OBJECTIVES: To assess the efficacy and safety of aclidinium bromide in stable COPD.

SEARCH METHODS: We identified randomised controlled trials (RCT) from the Cochrane Airways Group Specialised Register of trials (CAGR), as well as www.clinicaltrials.gov, World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), US Food and Drug Administration (FDA) website and Almirall Clinical Trials Registry and Results. We contacted Forest Laboratories for any unpublished trials and checked the reference lists of identified articles for additional information. The last search was performed on 7 April 2014 for CAGR and 11 April 2014 for other sources.

SELECTION CRITERIA: Parallel-group RCTs of aclidinium bromide compared with placebo, long-acting beta2-agonists (LABA) or LAMA in adults with stable COPD.

DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed the risk of bias, and extracted data. We sought missing data from the trial authors as well as manufacturers of aclidinium. We used odds ratios (OR) for dichotomous data and mean difference (MD) for continuous data, and reported both with their 95% confidence intervals (CI). We used standard methodological procedures expected by The Cochrane Collaboration. We applied the GRADE approach to summarise results and to assess the overall quality of evidence.

MAIN RESULTS: This review included 12 multicentre RCTs randomly assigning 9547 participants with stable COPD. All the studies were industry-sponsored and had similar inclusion criteria with relatively good methodological quality. All but one study included in the meta-analysis were double-blind and scored low risk of bias. The study duration ranged from four weeks to 52 weeks. Participants were more often males, mainly Caucasians, mean age ranging from 61.7 to 65.6 years, and with a smoking history of 10 or more pack years. They had moderate to severe symptoms at randomisation; the mean post-bronchodilator forced expiratory volume in one second (FEV1) was between 46% and 57.6% of the predicted normal value, and the mean St George's Respiratory Questionnaire score (SGRQ) ranged from 45.1 to 50.4 when reported.There was no difference between aclidinium and placebo in all-cause mortality (low quality) and number of patients with exacerbations requiring a short course of oral steroids or antibiotics, or both (moderate quality). Aclidinium improved quality of life by lowering the SGRQ total score with a mean difference of -2.34 (95% CI -3.18 to -1.51; I(2) = 48%, 7 trials, 4442 participants) when compared to placebo. More patients on aclidinium achieved a clinically meaningful improvement of at least four units decrease in SGRQ total score (OR 1.49; 95% CI 1.31 to 1.70; I(2) = 34%; number needed to treat (NNT) = 10, 95% CI 8 to 15, high quality evidence) over 12 to 52 weeks than on placebo. Aclidinium also resulted in a significantly greater improvement in pre-dose FEV1 than placebo with a mean difference of 0.09 L (95% CI 0.08 to 0.10; I(2) = 39%, 9 trials, 4963 participants). No trials assessed functional capacity. Aclidinium reduced the number of patients with exacerbations requiring hospitalisation by 4 to 20 fewer per 1000 over 4 to 52 weeks (OR 0.64; 95% CI 0.46 to 0.88; I(2) = 0%, 10 trials, 5624 people; NNT = 77, 95% CI 51 to 233, high quality evidence) compared to placebo. There was no difference in non-fatal serious adverse events (moderate quality evidence) between aclidinium and placebo.Compared to tiotropium, aclidinium did not demonstrate significant differences for exacerbations requiring oral steroids or antibiotics, or both, exacerbation-related hospitalisations and non-fatal serious adverse events (very low quality evidence). Inadequate data prevented the comparison of aclidinium to formoterol or other LABAs.

METHODS: We analysed the total visits and discharge rates during periods of using the nebulizer and current pMDI-VMMS methods. The acceptance of pMDI-VMMS by patients and assistant medical officers (AMOs) were assessed by questionnaire.

RESULTS AND DISCUSSION: We analysed 3184 ED visits and responses from 103 patients and 32 AMOs. The direct discharge rate was similar for both nebulizer (n = 2162, 92.5%) and pMDI-VMMS method (n = 768, 90.7%) (p-value = 0.120). Twenty-eight patients (27.2%) favoured the pMDI-VMMS over the nebulizer, whereas 36 patients (35.0%) had no preference for either method. Sixty-four patients (62.1%) felt that the current pMDI-VMMS method was better or at least as effective in relieving their symptoms as a nebulizer. The current method was favoured over the nebulizer by twenty-seven AMOs (84.4%). Twenty-eight (87.5%) AMOs suggested that the current method was more effective than the nebulizer.

OBJECTIVES: To assess the efficacy and safety of umeclidinium bromide versus placebo for people with stable COPD.

SEARCH METHODS: We searched the Cochrane Airways Group Specialised Register (CAGR), ClinicalTrials.gov, the World Health Organization (WHO) trials portal, and the GlaxoSmithKline (GSK) Clinical Study Register, using prespecified terms, as well as the reference lists of all identified studies. Searches are current to April 2017.

