Harrison TW, Oborne J, Newton S, Tattersfield AE. Lancet. 2004;363:271–275
Purpose of the Study.
The investigators proposed to determine if doubling the dose of inhaled corticosteroids (ICSs) to treat deteriorating asthma control reduced the need for starting oral corticosteroids.
The study population included 390 nonsmoking individuals aged ≥16 years, with stable asthma requiring regular ICS use and a course of oral corticosteroids or doubled dose of ICS in the past 12 months.
Participants recorded their daily morning peak flow and daytime symptom score on a 4-point scale. After a 2- to 4-week run-in period, an independent pharmacist randomly allocated participants to receive active or placebo study inhalers, matched to their usual ICS, inhaler type, and dose. Patients were stratified into low-to-moderate–dose (equivalent of beclomethasone dipropionate, ≤1000 μg/day) and high-dose groups based on their dose of ICS at study entry. They continued their usual ICS and added the study inhaler for 14 days if their morning peak flow fell by 15% or their daytime symptom score increased by 1 point compared with the run-in period means. Participants took 10 days of oral prednisolone (30 mg/day) if their peak flow fell 40% from the mean run-in value or if their asthma control deteriorated to where they would usually start oral corticosteroids.
Of the 192 participants in the active-inhaler group, 110 started their study inhaler (88 in the low-to-moderate–dose group), and of the 198 participants in the placebo-inhaler group, 97 started their study inhaler (74 in the low-to-moderate-dose group). Twenty-two participants (11%) in the active-inhaler group and 24 (12%) in the placebo group started prednisolone, for a risk ratio of 0.95 (95% confidence interval [CI]: 0.55, 1.64). Prednisolone was started because of a 40% peak-flow drop in 6 participants in the active group and 4 controls. In the low-to-moderate–dose group, 13 of 158 in the active group and 17 of 162 in the placebo group started prednisolone, for a risk ratio of 0.8 (95% CI: 0.4, 1.6). Doubling the dose of ICS led to a small reduction in the mean maximum fall of peak flow but did not change the time taken for peak flow or symptom scores to return to the baseline.
These findings do not support the effectiveness of doubling the dose of ICS to prevent the need for oral corticosteroids during asthma exacerbations.
This randomized, control trial questions a recommendation that is part of many asthma-exacerbation–management plans. Although the results of at least 1 other study support these findings, a longer study following individuals beyond their first need for oral corticosteroids, involving larger increases as well as doubling of ICS doses, evaluating objective measures such as peak flow and symptom scores in all patients at the time of starting oral corticosteroids, and including younger patients and those with milder disease may reveal a benefit to increasing the ICS dose in some situations and subgroups of asthmatics. However, if this study’s findings can be consistently replicated in children, we may need to modify our recommendations for early management of asthma exacerbations.