Quadrupling the dose of inhaled corticosteroid to prevent asthma exacerbations: a randomized, double-blind, placebo-controlled, parallel-group clinical trial. Treatment of acute asthmatic exacerbations with an increased dose of inhaled steroid. Doubling the dose of inhaled corticosteroid to prevent asthma exacerbations: randomised controlled trial. Doubling the dose of budesonide versus maintenance treatment in asthma exacerbations. Low-dose budesonide with the addition of an increased dose during exacerbations is effective in long-term asthma control. On behalf of the Italian Study Group.
Asthma exacerbations are unpredictable, disruptive, and frightening, and are therefore important to prevent.
                We investigated whether a policy of quadrupling the dose of inhaled corticosteroid when asthma control starts to deteriorate reduces asthma exacerbations requiring treatment with oral corticosteroids.
                A total of 403 people with asthma were given a self-management plan and randomized to take an active or placebo corticosteroid inhaler in addition to their usual asthma treatment when their PEF fell by 15% on 2 consecutive days or by 30% on 1 day. The study inhalers provided a quadrupling or no change in corticosteroid dose.
                Eighteen of 197 (9%) and 29 of 203 (14%) participants had an exacerbation of asthma requiring treatment with oral corticosteroids in the active and placebo groups, respectively, giving a risk ratio of 0.64 (95% confidence interval, 0.37-1.11, P = 0.11). Of the 94 participants who started the study inhaler far fewer required treatment with oral corticosteroids in the active compared with the placebo group: 12 of 56 (21%) in the active group and 19 of 38 (50%) in the placebo group, giving a risk ratio of 0.43 (95% confidence interval, 0.24-0.78, P = 0.004).
                Although our primary outcome did not reach statistical significance, quadrupling the dose of inhaled corticosteroid when asthma control starts to deteriorate appears to reduce acute exacerbations of asthma and deserves further investigation. Clinical trial registered with www.controlled-trials.com (ISRCTN 46018181). To investigate the efficacy of an increased dose of inhaled steroid used within the context of an asthma self management plan for treating exacerbations of asthma.
                Randomised, double blind, placebo controlled, crossover trial.
                Twenty eight children aged 6-14 years with asthma of mild to moderate severity were studied for six months. Eighteen pairs of exacerbations were available for analysis, during which subjects took an increased dose of inhaled steroids or continued on the same dose.
                There was no significant difference between increasing inhaled steroids or placebo on morning or evening peak expiratory flow rates (PEFRs), diurnal peak flow variability, or symptom scores in the two weeks following an asthma exacerbation. Difference (95% confidence intervals) in baseline PEFR on days 1-3 were 3.4% (-3.5% to 10.4%) and -0.9% (-4.7% to 2.9%) for inhaled steroid and placebo, respectively. Spirometric function and the parents' opinion of the effectiveness of asthma medications at each exacerbation were also not significantly different between inhaled steroid or placebo.
                This study suggests that increasing the dose of inhaled steroids at the onset of an exacerbation of asthma is ineffective and should not be included in asthma self management plans. Asthma self-management plans that include doubling the dose of inhaled corticosteroid when the condition deteriorates improve asthma control. Whether doubling the dose of corticosteroid in isolation is effective is unknown. We undertook a randomised controlled trial to investigate the effects of doubling the dose of inhaled corticosteriods when asthma deteriorates.
                390 individuals with asthma who were at risk of an exacerbation monitored their morning peak flow and asthma symptoms for up to 12 months. When peak flow or symptoms started to deteriorate, participants added an active or placebo corticosteroid inhaler to their usual corticosteroid for 14 days to produce a doubling or no change in dose. The primary outcome was the number of individuals starting oral prednisolone in each group.
                During 12 months, 207 (53%) started their study inhaler and 46 (12%) started prednisolone--22 (11%) of 192 and 24 (12%) of 198 in the active and placebo groups, respectively. The risk ratio for starting prednisolone was therefore 0.95 (95% CI 0.55-1.64, p=0.8).
