Tissue-resident macrophages may be trained to confer an enhanced response to heterologous restimulation and thus foster versatile trained immunity (TI) against both infections and tumors. However, the key priming signals that contribute to such functional versatility in trained macrophages are not fully understood. Here, we show that influenza A virus (IAV) infection in mice induces lasting transcriptional imprints of acute type-I interferon (IFN-I) signaling in lung-resident alveolar macrophages (AMs) that confer balanced antibacterial and antitumor TI responses. In both IAV-infected mice and an ex vivo cytokine-mediated training system, IFN-I signaling is critical for the development of antitumor TI functions, although it limits antibacterial TI functions in AMs. Moreover, human AMs carrying transcriptional imprints of IFN-I signaling are associated with immune activation in lung cancer tissues. Our findings highlight IFN-I as a key priming signal required for the development of versatile TI functions in AMs with balanced antibacterial and antitumor potential.

To investigate the clinical application value of a novel disposable cuffless tracheostomy cannula during the decannulation transition period in high-risk patients, and to evaluate its efficacy and safety in maintaining airway patency, reducing decannulation-related risks, and improving patient outcomes. This study was a prospective observational study enrolling 35 patients with high-risk airways admitted between June 2023 and April 2025. All patients had a history of tracheostomy and had been weaned from mechanical ventilation. According to clinical conditions, the disposable cuffless tracheostomy cannula was inserted as a transitional airway support after removal of T-tubes, tracheal stents, metal cannulas, or endotracheal tubes. Routine capping observation was performed for 48–72 h postoperatively, and the device was removed after tolerance assessment. The primary outcome was decannulation success rate; secondary outcomes included the incidence of airway events requiring reintervention at 30 days, 90 days, and during long-term follow-up after decannulation. Among the 35 patients, the pre-insertion statuses were as follows: T-tube placement in 10 cases, metal cannula in 21 cases, endotracheal tube in 2 cases, and spontaneous breathing via nose and mouth in 2 cases. The disposable cannula was successfully removed with complete weaning from the artificial airway in 32 patients, yielding a decannulation success rate of 91.4

BackgroundLung adenocarcinoma (LUAD) is a highly heterogeneous disease, bringing daunting challenges in prognosis prediction. Alterations in mitochondrial dynamics (MD) are crucial in tumor generation and progression. Therefore, this study is the first to build a prognostic model based on mitochondrial dynamics-related genes (MDRGs) to predict microenvironment and potential drugs for LUAD.MethodsLUAD transcriptomic data were sourced from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO), respectively. First, differentially expressed genes (DEGs) were screened between normal and LUAD samples in the TCGA cohort. The intersection of DEGs and MDRGs yielded differentially expressed MDRGs (DE-MDRGs). Then, a prognostic model was constructed through univariate Cox regression, LASSO Cox regression, and multivariate Cox regression analysis. A nomogram was graphed using clinical factors and the MD-related risk score (MDRS). The predictive performance of the model and the nomogram was evaluated using ROC curves. Finally, analyses on tumor microenvironment (TME), mutation, and predicted in vitro drug response were undertaken.ResultsA prognostic model based on 8 MDRGs (SLC52A3, HMGA2, CPS1, GLS2, CYP27A1, CFTR, STAR, and DRP2) was established, demonstrating relatively accurate predictive ability. The low-MDRS group had higher levels of immune cell infiltration, such as aDCs, B cells, neutrophils, and tumor-infiltrating lymphocytes. We also discovered that the tumor mutation burden in the high-MDRS group was considerably higher than that in the low-MDRS group. Additionally, the low-MDRS group was more sensitive to AZD8055, ZM447439, ERK-6604, SB505124, Tozasertib, and BMS-754807, while the high-MDRS group was more sensitive to BI-2536 and Venetoclax.ConclusionThis work set up a prognostic model for LUAD based on 8 MDRGs, pinpointing promising biomarkers and targets for LUAD treatment.

