Daily Respiratory Research Analysis

BACKGROUND: Chronic obstructive pulmonary disease (COPD), the third leading cause of global mortality, remains a significant challenge in long-term management. While dual bronchodilators (LAMA/LABA) and inhaled corticosteroid combination therapies (ICS/LABA) alleviate symptoms, patients continue to face elevated risks of all-cause mortality and cardiovascular events. Recent studies suggest that triple therapy (ICS/LAMA/LABA) may improve outcomes by reducing acute exacerbations and systemic inflammation. However, its long-term effects on mortality and cardiovascular safety remain controversial, highlighting the critical need for systematic evidence to inform clinical decision-making. METHODS: A systematic search of PubMed, Embase, and the Cochrane Library (up to July 2024) identified 13 randomized controlled trials (RCTs) comparing triple therapy with dual therapies (LAMA/LABA or ICS/LABA) in patients with moderate-to-severe COPD. Outcomes included all-cause mortality, exacerbation rates, and cardiovascular adverse events of special interest (CVAESI). Risk ratios (RR) with 95% confidence intervals (CI) were calculated using fixed- or random-effects models based on heterogeneity (assessed via I² statistics). Subgroup analyses explored heterogeneity across drug combinations, supplemented by sensitivity analyses and publication bias assessments. RESULTS: Compared to LAMA/LABA dual therapy, triple therapy significantly reduced all-cause mortality (RR = 0.76, 95% CI = 0.60-0.97, p = 0.03), moderate-to-severe exacerbation risk (RR = 0.93, 95% CI = 0.90-0.97, p = 0.0003), and overall CVAESI incidence (RR = 0.75, 95% CI = 0.61-0.93, p = 0.008), with a 38% reduction in severe CVAESI (hospitalized or fatal events: RR = 0.62, 95% CI = 0.45-0.86, p = 0.004). Subgroup analyses demonstrated that the BGF regimen achieved superior reductions in CVAESI (RR = 0.72, 95% CI = 0.58-0.89, p = 0.003) and severe CVAESI (RR = 0.61, 95% CI = 0.47-0.79, p = 0.0002) compared to other triple therapies. Although BGF showed only a nonsignificant trend toward mortality reduction (RR = 0.77, 95% CI = 0.58-1.03, p = 0.08), it exhibited greater efficacy in reducing exacerbations (RR = 0.72 vs. non-BGF regimens) and cardiovascular risks. Non-BGF triple therapies yielded inconclusive results due to limited sample sizes and substantial heterogeneity (I²=62-83%, subgroup difference p < 0.05). Sensitivity analyses confirmed the stability of pooled estimates (< 5% variation upon study exclusion), with no significant publication bias detected via funnel plots or Begg's test (p > 0.05). CONCLUSION: This study confirms that ICS/LAMA/LABA triple therapy significantly reduces mortality, exacerbations, and cardiovascular risks in moderate-to-severe COPD compared to LAMA/LABA dual therapy. The BGF regimen, with optimized drug delivery and synergistic anti-inflammatory/bronchodilatory effects, shows superior clinical benefits, especially in high-risk patients. However, triple therapy did not improve survival or cardiovascular outcomes versus ICS/LABA. Differences in ICS pharmacokinetics highlight the need for personalized strategies based on eosinophil levels and adherence. BGF may be considered a preferred option for patients at high risk of exacerbations or with cardiovascular comorbidities. Future studies should compare triple therapies head-to-head and standardize cardiovascular endpoints to clarify long-term outcomes.

BACKGROUND: CT scans are the current gold standard for disease monitoring for Pleural mesothelioma (PM), with radiology reported using the modified RECIST criteria. While mRECIST has its own challenges, attending for CT scans adds time and expense. A blood-based biomarker which tracks disease status could enable more responsive, community-based disease monitoring. This study evaluated the relationship between serial serum mesothelin (SM) levels and disease status. METHODS: Patients with PM were recruited from Assess-Meso, a multi-centre prospective cohort study of patients with mesothelioma, between 28/2/2019 and 31/12/2023. Logistic regression, adjusted for sex, age, histology, performance status, eGFR and treatment, was used to assess the relationship between serial SM and radiological disease status. Prespecified sub-group analyses stratified participants by initial SM and treatment status. RESULTS: 156 patients had ≥ 2 SM measurements with paired CT scans. Rising SM was associated with disease progression in the coincident time period (Adj OR 1.11, 95 % CI 1.03-1.19) and the subsequent 6 months (Adj OR 1.13, 1.03-1.23), regardless of initial SM. A 25 % change in SM was the optimal threshold, with a 25 % rise associated with disease progression (Adj OR 2.68 (1.52-4.73)) with sensitivity and specificity of 48.7 % (43.1 %-54.4 %) and 75.7 % (70.8 %-80.5 %) respectively. For patients receiving treatment, falling SM predicted subsequent disease response (Adj OR 1.37, 1.16-1.61). CONCLUSIONS: Serial SM is a reliable response biomarker in PM, regardless of initial value and treatment status. These results support the use of SM in routine clinical care as an adjunct to CT scans, with several benefits over radiological monitoring.

BACKGROUND: The "type 2 (T2)-high" phenotype has a relatively well-defined pathophysiology compared with "T2-low" asthma. T2-low asthma has been mostly studied among severe asthma cases. OBJECTIVE: To estimate the proportion and assess the clinical features of asthma with low T2 markers in a general asthma population, including all severities. METHODS: Participants with current asthma from the population-based adult West Sweden Asthma Study were included. High T2 markers were defined as the blood eosinophil count ≥0.15 × 10 RESULTS: In total, 896 participants were included, of whom 14.3% had low T2 markers. The low T2 marker group had female predominance and had later asthma-onset age compared with the high T2 marker group. Participants with low T2 markers had better spirometry results in terms of airflow obstruction parameters but had more asthma-related emergency visits in the past 12 months than those with asthma with high T2 markers. CONCLUSIONS: In a general adult asthma population, 1 in 7 individuals have low T2 markers according to the criteria used in this study. Importantly, these individuals had better lung function than individuals with high T2 markers but a significantly increased risk of asthma exacerbations. Thus, having asthma with low T2 markers is an independent risk factor for exacerbations, which should be considered when assessing patients with asthma clinically.