title: Long-Acting β-Agonist in Combination or Separate Inhaler as Step-Up Therapy for Children with Uncontrolled Asthma Receiving Inhaled Corticosteroids.
abstract: Adding a long-acting β2-agonist (LABA) to inhaled corticosteroids (ICS) using a fixed-dose combination (FDC) inhaler is the UK guideline recommendation for children aged more than 4 years with uncontrolled asthma. The evidence of benefit of adding an FDC inhaler over a separate LABA inhaler is limited.
  
  
  
  The objective of this study was to compare the effectiveness of a LABA added as an FDC inhaler, and as a separate inhaler, in children with uncontrolled asthma.
  
  
  
  Two UK primary care databases were used to create a matched cohort study with a 2-year follow-up period. We included children prescribed their first step-up from ICS monotherapy. Two cohorts were formed for children receiving an add-on LABA as an FDC inhaler, or a separate LABA inhaler. Matching variables and confounders were identified by comparing characteristics during a baseline year of follow-up. Outcomes were examined during the subsequent year. The primary outcome was an adjusted odds ratio for overall asthma control (defined as follows: no asthma-related hospital admission or emergency room visit, prescription for oral corticosteroids or antibiotic with evidence of respiratory consultation, and ≤2 puffs of short-acting β-agonist daily).
  
  
  
  The final study consisted of 1330 children in each cohort (mean age 9 years; 59% male). In the separate ICS+LABA cohort, the odds of achieving overall asthma control were lower (adjusted odds ratio, 0.77 [95% confidence interval, 0.66-0.91]; P = .001) compared with the FDC cohort.
  
  
  
  The study demonstrates a small but significant benefit in achieving asthma control from an add-on LABA as an FDC, compared with a separate inhaler and this supports current guideline recommendations.
authors.affiliation: Department of Child Health, Royal Aberdeen Children's Hospital, University of Aberdeen, Aberdeen, United Kingdom. Electronic address: s.w.turner@abdn.ac.uk.
authors.forename: Steve
authors.initials: S
authors.lastname: Turner
authors.affiliation: Research in Real-life Ltd, Cambridge, United Kingdom.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Richardson
authors.affiliation: Centre for Respiratory Medicine and Allergy, Institute of Inflammation and Repair, Manchester Academic Health Science Centre, The University of Manchester and University Hospital of South Manchester, NHS Foundation Trust, Manchester, United Kingdom.
authors.forename: Clare
authors.initials: C
authors.lastname: Murray
authors.affiliation: Primary Care and Population Sciences, University of Southampton and NIHR Wessex CLAHRC and NIHR Southampton Biomedical Research Unit, Southampton, United Kingdom.
authors.forename: Mike
authors.initials: M
authors.lastname: Thomas
authors.affiliation: Research in Real-life Ltd, Cambridge, United Kingdom.
authors.forename: Elizabeth V
authors.initials: EV
authors.lastname: Hillyer
authors.affiliation: Research in Real-life Ltd, Cambridge, United Kingdom.
authors.forename: Anne
authors.initials: A
authors.lastname: Burden
authors.affiliation: Research in Real-life Ltd, Cambridge, United Kingdom; Academic Primary Care, University of Aberdeen, Aberdeen, United Kingdom.
authors.forename: David B
authors.initials: DB
authors.lastname: Price
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D058666:Adrenergic beta-2 Receptor Agonists / Q000627:therapeutic use*; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004338:Drug Combinations; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D036501:Metered Dose Inhalers / Q000706:statistics & numerical data*; D017410:Practice Guidelines as Topic; D012008:Recurrence; D016896:Treatment Outcome; D006113:United Kingdom
chemical_list: D000305:Adrenal Cortex Hormones; D058666:Adrenergic beta-2 Receptor Agonists; D018927:Anti-Asthmatic Agents; D004338:Drug Combinations
keywords: Asthma; Child; Inhaled corticosteroid; Long-acting β-agonist; Step-up therapy