title: Predictors of symptoms are different from predictors of severe exacerbations from asthma in children.
abstract: BACKGROUND
  Asthma therapy is typically prescribed and titrated based on patient or parent self-report of symptoms. No longitudinal studies have assessed the relationship between symptoms and severe asthma exacerbations in children. The goal of our study was (1) to assess the association of asthma symptoms with severe asthma exacerbations and (2) to compare predictors of persistent asthma symptoms and predictors of severe asthma exacerbations.
  
  
  METHODS
  The Childhood Asthma Management Program was a multicenter clinical trial of 1,041 children randomized to receive budesonide, nedocromil, or placebo (as-needed β-agonist). We conducted a post hoc analysis of diary cards that were completed by subjects on a daily basis to categorize subjects as having persistent vs intermittent symptoms. We defined a severe asthma exacerbation as an episode requiring ≥ 3 days use of oral corticosteroids, hospitalization, or ED visit due to asthma based on self-report at study visits every 4 months.
  
  
  RESULTS
  While accounting for longitudinal measures, having persistent symptoms from asthma was significantly associated with having severe asthma exacerbations. Predictors of having persistent symptoms compared with intermittent symptoms included not being treated with inhaled corticosteroids, lower FEV(1)/FVC ratio, and a lower natural logarithm of provocative concentration of methacholine producing a 20% decline in FEV(1) (lnPC(20)). Predictors of having one or more severe asthma exacerbations included younger age, history of hospitalization or ED visit in the prior year, ≥ 3 days use of oral corticosteroids in the prior 3 months, lower FEV(1)/FVC ratio, lower lnPC(20), and higher logarithm to the base 10 eosinophil count; treatment with inhaled corticosteroids was predictive of having no severe asthma exacerbations.
  
  
  CONCLUSIONS
  Patients with persistent symptoms from asthma were more likely to experience severe asthma exacerbations. Nevertheless, demographic and laboratory predictors of having persistent symptoms are different from predictors of severe asthma exacerbations. Although symptoms and exacerbations are closely related, their predictors are different. The current focus of the National Asthma Education and Prevention Program guidelines on the two separate domains of asthma control, impairment and risk, are supported by our analysis.
authors.affiliation: Center for Child Health Care Studies, Department of Population Medicine, Harvard Pilgrim Health Care Institute and Harvard Medical School, Boston, MA; Department of Pediatrics, Children's Hospital, Boston, MA; Harvard Medical School, Department of Medicine, Brigham and Women's Hospital, Boston, MA. Electronic address: ann.wu@childrens.harvard.edu.
authors.forename: Ann Chen
authors.initials: AC
authors.lastname: Wu
authors.affiliation: Harvard Medical School, Department of Medicine, Brigham and Women's Hospital, Boston, MA; Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, MA; Center for Genomic Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA.
authors.forename: Kelan
authors.initials: K
authors.lastname: Tantisira
authors.affiliation: Center for Child Health Care Studies, Department of Population Medicine, Harvard Pilgrim Health Care Institute and Harvard Medical School, Boston, MA; Harvard Medical School, Department of Medicine, Brigham and Women's Hospital, Boston, MA.
authors.forename: Lingling
authors.initials: L
authors.lastname: Li
authors.affiliation: Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, MA.
authors.forename: Brooke
authors.initials: B
authors.lastname: Schuemann
authors.affiliation: Harvard Medical School, Department of Medicine, Brigham and Women's Hospital, Boston, MA; Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, MA; Center for Genomic Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA.
authors.forename: Scott T
authors.initials: ST
authors.lastname: Weiss
authors.affiliation: Harvard Medical School, Department of Medicine, Brigham and Women's Hospital, Boston, MA; Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, MA.
authors.forename: Anne L
authors.initials: AL
authors.lastname: Fuhlbrigge
mesh_terms: D000280:Administration, Inhalation; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage; D001249:Asthma / Q000175:diagnosis* / Q000188:drug therapy / Q000503:physiopathology; D016084:Bronchoconstriction / Q000187:drug effects*; D001993:Bronchodilator Agents / Q000008:administration & dosage; D019819:Budesonide / Q000008:administration & dosage*; D002648:Child; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D017835:Nedocromil / Q000008:administration & dosage*; D011379:Prognosis; D012008:Recurrence; D012720:Severity of Illness Index; D013997:Time Factors
chemical_list: D018927:Anti-Asthmatic Agents; D001993:Bronchodilator Agents; D017835:Nedocromil; D019819:Budesonide