Daily Respiratory Research Analysis

IMPORTANCE: Acute respiratory distress syndrome (ARDS) represents a frequent and serious complication after cardiovascular surgery. Although sivelestat, a specific neutrophil elastase inhibitor, has demonstrated therapeutic potential in preliminary studies, the evidence remains limited by methodological constraints of observational designs and underpowered studies. OBJECTIVE: To evaluate the efficacy of sivelestat vs placebo in reducing the incidence of postoperative ARDS and associated complications among patients undergoing major cardiovascular procedures. DESIGN, SETTING, AND PARTICIPANTS: This single-center, randomized, placebo-controlled clinical trial conducted at a tertiary care academic medical center om China enrolled 424 participants between February 15, 2024, and April 16, 2025, with a 90-day postoperative follow-up period. Participants were consecutive patients scheduled for cardiovascular surgery, including coronary artery bypass grafting, valve surgeries, ascending aortic reconstruction, combined procedures, congenital heart defect repairs, and cardiac tumor resections. INTERVENTIONS: Participants were randomly allocated (1:1) to receive either continuous intravenous sivelestat (0.2 mg/kg/h), initiated immediately on intensive care unit (ICU) admission postoperatively and continued for up to 7 days or until ICU discharge; or volume-matched 0.9% sodium chloride placebo administered on an identical schedule. MAIN OUTCOMES AND MEASURES: The primary outcome was the incidence of ARDS. Secondary outcomes included serial measurements of inflammatory biomarkers, including interleukin 6 and interleukin 8, tumor necrosis factor, systemic immune-inflammation index, and serum neutrophil elastase, on postoperative days 1, 3, 5, and 7, along with ARDS-related clinical outcomes including death, pneumonia, and reintubation. Analysis was performed on an intention-to-treat basis. RESULTS: Among 424 randomized patients, 382 completed the trial (mean [SD] age, 62.9 [6.2] years; 210 male [55.0%]). Adverse events monitored for safety did not differ between groups. The sivelestat group had significantly lower rates of ARDS (16.8% [32 of 190] vs 31.2% [60 of 192]; P < .001), and 90-day mortality (1.1% [2 of 190] vs 5.2% [10 of 192]; P = .02). Postoperative inflammatory biomarkers, including neutrophil elastase and interleukin 6, were significantly reduced in the sivelestat group. CONCLUSION AND RELEVANCE: In this single-center, randomized, placebo-controlled clinical trial of patients undergoing cardiovascular surgery, sivelestat significantly reduced ARDS incidence and 90-day all-cause mortality. Sivelestat attenuated neutrophil-driven inflammation by dynamically suppressing neutrophil elastase and reducing key downstream biomarkers. These preliminary findings suggest sivelestat may be a pharmacologic option to mitigate ARDS in cardiovascular procedures. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06276569.

BACKGROUND: The incidence of lung diseases has been increasing in recent years, especially lung cancer and interstitial lung disease. However, the diagnosis of lung diseases such as lung cancer and ILD still has some limitations. Therefore, finding an appropriate imaging agent and technique is of great clinical value for the diagnostic evaluation of lung diseases. METHOD: A thorough search of all relevant literature up to 20 June 2024 was undertaken. Studies evaluating lung lesions with FAPI PET were screened and patient diagnostic data were extracted. Risk of bias was checked by the QUADAS-2. Meta-analysis was performed in STATA17.0. Subgroups were analysed for the effectiveness of FAPI PET/CT in the diagnostic assessment of various lung diseases. RESULT: 19 studies were finally sieved. Meta-analysis showed that the sensitivity of FAPI PET/CT for the detection of lung tumours was 0.99 (95% CI: 0.90-1.00), with a specificity of 0.82 (95% CI: 0.72-0.89). The sensitivity of FAPI PET/CT for the assessment of non-neoplastic lesions was 0.93 (95% CI: 0.72-0.99) and the specificity was 0.96 (95% CI: 0.79-0.99). Subgroup analysis showed that FAPI PET/CT had a sensitivity of 0.93 (95% CI: 0.83-0.97) in lung tumour staging ( CONCLUSION: Our results show that FAPI PET/CT has an excellent diagnostic performance for lung tumours and non-tumour lesions.

RATIONALE: The mechanisms driving epithelial pathology in COPD are steadily being unveiled, confirming a role for inflammation in the disease. This study explored the interleukin (IL)-6/STAT3 axis, previously reported to link inflammation and epithelial-to-mesenchymal transition, two features of COPD at the airway epithelium level. METHODS: Bronchoalveolar lavage fluid (BALF) and surgical lung tissue were obtained from nonsmoker controls, smokers and COPD patients. The activation of STAT3 and IL-6 levels were measured in these samples. Primary air-liquid interface (ALI) cultures were carried out from nonsmokers, smokers and COPD patients, and IL-6 release and RESULTS: IL-6 and Tyr705-phospho-STAT3 levels were increased in samples from COPD patients compared to controls, both in BALF and in the airway epithelium, as well as in ALI cultures. BEAS-2B cells exposed to COPD sputum supernatants displayed STAT3 activation that was inhibited by the pan-gp130 blocking monoclonal antibody. In addition, stimulation of ALI cultures with IL-6 induced increased vimentin expression and fibronectin release and reduced the expression of apical junctional complexes proteins, indicating epithelial-to-mesenchymal transition. Finally, no impact on airway cell differentiation was observed. CONCLUSIONS: The IL-6/STAT3 axis is activated in the COPD airway epithelium, presumably contributing to epithelial-to-mesenchymal transition.