Increased Dose of Inhaled Corticosteroid versus Add-On Long-acting β-Agonist for Step-Up Therapy in Asthma

Ann Am Thorac Soc. 2015 Jun;12(6):798-806. doi: 10.1513/AnnalsATS.201412-580OC.


Rationale: Guidelines advocate adding long-acting β-agonist (LABA) to inhaled corticosteroid as the preferred step-up therapy to increasing inhaled corticosteroid dose for patients with uncontrolled asthma on inhaled corticosteroid monotherapy. However, less than 5% of patients with asthma qualify for the randomized controlled trials on which guidelines are based. Thus, real-world data are needed to complement the results of randomized trials with narrow entry criteria.

Objectives: To compare the effectiveness of stepping up asthma therapy with an increased dose of various types of inhaled corticosteroid as compared with add-on LABA.

Methods: We performed a historical matched cohort study using large primary care databases to compare asthma step-up therapy with small- and standard size-particle inhaled corticosteroid versus added LABA for patients 12-80 years old. As outcomes, we examined a composite of asthma control and rates of severe exacerbations.

Measurements and main results: The odds of asthma control and rates of severe exacerbations over one outcome year were comparable with increased inhaled corticosteroid dose versus added LABA. The adjusted odds ratios (95% confidence interval) for achieving asthma control with increased inhaled corticosteroid dose versus inhaled corticosteroid/LABA were 0.99 (0.88-1.12) for small-particle inhaled corticosteroid (n = 3,036 per cohort) and 0.85 (0.67-1.07) for standard size-particle inhaled corticosteroid (n = 809 per cohort). The adjusted rate ratios (95% confidence interval) for severe exacerbations, compared with inhaled corticosteroid/LABA combination inhaler, were 1.04 (0.91-1.20) and 1.18 (0.92-1.54), respectively. The results were not affected by smoking status.

Conclusions: When applied to a broad primary care population, antiinflammatory therapy using increased doses of small- or standard size-particle inhaled corticosteroid is as effective as adding LABA, as measured by outcomes important to both patients and providers. Real-world populations and outcomes need to be taken into consideration when formulating treatment recommendations.

Keywords: adrenergic β2-agonists; antiasthmatic agents; bronchodilator agents; disease exacerbation; glucocorticoids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adrenergic beta-2 Receptor Agonists* / administration & dosage
  • Adrenergic beta-2 Receptor Agonists* / adverse effects
  • Adult
  • Anti-Asthmatic Agents / administration & dosage
  • Anti-Asthmatic Agents / adverse effects
  • Asthma / drug therapy*
  • Asthma / epidemiology
  • Asthma / physiopathology
  • Cohort Studies
  • Comparative Effectiveness Research
  • Databases, Factual
  • Delayed-Action Preparations
  • Disease Progression
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination / methods
  • Female
  • Glucocorticoids* / administration & dosage
  • Glucocorticoids* / adverse effects
  • Humans
  • Male
  • Middle Aged
  • Outcome Assessment, Health Care
  • United Kingdom / epidemiology


  • Adrenergic beta-2 Receptor Agonists
  • Anti-Asthmatic Agents
  • Delayed-Action Preparations
  • Glucocorticoids