Bronchoscopic Lung Volume Reduction as the Treatment of Choice versus Robotic-Assisted Lung Volume Reduction Surgery in Similar Patients with Emphysema - An Initial Experience of the Benefits and Complications.

Objective: There is an assumption that because EBLVR requires less use of hospital resources, offsetting the higher cost of endobronchial valves, it should therefore be the treatment of choice wherever possible. We have tested this hypothesis in a retrospective analysis of the two in similar groups of patients. Methods: In a 4-year experience, we performed 177 consecutive LVR procedures: 83 patients underwent Robot Assisted Thoracoscopic (RATS) LVRS and 94 EBLVR. EBLVR was intentionally precluded by evidence of incomplete fissure integrity or intra-operative assessment of collateral ventilation. Unilateral RATS LVRS was performed in these cases together with those with unsuitable targets for EBLVR. Results: EBLVR was uncomplicated in 37 (39%) cases; complicated by post-procedure spontaneous pneumothorax (SP) in 28(30%) and required revision in 29 (31%). In the LVRS group, 7 (8%) patients were readmitted with treatment-related complications, but no revisional procedure was needed. When compared with uncomplicated EBLVR, LVRS had a significantly longer operating time: 85 (14-82) vs 40 (15-151) minutes (p<0.001) and hospital stay: 7.5 (2-80) vs 2 (1-14) days (p<0.01). However, LVRS had a similar total operating time to both EBLVR requiring revision: 78 (38-292) minutes and hospital stay to EBLVR complicated by pneumothorax of 11.5 (6.5-24.25) days. Use of critical care was significantly longer in RATS group, and it was also significantly longer in EBV with SP group than in uncomplicated EBV group. Conclusion: Endobronchial LVR does use less hospital resources than RATS LVRS in comparable groups if the recovery is uncomplicated. However, this advantage is lost if one includes the resources needed for the treatment of complications and revisional procedures. Any decision to favour EBLVR over LVRS should not be based on the assumption of a smoother, faster perioperative course.

A three month old infant with severe respiratory distress.

This case report discusses the diagnostic challenge of congenital lobar emphysema (CLE) in a three-month old infant with severe respiratory distress. The infant was initially misdiagnosed and managed as a case of pneumothorax. This case highlights the importance of CT scans as a diagnostic tool for early diagnosis and lifesaving management of CLE. It also signifies the need for adequate funds and infrastructure in the health care system especially in rural areas of developing countries like Pakistan.

Association between emphysema and other pulmonary computed tomography patterns in primary varicella pneumonia: A retrospective cohort study.

This study aims to evaluate chest computed tomography (CT) findings in hospital patients with primary varicella pneumonia (PVP). We retrospectively analyzed CT images of 77 PVP patients using 3D Slicer, an open-source software, to model lesions and lungs. This retrospective cohort study was approved by the Institutional Review Board (Ethical Committee, Renmin Hospital, Hubei University of Medicine, Shiyan, China) and waived the requirement for written informed consent. The left lung was more frequently and severely affected in PVP, with significant differences between the 2 groups in CT involvement percentage of each lung region, except for total lung inflation. Group A showed higher median percentages of lung collapse compared to Group B. The extent of left lung involvement is a critical predictor of emphysema in PVP patients, highlighting the importance of also monitoring the right lung for more severe cases. Lower emphysema levels correspond to more collapsed and infiltrated lung segments, suggesting a more severe clinical presentation.

Smoking-Related Interstitial Lung Disease and Emphysema.

Diagnosis and treatment of patients with smoking-related lung diseases often requires multidisciplinary contributions to optimize care. Imaging plays a key role in characterizing the underlying disease, quantifying its severity, identifying potential complications, and directing management. The primary goal of this article is to provide an overview of the imaging findings and distinguishing features of smoking-related lung diseases, specifically, emphysema/chronic obstructive pulmonary disease, respiratory bronchiolitis-interstitial lung disease, smoking-related interstitial fibrosis, desquamative interstitial pneumonitis, combined pulmonary fibrosis and emphysema, pulmonary Langerhans cell histiocytosis, and E-cigarette or vaping related lung injury.

Mechanical and morphological characterization of the emphysematous lung tissue.

