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

Elliot Israel, Nicolas Roche, Richard J Martin, Gene Colice, Paul M Dorinsky, Dirkje S Postma, Theresa W Guilbert, Willem Mc van Aalderen, Jonathan Grigg, Elizabeth V Hillyer, Anne Burden, Julie von Ziegenweidt, Victoria Thomas, David B. Price

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)


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

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

METHODS: We performed a historical matched cohort study utilizing large primary care databases to compare asthma step-up therapy with small- and standard size-particle inhaled corticosteroid vs. 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 1 outcome year were comparable with increased inhaled corticosteroid dose vs. added LABA. The adjusted odds ratios (95% CI) for achieving asthma control with increased inhaled corticosteroid dose vs inhaled corticosteroid/LABA were 0.99 (0.88-1.12) for small-particle inhaled corticosteroid (n=3036 per cohort) and 0.85 (0.67-1.07) for standard size-particle inhaled corticosteroid (n=809 per cohort). The adjusted rate ratios (95% CI) 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, anti-inflammatory therapy utilizing 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.

Original languageEnglish
Pages (from-to)798-806
Number of pages9
JournalAnnals of the American Thoracic Society
Issue number6
Early online date10 Mar 2015
Publication statusPublished - 1 Jun 2015


  • adrenergic β2-agonists
  • antiasthmatic agents
  • bronchodilator agents
  • disease exacerbation
  • glucocorticoids


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