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Severe Exacerbations and Decline in Lung Function in Asthma

¹ Department of Medicine, McMaster University, Hamilton, Ontario, Canada; ² University of Odense, Department of Pediatrics, Kolding Hospital, Kolding, Denmark; ³ AstraZeneca R&D, Lund, Sweden; ⁴ University of British Columbia, Vancouver, British Columbia, Canada; ⁵ University of Wisconsin, Madison, Wisconsin

Correspondence and requests for reprints should be addressed to Paul O'Byrne, M.B., F.R.C.P., Department of Medicine, McMaster University Medical Center, 1,200 Main St. West, Hamilton, ON L8N 3Z5, Canada. E-mail: obyrnep{at}mcmaster.ca

Rationale: To evaluate the association between asthma exacerbations and the decline in lung function, as well as the potential effects of an inhaled corticosteroid, budesonide, on exacerbation-related decline in patients with asthma.

Objectives: To determine whether severe asthma exacerbations are associated with a persistent decline in lung function.

Methods: The START (inhaled steroid treatment as regular therapy in early asthma) study was a 3-year, randomized, double-blind study of 7,165 patients (5–66 yr) with persistent asthma for less than 2 years, to determine whether early intervention with low-dose inhaled budesonide prevents severe asthma-related events (exacerbations requiring hospitalization or emergency treatment) and decline in lung function.

Measurements and Main Results: There were 315 patients who experienced at least one severe asthma exacerbation, of which 305 were analyzable, 190 in the placebo group and 115 in the budesonide group. In the placebo group, the change in post-bronchodilator FEV₁ % predicted from baseline to the end of the study, in patients who did or did not experience a severe exacerbation was –6.44% and –2.43%, respectively (P < 0.001). A significant difference was seen in both children and in adults, but not in adolescents. In the budesonide group, the change in the post-bronchodilator FEV₁ % predicted in patients who did or did not experience a severe exacerbation was –2.48% and –1.72%, respectively (P = 0.57). The difference in magnitude of reduction afforded by budesonide, in patients who experienced at least one severe asthma-related event compared with those who did not, was statistically significant (P = 0.042).

Conclusions: Severe asthma exacerbations are associated with a more rapid decline in lung function. Treatment with low doses of inhaled corticosteroid is associated with an attenuation of the decline.

Clinical trial registered with www.clinicaltrials.gov (NCT00641914).

Key Words: asthma • lung function • inhaled corticosteroids • early intervention

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Patients with asthma can lose lung function more rapidly than patients without asthma. The reason why this occurs in some patients and not others is unknown. What This Study Adds to the Field This study identified that severe asthma exacerbations are associated with a more rapid loss in lung function, and that this did not occur in patients taking inhaled corticosteroids.

 

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