SELECTION CRITERIA: We included randomised controlled trials (RCTs) of parallel design comparing umeclidinium bromide versus placebo in people with COPD, for at least 12 weeks.

DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. If we noted significant heterogeneity in the meta-analyses, we subgrouped studies by umeclidinium dose.

MAIN RESULTS: We included four studies of 12 to 52 weeks' duration, involving 3798 participants with COPD. Mean age of participants ranged from 60.1 to 64.6 years; most were males with baseline mean smoking pack-years of 39.2 to 52.3. They had moderate to severe COPD and baseline mean post-bronchodilator forced expiratory volume in one second (FEV1) ranging from 44.5% to 55.1% of predicted normal. As all studies were systematically conducted according to prespecified protocols, we assessed risk of selection, performance, detection, attrition, and reporting biases as low.Compared with those given placebo, participants in the umeclidinium group had a lesser likelihood of developing moderate exacerbations requiring a short course of steroids, antibiotics, or both (odds ratio (OR) 0.61, 95% confidence interval (CI) 0.46 to 0.80; four studies, N = 1922; GRADE: high), but not specifically requiring hospitalisations due to severe exacerbations (OR 0.86, 95% CI 0.25 to 2.92; four studies, N = 1922, GRADE: low). The number needed to treat for an additional beneficial outcome (NNTB) to prevent an acute exacerbation requiring steroids, antibiotics, or both was 18 (95% CI 13 to 37). Quality of life was better in the umeclidinium group (mean difference (MD) -4.79, 95% CI -8.84 to -0.75; three studies, N = 1119), and these participants had a significantly higher chance of achieving a minimal clinically important difference of at least four units in St George's Respiratory Questionnaire (SGRQ) total score compared with those in the placebo group (OR 1.45, 95% CI 1.16 to 1.82; three studies, N = 1397; GRADE: moderate). The NNTB to achieve one person with a clinically meaningful improvement was 11 (95% CI 7 to 29). The likelihood of all-cause mortality, non-fatal serious adverse events (OR 1.33; 95% CI 0.89 to 2.00; four studies, N = 1922, GRADE: moderate), and adverse events (OR 1.06, 95% CI 0.85 to 1.31; four studies, N = 1922; GRADE: moderate) did not differ between umeclidinium and placebo groups. The umeclidinium group demonstrated significantly greater improvement in change from baseline in trough FEV1 compared with the placebo group (MD 0.14, 95% CI 0.12 to 0.17; four studies, N = 1381; GRADE: high). Symptomatic improvement was more likely in the umeclidinium group than in the placebo group, as determined by Transitional Dyspnoea Index (TDI) focal score (MD 0.76, 95% CI 0.43 to 1.09; three studies, N = 1193), and the chance of achieving a minimal clinically important difference of at least one unit improvement was significantly higher with umeclidinium than with placebo (OR 1.71, 95% CI 1.37 to 2.15; three studies, N = 1141; GRADE: high). The NNTB to attain one person with clinically important symptomatic improvement was 8 (95% CI 5 to 14). The likelihood of rescue medication usage (change from baseline in the number of puffs per day) was significantly less for the umeclidinium group than for the placebo group (MD -0.45, 95% CI -0.76 to -0.14; four studies, N = 1531).

OBJECTIVE: The objective of this paper is to review the recent literature on vesicular drug delivery systems containing curcumin.

METHODS: We have collated and summarized various recent attempts made to develop different controlled release drug delivery systems containing curcumin which would be of great interest for herbal, formulation and biological scientists. There are several vesicular nanotechnological techniques involving curcumin which have been studied recently, targeting pulmonary diseases.

RESULTS: Different vesicular systems containing curcumin are being studied for their therapeutic potential in different respiratory diseases. There has been a renewed interest in formulations containing curcumin recently, primarily owing to the broad spectrum therapeutic potential of this miracle substance. Various types of formulations, containing curcumin, targeting different bodily systems have recently emerged and, nevertheless, the search for newer frontiers with this drug goes on.

OBJECTIVES: To assess the efficacy and safety of combined aclidinium bromide and long-acting beta2-agonists in stable COPD.

SEARCH METHODS: We searched the Cochrane Airways Group Specialised Register (CAGR), ClinicalTrials.gov, World Health Organization (WHO) trials portal, United States Food and Drug Administration (FDA) and manufacturers' websites as well as the reference list of published trials up to 12 October 2018.

SELECTION CRITERIA: Parallel-group randomised controlled trials (RCTs) assessing combined aclidinium bromide and LABAs in people with stable COPD.

DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane for data collection and analysis. The primary outcomes were exacerbations requiring a short course of an oral steroid or antibiotic, or both; quality of life measured by a validated scale and non-fatal serious adverse events (SAEs). Where the outcome or study details were not reported, we contacted the study investigators or pharmaceutical company trial co-ordinators (or both) for missing data.

MAIN RESULTS: We identified RCTs comparing aclidinium/formoterol FDC versus aclidinium, formoterol or placebo only. We included seven multicentre trials of four to 52 weeks' duration conducted in outpatient settings. There were 5921 participants, whose mean age ranged from 60.7 to 64.7 years, mostly men with a mean smoking pack-years of 46.4 to 61.3 of which 43.9% to 63.4% were current smokers. They had a moderate-to-severe degree of COPD with a mean postbronchodilator forced expiratory volume in one second (FEV1) between 50.5% and 61% of predicted normal and the baseline mean FEV1 of 1.23 L to 1.43 L. We assessed performance and detection biases as low for all studies whereas selection, attrition and reporting biases were either low or unclear.FDC versus aclidiniumThere was no evidence of a difference between FDC and aclidinium for exacerbations requiring steroids or antibiotics, or both (OR 0.95, 95% CI 0.71 to 1.27; 2 trials, 2156 participants; moderate-certainty evidence); quality of life measured by St George's Respiratory Questionnaire (SGRQ) total score (MD -0.92, 95% CI -2.15 to 0.30); participants with significant improvement in SGRQ score (OR 1.17, 95% CI 0.97 to 1.41; 2 trials, 2002 participants; moderate-certainty evidence); non-fatal SAE (OR 1.19, 95% CI 0.79 to 1.80; 3 trials, 2473 participants; moderate-certainty evidence); hospital admissions due to severe exacerbations (OR 0.62, 95% CI 0.29 to 1.29; 2 trials, 2156 participants; moderate-certainty evidence) or adverse events (OR 0.95, 95% CI 0.76 to 1.18; 3 trials, 2473 participants; moderate-certainty evidence). Compared with aclidinium, FDC improved symptoms (Transitional Dyspnoea Index (TDI) focal score: MD 0.37, 95% CI 0.07 to 0.68; 2 trials, 2013 participants) with a higher chance of achieving a minimal clinically important difference (MCID) of at least one unit improvement (OR 1.34, 95% CI 1.11 to 1.62; high-certainty evidence); the number needed to treat for an additional beneficial outcome (NNTB) being 14 (95% CI 9 to 39).FDC versus formoterolWhen compared to formoterol, combination therapy reduced exacerbations requiring steroids or antibiotics, or both (OR 0.78, 95% CI 0.62 to 0.99; 3 trials, 2694 participants; high-certainty evidence); may decrease SGRQ total score (MD -1.88, 95% CI -3.10 to -0.65; 2 trials, 2002 participants; low-certainty evidence; MCID for SGRQ is 4 units); increased TDI focal score (MD 0.42, 95% CI 0.11 to 0.72; 2 trials, 2010 participants) with more participants attaining an MCID (OR 1.30, 95% CI 1.07 to 1.56; high-certainty evidence) and an NNTB of 16 (95% CI 10 to 60). FDC lowered the risk of adverse events compared to formoterol (OR 0.78, 95% CI 0.65 to 0.93; 5 trials, 3140 participants; high-certainty evidence; NNTB 22). However, there was no difference between FDC and formoterol for hospital admissions, all-cause mortality and non-fatal SAEs.FDC versus placeboCompared with placebo, FDC demonstrated no evidence of a difference in exacerbations requiring steroids or antibiotics, or both (OR 0.82, 95% CI 0.60 to 1.12; 2 trials, 1960 participants; moderate-certainty evidence) or hospital admissions due to severe exacerbations (OR 0.55, 95% CI 0.25 to 1.18; 2 trials, 1960 participants; moderate-certainty evidence), although estimates were uncertain. Quality of life measure by SGRQ total score was significantly better with FDC compared to placebo (MD -2.91, 95% CI -4.33 to -1.50; 2 trials, 1823 participants) resulting in a corresponding increase in SGRQ responders who achieved at least four units decrease in SGRQ total score (OR 1.72, 95% CI 1.39 to 2.13; high-certainty evidence) with an NNTB of 7 (95% CI 5 to 12). FDC also improved symptoms measured by TDI focal score (MD 1.32, 95% CI 0.96 to 1.69; 2 studies, 1832 participants) with more participants attaining at least one unit improvement in TDI focal score (OR 2.51, 95% CI 2.02 to 3.11; high-certainty evidence; NNTB 4). There were no differences in non-fatal SAEs, adverse events and all-cause mortality between FDC and placebo.Combination therapy significantly improved trough FEV1 compared to aclidinium, formoterol or placebo.