Irreversible alveolar airspace enlargement is the main characteristic of pulmonary emphysema, which has been extensively studied using animal models. While the alterations in lung mechanics associated with these morphological changes have been documented in the literature, the study of the mechanical behavior of parenchymal tissue from emphysematous lungs has been poorly investigated. In this work, we characterize the mechanical and morphological properties of lung tissue in elastase-induced emphysema rat models under varying severity conditions. We analyze the non-linear tissue behavior using suitable hyperelastic constitutive models that enable to compare different non-linear responses in terms of hyperelastic material parameters. We further analyze the effect of the elastase dose on alveolar morphology and tissue material parameters and study their connection with respiratory-system mechanical parameters. Our results show that while the lung mechanical function is not significantly influenced by the elastase treatment, the tissue mechanical behavior and alveolar morphology are markedly affected by it. We further show a strong association between alveolar enlargement and tissue softening, not evidenced by respiratory-system compliance. Our findings highlight the importance of understanding tissue mechanics in emphysematous lungs, as changes in tissue properties could detect the early stages of emphysema remodeling. STATEMENT OF SIGNIFICANCE: Gas exchange is vital for life and strongly relies on the mechanical function of the lungs. Pulmonary emphysema is a prevalent respiratory disease where alveolar walls are damaged, causing alveolar enlargement that induces harmful changes in the mechanical response of the lungs. In this work, we study how the mechanical properties of lung tissue change during emphysema. Our results from animal models show that tissue properties are more sensitive to alveolar enlargement due to emphysema than other mechanical properties that describe the function of the whole respiratory system.

Design of the multicentre randomised controlled BENTO trial to demonstrate patient-relevant benefit of bronchoscopic lung volume reduction using thermal vapour ablation in the German healthcare system for patients with upper lobe emphysema: a study protocol.

INTRODUCTION: Application of vapour ablation as a novel approach to lung volume reduction has positive effects in patients with severe emphysema. The BENTO study is a randomised, controlled, open, multicentre trial, to assess the effects of bronchoscopic thermal vapour ablation (BTVA) in the German healthcare system. METHODS AND ANALYSIS: Patients with bilateral heterogeneous emphysema of the upper lobes in Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 3/4 will be enrolled in this trial and will receive either standard medical management alone (according to GOLD guidelines) or BTVA treatment with the InterVapor system together with standard medical management. Patients will be randomised in a 2:1 ratio (treatment group:control group). A total of 224 patients will be enrolled at 15 study sites. The primary endpoint is the change in patient-reported disease-specific quality of life, as measured by the St George's Respiratory Questionnaire for chronic obstructive pulmonary disease patients between randomisation and the 9-month follow-up visit. Secondary endpoints include adverse events, mortality, vital status, changes in lung function parameters, exercise capacity and other efficacy measures at 3, 9 and 12 months.The BENTO trial was commissioned by the German Federal Joint Committee, to demonstrate that this approach is an efficient and safe treatment option in the German healthcare system. ETHICS AND DISSEMINATION: The protocol has been approved by the lead ethics committee in Germany (Ethics Committee of the Medical Faculty of Heidelberg) and until present also by the following ethics committees: Ethics Committee of the Medical Faculty of Duisburg-Essen, Ethics Committee of the Medical Faculty of Martin-Luther-University Halle-Wittenberg, Ethics Committee of the State Medical Association of Hessen, Ethics Commission of the State Office for Health and Social Affairs of the State of Berlin, Ethics Committee of the Medical Faculty of Greifswald. The results will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT05717192.

Twenty four-month follow-up after bullectomy, unilateral and bilateral lung volume reduction surgery: a single-center retrospective analysis of consecutive cases.