Severe asthma is characterized by persistent airway inflammation and epithelial injury. Pyroptosis, a Caspase-1–dependent inflammatory cell death pathway, has been implicated in airway inflammation. FBXW7, an E3 ubiquitin ligase involved in inflammatory regulation, may play a role in this process; however, its function in severe asthma remains unclear. Human microarray datasets from the Gene Expression Omnibus (GEO) were analyzed to identify differentially expressed genes and potential biomarkers using bioinformatics and machine learning approaches. Experimental validation was performed using murine asthma models, including ovalbumin (OVA)-induced and OVA/LPS-induced models. Airway epithelium–specific FBXW7 conditional knockout mice were generated to assess in vivo function. In vitro, murine lung epithelial (MLE12) cells with FBXW7 knockout or overexpression were used to evaluate pyroptosis and inflammatory responses following LPS/ATP stimulation. Cytokine levels, Caspase-1 expression, and signaling pathways were analyzed using ELISA, Western blotting, and immunofluorescence. FBXW7 expression was significantly decreased in severe asthma compared with mild-to-moderate asthma, while Caspase-1 expression was increased. Machine learning analyses identified FBXW7 and Caspase-1 as potential biomarkers in severe asthma. In murine models, FBXW7 downregulation was more pronounced in severe asthma and was associated with increased inflammatory cell infiltration and cytokine production. FBXW7-deficient mice exhibited significantly elevated bronchoalveolar lavage fluid (BALF) inflammatory cell counts and increased IL-1β secretion compared with wild-type controls. In vitro experiments using MLE12 cell lines with FBXW7 overexpression, knockout, and wild-type backgrounds exhibited significant differences in Caspase-1 expression and altered secretion of inflammatory cytokines IL-18 and IL-1β under LPS/ATP-induced pyroptotic conditions, while pharmacological inhibition of Caspase-1 corrected aberrant cytokine secretion. However, mRNA levels of these cytokines remained stable, indicating that FBXW7 controls IL-18/IL-1β maturation/secretion via Caspase-1. Thus, the association among FBXW7, Caspase-1 and cGAS-STING was tested. FBXW7 suppresses airway epithelial pyroptosis and inflammation in severe asthma by regulating Caspase-1, potentially via the cGAS–STING pathway. These findings highlight FBXW7 as a potential biomarker for severe asthma.

Shape-sensing robotic-assisted bronchoscopy (ssRAB) represents a major advancement in the bronchoscopic evaluation of pulmonary nodules suspicious for malignancy. Its use has expanded across multiple countries and healthcare systems; however, no global consensus currently exists to guide clinical practice or address areas of uncertainty. This first world expert consensus was developed by an international panel of 18 specialists in interventional pulmonology and ssRAB, representing 13 hospitals across three continents. The process included a systematic literature review, followed by multiple rounds of structured questionnaires, sharing of clinical experience, and informed discussion, in order to identify key domains and establish consensus statements. A total of 38 recommendations were generated across domains including indications and contraindications, procedural set up, practical workflow, anesthesia considerations, diagnostic tools, training, reporting standards, and safety practices of ssRAB. Full consensus (100% agreement) was achieved for all 38 statements following three voting rounds and extensive discussion. This first international expert consensus provides comprehensive, evidence-informed guidance on the clinical use of ssRAB. It also highlights areas of ongoing uncertainty and can serve as a foundation for future research, education, and guideline development in this rapidly evolving field.

Objective To assess the feasibility and safety of bronchoscopy-guided synergistic pulsed irreversible electroporation (S-IRE) for ablating pulmonary tissues. Methods Three Bama pigs underwent bronchoscopy-guided S-IRE ablation at pulmonary target sites (near airways, vessels, pleura, and parenchyma), using synergistic microsecond and nanosecond pulses (S-IRE) delivered via a catheter. Tissue samples were collected at postoperative days 3 and 28. Preoperative and postoperative assessments, including blood biochemistry, coagulation function tests, computed tomography (CT) assessment and histopathological examination, were conducted. Results All procedures were successfully completed without complications such as muscle twitching, bleeding, pneumothorax, or cardiac issues. Preoperative and serially postoperative CT imaging demonstrated immediate post-procedural changes within the ablation zone, characterized by high-density areas with minimal peripheral exudation. Postoperative pathological examination found well-demarcated ablation zones, distinct from the surrounding tissues. A clearly defined ablation zone was evident on CT by postoperative day 3. Subsequently, the zone exhibited progressive reduction in size and absorption over time. By postoperative day 28, the ablation zone had undergone significant reduction in size, exhibiting indistinct borders, being filled with granulation tissue, and indicating progressive healing. Throughout the follow-up period, imaging showed no evidence of filling defects or lumen stenosis within adjacent blood vessels or bronchi. Conclusion This porcine model provides preliminary evidence supporting the safety and efficacy of bronchoscopy-guided S-IRE. As a novel natural orifice, non-thermal physical ablation technique, it may offer a safe, effective, and minimally invasive therapeutic choice for patients with pulmonary malignant nodules located adjacent to critical structures or deemed unsuitable for surgical resection.

