Low-dose Beclomethasone Research Articles

Zileuton added to low-dose inhaled beclomethasone for the treatment of moderate to severe persistent asthma

To assess the therapeutic effects of oral zileuton tablets combined with low-dose beclomethasone compared to doubling the dose of beclomethasone, in improving lung function and reducing asthma symptoms. Randomized, active-control, double-blind, parallel, multi-center study of zileuton (400 or 600 mg QID)+200 microg beclomethasone dipropionate (BDP) BID versus placebo+BDP 400 microg BID in asthmatics with baseline FEV(1) percent predicted values between 40% and 80% following a single-blind ICS (BDP 200 microg BID) 2-week run-in. During the 3-month double-blind treatment period, assessments included safety, daytime and nighttime symptoms, acute asthma exacerbations, beta(2)-agonist use, AM and PM peak expiratory flow (PEF) and FEV(1). The addition of a 5-lipoxygenase (5-LO) inhibitor added to a low-dose of BDP showed no significant difference in FEV(1) compared to doubling the dose of BDP. FEV(1) improved in all 3 treatment groups, with mean increases of 10% with zileuton 600 mg QID+BDP 200 microg BID, 12% with zileuton 400mg QID+BDP 200 microg BID, and 11% with BDP 400 microg BID by study end. Within each treatment group, there were significant improvements in asthma symptoms and AM and PM PEF compared to baseline. No significant differences were observed between groups with regards to salbutamol use, acute asthma exacerbations, the requirement for oral/parenteral corticosteroids and adverse clinical events. The addition of a 5-LO inhibitor added to low-dose beclomethasone may be an alternative to higher-doses of ICS in patients unable to achieve sufficient asthma control on low-dose ICS therapy.

Correction: Low-Dose Inhaled Corticosteroids and the Prevention of Death from Asthma.

Low-dose inhaled corticosteroids and the prevention of death from asthma S Suissa, P Ernst, S Benayoun, M Baltzan, B Cai Background: Although inhaled corticosteroids are effective for the treatment of asthma, it is uncertain whether their use can prevent death from asthma. Methods: We used the Saskatchewan Health data bases to form a population-based cohort of all subjects from 5–44 years of age who were using antiasthma drugs during the period 1975–1991. We followed subjects until the end of 1997, their 55th birthday, death, emigration, or termination of health insurance coverage, whichever came first. We conducted a nested case-control study in which subjects who died of asthma were matched with controls within the cohort according to the length of follow-up at the time of death of the case patient (the index date), the date of study entry, and the severity of asthma. We calculated rate ratios after adjustment for the subject's age and sex; the number of prescriptions of theophylline, nebulized and oral beta-adrenergic agonists, and oral corticosteroids in the year before the index date; the number of canisters of inhaled beta-adrenergic agonists used in the year before the index date; and the number of hospitalizations for asthma in the two years before the index date. Results: The cohort consisted of 30,569 subjects. Of the 562 deaths, 77 were classified as due to asthma. We matched the 66 subjects who died of asthma for whom there were complete data with 2681 controls. Fifty-three percent of the case patients and 46% of the control patients had used inhaled corticosteroids in the previous year, most commonly low-dose beclomethasone. The mean number of canisters was 1.18 for the patients who died and 1.57 for the controls. On the basis of a continuous dose-response analysis, we calculated that the rate of death from asthma …

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Beyond Our Pages

Low-dose inhaled corticosteroids and the prevention of death from asthma.

Although inhaled corticosteroids are effective for the treatment of asthma, it is uncertain whether their use can prevent death from asthma. We used the Saskatchewan Health data bases to form a population-based cohort of all subjects from 5 through 44 years of age who were using antiasthma drugs during the period from 1975 through 1991. We followed subjects until the end of 1997, their 55th birthday, death, emigration, or termination of health insurance coverage; whichever came first. We conducted a nested case-control study in which subjects who died of asthma were matched with controls within the cohort according to the length of follow-up at the time of death of the case patient (the index date), the date of study entry, and the severity of asthma. We calculated rate ratios after adjustment for the subject's age and sex; the number of prescriptions of theophylline, nebulized and oral beta-adrenergic agonists, and oral corticosteroids in the year before the index date; the number of canisters of inhaled beta-adrenergic agonists used in the year before the index date; and the number of hospitalizations for asthma in the two years before the index date. The cohort consisted of 30,569 subjects. Of the 562 deaths, 77 were classified as due to asthma. We matched the 66 subjects who died of asthma for whom there were complete data with 2681 controls. Fifty-three percent of the case patients and 46 percent of the control patients had used inhaled corticosteroids in the previous year, most commonly low-dose beclomethasone. The mean number of canisters was 1.18 for the patients who died and 1.57 for the controls. On the basis of a continuous dose-response analysis, we calculated that the rate of death from asthma decreased by 21 percent with each additional canister of inhaled corticosteroids used in the previous year (adjusted rate ratio, 0.79; 95 percent confidence interval, 0.65 to 0.97). The rate of death from asthma during the first three months after discontinuation of inhaled corticosteroids was higher than the rate among patients who continued to use the drugs. The regular use of low-dose inhaled corticosteroids is associated with a decreased risk of death from asthma.

