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Introduction: Benign airway stenosis (BAS) is a severe pathologic condition. Complex stenosis has a high recurrence rate and requires repeated bronchoscopic interventions for achieving optimal control, leading to recurrent BAS (RBAS) due to intraluminal granulation. Methods: This study explored the potential of autologous regenerative factor (ARF) for treating RBAS using a post-intubation tracheal stenosis canine model. Bronchoscopic follow-ups were conducted, and RNA-seq analysis of airway tissue was performed. A clinical study was also initiated involving 17 patients with recurrent airway stenosis. Results: In the animal model, ARF demonstrated significant effectiveness in preventing further collapse of the injured airway, maintaining airway patency and promoting tissue regeneration. RNA-seq results showed differential gene expression, signifying alterations in cellular components and signaling pathways. The clinical study found that ARF treatment was well-tolerated by patients with no severe adverse events requiring hospitalization. ARF treatment yielded a high response rate, especially for post-intubation tracheal stenosis and idiopathic tracheal stenosis patients. Conclusion: The study concludes that ARF presents a promising, effective, and less-invasive method for treating RBAS. ARF has shown potential in prolonging the intermittent period and reducing treatment failure in patients with recurrent tracheal stenosis by facilitating tracheal mucosal wound repair and ameliorating tracheal fibrosis. This novel approach could significantly impact future clinical applications. [ABSTRACT FROM AUTHOR]

Adult lung resident stem/progenitor cells, including P63+ progenitor cells, have demonstrated the capacity for regeneration of lung epithelium in preclinical models. Here, we report a clinical trial of intrapulmonary P63+ progenitor cell transplantation in 28 participants with stage II to IV chronic obstructive pulmonary disease (COPD). Autologous P63+ progenitor cells were isolated from the airway basal layer of participants in the intervention group via bronchoscopic brushing, cultured for 3 to 5 weeks, and then transplanted back into the lungs via bronchoscopy at 0.7 × 106 to 5.2 × 106 cells per kilogram of body weight. Twenty patients were evaluable at the end of the study (intervention group, n = 17; control group, n = 3). No grade 3 to 5 adverse events (AEs) or serious AEs occurred. Although bronchoscopy-associated AEs were recorded in participants in the intervention group, other AEs were not substantial different between groups. Twenty-four weeks after transplantation, participants in the intervention group displayed improvement in gas transfer capacity [diffusing capacity of the lung for carbon monoxide (DLCO) change from baseline: +18.2%], whereas the control group experienced a decrease (DLCO change from baseline: −17.4%; P = 0.008). Furthermore, participants in the intervention group showed >30-meter increase in walking distance within 6 minutes. Transcriptomic analysis of progenitor cells isolated from responding and nonresponding individuals in the intervention group showed that higher expression of P63 was associated with treatment efficacy. In conclusion, transplantation of cultured P63+ lung progenitor cells was safe and might represent a potential therapeutic strategy for COPD. Editor's summary: Chronic obstructive pulmonary disease (COPD) results in damage to both the airways and the lung parenchyma, but a treatment that potentially reverses this damage in patients has not yet been identified. Building on previous preclinical work, Wang and colleagues conducted an early, open-label clinical trial of autologous P63+ lung progenitor cells for the treatment of patients with COPD. Cells were collected during bronchoscopy, expanded over several weeks, and then were administered back into the patients' lungs, again by bronchoscopy. The treated group showed improvements in the diffusing capacity of the lung for carbon monoxide and the 6-minute walk distance at 24 weeks' follow-up, supporting further clinical studies of P63+ lung progenitor cells for the treatment of COPD. —Melissa L. Norton [ABSTRACT FROM AUTHOR]

