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Inhaled therapies for chronic obstructive pulmonary disease: a systematic review and meta-analysis.

ABSTRACT: OBJECTIVES:To integrate evidence from randomised controlled trials (RCTs) and observational studies on the efficacy of inhaled treatments for chronic obstructive pulmonary disease using network meta-analyses. METHODS:Systematic searches MEDLINE and Embase based on predetermined criteria. Network meta-analyses of RCTs investigated efficacy on exacerbations (long-term: ?20 weeks of treatment; short-term: <20 weeks), lung function (?12 weeks), health-related quality of life, mortality and adverse events. Qualitative comparisons of efficacies between RCTs and observational studies. RESULTS:212 RCTs and 19 observational studies were included. Compared with combined long-acting beta-adrenoceptor agonists and long-acting muscarinic antagonists (LABA+LAMA), triple therapy (LABA+LAMA+inhaled corticosteroid) was significantly more effective at reducing exacerbations (long-term 0.85 (95% CI: 0.78 to 0.94; short-term 0.67 (95% CI: 0.49 to 0.92)) and mortality (0.72 (95% CI: 0.59 to 0.89)) but was also associated with increased pneumonia (1.35 (95% CI: 1.10 to 1.67)). No differences in lung function (0.02 (95% CI: -0.10 to 0.14)), health-related quality of life (-1.12 (95% CI: -3.83 to 1.59)) or other adverse events (1.02 (95% CI: 0.96 to 1.08)) were found. Most of the observational evidence trended in the same direction as pooled RCT data. CONCLUSION:Further evidence, especially pragmatic trials, are needed to fully understand the characteristics of patient subgroups who may benefit from triple therapy and for those whom the extra risk of adverse events, such as pneumonia, may outweigh any benefits. PROSPERO REGISTRATION NUMBER:CRD42018088013.

SUBMITTER: Axson EL

PROVIDER: S-EPMC7526304 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Inhaled therapies for chronic obstructive pulmonary disease: a systematic review and meta-analysis.

Axson Eleanor L EL Lewis Adam A Potts James J Pang Marie M Dickinson Scott S Vioix Helene H Quint Jennifer K JK

BMJ open 20200929 9

<h4>Objectives</h4>To integrate evidence from randomised controlled trials (RCTs) and observational studies on the efficacy of inhaled treatments for chronic obstructive pulmonary disease using network meta-analyses.<h4>Methods</h4>Systematic searches MEDLINE and Embase based on predetermined criteria. Network meta-analyses of RCTs investigated efficacy on exacerbations (long-term: ≥20 weeks of treatment; short-term: <20 weeks), lung function (≥12 weeks), health-related quality of life, mortalit ...[more]

PMID: 32994234

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Project description:BACKGROUND:Although exacerbation and mortality are the most important clinical outcomes of stable chronic obstructive pulmonary disease (COPD), the drug classes that are the most efficacious in reducing exacerbation and mortality among all possible inhaled drugs have not been determined. METHODS AND FINDINGS:We performed a systematic review (SR) and Bayesian network meta-analysis (NMA). We searched Medline, EMBASE, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, the European Union Clinical Trials Register, and the official websites of pharmaceutical companies (from inception to July 9, 2019). The eligibility criteria were as follows: (1) parallel-design randomized controlled trials (RCTs); (2) adults with stable COPD; (3) comparisons among long-acting muscarinic antagonists (LAMAs), long-acting beta-agonists (LABAs), inhaled corticosteroids (ICSs), combined treatment (ICS/LAMA/LABA, LAMA/LABA, or ICS/LABA), or a placebo; and (4) study duration ? 12 weeks. This study was prospectively registered in International Prospective Register of Systematic Reviews (PROSPERO; CRD42017069087). In total, 219 trials involving 228,710 patients were included. Compared with placebo, all drug classes significantly reduced the total exacerbations and moderate to severe exacerbations. ICS/LAMA/LABA was the most efficacious treatment for reducing the exacerbation risk (odds ratio [OR] = 0.57; 95% credible interval [CrI] 0.50-0.64; posterior probability of OR > 1 [P(OR > 1)] < 0.001). In addition, in contrast to the other drug classes, ICS/LAMA/LABA and ICS/LABA were associated with a significantly higher probability of reducing mortality than placebo (OR = 0.74, 95% CrI 0.59-0.93, P[OR > 1] = 0.004; and OR = 0.86, 95% CrI 0.76-0.98, P[OR > 1] = 0.015, respectively). The results minimally changed, even in various sensitivity and covariate-adjusted meta-regression analyses. ICS/LAMA/LABA tended to lower the risk of cardiovascular mortality but did not show significant results. ICS/LAMA/LABA increased the probability of pneumonia (OR for triple therapy = 1.56; 95% CrI 1.19-2.03; P[OR > 1] = 1.000). The main limitation is that there were few RCTs including only less symptomatic patients or patients at a low risk. CONCLUSIONS:These findings suggest that triple therapy can potentially be the best option for stable COPD patients in terms of reducing exacerbation and all-cause mortality.