Background: Following the 2021 first International Consensus on Severe Lung Cancer, global attention to patients with PS 2-4 has grown significantly. Recent advances in novel therapies, interventional techniques, and supportive care, along with emerging real world data, have expanded treatment opportunities for this population. To incorporate these advances, we have updated the consensus. Methods: A multidisciplinary panel comprising experts from oncology, radiation oncology, thoracic surgery, radiology, interventional medicine, respiratory medicine, critical care medicine, and nursing. After being presented with a comprehensive review of the current evidence pertaining to severe lung cancer and thorough discussions, the panel reached a consensus on 11 recommendations, each with over 70% expert agreement. Results: The 11 consensus points focused on definition and causes (n=2), assessment and general strategies (n=4), and specific treatment modalities (n=5) were updated or newly developed. This updated consensus emphasizes dynamic and precise detection, robust life support, flexible application of novel therapies, and MDT guided treatment adjustment based on PS dynamics. Early rehabilitation and comprehensive supportive care are integral to disease management. Conclusions: This consensus updates the definition, diagnostic evaluation, and treatment strategies, providing a practical framework for clinicians based on current evidence and multidisciplinary expert consensus. Prospective trials focusing specifically on patients with severe lung cancer are urgently needed.

Robotic-assisted bronchoscopy (RAB) may improve diagnosis of peripheral pulmonary lesions (PPLs), particularly when lesion localization and sampling are technically demanding. However, direct real-world comparisons between shape-sensing RAB (ss-RAB) and virtual bronchoscopic navigation (VBN) remain limited. We retrospectively reviewed patients who underwent navigational bronchoscopy for PPLs at a single center. Propensity score matching (PSM) was used to balance baseline characteristics between the ss-RAB and VBN groups. Diagnostic yield, tool-in-lesion (TIL) rate, sensitivity for malignancy, adverse events, and learning curves of ss-RAB were evaluated. Learning curves were assessed using cumulative sum analysis based on procedure time and diagnostic success. Following 1:1 PSM, 234 patients were included, with 117 in each group. Final malignancy prevalence was 74.8

Background:Currently, Endobronchial ultrasound (EBUS) and rapid on-site evaluation (ROSE) are extensively utilized in the clinical practice of respiratory medicine. The combined diagnostic approach has been shown to enhance the clinical diagnostic accuracy; however, certain controversies remain. Methods:This study included 200 patients who underwent endobronchial ultrasound combined with transbronchial lung biopsy with a guide sheath (EBUS-GS-TBLB) or endobronchial ultrasound combined with transbronchial needle aspiration (EBUS-TBNA) and received histopathological diagnoses at the Bronchoscopy Department, from January 2021 to January 2022. Of these, 168 patients were assigned to the ROSE group and 32 to the non-ROSE group. The diagnosis rates of EBUS-GS-TBLB and EBUS-TBNA, both with and without ROSE, along with the secondary biopsy rate, complication probability, and mean number of biopsies, were compared to analyze the differences between tumors and non-tumors. The safety of EBUS-GS-TBLB and EBUS-TBNA was also evaluated. Results:The overall diagnostic accuracy was 85.71% in the ROSE group and 65.62% in the non-ROSE group. The diagnostic accuracy of the ROSE group was significantly higher than that of the non-ROSE group (P < 0.05). Compared to the non-ROSE group, the rate of secondary biopsy in the ROSE group was significantly reduced (P < 0.05), particularly in non-tumor cases. However, there was no significant difference in the incidence of complications and the average number of biopsies between the two groups (P > 0.05). Compared to the EBUS-GS-TBLB group, the EBUS-TBNA group showed a significantly lower incidence of complications and fewer biopsies (P < 0.05). Conclusion:The integration of ROSE with EBUS enhanced the diagnostic rate and reduced the need for secondary examinations in the biopsy diagnosis of lung lesions, particularly in the definitive diagnosis of non-neoplastic lesions. The combination of ROSE technology appears to be more advantageous. Compared to EBUS-GS-TBLB, EBUS-TBNA demonstrated a lower incidence of complications and fewer biopsies.

