Background: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide, largely driven by the accumulation of senescent bronchial epithelial cells, which contribute to inflammation and tissue remodeling. This study investigates the therapeutic potential of nuclear factor erythroid 2-related factor 2 (Nrf2) activation in targeting senescence-related changes to alleviate COPD progression.

Methods: Single-cell transcriptome analysis, in vitro COPD cell models, and a COPD mouse model were utilized to examine the effects of Nrf2 activation. Specifically, the study focused on the impact of Nrf2 on senescent ciliated epithelial cells and the associated secretory phenotype. Respiratory function tests and lung pathology assessments were conducted to evaluate the intervention’s efficacy in the mouse model.

Results: The study identified a significant presence of senescent ciliated epithelial cells in COPD patients, contributing to disease progression. Nrf2 activation in vitro reduced senescence markers, enhanced cell proliferation, and decreased inflammatory cytokines. In vivo, Nrf2 activation significantly improved lung function and reduced pathological damage in the COPD mouse model.

Conclusions: The findings underscore the potential of Nrf2 activation as a therapeutic strategy to mitigate COPD progression by modulating the senescence-associated secretory phenotype (SASP). This study suggests that Nrf2 activators could offer a promising approach to improving clinical outcomes for COPD patients.

Keywords: Chronic obstructive pulmonary disease (COPD); nuclear factor erythroid 2-related factor 2 activator (Nrf2 activator); epithelial cell senescence; senescence-related secretory phenotype; single-cell transcriptome sequencing

Background: The endobronchial ultrasound (EBUS) elastography is a diagnostic tool used for measuring the elasticity of intrathoracic lesions. It is still essential for discussions about how accurate elastography is at identifying benign and malignant mediastinal and hilar lymph nodes. The objective of this study was to investigate the diagnostic utility of EBUS elastography and to determine the variables affecting this procedure.

Methods: We conducted a single-center, retrospective study involving patients with suspected lung cancer who underwent EBUS elastography followed by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) at Zhejiang Cancer Hospital between October 2021 and March 2023. The pathological results of EBUS-TBNA, validated through a six-month follow-up, served as the gold standard. Each lymph node had its ultrasonic elastography indices recorded, including the elastography grading score, blue color ratio (BCR), blue color score, and short axis diameter. The diagnostic efficacy of elastography was assessed using the receiver operating characteristic (ROC) curve, which differentiated between benign and malignant lymph nodes. To investigate the factors impacting the elastography indices, multivariate logistic regression was used with multiple serological markers, lymph node location, and pathology.

Results: Of the 168 patients, 322 lymph nodes were punctured, with 175 (54.3%) being malignant. The area under the ROC curve (AUC) for the combined index of elastography grading score and short-axis diameter was 0.702 [95% confidence interval (CI): 0.645–0.759]. While the pathology of the lymph nodes was found to influence the BCR, BCR was unable to distinguish between lymph nodes with benign conditions and those with small cell carcinoma.

Conclusions: The use of elastography data alone may be inadequate for diagnosing metastatic lymph nodes. However, elastography can provide supplementary diagnostic information during EBUS-TBNA. Invasive EBUS-TBNA remains recommended as it aids in the identification of malignant lymph nodes when used in conjunction with pathological, radiological, and clinical findings.

Keywords: Endobronchial ultrasound (EBUS); elastography; endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA); lung cancer; mediastinal lymph node metastasis

Background: Positional indications for sublobar resection have been increasingly focused by clinical surgeons while the surgical strategies for cases involving inter-multisegmental veins (IMSVs) remain underreported. We want to further clarify the positional indications for sublobar resection in patients with clinical T1a–bN0 non-small cell lung cancer (NSCLC).

Methods: The clinical data of 686 patients from August 2021 to July 2022 were retrospectively analyzed. In the three-dimensional (3D) reconstruction images, we analyzed the prevalence and drainage patterns of typical IMSVs, specifically focusing on the lateral vein (Vl) in the upper lobes and the branches of the superior segmental vein (V⁶b) in the lower lobes. The potential association between lesion locations and surgical strategy was also analyzed.