PURPOSE: While pharmacologic therapy remains the cornerstone of lung emphysema treatment, surgery is an additional therapeutic option in selected patient groups with advanced emphysema. The aim of lung volume reduction surgery (LVRS) is to improve lung function, exercise capacity, quality of life and survival. We sought to determine the therapeutic value of surgical resection in specific patients with lung emphysema. PATIENTS AND METHODS: A retrospective study was performed consisting of 58 patients with lung emphysema who underwent surgical intervention over a 10-year period and were followed for 2 years postoperatively. The clinical characteristics recorded were FEV1 (forced expiratory volume in 1 s), the 6-min walk test (6-MWT), the Modified Medical Research Council (mMRC), body mass index (BMI) and quality of life prior to and 6, 12 and 24 months after surgical intervention. Moreover, all peri- and post-operative complications were noted. RESULTS: Out of 58 emphysema patients (72% male, FEV1 (L) 2.21 ± 0.17, RV (L) 3.39 ± 0.55), 19 underwent surgical bullectomy, 31 unilateral LVRS and 8 sequential bilateral LVRS. Six months after surgery, there was a statistically significant improvement in FEV1, RV, TLC, 6-MWT and mMRC. Over a period of 12 to 24 months postoperatively, clinical benefit gradually declines most likely due to COPD progression but patients still experienced a significant improvement in FEV1. The most common postoperative complications were persistent air leakage (> 7 days), arrhythmia and subcutaneous emphysema in 60%, 51.6% and 22.4%, respectively. No deaths were observed after surgical intervention. CONCLUSION: In a selected patient population, surgery led to significant improvement of lung function parameters, exercise capacity and quality of life. Over a period of 12 to 24 months postoperatively, clinical benefit gradually decreased most likely due to COPD progression.

Effect of emphysema on AI software and human reader performance in lung nodule detection from low-dose chest CT.

BACKGROUND: Emphysema influences the appearance of lung tissue in computed tomography (CT). We evaluated whether this affects lung nodule detection by artificial intelligence (AI) and human readers (HR). METHODS: Individuals were selected from the "Lifelines" cohort who had undergone low-dose chest CT. Nodules in individuals without emphysema were matched to similar-sized nodules in individuals with at least moderate emphysema. AI results for nodular findings of 30-100 mm3 and 101-300 mm3 were compared to those of HR; two expert radiologists blindly reviewed discrepancies. Sensitivity and false positives (FPs)/scan were compared for emphysema and non-emphysema groups. RESULTS: Thirty-nine participants with and 82 without emphysema were included (n = 121, aged 61 ± 8 years (mean ± standard deviation), 58/121 males (47.9%)). AI and HR detected 196 and 206 nodular findings, respectively, yielding 109 concordant nodules and 184 discrepancies, including 118 true nodules. For AI, sensitivity was 0.68 (95% confidence interval 0.57-0.77) in emphysema versus 0.71 (0.62-0.78) in non-emphysema, with FPs/scan 0.51 and 0.22, respectively (p = 0.028). For HR, sensitivity was 0.76 (0.65-0.84) and 0.80 (0.72-0.86), with FPs/scan of 0.15 and 0.27 (p = 0.230). Overall sensitivity was slightly higher for HR than for AI, but this difference disappeared after the exclusion of benign lymph nodes. FPs/scan were higher for AI in emphysema than in non-emphysema (p = 0.028), while FPs/scan for HR were higher than AI for 30-100 mm3 nodules in non-emphysema (p = 0.009). CONCLUSIONS: AI resulted in more FPs/scan in emphysema compared to non-emphysema, a difference not observed for HR. RELEVANCE STATEMENT: In the creation of a benchmark dataset to validate AI software for lung nodule detection, the inclusion of emphysema cases is important due to the additional number of FPs. KEY POINTS: • The sensitivity of nodule detection by AI was similar in emphysema and non-emphysema. • AI had more FPs/scan in emphysema compared to non-emphysema. • Sensitivity and FPs/scan by the human reader were comparable for emphysema and non-emphysema. • Emphysema and non-emphysema representation in benchmark dataset is important for validating AI.

Downregulation of Mirlet7 miRNA family promotes Tc17 differentiation and emphysema via de-repression of RORγt.

