High-dose inhaled corticosteroids versus add-on long-acting beta-agonists in asthma: an observational study

J Allergy Clin Immunol. 2009 Jan;123(1):116-121.e10. doi: 10.1016/j.jaci.2008.09.035. Epub 2008 Nov 4.


Background: Guidelines recommend that for patients uncontrolled on inhaled corticosteroids (ICSs), step-up options include an increase in ICS dosage or addition of a long-acting beta-agonist (LABA). Controversy persists about the best option in routine practice.

Objective: To compare asthma outcomes in patients whose first step-up from ICS monotherapy was by addition of LABA (LABA cohort) or increase in ICS dosage or formulation (ICS cohort).

Methods: Observational study using the General Practice Research Database, comparing outcomes in the following 12 months with regression modeling allowing for baseline cohort differences: age, sex, socioeconomic status, body mass index, comorbidity (rhinitis, heart disease), smoking status, short-acting beta-agonist (SABA) use, oral corticosteroid use, and use of asthma complicating medication.

Results: We found 46,930 patients in the ICS and 17,418 in the LABA cohort. In adjusted analysis, the odds ratio (95% CI) of successful treatment (no hospitalization, no oral corticosteroid use, average daily SABA use <1 dose/d) was lower in the ICS cohort (0.75; 0.72-0.79). The adjusted odds ratio of needing rescue SABA prescriptions was higher in the ICS cohort (1.67; 1.59-1.76). However, the adjusted odds of using any oral corticosteroids were lower (0.75; 0.71-0.78), particularly of using 3 or more courses (0.50, 0.46-0.55), and the adjusted odds of respiratory hospitalization were lower (0.69; 0.59-0.81).

Conclusion: Although symptomatic control and rescue bronchodilator use may be improved by the addition of a LABA to ICS, there may be a lower risk of severe exacerbations and hospitalizations from ICS dose increase.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adrenal Cortex Hormones / administration & dosage*
  • Adult
  • Asthma / drug therapy*
  • Bronchodilator Agents / administration & dosage*
  • Child
  • Databases, Factual
  • Female
  • Follow-Up Studies
  • Hospitalization
  • Humans
  • Male
  • Middle Aged
  • Models, Theoretical*
  • Regression Analysis
  • Risk Factors


  • Adrenal Cortex Hormones
  • Bronchodilator Agents