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Objective: To compare the safety and efficacy of anti-leukotrienes and inhaled glucocorticoids as monotherapy in people with asthma., Design: Systematic review of randomised controlled trials comparing anti-leukotrienes with inhaled glucocorticoids for 28 days or more in children and adults., Main Outcome Measure: Rate of exacerbations that required treatment with systemic glucocorticoids., Results: 13 trials (12 in adults, one in children) met the inclusion criteria; all were in people with mild and moderate asthma. Leukotriene receptor antagonists were compared with inhaled glucocorticoids at a daily dose equivalent to 400-450 microg beclometasone dipropionate. Patients treated with leukotriene receptor antagonists were 60% more likely to suffer an exacerbation requiring systemic glucocorticoids (relative risk 1.6, 95% confidence interval 1.2 to 2.2; number needed to treat 27, 13 to 81). A 130 ml greater improvement (80 ml to 170 ml) in forced expiratory volume in one second and a 19 l/min greater increase (14 l to 24 l) in morning peak expiratory flow rate were noted in favour of inhaled glucocorticoids. Differences in favour of inhaled glucocorticoids were also observed for nocturnal awakenings, use of rescue beta2 agonists, and days without symptoms. Risk of side effects was no different between groups, but leukotriene receptor antagonists were associated a 2.5-fold increase risk of withdrawals due to poor asthma control (relative risk 2.5, 1.8 to 3.5)., Conclusions: Inhaled glucocorticoids doses equivalent to 400 microg/day beclometasone are more effective than leukotriene receptor antagonists in the treatment of adults with mild or moderate asthma. There is insufficient evidence to conclude on the efficacy of anti-leukotrienes in children.

Objectives: To examine the evidence for the efficacy and glucocorticoid sparing effect of oral anti-leukotrienes taken daily as add-on therapy to inhaled glucocorticoids in patients with asthma., Design: Systematic review of randomised controlled trials of children and adults with asthma comparing the addition of anti-leukotrienes or placebo to inhaled glucocorticoids., Main Outcome Measures: The rate of exacerbations of asthma requiring rescue systemic glucocorticoids when the intervention was compared to the same or double dose of inhaled glucocorticoids, and the glucocorticoid sparing effect when the intervention was aimed at tapering the glucocorticoid., Results: Of 376 citations, 13 were included: 12 in adult patients and one in children. The addition of licensed doses of anti-leukotrienes to inhaled glucocorticoids resulted in a non-significant reduction in the risk of exacerbations requiring systemic steroids (two trials; relative risk 0.61, 95% confidence interval 0.36 to 1.05). No trials comparing the use of anti-leukotrienes with double the dose of inhaled glucocorticoids could be pooled. The use of anti-leukotrienes resulted in no overall group difference in the lowest achieved dose of inhaled glucocorticoids (three trials; weighted mean difference -44.43 microg/day, -147.87 to 59.02: random effect model) but was associated with a reduction in withdrawals owing to poor asthma control (four trials; relative risk 0.56, 0.35 to 0.89)., Conclusions: The addition of anti-leukotrienes to inhaled glucocorticoids may modestly improve asthma control compared with inhaled glucocorticoids alone but this strategy cannot be recommended as a substitute for increasing the dose of inhaled glucocorticoids. The addition of anti-leukotrienes is possibly associated with superior asthma control after tapering of glucocorticoids, but the glucocorticoids sparing effect cannot be quantified at present.

Objectives: To estimate the therapeutic and adverse effects of addition of inhaled anticholinergics to beta2 agonists in acute asthma in children and adolescents., Design: Systematic review of randomised controlled trials of children and adolescents taking beta2 agonists for acute asthma with or without the addition of inhaled anticholinergics., Main Outcome Measures: Hospital admission, pulmonary function tests, number of nebulised treatments, relapse, and adverse effects., Results: Of 37 identified trials, 10 were relevant and six of these were of high quality. The addition of a single dose of anticholinergic to beta2 agonist did not reduce hospital admission (relative risk 0.93, 95% confidence interval 0.65 to 1.32). However, significant group differences in lung function supporting the combination treatment were observed 60 minutes (standardised mean difference -0.57, -0.93 to -0.21) and 120 minutes (-0.53, -0.90 to -0.17) after the dose of anticholinergic. In contrast, the addition of multiple doses of anticholinergics to beta2 agonists, mainly in children and adolescents with severe exacerbations, reduced the risk of hospital admission by 30% (relative risk 0.72, 0.53 to 0.99). Eleven (95% confidence interval 5 to 250) children would need to be treated to avoid one admission. A parallel improvement in lung function (standardised mean difference -0.66, -0.95 to -0.37) was noted 60 minutes after the last combined inhalation. In the single study where anticholinergics were systematically added to every beta2 agonist inhalation, irrespective of asthma severity, no group differences were observed for the few available outcomes. There was no increase in the amount of nausea, vomiting, or tremor in patients treated with anticholinergics., Conclusions: Adding multiple doses of anticholinergics to beta2 agonists seems safe, improves lung function, and may avoid hospital admission in 1 of 11 such treated patients. Although multiple doses should be preferred to single doses of anticholinergics, the available evidence only supports their use in school aged children and adolescents with severe asthma exacerbation.