Environmental air irritants including nanosized carbon black (nCB) can drive systemic inflammation, promoting chronic obstructive pulmonary disease (COPD) and emphysema development. The let-7 microRNA (Mirlet7 miRNA) family is associated with IL-17-driven T cell inflammation, a canonical signature of lung inflammation. Recent evidence suggests the Mirlet7 family is downregulated in patients with COPD, however, whether this repression conveys a functional consequence on emphysema pathology has not been elucidated. Here, we show that overall expression of the Mirlet7 clusters, Mirlet7b/Mirlet7c2 and Mirlet7a1/Mirlet7f1/Mirlet7d, are reduced in the lungs and T cells of smokers with emphysema as well as in mice with cigarette smoke (CS)- or nCB-elicited emphysema. We demonstrate that loss of the Mirlet7b/Mirlet7c2 cluster in T cells predisposed mice to exaggerated CS- or nCB-elicited emphysema. Furthermore, ablation of the Mirlet7b/Mirlet7c2 cluster enhanced CD8+IL17a+ T cells (Tc17) formation in emphysema development in mice. Additionally, transgenic mice overexpressing Mirlet7g in T cells are resistant to Tc17 and CD4+IL17a+ T cells (Th17) development when exposed to nCB. Mechanistically, our findings reveal the master regulator of Tc17/Th17 differentiation, RAR-related orphan receptor gamma t (RORγt), as a direct target of Mirlet7 in T cells. Overall, our findings shed light on the Mirlet7/RORγt axis with Mirlet7 acting as a molecular brake in the generation of Tc17 cells and suggest a novel therapeutic approach for tempering the augmented IL-17-mediated response in emphysema.

Prognostic implication of 1-year decline in diffusing capacity in newly diagnosed idiopathic pulmonary fibrosis.

The progression of idiopathic pulmonary fibrosis (IPF) is assessed through serial monitoring of forced vital capacity (FVC). Currently, data regarding the clinical significance of longitudinal changes in diffusing capacity for carbon monoxide (DLCO) is lacking. We investigated the prognostic implications of a 1-year decline in DLCO in 319 patients newly diagnosed with IPF at a tertiary hospital between January 2010 and December 2020. Changes in FVC and DLCO over the first year after the initial diagnosis were reviewed; a decline in FVC ≥ 5% and DLCO ≥ 10% predicted were considered significant changes. During the first year after diagnosis, a significant decline in FVC and DLCO was observed in 101 (31.7%) and 64 (20.1%) patients, respectively. Multivariable analysis showed that a 1-year decline in FVC ≥ 5% predicted (aHR 2.74, 95% CI 1.88-4.00) and 1-year decline in DLCO ≥ 10% predicted (aHR 2.31, 95% CI 1.47-3.62) were independently associated with a higher risk of subsequent mortality. The prognostic impact of a decline in DLCO remained significant regardless of changes in FVC, presence of emphysema, or radiographic indications of pulmonary hypertension. Therefore, serial monitoring of DLCO should be recommended because it may offer additional prognostic information compared with monitoring of FVC alone.

Body composition impacts outcome of bronchoscopic lung volume reduction in patients with severe emphysema: a fully automated CT-based analysis.

Chronic Obstructive Pulmonary Disease (COPD) is characterized by progressive and irreversible airflow limitation, with individual body composition influencing disease severity. Severe emphysema worsens symptoms through hyperinflation, which can be relieved by bronchoscopic lung volume reduction (BLVR). To investigate how body composition, assessed through CT scans, impacts outcomes in emphysema patients undergoing BLVR. Fully automated CT-based body composition analysis (BCA) was performed in patients with end-stage emphysema receiving BLVR with valves. Post-interventional muscle and adipose tissues were quantified, body size-adjusted, and compared to baseline parameters. Between January 2015 and December 2022, 300 patients with severe emphysema underwent endobronchial valve treatment. Significant improvements were seen in outcome parameters, which were defined as changes in pulmonary function, physical performance, and quality of life (QoL) post-treatment. Muscle volume remained stable (1.632 vs. 1.635 for muscle bone adjusted ratio (BAR) at baseline and after 6 months respectively), while bone adjusted adipose tissue volumes, especially total and pericardial adipose tissue, showed significant increase (2.86 vs. 3.00 and 0.16 vs. 0.17, respectively). Moderate to strong correlations between bone adjusted muscle volume and weaker correlations between adipose tissue volumes and outcome parameters (pulmonary function, QoL and physical performance) were observed. Particularly after 6-month, bone adjusted muscle volume changes positively corresponded to improved outcomes (ΔForced expiratory volume in 1 s [FEV1], r = 0.440; ΔInspiratory vital capacity [IVC], r = 0.397; Δ6Minute walking distance [6MWD], r = 0.509 and ΔCOPD assessment test [CAT], r = -0.324; all p < 0.001). Group stratification by bone adjusted muscle volume changes revealed that groups with substantial muscle gain experienced a greater clinical benefit in pulmonary function improvements, QoL and physical performance (ΔFEV1%, 5.5 vs. 39.5; ΔIVC%, 4.3 vs. 28.4; Δ6MWDm, 14 vs. 110; ΔCATpts, -2 vs. -3.5 for groups with ΔMuscle, BAR% < -10 vs. > 10, respectively). BCA results among patients divided by the minimal clinically important difference for forced expiratory volume of the first second (FEV1) showed significant differences in bone-adjusted muscle and intramuscular adipose tissue (IMAT) volumes and their respective changes after 6 months (ΔMuscle, BAR% -5 vs. 3.4 and ΔIMAT, BAR% -0.62 vs. 0.60 for groups with ΔFEV1 ≤ 100 mL vs > 100 mL). Altered body composition, especially increased muscle volume, is associated with functional improvements in BLVR-treated patients.