The tow-pore domain (KCNK) potassium channel family is associated with tumor progression, but its prognostic value in lung adenocarcinoma (LUAD) remains unclear. In this study, we integrated data from the TCGA and GEO databases to identify 9 KCNK-related differentially expressed genes, and based on this, we classified two molecular subtypes with significantly different prognoses. A 11-gene prognostic model with independent prognostic value was constructed through regression analysis. Immuno-analysis revealed that the low-risk group had stronger immune infiltration and might be more suitable for immunotherapy. These findings reveal the prognostic significance of the KCNK genes and provide a reference for immunotherapy.

We report the first successful case of volume reduction of a giant emphysematous bulla (GEB) using the latest shape-sensing robotic-assisted bronchoscopy (ssRAB). The patient was a 70-year-old male with chronic obstructive pulmonary disease (COPD) who developed GEB. He had previously undergone endobronchial valve (EBV) removal due to pneumonia caused by long-term implantation of EBVs for bulla volume reduction after a left emphysematous bulla rupture and subsequent pneumothorax. The patient visited our hospital for gradually worsening shortness of breath over two months. Chest radiography and computed tomography (CT) showed a GEB compressing 60% of the right lung volume, with the largest part filling the entire cross-section of the right lower lung. Under general anesthesia and with the assistance of ssRAB, we precisely punctured the bulla, safely aspirated the gas within the bulla, and injected medical adhesive to close the bulla. Postoperatively, the patient's shortness of breath improved significantly, and a CT follow-up six months later showed that the bulla had reduced to about half of its original size. Our experience indicates the feasibility and potential benefits of the novel ssRAB for volume reduction of GEB. The long-term efficacy and safety of using ssRAB to reduce GEB need to be evaluated by larger-scale studies.

Osimertinib, the first approved third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), exhibits notable efficacy in EGFR-mutant non-small cell lung cancer (NSCLC). This is a prospective, multicenter, comprehensive genomic profile signature (GPS) study in paired tissue and plasma samples from 149 patients with advanced NSCLC harboring EGFR exon 19 deletion (Ex19del) or L858R mutation at the first-line treatment failure of osimertinib (NCT05219162). Next-generation sequencing (NGS) was used for comprehensive GPS analysis of paired tissue and plasma samples. Fluorescence in situ hybridization (FISH) and next-generation sequencing (NGS) were used for tissue samples, while droplet digital polymerase chain reaction (ddPCR) and NGS were used for plasma samples to perform a concordance analysis of MET amplification. At the first-line treatment failure of osimertinib (study entry), EGFR alterations in tissue samples included EGFR Ex19del (49.0%, 73/149), EGFR L858R mutation (43.0%, 64/149), EGFR amplification (32.9%, 49/149), EGFR L718Q/V mutation (4.7%, 7/149), and EGFR C797S mutation (3.4%, 5/149); bypass signaling activation and downstream pathway activation alterations included TP53 mutation (69.8%, 104/149) and MET amplification (30.9%, 46/149). Among the 136 patients with EGFR Ex19del/L858R mutation in tissue samples, 72.1% (98/136), 35.3% (48/136), and 32.4% (44/136) had TP53 mutations, EGFR amplification, and MET amplification, respectively. Taking tissue samples as references, the GPS in plasma samples showed high specificity (90.7–100%) for almost all genomic alterations. Compared with FISH (gene copy number [GCN] ≥10), the overall percent agreement of tissue NGS, optimized tissue NGS (GCN ≥ 8.63), plasma NGS, and plasma ddPCR for MET amplification were 75.0% (27/36), 100% (36/36), 88.9% (32/36), and 94.4% (34/36), respectively. This study represents the largest-scale, prospective study with paired tissue and plasma samples to enable comprehensive analysis of GPS, providing a novel perspective into coalterations at the first-line treatment failure of osimertinib. A plasma sample serves as a supplement for identifying GPS when a tissue sample is unavailable. Moreover, the integration of FISH, NGS, and ddPCR provided a comprehensive assessment of MET amplification.