Background: Transbronchial cryobiopsy (TBCB) is increasingly being identified as a potential alternative for the diagnosis of interstitial lung disease (ILD). The specimen size of TBCB is positively related to the freezing time. However, the proper initial freezing time for the clinical application of TBCB in ILD remains unknown. Methods: A prospective randomized parallel group study was employed to investigate ILD patients with unclear diagnosis, who were admitted to the First Affiliated Hospital of Guangzhou Medical University from May 2019 to October 2020 and required TBCB. All patients were randomly divided into 4 groups according to the different freezing times of TBCB: 3 s, 4 s, 5 s, and 6 s groups. All operations were performed under intravenous anesthesia with endotracheal intubation, 60–65 bar pressure of freezing gas source, and 1.9-mm cryoprobe. Compare differences among groups in specimen size, complications, pathological diagnosis efficiency, and multidisciplinary discussion (MDD) diagnostic efficiency. Results: A total of 100 patients were recruited and randomly assigned into 4 groups (n = 25 each group). The specimen sizes of TBCB in ILD were positively correlated with the freezing time (r = 0.639, p < 0.05). None of the patients experienced Grade 3 severe bleeding. Pneumothorax occurred in 1 patient in the 4 s, 5 s, and 6 s groups, respectively. The diagnostic yield of MDD in the 3 s, 4 s, 5 s, and 6 s groups were 64%, 88%, 88%, and 96%, respectively (p < 0.05), but showing no significant differences among 4 s, 5 s, and 6 s groups. Conclusions: The specimen size and diagnostic efficiency of TBCB in ILD increased with a longer freezing time. When the freezing gas pressure is 60–65 bar, we recommended 4 s as the initial freezing time of TBCB, and this time is associated with high diagnostic efficiency and low incidence of complications. [ABSTRACT FROM AUTHOR]

We comprehensively compared the therapeutic effects and safety of PD‐1/L1 antibodies (I), chemotherapy (C) or their combination (I + C) as first‐line treatments for advanced NSCLC. Online databases were searched to identify RCTs. Survival outcomes and safety events were pooled by indirect treatment comparison. Main subgroup analyses were conducted according to PD‐L1 expression. A total of 11 RCTs involving 6,731 patients were included. Overall, PD‐1/L1 inhibitors showed no difference to chemotherapy in PFS (HR 0.90, 0.65–1.24) and OS (HR 0.84, 0.64–1.09), while I + C was superior to chemotherapy both in PFS (HR 0.64, 0.58–0.71) and OS (HR 0.74, 0.62–0.89). I + C also showed advantages over PD‐1/L1 in PFS (HR 0.71, 0.51–0.99) but not OS (HR 0.88, 0.64–1.22). In the PD‐L1 < 1% subgroup, I + C was beneficial both in OS (HR 0.78, 0.67–0.90) and PFS (HR 0.72, 0.65–0.80) than chemotherapy. In PD‐L1 ≥ 50% population, PD‐1/L1 had longer OS than chemotherapy (HR 0.71, 0.60–0.84); I + C also had longer OS (HR 0.61, 0.49–0.77) and PFS (HR 0.41,0.34–0.49) than chemotherapy. In indirect analysis (PD‐L1 ≥ 50%), I + C was superior to PD‐1/L1 in terms of PFS (HR 0.54, 0.35–0.82), but not OS (HR 0.86, 0.65–1.14). Both treatment‐related and immune‐mediated adverse events occurred most frequently in the combination therapy group. We suggest that a combination regimen is preferable as first‐line treatment for NSCLC patients with different PD‐L1 expression, in the meanwhile, in cautious of side effects. What's new? Immunotherapies such as PD‐1 and PD‐L1 inhibitors have been highly effective in non‐small cell lung cancer (NSCLC). But how do they compare with standard chemotherapy? And what happens when the two modalities are combined? In this indirect comparative review, the authors found that the efficacy of treatment with anti‐PD‐1/L1 antibodies was not any better than with chemotherapy. However, when patients were treated with combined immuno‐ and chemotherapy, they generally had significantly better outcomes, regardless of the level of PD‐L1 expression by the tumor cells. [ABSTRACT FROM AUTHOR]

