Introduction:The best tissue sample is still very important for the diagnosis of mesothorax lymphadenopathy. In the past 20 years endobronchial ultrasound (EBUS) has been used efficiently in most cases of primary lung cancer disease or metastatic disease. Several new type of needles have been created such 19G, 18G and hybrid biopsies with cryoprobes. Rapid on-site evaluation (ROSE) is used as an additional initial diagnostic tool. Confocal microscopy is a method of rapid on-site evaluation. Patients and Methods:One hundred patients with mesothorax lymphadenopathy were biopsied with ebus and two groups were created one with rapid on-site evaluation with confocal microscopy and one by an operator with microscopic evaluation with sample preparation on cytoglasses. Our main objective was to assess parameters such as time, false negative results between the two techniques and technical issues such as the accessibility and evaluation between the two techniques. Safety was also evaluated. Results:Rapid on-site evaluation is more cost efficient with a cytologist on site, however; with a higher rate of false negative results. Accessibility with the Cellvizio® catheter was less possible in a few cases due to rigid angles within the airways especially for small lymphnodes ≤ 1.5 cm (L4L mainly). Discussion:Confocal is a safe and time-efficient technique for mesothorax lymphadenopathy. A high level of training is required for pulmonary physicians in order to assess the novel imaging technique. Definitely different parts of the lymphnode have to reached and evaluated in order to have a proper initial evaluation.

The incidence of benign airway stenosis (BAS) is on the rise, and current treatment options are associated with a significant risk of restenosis. Therefore, there is an urgent need to explore new and effective prevention and treatment methods. Animal models serve as essential tools for investigating disease mechanisms and assessing novel therapeutic strategies, and the scientific rigor of their construction and validation significantly impacts the reliability of research findings. This paper systematically reviews the research progress and evaluation systems of BAS animal models over the past decade, aiming to provide a robust foundation for the optimized construction of BAS models, intervention studies, and clinical translation. This effort is intended to facilitate the innovation and advancement in BAS prevention and treatment strategies.

The oxidative stress of macrophage plays pivotal roles of acute and chronic inflammation and chronic fibrotic phases, in which the metabolic mechanism needs to be further explored. In our research, multi-omics analyses of human and murine during Benign airway stenosis (BAS) biopsy identified ACOD1 as a hallmark of immunometabolic regulation during acute inflammation stage. ACOD1 knockout aggravated both acute and chronic inflammation, which increased the granulation tissue formation. The ACOD1-itaconate axis, along with its derivative, 4-octyl itaconate (4-OI), orchestrated acute and chronic inflammation, which attenuated the fibrosis of BAS. 4-OI upregulated FTH1 expression in macrophages by activating NRF2, which effectively suppressed oxidative stress and acute inflammation. Furthermore, 4-OI promoted the packaging of FTH1 into macrophage-derived exosomes, which were transferred to fibroblasts in a SCARA5-dependent manner, inducing fibroblast ferroptosis and alleviating chronic fibrosis. In sum, this study illustrates that the ACOD1-itaconate metabolic axis decreases oxidative stress and inflammation in macrophage, which attenuates fibrosis by inducing FTH1 transfer, offering a therapeutic target for fibrotic airway diseases.

The oxidative stress of macrophage plays pivotal roles of acute and chronic inflammation and chronic fibrotic phases, in which the metabolic mechanism needs to be further explored. In our research, multi-omics analyses of human and murine during Benign airway stenosis (BAS) biopsy identified ACOD1 as a hallmark of immunometabolic regulation during acute inflammation stage. ACOD1 knockout aggravated both acute and chronic inflammation, which increased the granulation tissue formation. The ACOD1-itaconate axis, along with its derivative, 4-octyl itaconate (4-OI), orchestrated acute and chronic inflammation, which attenuated the fibrosis of BAS. 4-OI upregulated FTH1 expression in macrophages by activating NRF2, which effectively suppressed oxidative stress and acute inflammation. Furthermore, 4-OI promoted the packaging of FTH1 into macrophagederived exosomes, which were transferred to fibroblasts in a SCARA5-dependent manner, inducing fibroblast ferroptosis and alleviating chronic fibrosis. In sum, this study illustrates that the ACOD1-itaconate metabolic axis decreases oxidative stress and inflammation in macrophage, which attenuates fibrosis by inducing FTH1 transfer, offering a therapeutic target for fibrotic airway diseases.