BACKGROUND:A novel airway balloon cryoablation (ABC) system using liquid nitrogen as cryogen was developed for bronchoscopic intervention in malignant central airway obstruction (MCAO). This study aimed to evaluate the efficacy and safety of this system. METHODS:This was a prospective, randomised, controlled, non-inferiority study that enrolled MCAO patients at 15 sites in China. Patients were assigned to the ABC group and the ERBOKRYOCA Cryosurgical (EC) system group in a 1:1 ratio. Airway tumour debulking with multimodality was permitted before cryoablation. The primary outcome was the airway patency rate after 6 weeks of intervention with a non-inferiority margin of -10%. Secondary outcomes included modified Medical Research Council (mMRC) Dyspnoea Scale and Karnofsky Performance Scale (KPS) assessment, and the duration of cryoablation. RESULTS:198 patients were randomised. After 6 weeks of intervention, the airway patency rate was 78.49% in the ABC group and 60.92% in the EC group, showing that the difference was over the non-inferiority margin of -10% at 17.58% (95% CI 4.35% to 30.80%), p<0.001. The mMRC and KPS scores were significantly improved after 3 and 6 weeks in both groups, with no difference. The duration of cryoablation was shortened remarkably in the ABC group (378.29±399.54 s vs 624.93±443.72 s, p<0.001). The prevalence of bleeding was similar in the two groups, without life-threatening events. CONCLUSIONS:The ABC system provided non-inferior and subsequent superior effect in airway patency rate compared with traditional carbon dioxide-driven cryoprobe in MCAO. This study supports this novel system as an alternative to cryoablation via bronchoscope for MCAO patients. TRIAL REGISTRATION NUMBER:ChiCTR2100042051.

Background:Although advancements in cancer therapies have substantially improved the survival of cancer patients, these treatments may also result in acute or chronic lung injury. Cancer treatment-related lung injury (CTLI) presents with a diverse array of clinical manifestations and can involve multiple sites. Due to the lack of specific diagnostic protocols, CTLI can deteriorate rapidly and may be life-threatening if not promptly addressed. Unfortunately, there is no universally accepted consensus document on the diagnosis and management of CTLI. Methods:A multidisciplinary panel comprising experts from respiratory and critical care medicine, oncology, radiation oncology, thoracic surgery, radiology, pathology, infectious diseases, pharmacy, and rehabilitation medicine participated in this consensus development. Through a systematic literature review and detailed panel discussions, the team formulated nine key recommendations. Results:This consensus document addresses the concept, epidemiology, pathogenesis, risk factors, diagnostic approach, evaluation workflow, management strategies, differential diagnosis, type-specific management and clinical staging of CTLI. Emphasis is placed on raising awareness among clinicians and therapeutic practices through comprehensive guidelines. Conclusions:The consensus provides a detailed diagnostic protocol for CTLI and introduces a structured management framework based on grading, typing, and staging. It highlights the critical role of multidisciplinary team (MDT) collaboration and emphasizes the need for individualized, whole-process patient care strategies to optimize clinical outcomes.

Background:Shape-sensing robotic-assisted bronchoscopy (ssRAB) is a new bronchoscopy technology that utilizes optic fibers to provide accurate position information and robotic-control to deliver improved maneuverability. This technology has been used in the United States since 2019 and investigated in China since 2021. In order to provide a standard practice and make the best use of this technology for managing peripheral pulmonary lesions (PPLs), experts developed the consensus. Methods:This consensus was developed using Delphi method. A panel comprising nine experts formulated eight consensus statements after a thorough review of clinical evidence and practical experience. During the second phase, a questionnaire was distributed to collect feedback on these statements from an external panel of 39 physicians. The percentage of responses and the percentage of agreement on each statement were calculated. The consensus was defined as achieved with an agreement percentage threshold of 80% or above. Results:The eight consensus statements formulated in phase 1 included recommendations for path planning, anesthesia, the use of radial endobronchial ultrasound (EBUS), the use of fluoroscopy and/or cone-beam computed tomography (CBCT) with ssRAB, solving computed tomography (CT)-to-body divergence, the use of sampling tools with ssRAB, cloud biopsy, and the use of rapid on-site evaluation (ROSE) with ssRAB. All panel physicians completed the questionnaire in phase 2. All the statements achieved positive consensus, with six receiving 100% agreement and two reaching 97.4% agreement. Conclusions:The document establishes a consensus on recommended practices for optimal utilization of ssRAB technology in the management of PPLs. The guidelines will be updated as new evidence emerges or additional ssRAB platforms are introduced into practice.

