Introduction:
Triple combinations of long-acting β2 agonist/long-acting muscarinic antagonist/inhaled corticosteroids (LABA/LAMA/ICS) are recommended for COPD patients with persistent symptoms and high risk of acute exacerbation. The increasing use of triple combination therapies has followed the reimbursement of the fixed-dose combination (FDC) dosage form since 2017. Numerous clinical trials were conducted to investigate the effectiveness of LABA/LAMA/ICS compared to LABA/ICS. However, real-world evidence regarding cardiovascular safety remains limited.

Aims:
This cohort study aimed to investigate the cardiovascular safety of LABA/LAMA/ICS FDC versus LABA/ICS FDC in patients with COPD in real-world settings.

Methods:
We identified patients with COPD who initiated LABA/LAMA/ICS or used LABA/ICS FDC from a nationwide Taiwanese database between 2017 and 2022. The outcomes of interest were hospitalized composite cardiovascular events, including acute myocardial infarction, unstable angina, heart failure, cardiac dysrhythmia, and ischemic stroke. We estimated propensity scores (PS) for each patient based on their baseline demographics, comorbidities, concurrent medications, and resource utilization. The Cox proportional regression model was applied to estimate the hazard ratios (HR) and the 95% confidence intervals (CI) for composite and individual cardiovascular outcomes comparing LABA/LAMA/ICS versus LABA/ICS after 1:10 variable-ratio PS matching.

Results:
The study population consisted of a total of 58,371 patients (n=8,189 for LABA/LAMA/ICS and n=50,182 for LABA/ICS). After 1:10 variable-ratio PS matching, 28,851 patients (n=5,836 for LABA/LAMA/ICS and n=23,015 for LABA/ICS) were included in the analysis. The HR of composite cardiovascular events comparing LABA/LAMA/ICS to LABA/ICS was 1.00 (95% CI, 0.78-1.28). The results did not materially change for individual cardiovascular outcomes and were similar across subgroup analyses stratified by patient characteristics, including age, sex, and COPD duration.

Conclusion:
In this population-based cohort study, we did not observe an increased cardiovascular risk associated with LABA/LAMA/ICS FDC compared to LABA/ICS FDC in patients with COPD.

Keywords:
Chronic obstructive pulmonary disease, LABA/LAMA/ICS, LABA/ICS, cardiovascular safety

Introduction. Chronic Obstructive Pulmonary Disease (COPD) is one of the major global public health concerns, projected to become the third leading cause of mortality by 2030. Economic considerations persist regarding the selection between dual therapy and triple therapy for COPD treatment.
Aims. To evaluate the cost-effectiveness of triple therapy with dual therapy in terms of quality-adjusted life years (QALYs) and exacerbations avoided in patients with COPD.
Methods. A systematic search was performed in PubMed, Google Scholar, Scopus, and Cost-Effectiveness Analysis (CEA) Registry for eligible cost-effectiveness and cost-utility studies published up to 31st October 2023. The risk of bias in the included studies was assessed using the modified Economic Evaluations Bias (ECOBIAS) checklist. Monetary values were extracted and standardized to purchasing power parity, then adjusted to 2023 U.S. Dollars. The pooled incremental net benefits (INBs) of quality-adjusted life years (QALYs) and exacerbations avoided for triple therapy versus dual therapy in COPD were analyzed using either Fixed or Random-effects models based on heterogeneity assessed by the I² statistic and Cochran’s Q test.
Results. Out of 116 studies, 10 were eligible, predominantly from high-income countries. The overall pooled INB of QALYs for triple therapy versus dual therapy was US$4969.19 (95% CI US$3620.16, US$6318.21; P=0.00001). In subgroup analysis, Budesonide/Glycopyrrolate/Formoterol fumarate (B/G/F) (2 studies) demonstrated the highest INB of US$5717.96, followed by Fluticasone Furoate/Umeclidinium/Vilanterol (FF/UMEC/VI) (6 studies) with an INB of US$5675.90. However, Tiotropium/Fluticasone/Salmeterol (TFS) (2 studies) showed the lowest value among the three. Regarding exacerbations avoided, the pooled INB was US$21163.81 (95% CI US$4788.62, US$37539.00; P=0.005). B/G/F exhibited the most favorable outcome with an INB of US$45540.51, followed by FF/UMEC/VI (US$14832.51) and TFS (US$10249.29), respectively.
Discussion. The comparison of triple therapy to dual therapy reveals significant differences in cost-effectiveness for improving QALYs and reducing exacerbations in COPD, with B/G/F showing the most favorable outcomes. However, the substantial heterogeneity highlights the need for further research and deeper understanding in this field. Heterogeneity is caused by study design (model or alongside clinical trials), population, country, GDP, or economic perspective taken.