Results: The prevalence of Vl, V⁶b2, and V⁶b3 was 58.5% (231/395), 98.3% (286/291), and 25.1% (73/291), respectively. Vl mainly drained into V²a+b (70/110, 63.6%) on the right and into V¹⁺²b+c (72/121, 59.5%) on the left. V⁶b2 and V⁶b3 mainly converged with other branches of the superior segmental vein. Limited resection was more feasible when the 2 cm simulated cutting margin of nodules did not involve IMSVs, or when lesions were located in the outer region. Multivariable logistic regression analyses identified four independent predictors for surgical procedure selection: (I) whether the 2 cm simulated cutting margin involves IMSVs; (II) diameter; (III) consolidation-to-tumour ratio (CTR); and (IV) depth ratio.

Conclusions: IMSVs exhibited high prevalences, with Vl showing diverse drainage patterns, while V⁶b2 and V⁶b3 displayed little variation. Depth ratio and the lesion’s relative location to the IMSVs were identified as longitudinal and transverse positional indications, respectively, for sublobar resection in patients with clinical T1a–bN0 NSCLC.

Keywords: Pulmonary nodule; three-dimensional reconstruction (3D reconstruction); inter-multisegmental vein (IMSV); sublobar resection

Background: Currently, mitral valve replacement is the primary method of reintervention for patients with rheumatic heart disease (RHD) after percutaneous mitral balloon commissurotomy (PMBC). This study aims to investigate the feasibility of mitral valve repair in such patients and report its therapeutic outcomes compared to mitral valve replacement.

Methods: Data from patients with previous PMBC who underwent mitral valve surgery as disease progression between January 2011 and August 2023 were retrospectively analyzed. The patients were divided into two groups: the repair group and the replacement group. The stabilized inverse probability of treatment weighting (SIPTW) method was used to balance baseline characteristic differences between the two groups. Clinical outcomes investigated included freedom from mitral valve reoperation and overall survival. Survival curves were generated with the Kaplan-Meier (K-M) method, and differences between groups were compared using the Log-rank test.

Results: A total of 210 patients were included in this study (32 in the repair group and 178 in the replacement group), with an average age of 56.6±10.0 years. After SIPTW, the baseline characteristics between the two groups were comparable. The median follow-up time for the entire cohort was 75.6 months. K-M analysis, adjusted for SIPTW, showed no significant differences between the two groups in terms of freedom from mitral valve reoperation and overall survival (Log-rank P=0.07 and 0.36, respectively).

Conclusions: According to our results, even if patients with RHD have previously undergone PMBC, there is still a possibility of mitral valve repair in suitable patients, with good clinical outcomes.

Keywords: Rheumatic heart disease (RHD); percutaneous mitral balloon commissurotomy (PMBC); mitral valve repair; mitral valve replacement

Background: Although coronavirus disease 2019 (COVID-19) is no longer classified as a Public Health Emergency of International Concern by World Health Organization, its global impact persists. Data on its impact in lung transplant recipients (LTRs) from China remain limited. This study aims to share clinical experiences and provide insights into managing LTRs with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Methods: We conducted a study on LTRs with COVID-19 caused by the Omicron variant from November 17, 2022, to May 1, 2023. Clinical information was gathered retrospectively through electronic medical records, questionnaires, or follow-up telephone calls.