Rationale: Despite the increasing use of high-flow nasal cannula (HFNC) oxygen therapy during endoscopy examination, its impact on high-risk patients remains uncertain. Objectives: We aimed to compare HFNC and conventional oxygen therapy (COT) during nasal bronchoscopy in patients at high risk for desaturation (morbid obesity, narrow trachea, or baseline hypoxemia and/or hypercapnia). Methods: In this multicenter randomized controlled trial, patients scheduled for bronchoscopy and presenting with any high-risk factors were randomly assigned to receive HFNC or COT after providing written consent. Vital signs, pulse oximetry (SpO2), and transcutaneous carbon dioxide were continuously monitored. The occurrence of desaturation (SpO2 ⩽ 90% lasted >10 s), frequency of examination interruption, and treatment escalation were compared between groups. Results: Of 148 initially enrolled patients, 6 withdrew, leaving 72 and 70 in the HFNC and COT groups, respectively. Most of the patients had airway stenosis. HFNC significantly reduced desaturation occurrence during bronchoscopy (34.7% vs. 61.4%; P = 0.016), with fewer instances of examination interruption (26.4% vs. 58.6%; P < 0.001) and less frequent treatment escalation (30.6% vs. 57.1%; P = 0.001). During the examination, the lowest SpO2 was higher with HFNC (94% [interquartile range, 87-98%] vs. 87.5% [79-93%]; P = 0.001), whereas the highest transcutaneous carbon dioxide was lower (64.6 [56.8-70.1] vs. 68.3 [62.3-77.0] mm Hg; P = 0.04). No significant differences were observed regarding the time to the first desaturation, bronchoscopy withdrawal, durations of desaturation and bronchoscopy examination, or occurrence of other adverse events between groups. Conclusions: In a high-risk population with predominant airway stenosis, HFNC significantly reduced desaturation occurrence, examination interruption, and treatment escalation during nasal bronchoscopy examination in high risk patients. Clinical trial registered with www.chictr.org.cn (ChiCTR2100055038).

Thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT), as a rare and highly malignant neoplasm associated with a high mortality risk, is easily confused with SMARCA4-deficient nonsmall-cell lung cancer (NSCLC). To date, no standard and effective protocol for thoracic SMARCA4-UT has been established. Immunotherapy has demonstrated efficacy in advanced NSCLC, achieving unprecedented survival benefits. However, immune-related adverse events (irAEs) remain a significant clinical challenge. Here, we reported the first case of thoracic SMARCA4-UT with immune-related cystitis and hypothyroidism, in which the patient benefited from first-line immune checkpoint inhibitor (ICI)-based combination therapy, achieving a remarkable overall survival of over 100 weeks. Furthermore, we performed a review and analysis of the diagnosis, differential diagnosis, immunotherapy, and prognosis of thoracic SMARCA4-UT, proposing that first-line therapy combining immunotherapy with platinum-based chemotherapy (induction and maintenance phases) with or without radiotherapy, may improve the prognosis of such patients. Additionally, we hypothesized a potential role of macrophages in the pathogenesis of immune-related cystitis for the first time and detailed the clinicopathological characteristics and evidence-based management of this irAE.