[Effect of SHP-1 knockout in airway epithelial cells on emphysema phenotype in chronic obstructive pulmonary disease in mice].

Objective: To construct and characterize conditional Src homology region 2 protein tyrosine phosphatase 1 (SHP-1) knockout mice in airway epithelial cells and to observe the effect of defective SHP-1 expression in airway epithelial cells on the emphysema phenotype in chronic obstructive pulmonary disease (COPD). Methods: To detect the expression of SHP-1 in the airway epithelium of COPD patients. CRISPR/Cas9 technology was used to construct SHP-1flox/flox transgenic mice, which were mated with airway epithelial Clara protein 10-cyclase recombinase and estrogen receptor fusion transgenic mice (CC10-CreER+/+), and after intraperitoneal injection of tamoxifen, airway epithelial SHP-1 knockout mice were obtained (SHP-1flox/floxCC10-CreER+/-, SHP-1Δ/Δ). Mouse tail and lung tissue DNA was extracted and PCR amplified to discriminate the genotype of the mice; the knockout effect of SHP-1 gene in airway epithelial cells was verified by qRT-PCR, Western blotting, and immunofluorescence. In addition, an emphysema mouse model was constructed using elastase to assess the severity of emphysema in each group of mice. Results: Airway epithelial SHP-1 was significantly downregulated in COPD patients. Genotyping confirmed that SHP-1Δ/Δ mice expressed CC10-CreER and SHP-1-flox. After tamoxifen induction, we demonstrated the absence of SHP-1 protein expression in airway epithelial cells of SHP-1Δ/Δ mice at the DNA, RNA, and protein levels, indicating that airway epithelial cell-specific SHP-1 knockout mice had been successfully constructed. In the emphysema animal model, SHP-1Δ/Δ mice had a more severe emphysema phenotype compared with the control group, which was manifested by disorganization of alveolar structure in lung tissue and rupture and fusion of alveolar walls to form pulmonary alveoli. Conclusions: The present study successfully established and characterized the SHP-1 knockout mouse model of airway epithelial cells, which provides a new experimental tool for the in-depth elucidation of the role of SHP-1 in the emphysema process of COPD and its mechanism.

Endobronchial valves for emphysema and persistent air-leak: 10-year experience in an Asian country.

BACKGROUND: Endobronchial valve (EBV) therapy, a validated method for bronchoscopic lung volume reduction (BLVR) in severe emphysema, has been explored for persistent air-leak (PAL) management. However, its effectiveness and safety in the Asian population require further real-world evaluation. In this study, we assessed the outcomes of treatment with EBV within this demographic. METHODS: We conducted a retrospective analysis of medical records from 11 Korean centers. For the emphysema cohort, inclusion criteria were patients diagnosed with emphysema who underwent bronchoscopy intended for BLVR. We assessed these patients for clinical outcomes of chronic obstructive pulmonary disease. All patients with PAL who underwent treatment with EBV were included. We identified the underlying causes of PAL and evaluated clinical outcomes after the procedure. RESULTS: The severe emphysema cohort comprised 192 patients with an average age of 70.3 years, and 95.8% of them were men. Ultimately, 137 underwent treatment with EBV. Three months after the procedure, the BLVR group demonstrated a significant improvement in forced expiratory volume in 1 s (+160 mL vs. +30 mL; P = 0.009). Radiographic evidence of lung volume reduction 6 months after BLVR was significantly associated with improved survival (adjusted hazard ratio 0.020; 95% confidence interval 0.038-0.650; P = 0.010). Although pneumothorax was more common in the BLVR group (18.9% vs. 3.8%; P = 0.018), death was higher in the no-BLVR group (38.5% vs. 54.5%, P = 0.001), whereas other adverse events were comparable between the groups. Within the subset of 18 patients with PAL, the predominant causes of air-leak included spontaneous secondary pneumothorax (44.0%), parapneumonic effusion/empyema (22.2%), and post-lung resection surgery (16.7%). Following the treatment, the majority (77.8%) successfully had their chest tubes removed. Post-procedural complications were minimal, with two incidences of hemoptysis and one of empyema, all of which were effectively managed. CONCLUSIONS: Treatment with EBV provides substantial clinical benefits in the management of emphysema and PAL in the Asian population, suggesting a favorable outcome for this therapeutic approach.