Results: A total of 227 LTRs were reviewed for infection with Omicron variant. After excluding 49 cases without confirmed SARS-CoV-2 infection, this left a final cohort of 178 infected LTRs, accounting for an infection rate of 78.4% (178/227). Of the patients, 50% (89/178) required hospitalization, with an average hospital stay of 16 days [interquartile range (IQR): 9.5–25.5 days]. Of the 89 hospitalized patients, 41.6% (37/89) eventually progressed to severe or critical disease, forming the severe/critical group (S/C group), while the remaining 58.4% (52/89) had mild or moderate disease (M/M group). In comparison to the M/M group, the S/C group had higher C-reactive protein (CRP) (59.6 vs. 16.8 mg/L, P<0.001), Erythrocyte sedimentation rate (45.5 vs. 22.5 mm/h, P=0.005) and D-dimer level (1.09 vs. 0.65 mg/L, P=0.01), but lower CD4⁺ T lymphocytes count (217 vs. 427 cells/µL, P=0.004). The S/C group had significantly higher rates of combined pulmonary bacterial infection (67.6% vs. 38.5%, P=0.006) and pulmonary fungal infection (73.0% vs. 38.5%, P=0.001) during the course of COVID-19, nearly double that of the M/M group. In a multivariate logistic analysis, elevated CRP (>41.8 mg/L), combined pulmonary fungal infection, and interstitial lung disease (ILD) as primary disease emerged as high-risk factors for developing the severe disease phenotype following Omicron variant infection in LTRs, with respective odds ORs values of 4.23 [95% confidence interval (CI): 1.68–11.23], 4.76 (95% CI: 1.59–15.64), and 5.13 (95% CI: 1.19–29.17). Receiver operating characteristic (ROC) curve analysis showed that CD4⁺ T lymphocyte count may be a strong marker for predicting death. At a cutoff of 404 cells/µL, sensitivity was 0.509, specificity 0.999, and area under the curve (AUC) was 0.806 (95% CI: 0.678–0.934). Ultimately, 13 recipients succumbed to COVID-19 related respiratory failure or secondary multiple organ dysfunction, resulting in an overall mortality rate of 7.3% (13/178).

Conclusions: LTRs are at high risk of secondary lung infections after Omicron. Key risk factors for severe disease include CRP >41.8 mg/L, ILD as primary disease, and pulmonary fungal infection. CD4+ T lymphocyte count may predict mortality risk in LTRs with COVID-19.

Keywords: Lung transplantation; Omicron; coronavirus disease 2019 (COVID-19); coronavirus; risk factor

Background: Cone-beam computed tomography (CBCT)-guided bronchoscopy is increasingly utilized for diagnosing peripheral pulmonary lesions (PPLs). We carried out the meta-analysis for assessing the efficacy and safety of CBCT-guided bronchoscopy for PPLs.

Methods: An extensive search in several databases was conducted to identify relevant articles. We evaluated the quality of studies with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. The pooled diagnostic yield (DY) and adverse event rate with the 95% confidence interval (CI) were computed. Subgroup analyses were performed according to additional use of navigation, use of radial endobronchial ultrasound (rEBUS), use of fixed or mobile CBCT, whether computed tomography (CT) spin was performed before biopsy to affirm tool-in-lesion, use of rapid onsite cytologic examination (ROSE), strictness of the definition of DY, and study design. Further analysis was performed to explore the association between odds of diagnosis with CBCT guided bronchoscopy and PPLs characteristics (>20 vs. ≤20 mm, non-upper lobe vs. upper lobe, with bronchus sign vs. without bronchus sign, and solid vs. non-solid) as well as sampling methods (forceps vs. fine needle aspiration, forceps vs. cryoprobe sampling). The pooled odds ratio (OR) and 95% CI were calculated. The significance level was set at 0.05. All analyses were performed by using meta package in R version 4.3.2.

Results: We included 23 studies involving 1,769 patients and 1,863 PPLs in the meta-analysis. The overall pooled DY of CBCT-guided bronchoscopy was 80.2% (95% CI: 76.0–84.1%). Subgroup analysis showed that the DY was highest when CBCT was used with robotic-assisted navigation bronchoscopy (pooled DY 87.5%; 95% CI: 81.5–92.4%), the DY was 78.9% (95% CI: 70.8–85.9%) when CBCT was used alone without other navigation techniques. Lesion size >20 mm, presence of bronchus sign and solid lesions were associated with significant increase in the odds of diagnosis with CBCT-guided bronchoscopy. Pooled adverse event rate was 2.3% (95% CI: 1.2–3.6%).

Conclusions: CBCT-guided bronchoscopy is a safe technique with high DY in diagnosing PPLs.

Keywords: Cone-beam computed tomography (CBCT); bronchoscopy; peripheral pulmonary lesions (PPLs); diagnostic yield (DY)