title: Predictors of severe exacerbations, poor asthma control, and β-agonist overuse for patients with asthma.
abstract: BACKGROUND
  Predictors of asthma exacerbations, poor asthma control, or extreme β-agonist overuse may be of clinical utility in the management of asthma.
  
  
  OBJECTIVE
  To investigate characteristics that predict subsequent adverse outcomes in asthma.
  
  
  METHODS
  An independent 24-week, randomized controlled trial of 303 adult patients with asthma who are at risk, which compared the efficacy of SMART (single budesonide-formoterol inhaler as maintenance and reliever therapy) with a fixed-dose regimen with salbutamol as reliever ("Standard"). Inhaled medication use was measured by electronic monitoring. Baseline characteristics that were predictors of subsequent severe asthma exacerbations, poor asthma control (Asthma Control Questionnaire -5 score ≥1.5), and "extreme" β-agonist overuse (>16 budesonide-formoterol actuations/d in SMART and >32 salbutamol actuations/d in Standard) were assessed by multivariate analyses.
  
  
  RESULTS
  FEV₁ % predicted (rate ratio [RR] 1.14 [95% CI, 1.03-1.27] per 10% lower), more previous exacerbations (RR 1.15 [95% CI, 1.01-1.31]), Standard therapy (RR 1.62 [95% CI, 1.07-2.47]), and female sex (RR 2.18 [95% CI, 1.29-3.67]) were associated with future severe exacerbations. Asthma Control Questionnaire--5 (regression coefficient 0.20 [95% CI, 0.13-0.27] per 0.5 points higher) and age (regression coefficient 0.09 [95% CI, 0.01-0.17] per decade older) were associated with future poorly controlled asthma. Higher reliever use (RR 1.63 [95% CI, 1.36-1.95] per categorical score in Asthma Control Questionnaire question no. 6), Māori ethnicity (RR 2.20 [95% CI, 1.43-3.38]) and FEV₁ % predicted (RR 1.16 [95% CI, 1.03-1.31] per 10% lower) were associated with future extreme β-agonist overuse.
  
  
  CONCLUSIONS
  Future severe asthma exacerbations, poor asthma control, and extreme β-agonist overuse are predicted by different baseline clinical and demographic characteristics and management approaches in at-risk asthma.
authors.affiliation: Medical Research Institute of New Zealand, Wellington, New Zealand; Capital and Coast District Health Board, Wellington, New Zealand; Division of Respiratory Medicine, School of Clinical Sciences, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Mitesh
authors.initials: M
authors.lastname: Patel
authors.affiliation: Medical Research Institute of New Zealand, Wellington, New Zealand; Capital and Coast District Health Board, Wellington, New Zealand.
authors.forename: Janine
authors.initials: J
authors.lastname: Pilcher
authors.affiliation: Clinical Management Group, Woolcock Institute of Medical Research, University of Sydney, Sydney, Australia.
authors.forename: Helen K
authors.initials: HK
authors.lastname: Reddel
authors.affiliation: Henderson Medical Centre, Auckland, New Zealand.
authors.forename: Victoria
authors.initials: V
authors.lastname: Qi
authors.affiliation: Henderson Medical Centre, Auckland, New Zealand.
authors.forename: Bill
authors.initials: B
authors.lastname: Mackey
authors.affiliation: Henderson Medical Centre, Auckland, New Zealand.
authors.forename: Tyronne
authors.initials: T
authors.lastname: Tranquilino
authors.affiliation: Division of Respiratory Medicine, School of Clinical Sciences, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Dominick
authors.initials: D
authors.lastname: Shaw
authors.affiliation: Pharmacology & Clinical Pharmacology, University of Auckland, Auckland, New Zealand.
authors.forename: Peter
authors.initials: P
authors.lastname: Black
authors.affiliation: Capital and Coast District Health Board, Wellington, New Zealand; School of Medicine, University of Otago, Wellington, New Zealand.
authors.forename: Mark
authors.initials: M
authors.lastname: Weatherall
authors.affiliation: Medical Research Institute of New Zealand, Wellington, New Zealand; Capital and Coast District Health Board, Wellington, New Zealand; School of Medicine, University of Otago, Wellington, New Zealand. Electronic address: richard.beasley@mrinz.ac.nz.
authors.forename: Richard
authors.initials: R
authors.lastname: Beasley
mesh_terms: D000280:Administration, Inhalation; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage* / Q000009:adverse effects; D000328:Adult; D000420:Albuterol / Q000008:administration & dosage* / Q000009:adverse effects; D001249:Asthma / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects; D019819:Budesonide / Q000008:administration & dosage* / Q000009:adverse effects; D018450:Disease Progression; D004338:Drug Combinations; D004983:Ethanolamines / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005541:Forced Expiratory Volume; D000068759:Formoterol Fumarate; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D036501:Metered Dose Inhalers; D008875:Middle Aged; D015999:Multivariate Analysis; D009520:New Zealand; D016017:Odds Ratio; D011446:Prospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D001993:Bronchodilator Agents; D004338:Drug Combinations; D004983:Ethanolamines; D005938:Glucocorticoids; D019819:Budesonide; D000420:Albuterol; D000068759:Formoterol Fumarate
keywords: Asthma; Electronic monitoring; Predictors; Risk; β-agonist