Introduction: We used CBCT application as one-stop-shop nodule orientated approach in regards to increase DY, reduce complication rate, reduce time on-table and economical costs with classical peripheral instruments including mini-cryoprobe (ERBE 1,1mm), rEBUS (Olympus) and standard RUFBs (Olympus Company) with at least 2mm working channel and 4,2mm outer diameter for the diagnosis of peripheral targets (iSPNs) in a prospective all-comers registry after detailed analysis of pre-interventional CT for vessel- and bronchus sign classes. Materials and Methods: From Jun 2017 until Nov 2019 in 90 all-comers patients between 16 and 95 years fit for bronchoscopy with 101 peripheral lesions in a daily routine scheme after informed consent about this prospective registry were included. For histological proven benign disease in any lesion patients had to adhere FU according radiological guidelines and further on by re-visits for at least 2 years after biopsy resulting into last visit in Feb 2022 without any drop-out. Present HRCT was mandatory to achieve one day before intervention. It had to be decided by the examiner mainly after analysis of the preset HRCT which of the 3 CBCT driven modalities were used for diagnostical approach: A) Pure endobronchial approach (CBCT, rEBUS, TBB), B) Pure transthoracical approach with a 21G core-biopsy needle (BIOPINCE needle) with CBCT only, or C) Combined approach as described below (CBCT, rEBUS, TTNA). As instruments were available common forceps and needles, EWC, curette and various RUFB (Olympus Company) mentioned in the materials section. A second CBCT was only allowed in the combined approach group to plan the 3D transthoracic approach in expiration whereas even a CBCT for tool-in-lesion control (TIL CBCT) was never allowed in all 3 groups. Results: In 100 lesions predefined modalities pure endobiopsy, pure TTNA and combined approaches were performed in 77, 9 and 14 lesions respectively without any pneumothorax or bleeding. In these 3 modalities we found confirmed (mostly specific) benign and malignant cases 47 and 30, 4 and 5, 2 and 12 respectively. Lesion sizes in the 3 different groups were (median, mean) 14 and 17,7mm (of those 41 invisible of 77 under XR (53%) in the pure endobiopsy group), 27 and 31mm (11% invisible under XR in the pure TTNA group), 18,5 and 23mm (35% invisible under XR in the combined group) respectively. In the 3 groups for the malignant cases 25 of 30, 5 of 5 and 12 of 12 were diagnosed correctly rendering a diagnostical yield of 42 in 47 malignant cases for the whole algorithm (89,4%) with sizes (mean, median) for the whole algorithm of 16 and 19,7mm respectively which is comparable to published data for robotic-assisted bronchoscopy yield. In regards to vessel sign analysis it has to be clearly stated that the significance level for outcome prediction is inferior to bronchus sign analysis. In multivariate analysis there was a clear tendency towards higher outcome prediction especially if a pulmonary artery branch leads into such target even when a bronchus sign is missing. For NY when comparing univariate analysis and partition model analysis at a set diameter of >11mm with significance (p=0,0052) the additional advantage of analysing a given vessel sign (especially pulmonary artery branches) seems to add on 19% of valuable outcome prediction. Conclusion: A nodule orientated approach in a manual CBCT-AF environment including typical instruments renders in experienced hands comparable results to robotic assisted bronchoscopy even without UTN bronchoscopes or other specialized, therefore expensive tools. In multivariate analysis only bronchus sign analysis revealed significant (p = 0,05) prediction of navigational yield outcome prediction whereas vessel sign analysis increases highly the odds ratio in favor of positive outcome prediction but without significance at the given level. In a partition model to erase outliers at a set iSPN diameter >11mm vessel sign analysis (especially pulmonary artery branches) renders a significant and ameliorated prediction of NY.

Background The diagnostic yield of radial endobronchial ultrasound (r-EBUS) for the diagnosis of peripheral pulmonary lesions (PPLs) varies between studies and is affected by multiple factors. We aimed to evaluate the efficacy and safety of r-EBUS, and to explore the factors influencing the diagnostic yield of r-EBUS in patients with PPLs. Methods The PubMed, Web of Science, and EMBASE databases were searched to identify relevant studies that used r-EBUS for diagnosing PPLs from the date of inception to Dec 2022. Meta-analysis was conducted using Review Manager 5.4 and Stata 15.1. Results An analysis of 46 studies with a total of 7,252 PPLs was performed. The pooled diagnostic yield of r-EBUS was 73.4% (95% CI: 69.9%-76.7%), with significant heterogeneity detected among studies (I2=90%, P<0.001). Further analysis demonstrated PPLs located in the middle or lower lobe, >2 cm in size, malignant in type, solid in appearance on computerized tomography (CT), present in bronchus sign, the within probe location, and the addition of rapid on-site evaluation (ROSE) were associated with increased diagnostic yield, whereas use of a guide sheath (GS), bronchoscopy type, and a multimodality approach failed to influence the outcome. The pooled incidence rates of overall complications, pneumothorax and moderate and severe bleeding were 3.1% (95% CI: 2.1%-4.3%), 0.4% (95% CI: 0.1%-0.7%) and 1.1% (95% CI: 0.5%-2.0%), respectively. Conclusions r-EBUS has an appreciable diagnostic yield and an excellent safety manifestation when used to deal with PPLs.

In recent years, advances in interventional bronchoscopy have led to safer and more effective solutions for the diagnosis and treatment of respiratory diseases. However, the techniques currently used to diagnose and treat peripheral pulmonary lesions (PPL) have certain limitations. Robotic-assisted bronchoscopy (RAB) offers a new solution to these limitations. Currently, three RABs have been approved by the US Food and Drug Administration (FDA) and are successfully marketed, while two domestic RABs are in the research and development stage. This article provided an overview of the advantages and disadvantages of various techniques and introduced five RABs in detail. It also discussed the advantages and disadvantages of RAB technology and future trends in its development.