                We recorded little evidence to support the widely recommended intervention of doubling the dose of inhaled corticosteroid when asthma control starts to deteriorate. Previous guidelines recommend doubling the daily dose of maintenance inhaled corticosteroid to treat or prevent progression of exacerbations of asthma.
                Over a 6 month period a cohort of patients were evaluated prospectively and randomised in a double blind controlled trial to treatment with either a continued maintenance dose (MD) of inhaled corticosteroid or doubling the dose (DD) at the time of an exacerbation.
                A total of 290 patients were randomised (33% male) and 98 (DD, n = 46) experienced evaluable asthma exacerbations during the study period. Mean (SD) baseline characteristics at randomisation (age 33.5 (14.0) years; forced expiratory volume in 1 second (FEV(1)) 2.8 (0.7) l; peak expiratory flow (PEF) 422.9 (110.5) l/min) were similar in both groups. In the DD group 41% of patients were considered treatment failures because they either required systemic steroids (n = 12), had an unscheduled visit to a physician (n = 1), or their asthma did not return to baseline (n = 6). This did not differ from the MD group in which 40% were treatment failures (n = 9, 0, and 12, respectively; p = 0.94).
                In patients who regularly take an inhaled corticosteroid, doubling the maintenance dose may not affect the pattern of the exacerbation. This study was designed to compare the effects of a 6-month treatment with budesonide 100 microg bid (low dose) and 400 microg bid (standard reference dose) in controlling symptoms and lung function in a group of asthmatics with moderate asthma (baseline FEV(1) > or = 50% and < or = 90% of predicted values) previously treated with inhaled beclomethasone dipropionate (500 to 1,000 microg/d). Moreover, we investigated whether or not asthma exacerbations could be treated by a short-term increase in the daily dose of budesonide.
                After a 2-week run-in period and 1-month treatment with a high dose of budesonide (800 microg bid), 213 patients with moderate asthma were assigned to randomized treatments. Daily treatment included budesonide (bid) plus an additional treatment in case of exacerbation (qid for 7 days). Treatments were as follows: budesonide 400 microg plus placebo (group 1); budesonide 100 microg plus budesonide 200 microg (group 2); and budesonide 100 microg plus placebo (group 3). Symptoms and a peak expiratory flow (PEF) diary were recorded and lung function was measured each month. An exacerbation was defined as a decrease in PEF > 30% below baseline values on 2 consecutive days.
                We found that that 1-month treatment with a high budesonide dose remarkably reduced all asthma symptoms. Moreover, symptoms were under control in all treatment groups throughout the study period. Similarly, lung function improved and remained stable, and no relevant differences between groups were observed. In each treatment group, the majority of patients had no exacerbations. In patients treated with the standard budesonide dose (group 1), the number of exacerbations and days with exacerbations were significantly lower than in group 3 (intention-to-treat analysis). Additionally, patients treated with low budesonide dose plus budesonide (group 2) experienced a significantly lower number of exacerbations and days with exacerbations compared to group 3 (per-protocol analysis).
                This study demonstrates that when patients with moderate asthma had reached a stable clinical condition with a high dose of budesonide, a low dose of budesonide (200 microg/d) is as effective as the standard dose (800 microg/d) in the control of symptoms and lung function over a period of several months. Furthermore, results showed that the addition of inhaled budesonide (800 microg/d) at onset of an asthmatic exacerbation has a beneficial clinical effect.
There is very little evidence from trials in children. In adults with asthma on daily maintenance ICS, a self-initiated ICS increase to 1000 to 2000 mcg/day at the onset of an exacerbation is not associated with a statistically significant reduction in the risk of exacerbations requiring rescue oral corticosteroids. More research is needed to assess the effectiveness of increased ICS doses at the onset of asthma exacerbations (particularly in children).