ICON Clinical Research, San Francisco, Calif.
authors.forename: Dave P
authors.initials: DP
authors.lastname: Miller
authors.affiliation: Genentech, Inc., South San Francisco, Calif.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Dorenbaum
authors.affiliation: Department of Allergy, Kaiser Permanente Southern California, San Diego, Calif.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Zeiger
mesh_terms: D000328:Adult; D000368:Aged; D001249:Asthma / Q000523:psychology / Q000628:therapy*; D015331:Cohort Studies; D017281:Cost of Illness; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D017410:Practice Guidelines as Topic; D011446:Prospective Studies; D011788:Quality of Life
keywords: Anti-asthmatic agents; Asthma guidelines; Asthma therapy; Exacerbations; Severe or difficult-to-treat asthma; Uncontrolled asthma