Salmeterol Added to Inhaled Corticosteroid Therapy Is Superior to Doubling the Dose of Inhaled Corticosteroids: A Randomized Clinical Trial

This randomized, double-blind, double-dummy, parallel group clinical trial compared the efficacy and safety of adding salmeterol xinafoate to concurrent inhaled beclomethasone dipropionate therapy with doubling the dose of beclo-methasone dipropionate in patients experiencing symptoms on low-dose beclomethasone. Salmeterol added to low-dose beclomethasone was superior (p ≤ 0.05) to doubling the dose of beclomethasone in improving peak expiratory flow (PEF) and forced expiratory volume in 1 sec (FEV1), and in reducing symptoms of asthma, sleep loss, nighttime awakenings, and use of albuterol. Both treatment regimens had comparable safety profiles. In asthma patients inadequately controlled despite the use of low-dose inhaled corticosteroids (i.e., less than 400 μg per day), the addition of salmeterol may be a more effective treatment option than doubling the dose of inhaled corticosteroids.

Evaluation of factors that allow the clinician to taper inhaled corticosteroids in childhood asthma

Inhaled corticosteroids are potent and effective treatment agents for controlling symptoms of childhood asthma. However, there are no predictive factors that help to determine which patients with asthma are likely to be tapered off inhaled corticosteroids successfully. We examined whether any factor or combination of factors could help the clinician safely discontinue inhaled steroid therapy. Thirty-six asthmatic children whose symptoms were stable on low-dose beclomethasone dipropionate (BDP) were divided by parental choice into two groups: maintenance BDP (n = 11) and no BDP (n = 25). Methacholine inhalation tests were performed at the beginning of the study and after 1 month. Twelve children (48%) who had BDP discontinued developed exacerbations after 2–3 months, whereas there were no problems in the maintenance group. The no BDP group was retrospectively divided into two subgroups: exacerbation (+) and (−). The threshold to methacholine in the exacerbation (+) subgroup decreased significantly in advance of clinical symptoms. The two subgroups were analyzed statistically by two-group discriminant function analysis. The change in threshold to methacholine, the dose and potency of drugs, duration of asthma and gender (female) correlated with exacerbation. These results suggest that discontinuation of inhaled steroids should be done carefully, even in stable asthmatic children. The methacholine inhalation test, gender, drugs and history may be used as references for discontinuing inhaled steroids.

Dose-dependent inhibitory effect of inhaled beclomethasone on late asthmatic reactions and increased responsiveness to methacholine induced by toluene diisocyanate in sensitised subjects

To determine whether inhaled beclomethasone, both at low and at high doses, inhibits late asthmatic reactions and the associated increase in airway responsiveness induced by toluene diisocyanate (TDI), we studied 9 sensitised subjects. Low dose beclomethasone (200 μg bid), high dose beclomethasone aerosol (1000 μg bid), and placebo were administered for 7 days before TDI inhalation challenge to each subject, according to a double-blind, crossover study design. The washout period between the treatments was at least 1 week. When the subjects were treated with placebo, forced expiratory volume in 1 sec (FEV 1) markedly decreased after exposure to TDI. By contrast, high dose beclomethasone prevented the late asthmatic reaction and the low dose partially inhibited the reaction. With placebo the mean (±SE) value of FEV 1 4 h after exposure to TDI was 2.6 ± 0.17 L, which went to 3.3±0.12 after low dose beclomethasone, and to 3.5±0.15 L after high dose of beclomethasone (significant difference in the decrease of FEV 1 in the 8 h after exposure to TDI, between treatments: F = 9.87, (P < 0.001), After treatment with placebo or with low dose beclomethasone, airway responsiveness to methacholine increased 8 h after exposure to TDI. With placebo, the PD 20 decreased from 0.66 mg (Geometric Standard Error of the Mean [GSEM], 1.38) to 0.18 mg (GSEM, 1.46); with low dose inhaled beclomethasone, the PD 20 decreased from 0.93 mg (GSEM, 1.42) to 0.36 mg (GSEM, 1.63). By contrast, airway responsiveness to methacholine did not change 8 h after exposure to TDI in subjects treated with high dose inhaled beclomethasone: the PD 20 was 0.78 mg (GSEM, 1.51) before and 0.71 mg (GSEM, 1.58) after exposure to TDI. The protective effect of beclomethasone was obtained without side effects and without changes in serum cortisol levels (08.00) in any of the nine examined subjects. These results suggest that the inhibitory effect of inhaled beclomethasone on TDI-induced late asthmatic reactions and increased responsiveness is dose-dependent.