Aim/Objective: Although traditional Chinese medicine (TCM) is commonly prescribed as an adjuvant therapy for chronic obstructive pulmonary disease (COPD), evidences supporting the effect of the TCM and western medicine (WM) combination remain unclear. We aimed to evaluate the efficacy of concurrent use of TCM and WM for chronic disease management in patients with COPD.
Methods: Patients who had COPD were selected as the study cohort from the National Health Insurance Research Database of Taiwan. The date of the initial COPD diagnosis, along with the following 365 days, is considered the index period, with the day of the first diagnosis designated as the COPD diagnosis date and the addition of 365 days as the index date. Those COPD patients were classified as TCM users or TCM nonusers. An 1:4 propensity score matching will be conducted, pairing one TCM user with four TCM nonusers. Within 730 days after the index date, the occurrence of acute exacerbations (AE) of COPD is defined as the study outcome. The stratified univariate and multivariate Cox proportional hazard models were used to present hazard ratios and 95% confidence intervals.
Results: The study cohort comprised 1,414,906 eligible patients. After propensity score matching, TCM users remained 86,510 cases and 346,034 TCM nonusers were selected. After adjusting for the confounding effects of demographics, comorbidities, and use of other medications, we obtained consistent results for the 3 models. Compared with TCM nonusers, those using TCM concurrently with WM had a lower risk of AE. The adjusted hazard ratio from Models 1 to 3 were 0.90 (95% CI: 0.88-0.92), 0.91 (95% CI: 0.89-0.94), and 0.76 (95% CI: 0.74-0.79), respectively.
Conclusion: For patients with COPD, the concurrent uses of TCM and WM could decrease the risk of AE.

Introduction
Although CDC recommended pneumococcal vaccination for all chronic obstructive pulmonary disease (COPD) patients, the vaccination coverage within this high-risk group especially in aged 19-64 remains suboptimal.

Objective
To investigate the trend, pattern, and the characteristics associated with pneumococcal vaccine uptake among US COPD population from 2018 to 2022.

Methods
The 2018 - 2022 U.S. National Health Interview Survey were used to conduct this study. Adults with COPD and age between 19-64 years were identified through self-reported survey questionnaires. The pneumococcal vaccination coverage was the dependent variable which was measured by respondents self-reported the following question: “Have you ever had a pneumonia shot?” Prevalence and trends of pneumococcal vaccination coverage was adjusted for the NHIS complex sampling design with the clustering and stratification. Multivariable logistic regression models were performed to identify factors associated with pneumococcal vaccination coverage.

Results
Prevalence of pneumococcal vaccination among aged 19-64 years with COPD was increased from 39.5% in 2018 to 43.37% (P=0.18). In adjusted analysis, those who were more likely to receive pneumococcal vaccine were women (OR:1.73, 95% CI:1.11-2.68), Asian (OR:6.92, 95% CI:1.33-36.07), having health insurance (OR:3.69, 95% CI:1.33-1.21), being former drinkers (OR:3.36, 95% CI:1.28-8.80), and having additional comorbidities (OR:2.28, 95% CI:1.38-3.75). Characteristics including education, household income, having a usual place for healthcare, BMI, smoking status were found not statistically significantly associated with the pneumococcal vaccine uptake in the multivariable-adjusted model.

Conclusion
Pneumococcal vaccination coverage in COPD aged 19-64 years with COPD has slightly increased from 2018 to 2022. Healthcare professionals should still actively advocate for pneumococcal vaccination for all COPD patients, especially men, uninsured, and those without other comorbidities.

Keywords: Pneumococcal vaccination; chronic obstructive pulmonary disease (COPD); coverage; vaccination

-Introduction
Better glycemic control in diabetic patients may reduce asthma exacerbations. Sodium-glucose cotransporter 2 (SGLT2) inhibitors and GLP-1 receptor agonists (GLP-1 RAs) show similar glucose-lowering effects, while dipeptidyl peptidase-4 (DPP-4) inhibitors may be less effective.

-Aims
To evaluate the effects of SGLT2 inhibitors and GLP-1 RAs versus DPP-4 inhibitors on asthma exacerbations in diabetic patients.

-Methods
We conducted a retrospective cohort study using the National Health Insurance Research Database (NHIRD). Adult patients with type 2 diabetes and asthma, without a history of asthma exacerbation, were newly prescribed SGLT2 inhibitors, GLP-1 RAs, or DPP-4 inhibitors between 2016 and 2020. Target trial emulation and propensity score matching were used to enhance causal inferences. The composite asthma exacerbation outcome was defined as clinical visits for asthma exacerbation or systemic corticosteroid use. Patients were followed until the outcome, death, or December 31, 2020. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using the Cox proportional hazards model.

-Results
The first cohort included 27,170 patients (4,897 on SGLT2 inhibitors, 22,273 on DPP-4 inhibitors). The second cohort included 23,839 patients (440 on GLP-1 RAs, 23,399 on DPP-4 inhibitors). SGLT2 inhibitors (HR 0.82; 95% CI 0.73-0.93) and GLP-1 RAs (HR 0.71; 95% CI 0.48-1.04) showed lower risks of composite asthma exacerbation compared with DPP-4 inhibitors. Results for individual outcomes were consistent with the primary analysis. SGLT2 inhibitors (HR 0.64; 95% CI 0.57-0.71) and GLP-1 RAs (HR 0.91; 95% CI 0.68-1.21) also demonstrated lower all-cause mortality risk.

-Discussion/Conclusion
Our study suggests significant differences in asthma exacerbation risk between SGLT2 inhibitors and DPP-4 inhibitors in routine care. GLP-1 RAs also showed a lower risk, though not statistically significant due to sample size limitations. SGLT2 inhibitors might be a choice for type 2 diabetes patients with asthma, but further large-scale studies are needed to validate these findings.