Endobronchial coil lung volume reduction performed on patients with emphysema dominant COPD: Long term follow-up results.

Introduction: Chronic obstructive pulmonary disease (COPD) is a commonly seen, preventable, and treatable disease with permanent respiratory symptoms and air entrapment that is caused by particle exposure. In case of limited response to traditional treatment protocols, lung volume reduction may be performed in patients with emphysema dominant patterns. In this study, long term follow-up results of the patients who had been operated on by minimal invasive bronchoscopic lung volume reduction surgery by coil placement were reported. Materials and Methods: Records of the patients operated on by coil placement were retrospectively investigated, and pulmonary function test (PFT), echocardiography (ECHO), six-minute walking test (6MWT), tomography images, ventilation scintigraphy, and clinical summaries were evaluated. Out of 34 initial candidates, 18 patients were included in the study. Wilcoxon signed-rank test and Spearman's rho were utilized to compare interventions and follow-up testing. Result: The average age of 18 patients was 62 (50-74) years, and except for one patient, all were males (n= 17). Fifteen patients were operated bilaterally, and the rest were unilaterally operated, with an average of 10 coils placed per coil placement. An average of 90 days was between bronchoscopic coil placement, with a follow-up duration of 45 days in between. Mean total follow-up duration was 794 (± 424) days. Pneumonia and pneumonitis were seen in 33% of patients within the first month. Mortality from respiratory causes was found to be 11%, while mortality from all causes was found to be 22%. Statistical difference was observed regarding 6MWT after bronchoscopic volume reduction when compared the initial preoperative values. However, this difference was later lost statistically at the second follow-up performed after the completion of both sides. A benefit in improved resting saturation was observed after the second procedure, which was not evident after unilateral intervention. However, similiar to 6MWT, this benefit was lost at the second follow-up, with resting saturation instead being effected negatively. No difference was observed in PFT results; however, a correlation was seen between FEV1 and walking distance. No specific correlation had been seen in the ECHO evaluation. Conclusions: Benefits regarding 6MWT and resting saturation were observed in patients undergoing minimal invasive bronchoscopic lung volume reduction surgery with coils. This benefit was evident in the short term but was lost as the follow-up duration increased. A relatively high morbidity and mortality rate was also present, further stating the risky nature of pulmonary intervention, even minimally invasive procedures, on patients with COPD.

Association of IL-33 in modeling type-2 airway inflammation and pulmonary emphysema in mice.

We developed pulmonary emphysema and a type 2 airway inflammation overlap mouse model. The bronchoalveolar lavage (BAL) interleukin 13 (IL-13), IL-4, and IL-5 levels in the overlap model were higher than in the pulmonary emphysema model and lower than in the type 2 airway inflammation model, but IL-33 level in the lung was higher than in other models. IL-33 and interferon-γ (IFNγ) in lungs may control the severity of a type 2 airway inflammation in lung.

Stenotrophomonas maltophilia contributes to smoking-related emphysema through IRF1-triggered PANoptosis of alveolar epithelial cells.

