Background: Chronic obstructive pulmonary disease (COPD) is a progressive lung disease marked by airway inflammation and obstruction. Ensifentrine is a novel inhaled PDE3 and PDE4 inhibitor with both bronchodilator and anti-inflammatory effects. Objectives: Comprehensively review the available evidence on ensifentrine and its potential role in COPD management. Design: Systematic review and meta-analysis with trial sequential analysis of randomized clinical trials. Data sources and methods: We systematically searched PubMed, Scopus, ScienceDirect, Cochrane Library, and Medline for clinical trials published between 2018 and August 2024 that evaluated the safety and efficacy of ensifentrine in patients with COPD. We assessed study quality using the RoB 2 tool and conducted the meta-analysis with the “meta” package in R (version 4.3.2), using the mean difference with a 95% confidence interval to evaluate changes in outcomes. Results: Five studies met the predefined inclusion criteria with 2519 participants. At week 12, the pooled analysis indicated that forced expiratory volume in 1 s (FEV ₁ ) and trough FEV ₁ were significantly increased in the ensifentrine group (mean difference (MD): 91.32; 95% CI: 69.63 to 113.01) and (MD: 40.90; 95% CI: 19.65 to 62.15), respectively. At week 24, the pooled analysis indicated that the evaluating respiratory symptoms total score was significantly decreased in the ensifentrine group (MD: −0.81; 95% CI: −1.36 to −0.27), transition dyspnea index score was significantly increased in the ensifentrine group (MD: 0.96; 95% CI: 0.62 to 1.29), no significant difference was observed in rescue medication use (MD: −0.30; 95% CI: −0.60 to 0.00), and no significant difference was observed in St. George’s Respiratory Questionnaire total score (MD: −1.46; 95% CI: −3.22 to 0.30). Based on subgroup analysis, higher doses were associated with more favorable results. Conclusion: In conclusion, owing to its dual effects, ensifentrine has a significant impact on improving pulmonary function and quality of life with minimal side effects. Promising results are expected if implied by synergizing with other drugs, however, more studies are needed to study the long-term effect on disease progression. Trial registration: The study protocol was published via PROSPERO: International Prospective Register of Systematic Reviews (#CRD42024570799).

Background: Adjuvant radiation therapy for breast cancer improves survival but may expose thoracic organs to low-dose radiation, potentially increasing the risk of second primary lung cancer (SPLC). Prior studies have not adequately examined how SPLC risk varies across racial and ethnic groups or whether social factors influence incidence and survival outcomes. Objectives: To quantify racial and ethnic disparities in SPLC incidence and survival among breast cancer survivors treated with radiation and assess the potential protective role of marital status. Methods: We used SEER-17 registry data to identify patients diagnosed with a first malignant primary breast cancer from 2000 to 2022 who received radiotherapy. Patients who died within two months of diagnosis were excluded. Standardized incidence ratios (SIRs) were calculated to compare observed to expected SPLC cases across racial and ethnic groups, stratified by latency intervals (2–11, 12–59, 60–119, and ≥120 months) and marital status. Racial categories included White, Black, Asian or Pacific Islander (API), and American Indian or Alaska Native (AI/AN); ethnicity was categorized as Hispanic or non-Hispanic. Five-year overall survival after SPLC was estimated using Kaplan–Meier analysis, and mean age at death was calculated by subgroup. Results: Among 558,493 radiotherapy-treated breast cancer patients, 6,674 developed SPLC (1.19%). Risk varied significantly by race (p < 0.05). Black survivors had a 21% excess risk (SIR 1.21, 95% CI: [1.12–1.31]), peaking 5–10 years post-treatment (SIR 1.44, [1 .26-1.63]) and remaining elevated beyond 10 years (SIR 1.24, [1.05-1.45]). API patients had a 23% overall excess risk (SIR 1.23, [1.11-1.36]), while AI/AN patients had the highest overall risk (SIR 1.82, [1.24-2.57]), particularly in the 12–59 month window (SIR 2.29, [1.25-3.84]) and ≥120 months (SIR 2.38, [1.19-4.26]). White survivors had no sustained increased risk (SIR 0.96, [0.93-0.98]), aside from a short-term rise in the first post-treatment year. Hispanic patients had consistently lower SPLC risk (overall SIR 0.72, [0.65-0.79]), while non-Hispanics had a transient early increase but an overall neutral risk (SIR 1.01, [0.99-1.04]). Marital status was protective: married individuals had a 12% lower SPLC incidence (SIR 0.88, 95% CI 0.85–0.91). Five-year overall survival after SPLC was 28.0%, with significant variation by race and ethnicity (p = 0.002). API (32.2%) and AI/AN (32.5%) patients had the highest survival, followed by White (28.0%) and Black patients (25.6%). Hispanic patients had the best outcomes, with 37.4% five-year survival and a mean age at death of 65.5 years, compared to 27.0% and 55.0 years for non-Hispanics (p = 0.005). Married patients had higher five-year survival (31.8%) and older mean age at death (64.3 years) compared to unmarried patients (25.0%, 48.6 years; p < 0.001). Conclusion: Radiation-associated SPLC risk and prognosis vary significantly by race, ethnicity, and marital status. Black and API survivors face sustained elevated risk; AI/AN survivors experience high early and long-term risk, while White and Hispanic survivors show no increased risk overall. Hispanic and married patients experience better survival after SPLC. These findings underscore the need for race and context aware survivorship counseling and suggest consideration of personalized lung cancer screening thresholds for breast cancer survivors receiving radiotherapy.