A Systematic Review of the Efficacy and Safety of a Fixed-Dose Combination of Umeclidinium and Vilanterol for the Treatment of COPD.

BACKGROUND: COPD guidelines recommend the combined use of inhaled long-acting ß2-agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) if symptoms are not improved by a single agent. This systematic review tested the hypothesis that the bronchodilator effect of the LABA/LAMA combination, umeclidinium (UMEC)/vilanterol (VIL), would translate into better outcomes without incurring increased adverse events (AEs). METHODS: This was a systematic review of randomized, placebo-controlled or crossover trials (> 4 weeks) involving UMEC/VIL compared with its monocomponents, tiotropium, or fluticasone/salmeterol. Primary outcomes were trough FEV1, serious adverse events (SAEs), and serious cardiovascular events (SCVEs). RESULTS: Eleven trials from 10 studies (9,609 patients) showed that UMEV/VIL provided superior improvements in lung function compared with UMEC, VIL, tiotropium, and fluticasone propionate/salmeterol (mean trough FEV1, 60, 110, 90, and 90 mL, respectively; P < .0001). Also, UMEC/VIL had a greater likelihood of demonstrating a minimal clinically important difference on the Transition Dyspnea Index compared with UMEC and VIL (number needed to treat for benefit [NNTB] = 14 and 10, respectively). UMEC/VIL therapy significantly reduced the risk of COPD exacerbations compared with UMEC and VIL (NNTB = 42 and 41, respectively). On the contrary, we noted no significant differences between UMEC/VIL and tiotropium with respect to dyspnea, health status, or risk of COPD exacerbation. Regarding safety issues, the incidence of AEs, SAEs, SCVEs, and mortality on treatment was similar across treatments, suggesting reduced safety concerns with the use of the UMEC/VIL combination. CONCLUSIONS: Once-daily inhaled UMEC/VIL showed superior efficacy compared with its monocomponents, tiotropium, and fluticasone/combination in patients with moderate to severe COPD.

Formoterol for acute asthma in the emergency department: a systematic review with meta-analysis.

BACKGROUND: Although several published studies have suggested that formoterol fumarate could be equivalent to short-acting beta2-agonists (SABAs) for the treatment of asthma exacerbations, its role in acute asthma treatment remains undefined. OBJECTIVE: To evaluate the efficacy and safety of inhaled formoterol (compared with SABAs) for the emergency department treatment of patients with acute asthma. METHODS: Systematic searches were conducted in MEDLINE, EMBASE, the Cochrane Controlled Trials Register, and manufactures' trial registers, without language restriction. The primary outcomes were spirometric measures. The secondary outcomes included final serum potassium level, heart rate, electrocardiographic QT interval corrected for heart rate, and total withdrawals. RESULTS: Nine randomized controlled trials (including 576 participants) were selected. No significant difference could be detected between formoterol and SABAs for any of the selected time points: at 30 to 40 minutes after the first administration of study drugs (standardized mean difference, -0.19; 95% confidence interval, -0.56 to 0.17; I2 = 75%), at the end of treatment (standardized mean difference, -0.25; 95% confidence interval, -0.72 to 0.13; I2 = 89%), and at 60 to 90 minutes after the last dose (standardized mean difference, -0.13; 95% confidence interval, -0.55 to 0.28; I2 = 80%). Similarly, there were no significant differences between formoterol and SABAs regarding final serum potassium level, heart rate, QT interval, hospitalization rate, and total withdrawals. CONCLUSIONS: This review suggests that high-dose formoterol administered via dry powder inhaler is well tolerated and provides rapid and effective bronchodilation, similar to high-dose salbutamol or terbutaline via metered-dose inhaler or nebulizer. Formoterol may be used in the treatment of acute asthma in the emergency department setting.

Inhaled therapy for acute adult asthma.

PURPOSE OF REVIEW: To evaluate recent developments on emergency department inhalotherapy in non-intubated acute adult asthma patients. RECENT FINDINGS: There is evidence that high-flow oxygen can be associated with hypercarbia, and that full humidification of the inspired gases should be recommended. On the contrary, there is a lack of evidence to support the role of heliox in the initial treatment of acute asthma. Specific short-acting inhaled beta(2)-agonists are the drugs of choice. A more rapid and profound bronchodilatation with fewer side effects and less time of treatment can be achieved when sufficient doses are given using pressurized meter dose inhalers and large-volume valved-spacers, particularly in patients with the most severe obstruction. Findings argue against the routine use of continuous nebulization. High and repetitive doses of ipratropium bromide in combination with beta(2)-agonists are indicated as first line treatment of severe acute asthma. There is insufficient evidence that inhaled corticosteroids alone are as effective as systemic corticosteroids. Finally, the combination of nebulized magnesium and albuterol provides no benefit in addition to that provided by therapy with albuterol in patients with mild-to-moderate asthma exacerbations. SUMMARY: According to the latest evidence, the goals of treatment may be summarized as follows: maintenance of adequate arterial oxygen saturation with supplemental oxygen, relief of airflow obstruction by administration of inhaled beta-agonists and anticholinergics, and reduction of airway inflammation and prevention of future relapses by using early administration of systemic corticosteroids.