Cigarette smoke (CS), the main source of indoor air pollution and the primary risk factor for respiratory diseases, contains chemicals that can perturb microbiota through antibiotic effects. Although smoking induces a disturbance of microbiota in the lower respiratory tract, whether and how it contributes to initiation or promotion of emphysema are not well clarified. Here, we demonstrated an aberrant microbiome in lung tissue of patients with smoking-related COPD. We found that Stenotrophomonas maltophilia (S. maltophilia) was expanded in lung tissue of patients with smoking-related COPD. We revealed that S. maltophilia drives PANoptosis in alveolar epithelial cells and represses formation of alveolar organoids through IRF1 (interferon regulatory factor 1). Mechanistically, IRF1 accelerated transcription of ZBP1 (Z-DNA Binding Protein 1) in S. maltophilia-infected alveolar epithelial cells. Elevated ZBP1 served as a component of the PANoptosome, which triggered PANoptosis in these cells. By using of alveolar organoids infected by S. maltophilia, we found that targeting of IRF1 mitigated S. maltophilia-induced injury of these organoids. Moreover, the expansion of S. maltophilia and the expression of IRF1 negatively correlated with the progression of emphysema. Thus, the present study provides insights into the mechanism of lung dysbiosis in smoking-related COPD, and presents a potential target for mitigation of COPD progression.

Optimizing clinical outcomes for bronchoscopic lung volume reduction with Zephyr® valves.

Bronchoscopic lung volume reduction treatment with Zephyr one-way valves is an effective guideline-based treatment option for patients with severe emphysema and hyperinflation. However, in some cases the treatment response is less than anticipated or there might be a loss of initial treatment effect. Reasons for the lack of response can include incorrect assessment of collateral ventilation, improper valve placement, or patient related factors. Loss of initial benefit can be due to granulation tissue formation and subsequent valve dysfunction, or there may be side effects such as excessive coughing or infectious problems. Careful follow-up after treatment with valves is important and evaluation with a CT scan and/or bronchoscopy is helpful if there is no improvement after treatment or loss of initial benefit. This paper aims to describe the most important causes and provide a strategy of how to approach and manage these patients.

Delayed targeted atelectasis in a case of bronchoscopic lung volume reduction with endobronchial valves.

A woman in her late 60s with severe chronic obstructive pulmonary disease (COPD) and emphysema underwent bronchoscopic lung volume reduction (BLVR) with endobronchial valves (EBV) to address hyperinflation. The initial EBV placement has led to partial lobar atelectasis of the left lower lobe and resulted in significant improvement in the patient's symptoms and lung function. However, valve migration occurred later due to pneumothorax unrelated to valves, leading to suboptimal clinical improvement. The patient achieved delayed full lobar atelectasis 21 months after EBV placement, which led to a significant clinical improvement. The patient decided to be delisted from the lung transplant list due to the improvement. This case highlights the importance of considering delayed atelectasis as a possible outcome of EBV placement and suggests the need for further exploration of the long-term implications and associations of this procedure.

Inhibition of GBP5 activates autophagy to alleviate inflammatory response in LPS-induced lung injury in mice.

BACKGROUND: Pulmonary emphysema is a condition that causes damage to the lung tissue over time. GBP5, as part of the guanylate-binding protein family, is dysregulated in mouse pulmonary emphysema. However, the role of GBP5 in lung inflammation in ARDS remains unveiled. METHODS: To investigate whether GBP5 regulates lung inflammation and autophagy regulation, the study employed a mouse ARDS model and MLE-12 cell culture. Vector transfection was performed for the genetic manipulation of GBP5. Then, RT-qPCR, WB and IHC staining were conducted to assess its transcriptional and expression levels. Histological features of the lung tissue were observed through HE staining. Moreover, ELISA was conducted to evaluate the secretion of inflammatory cytokines, autophagy was assessed by immunofluorescent staining, and MPO activity was determined using a commercial kit. RESULTS: Our study revealed that GBP5 expression was altered in mouse ARDS and LPS-induced MLE-12 cell models. Moreover, the suppression of GBP5 reduced lung inflammation induced by LPS in mice. Conversely, overexpression of GBP5 diminished the inhibitory impact of LPS on ARDS during autophagy, leading to increased inflammation. In the cell line of MLE-12, GBP5 exacerbates LPS-induced inflammation by blocking autophagy. CONCLUSION: The study suggests that GBP5 facilitates lung inflammation and autophagy regulation. Thus, GBP5 could be a potential therapeutic approach for improving ARDS treatment outcomes, but further research is required to validate these findings.