Single pulmonary nodules are a difficult to diagnose imagining artifact.Currently novel diagnostic tools such as Radial-EBUS with or not C-ARM flouroscopy, electromagnetic navigation systems, robotic bronchoscopy and cone beam-compuer tomography (CBCT) can assist in the optimal guidance of biopsy equipment.After diagnosis of lung cancer or metastatic disease as pulmonary nodule, then surgery or ablation methods as local treatment can be applied.The percutaneous ablation systems under computed tomography guidance with radiofrequency, microwave, cryo and thermosphere have been used for several years.In the past 10 years extensive research has been made for endobronchial ablation systems and methods.We will present and comment on the two different ablation methods and present up to date data.

SMARCA4-deficient undifferentiated thoracic tumor is extremely invasive. This tumor with poor prognosis is easily confused with SMARCA4-deficent non-small cell lung cancer or sarcoma. Standard and efficient treatment has not been established. In this review, we summarized the etiology, pathogenesis and diagnosis, reviewed current and proposed innovative strategies for treatment and improving prognosis. Immunotherapy, targeting tumor microenvironment and epigenetic regulator have improved the prognosis of cancer patients. We summarized clinicopathological features and immunotherapy strategies and analyzed the progression-free survival (PFS) and overall survival (OS) of patients with SMARCA4-UT who received immune checkpoint inhibitors (ICIs). In addition, we proposed the feasibility of epigenetic regulation in the treatment of SMARCA4-UT. To our knowledge, this is the first review that aims to explore innovative strategies for targeting tumor microenvironment and epigenetic regulation and identify potential benefit population for immunotherapy to improve the prognosis.

An increasing number of peripheral pulmonary lesions (PPLs) requiring tissue verification to establish a definite diagnosis for further individualized management are detected due to the growing adoption of lung cancer screening by chest computed tomography (CT), especially low-dose CT. However, the morphological diagnosis of PPLs remains challenging. Transbronchial lung cryobiopsy (TBLC) that can retrieve larger specimens with more preserved cellular architecture and fewer crush artifacts in comparison with conventional transbronchial forceps biopsy (TBFB), as an emerging technology for diagnosing PPLs, has been demonstrated to have the potential to resolve the clinical dilemma pertaining to currently available sampling devices (e.g., forceps, needle and brush) and become a diagnostic cornerstone for PPLs. Of note, with the introduction of the 1.1 mm cryoprobe that will be more compatible with advanced bronchoscopic navigation techniques, such as radial endobronchial ultrasound (r-EBUS), virtual bronchoscopic navigation (VBN) and electromagnetic navigation bronchoscopy (ENB), the use of TBLC is expected to gain more popularity in the diagnosis of PPLs. While much remains for exploration using the TBLC technique for diagnosing PPLs, it can be envisaged that the emergence of additional studies with larger data accrual will hopefully add to the body of evidence in this field.

Background and objective: Recently, endobronchial ultrasonography with guide sheath-guided (EBUS-GS) has been increasingly used in the diagnosis of peripheral pulmonary lesions (PPLs) from human natural orifice. However, the diagnostic rate is still largely dependent on the location of the lesion and the probe. Here, we reported a new procedure to improve the diagnostic rate of EBUS-transbronchial lung cryobiopsy (EBUS-TBLC), which performed under general anesthesia with laryngeal mask airway (LMA) in all of the patients. This study retrospectively evaluated the diagnosis of PPLs with 'blind-ending' type (Type I) and 'pass-through' type procedures (Type II) of EBUS-GS-TBLB or EBUS-TBLC respectively. Methods: Retrospective review of 136 cases performed by EBUS-GS-TBLB or EBUS-TBLC for PPLs over 2 years. Results: A total of 126 cases EBUS-GS-TBLB or EBUS-TBLC were performed during the study period. Among them, 66 (52.4%) were performed Type I and 60 (47.6%) were performed Type II. Clinical baseline characteristics did not differ between two groups. The overall diagnosis rate of 126 patients with EBUS-GS-TBLB or EBUS-TBLC was 73% (92/126), and different method type have significant influence on the diagnostic yield (P = 0.012, x2 = 4.699). Among them, diagnostic yields for Type I with forceps biopsy (n=34), Type I with cryobiopsy (n=32), Type II with forceps biopsy (n=30), and Type II with cryobiopsy (n=30) were 72.5%, 64.5%, 70.4% and 74.2% respectively (Figure 2A). The study further compared the outcomes of different procedures in concentric and eccentric lesion. Diagnostic yields for Type I with eccentric (n=30), Type I with concentric (n=36), Type II with eccentric (n=34), and Type II with concentric (n=26) were 58.2%, 76.9%, 60.2% and 74.8%, respectively (P < 0.05). The incidence of complications in 126 patients was 2.6%. Conclusion: EBUS-GS-TBLB and EBUS-TBLC both are very safe and highly diagnostic technique; different method types have significant influence on the diagnostic yield. Moreover, Type II procedure has higher diagnostic yield. In addition, Type I with eccentric had the lowest diagnosis yield.

