Asthma and lower airway disease
The relationship between combination inhaled corticosteroid and long-acting β-agonist use and severe asthma exacerbations in a diverse population

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Background

Safety concerns surround the use of long-acting β-agonists (LABAs) for the treatment of asthma, even in combination with inhaled corticosteroids (ICSs) and particularly in high-risk subgroups.

Objective

To estimate the effect of ICS therapy and fixed-dose ICS/LABA combination therapy on severe asthma exacerbations in a racially diverse population.

Methods

ICS and ICS/LABA exposure was estimated from pharmacy data for patients with asthma aged 12 to 56 years who were members of a large health maintenance organization. ICS and ICS/LABA use was estimated for each day of follow-up to create a moving window of exposure. Proportional hazard models were used to assess the relationship between ICS and ICS/LABA combination therapy and severe asthma exacerbations (ie, use of oral corticosteroids, asthma-related emergency department visit, or asthma-related hospitalization).

Results

Among the 1828 patients who met the inclusion criteria, 37% were African American, 46% were treated with ICS therapy alone, and 54% were treated with an ICS/LABA combination. Models assessing the risk of severe asthma exacerbations among individuals using ICS treatment alone and ICS/LABA combination therapy suggested that the overall protective effect was as good or better for ICS/LABA combination therapy when compared with ICS treatment alone (hazard ratio, 0.65 vs 0.72, respectively). Analyses in several subgroups, including African American patients, showed a similar statistically significant protective association for combination therapy.

Conclusion

Treatment with ICS/LABA fixed-dose combination therapy appeared to perform as well as or better than ICS treatment alone in reducing severe asthma exacerbations; this included multiple high-risk subgroups.

Section snippets

Study population and data sources

The study protocol was reviewed and approved by the institutional review boards of Henry Ford Hospital and Wayne State University. Subjects were identified from an integrated health system serving the primary and specialty health care needs of individuals in southeastern Michigan. The population was limited to individuals who were enrolled in the affiliated health maintenance organization and therefore had electronic information available for health-care visits and prescription fills both

Results

We identified 1828 individuals with asthma who met the study criteria and who received at least 2 prescriptions for an ICS (n = 846) or an ICS/LABA combination (n = 982) between January 1, 2003, and December 31, 2010. These individuals had a total of 3791 person-years of follow-up (ie, a mean follow-up of 2.1 years per person; SD, 2.0 years): 1368 person-years of follow-up for individuals on ICS therapy (mean, 1.6 years per person; SD, 1.7 years) and 2423 person-years of follow-up for

Discussion

In this large, population-based observational study we found that exposure to ICS/LABA combination therapy appeared to have an overall protective effect on asthma exacerbations that was as good as or better than that observed for ICS treatment alone. To our knowledge this is the first study to attempt to measure actual ICS and ICS/LABA exposure (and variation in exposure over time) with regard to asthma exacerbations. Moreover, we demonstrated that the protective effect of ICS/LABA combination

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    • Cited by (0)

    This work was supported by grants from the Fund for Henry Ford Hospital, the American Asthma Foundation, the National Institute of Allergy and Infectious Diseases (grant nos. R01AI079139 and R01AI061774), the National Heart, Lung, and Blood Institute (grant no. R01HL079055), and the National Institute of Diabetes and Digestive and Kidney Diseases (grant no. R01DK064695), National Institutes of Health. This work represents a partial requirement for a Masters of Public Health degree at the Department of Family Medicine and Public Health Sciences, Wayne State University for Karen E. Wells.

    Disclosure of potential conflict of interest: L. K. Williams has received research support from the National Institutes of Health (National Institute of Allergy and Infectious Diseases, National Heart, Lung, and Blood Institute, and National Institute of Diabetes and Digestive and Kidney Diseases) and the American Asthma Foundation. The rest of the authors declare that they have no relevant conflicts of interest.

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