Background and Objective Methods Results Conclusion Radiofrequency ablation (RFA) is an emerging treatment of lung cancer, yet it is accompanied by certain safety concerns and operational limitations. This first multi‐centre, large‐scale clinical trial aimed to investigate the technical performance, efficacy and safety of an innovative transbronchial RFA system for lung tumours.The study enrolled patients with malignant lung tumours who underwent transbronchial RFA using an automatic saline microperfusion system between January 2021 and December 2021 across 16 medical centres. The primary endpoint was the complete ablation rate. The performance and safety of the technique, along with the 1‐year survival rates, were evaluated.This study included 126 patients (age range: 23–85 years) with 130 lung tumours (mean size: 18.77 × 14.15 mm) who had undergone 153 transbronchial RFA sessions, with a technique success rate of 99.35% and an average ablation zone size of 32.47 mm. At the 12‐month follow‐up, the complete ablation rate and intrapulmonary progression‐free survival rates were 90.48% and 88.89%, respectively. The results of patients with ground‐glass nodules (GGNs) were superior to those of the patients with solid nodules (12‐month complete ablation rates: solid vs. pure GGN vs. mixed GGN: 82.14% vs. 100% vs. 96.08%, p = 0.007). No device defects were reported. Complications such as pneumothorax, haemoptysis, pleural effusion, pulmonary infection and pleural pain were observed in 3.97%, 6.35%, 8.73%, 11.11% and 10.32% of patients, respectively. Two subjects died during the follow‐up period.Transbronchial RFA utilizing an automatic saline microperfusion system is a viable, safe and efficacious approach for the treatment for lung tumours, particularly for patients with GGNs. [ABSTRACT FROM AUTHOR]

Adult lung resident stem/progenitor cells, including P63 + progenitor cells, have demonstrated the capacity for regeneration of lung epithelium in preclinical models. Here, we report a clinical trial of intrapulmonary P63 + progenitor cell transplantation in 28 participants with stage II to IV chronic obstructive pulmonary disease (COPD). Autologous P63 + progenitor cells were isolated from the airway basal layer of participants in the intervention group via bronchoscopic brushing, cultured for 3 to 5 weeks, and then transplanted back into the lungs via bronchoscopy at 0.7 × 10 6 to 5.2 × 10 6 cells per kilogram of body weight. Twenty patients were evaluable at the end of the study (intervention group, n = 17; control group, n = 3). No grade 3 to 5 adverse events (AEs) or serious AEs occurred. Although bronchoscopy-associated AEs were recorded in participants in the intervention group, other AEs were not substantial different between groups. Twenty-four weeks after transplantation, participants in the intervention group displayed improvement in gas transfer capacity [diffusing capacity of the lung for carbon monoxide (DLCO) change from baseline: +18.2%], whereas the control group experienced a decrease (DLCO change from baseline: -17.4%; P = 0.008). Furthermore, participants in the intervention group showed >30-meter increase in walking distance within 6 minutes. Transcriptomic analysis of progenitor cells isolated from responding and nonresponding individuals in the intervention group showed that higher expression of P63 was associated with treatment efficacy. In conclusion, transplantation of cultured P63 + lung progenitor cells was safe and might represent a potential therapeutic strategy for COPD.

Background: Treatment-naive epidermal growth factor receptor (EGFR) T790M mutation is more inclined to coexist with L858R than with 19 del in non-small cell lung cancer (NSCLC) patients. However, EGFR-tyrosine kinase inhibitors (EGFR-TKIs) might alter this status. We sought to compare the prevalence of T790M upon acquired resistance to EGFR-TKIs between 19 del and L858R by assembling all existing data., Methods: Electronic databases were comprehensively searched for eligible studies. The primary endpoint was the odds ratio (OR) of T790M mutation in NSCLC co-existing with L858R mutation and 19 del upon resistance to first-generation EGFR-TKIs. A random effects model was used. Stratified analysis was performed based on study type (retrospective and prospective), race (Asians and Caucasians) and sample type (tissue and plasma)., Results: A total of 25 studies involving 1,770 patients were included. The overall T790M existent rate was 45.25%. Post-resistance T790M was more frequent in 19 del than in L858R mutated patients (53% vs. 36%; OR 1.87; P<0.001). All outcomes of subgroup and overall analyses were similar. In contrast, we re-analyzed the previous meta-analysis, finding that the pooled rate of pretreatment T790M was 14% and 22% in 19 del and L858R respectively (OR 0.59; P<0.001). The increase of T790M rate was 2.79-fold in 19 del and only 0.63-fold in L858R in the course of EGFR-TKIs therapy., Conclusions: Opposite to the situation of de novo T790M, it was observed that T790M was more frequent in exon 19 deletion than in L858R among patients with acquired resistance to EGFR-TKIs. The difference in T790M alteration between 19 del and L858R encourages development of detection or treatment strategies for the specific resistance mechanism., Competing Interests: Conflict of Interest: The authors have no conflicts of interest to declare.