Background: Pulmonary hypertension is common symptom among several diseases. The consequences are severe for several organs. Pulmonary hypertension is usually under-diagnosed and the main symptom observed is dyspnea with or without exercise. Currently we have several treatment modalities administered orally, via inhalation, intravenously and subcutaneously. In advanced disease then heart or lung transplantation is considered. The objective of the study was to investigate the optimum method of aerosol production for the drugs: iloprost, paclitaxel and the novel sotatercept. Materials and Methods: In our experiment we used the drugs iloprost, paclitaxel and the novel sotatercept, in an experimental concept of nebulization. We performed nebulization experiments with 3 jet nebulizers and 3 ultrasound nebulizers with different combinations of residual cup designs, and residual cup loadings in order to identify which combination produces droplets of less than 5μm in mass median aerodynamic diameter. Results: We concluded that paclitaxel cannot produce small droplets and is also still very greasy and possible dangerous for alveoli. However; iloprost vs sotatercept had smaller droplet size formation at both inhaled technologies (1.37<2.23 and 1.92<3.11, jet and ultrasound respectively). Moreover; residual cup designs C and G create the smallest droplet size in both iloprost and sotatercept. There was no difference for the droplet formation between the facemask and cone mouthpieces. Discussion: Iloprost and sotatercept can be administered as aerosol in any type of nebulisation system and they are both efficient with the residual cups loaded with small doses of the drug (2.08 and 2.12 accordingly).

Introduction: Lung cancer is still diagnosed at an advanced stage due to lack of early disease symptoms. Areas covered: We have techniques and equipment for rapid on site evaluation of pulmonary lesions. However, with new technology or a combination of technologies in the diagnostic suite the cost of biopsy is rising. Expert opinion: The cost of diagnostic equipment and tools differ between the national health system and private sector. This is due to the economic crisis that our country entered in 2008. The costs for every procedure for lung cancer has not been updated for more than 15 years, and therefore in several cases the reimbursement for the hospitals is lower for both national and private sector.

PurposeTo evaluate the operability and safety of bronchoscopic domestic one-way endobronchial valves (EBV) on animals.MethodsNine pigs were randomly assigned (2:1) to receive domestic one-way EBV (the experimental group, n = 6) and Zephyr® EBV (the control group, n = 3). Routine blood tests, arterial blood gases, and CT scans of the lungs were performed 1 day pre-procedure in addition to 1 week and 1 month post-procedure to assess changes in blood markers and lung volumes. At 1 month post-procedure, the animals were sacrificed, followed by removal of all valves via bronchoscopy. Pathological examinations of critical organs were subsequently performed.ResultsA total of 15 valves were placed in the experimental group and 6 valves were placed in the control group, without serious complications. Routine blood tests and arterial blood gas examinations at 1 day pre-procedure, 1 week post-procedure, and 1 month post-procedure did not differ significantly in both groups. No EBV displacement was noted under bronchoscopy, and the valve was smoothly removable by bronchoscope at 1 month post-procedure. At 1 week post-procedure, varying degrees of target lung lobe volume reduction were observed on lung CT in both groups. Lung volume reduction was achieved at 1 month post-procedure in both groups, without significant statistical difference. Although 3 cases in the experimental group and 1 case in the control group developed varying degrees of pneumonia, the inflammatory response did not increase over time during the experimental period. Pathological examination revealed no significant abnormal changes in the critical organs for both groups.ConclusionOur results demonstrate that domestic EBV is safe and reliable for endobronchial application in general-grade laboratory white pigs. The safety of domestic EBV is similar to that of Zephyr® EBV, with good ease of use and operability. This kind of domestic EBV can meet the safety evaluation requirements for animal testing.