Project description:BackgroundThe fracture risk of patients with chronic obstructive pulmonary disease (COPD) treated with inhaled corticosteroids is controversial. And some large-scale randomized controlled trials have not solved this problem. The purpose of our systematic review and meta-analysis including 44 RCTs is to reveal the effect of inhaled corticosteroids on the fracture risk of COPD patients.MethodsTwo reviewers independently retrieved randomized controlled trials of inhaled corticosteroids or combinations of inhaled corticosteroids in the treatment of COPD from PubMed, Embase, Medline, Cochrane Library, and Web of Science. The primary outcome was a fracture event. This study was registered at PROSPERO (CRD42022366778).ResultsForty-four RCTs were performed in 87,594 patients. Inhaled therapy containing ICSs (RR, 1.19; 95%CI, 1.04-1.37; P = 0.010), especially ICS/LABA (RR, 1.30; 95%CI, 1.10-1.53; P = 0.002) and triple therapy (RR, 1.49; 95%CI, 1.03-2.17; P = 0.04) were significantly associated with the increased risk of fracture in COPD patients when compared with inhaled therapy without ICSs. Subgroup analyses showed that treatment duration ≥ 12 months (RR, 1.19; 95%CI, 1.04-1.38; P = 0.01), budesonide therapy (RR, 1.64; 95%CI., 1.07-2.51; P = 0.02), fluticasone furoate therapy (RR, 1.37; 95%CI, 1.05-1.78; P = 0.02), mean age of study participants ≥ 65 (RR, 1.27; 95%CI, 1.01-1.61; P = 0.04), and GOLD stage III(RR, 1.18; 95%CI, 1.00-1.38; P = 0.04) were significantly associated with an increased risk of fracture. In addition, budesonide ≥ 320 ug bid via MDI (RR, 1.75; 95%CI, 1.07-2.87; P = 0.03) was significantly associated with the increased risk of fracture.ConclusionInhalation therapy with ICSs, especially ICS/LABA or triple therapy, increased the risk of fracture in patients with COPD compared with inhaled therapy without ICS. Treatment duration, mean age of participants, GOLD stage, drug dosage form, and drug dose participated in this association. Moreover, different inhalation devices of the same drug also had differences in risk of fracture.

Project description:Chronic obstructive pulmonary disease (COPD) is a common lung disease that causes restricted airflow and breathing problems. Globally, COPD is the third leading cause of death and low- and middle-income countries account for the majority of these deaths. There is limited information on COPD's prevalence in East Africa. Thus the purpose of this systematic review and meta-analysis is to estimate the pooled prevalence of COPD in East Africa.A computerized systematic search using multiple databases was performed in search of relevant English articles from the inception of the databases to August 2023. All the authors independently extracted the data. R and RStudio software were used for statistical analysis. Forest plots and tables were used to represent the data. The statistical heterogeneity was evaluated using I2 statistics. There was heterogeneity between the included articles. Therefore, a meta-analysis of random effects models was used to estimate the overall pooled prevalence of COPD in East Africa. A funnel plot test was used to examine possible publication bias.The database search produced 512 papers. After checking for inclusion and exclusion criteria, 43 full-text observational studies with 68 553 total participants were found suitable for the review. The overall pooled prevalence of COPD in East Africa was 13.322%. The subgroup analysis found the COPD pooled prevalence in the different countries was 18.994%, 7%, 15.745%, 9.032%, 15.026% and 11.266% in Ethiopia, Uganda, Tanzania, Malawi, Sudan, and Kenya, respectively. Additionally, the subgroup analysis of COPD by study setting among community-based studies was 12.132% and 13.575% for hospital-based studies.According to the study's findings, approximately one of every seven individuals in East Africa has COPD, indicating a notably high prevalence of the disease. Thus governments and other stakeholders working on non-communicable disease control should place an emphasis on preventive measures to minimize the burden of COPD.

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Inhaled therapies for chronic obstructive pulmonary disease: a systematic review and meta-analysis.

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Inhaled therapies for chronic obstructive pulmonary disease: a systematic review and meta-analysis.

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