INTRODUCTION:Wearable devices have been developed that can continuously monitor physiologic variables. One device, Circul® (Bodimetrics Corp, Los Angeles, CA), with a form factor of a ring, measures several variables (SpO2, movement, heart rate). OBJECTIVES:To evaluate the potential utility of this device in detecting sleep breathing disorders. MATERIALS AND METHODS:OSA severity measured by the oxygen desaturation Index (ODI) using a wearable oximetric Circul® ring (ODI as defined by 3 % desaturation - cODI3 %) was compared with the gold standard, polysomnography (PSG) in patients suspected of having sleep-disordered breathing. The Circul data was autoscored by the device's software; a technician scored the PSG data. The sensitivity (S), and specificity (E) for the different thresholds for cODI3 % compared to the PSG AHI and PSG ODI, were calculated. RESULTS:164 patients (age = 44.8 years + 12.3 (SD)) were enrolled. Using the PSG-derived AHI as the reference for classification, the best cut-off points were: OSA = AHI ≥ 5: cODI3 % ≥ 4.3 (S 87.8 %, E 93.8 %); OSA = AHI ≥ 15: cODI3 % ≥ 13.1 (S 76 %, E 100 %); OSA = AHI ≥ 30 = : cODI3 % ≥ 16.2 (S 85.7 %, E 92 %); Using the ODI from the PSG as the reference for classification, the respective cut-off points were: OSA=ODI ≥ 5: cODI3 % ≥ 4.3 (S 93.4 %, E 88.9 %); OSA=ODI ≥ 15:cODI3 % ≥ 13.1 (S85.2 %, E98.4 %); OSA=ODI ≥ 30: cODI3 % ≥ 18.7 (S 98.4 %, E 92.2 %). CONCLUSIONS:Circul® oximetry demonstrated good diagnostic accuracy compared to the gold standard in determining OSA severity. cODI3 % greater than 13 suggests that significant OSA might be present.

BACKGROUND:Existing virtual bronchoscopic navigation (VBN) biopsy systems are ineffective in reconstructing small airway trees of 2-3 mm, which leads to an inability to accurately guide the biopsy of peripheral pulmonary lesions (PPL). This study intended to compare the diagnostic rate of PPL by the modified SARS-pro (small airway reconstruction system-pro) system and the original VBN system. METHODS:This single-center randomized controlled trial enrolled subjects aged ≥18 years who had one or more PPLs between August 2023 and December 2024 at a hospital. Subjects were randomly assigned to the SARS-pro system and the VBN system (1:1). The outcomes were the diagnostic positive rate of PPL and adverse events in subjects. The diagnosis rate outcomes were evaluated in the per-protocol set (PPS). RESULTS:Ninety-five eligible subjects were recruited, 95 subjects were included in the full analysis set (FAS), and 92 subjects were included in PPS. The SARS-pro system exhibited a higher positive diagnostic rate for PPL than the VBN system on FAS [43 (91.49%) vs. 30 (62.50%), P = 0.002] and PPS [43 (93.48%) vs. 30 (65.22%), P = 0.002]. Furthermore, the positive diagnostic rate of PPL was significantly higher for the SARS-pro system than for the VBN system in some characteristic subgroups, such as females, no smoking history, lesion size of 1-2 cm, and no bronchial signs. CONCLUSION:The improved SARS-pro system presented a higher diagnostic rate for PPL than the VBN system, which may suggest the application of deep learning technology in improving the diagnostic rate of lung biopsy.