Safety and efficacy of a novel transbronchial radiofrequency ablation system for lung tumours: One year follow-up from the first multi-centre large-scale clinical trial (BRONC-RFII).

BACKGROUND AND OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Deep Learning-Based Segmentation of Airway Morphology from Endobronchial Optical Coherence Tomography.

BACKGROUND: Manual measurement of endobronchial optical coherence tomography (EB-OCT) images means a heavy workload in the clinical practice, which can also introduce bias if the subjective opinions of doctors are involved. OBJECTIVE: We aim to develop a convolutional neural network (CNN)-based EB-OCT image analysis algorithm to automatically identify and measure EB-OCT parameters of airway morphology. METHODS: The ResUNet, MultiResUNet, and Siamese network were used for analyzing airway inner area (Ai), airway wall area (Aw), airway wall area percentage (Aw%), and airway bifurcate segmentation obtained from EB-OCT imaging, respectively. The accuracy of the automatic segmentations was verified by comparing with manual measurements. RESULTS: Thirty-three patients who were diagnosed with asthma (n = 13), chronic obstructive pulmonary disease (COPD, n = 13), and normal airway (n = 7) were enrolled. EB-OCT was performed in RB9 segment (lateral basal segment of the right lower lobe), and a total of 17,820 OCT images were collected for CNN training, validation, and testing. After training, the Ai, Aw, and airway bifurcate were readily identified in both normal airway and airways of asthma and COPD. The ResUNet and the MultiResUNet resulted in a mean dice similarity coefficient of 0.97 and 0.95 for Ai and Aw segmentation. The accuracy Siamese network in identifying airway bifurcate was 96.6%. Bland-Altman analysis indicated there was a negligible bias between manual and CNN measurements for Ai (bias = -0.02 to 0.01, 95% CI = -0.12 to 0.14) and Aw% (bias = -0.06 to 0.12, 95% CI = -1.98 to 2.14). CONCLUSION: EB-OCT imaging in conjunction with ResUNet, MultiResUNet, and Siamese network could automatically measure normal and diseased airway structure with an accurate performance.

Hierarchical clock-scale hand-drawn mapping as a simple method for bronchoscopic navigation in peripheral pulmonary nodule.

BACKGROUND: A feasible and economical bronchoscopic navigation method in guiding peripheral pulmonary nodule biopsy is lacking. OBJECTIVE: To investigate the utility of hierarchical clock-scale hand-drawn mapping for bronchoscopic navigation in peripheral pulmonary nodules. METHODS: We developed a hierarchical clock-scale hand-drawn mapping for bronchoscopic navigation in peripheral pulmonary nodules. Patients with peripheral pulmonary nodules were recruited and assigned to two groups in this retrospective study, subjects in VBN group received conventional bronchoscopy in conjunction with virtual bronchoscopic navigation (VBN) and radial probe endobronchial ultrasound (RP-EBUS) for biopsy (VBN group), while HBN group underwent ultrathin bronchoscopy and RP-EBUS under the guidance of hand-drawn bronchoscopic navigation (HBN). The demographic characteristics, procedural time, operating cost and diagnostic yield were compared between these two groups. RESULTS: Forty-eight patients with peripheral pulmonary nodule were enrolled in HBN group, while 42 in VBN group. There were no significant differences between VBN and HBN groups in terms of age, gender, lesion size, location and radiographic type. The time of planning pathway (1.32 vs. 9.79 min, P < 0.001) and total operation (23.63 vs. 28.02 min, P = 0.002), as well as operating cost (758.31 ± 125.21 vs.1327.70 ± 116.25 USD, P < 0.001) were markedly less in HBN group, compared with those in VBN group. The pathological diagnostic efficiency of benign and malignant disease in HBN group appeared similar with those in VBN group, irrespective of the size of pulmonary lesion (larger or smaller than 20 mm). The total diagnostic yield of HBN had no marked difference from that of VBN (75.00% vs. 61.90%, P = 0.25). CONCLUSIONS: Hierarchical clock-scale hand-drawn mapping for bronchoscopic navigation could serve as a feasible and economical method for guiding peripheral pulmonary nodule biopsy, providing a comparable diagnostic yield in comparison with virtual bronchoscopic navigation.

A clinical and canine experimental study in small-airway response to bronchial thermoplasty: Role of the neuronal effect.

BACKGROUND: The effects of bronchial thermoplasty (BT) on smooth muscle (SM) and nerves in small airways are unclear. METHODS: We recruited 15 patients with severe refractory asthma, who received BT treatment. Endobronchial optical-coherence tomography (EB-OCT) was performed at baseline, 3 weeks' follow-up and 2 years' follow-up to evaluate the effect of BT on airway structure. In addition, we divided 12 healthy beagles into a sham group and a BT group, the latter receiving BT on large airways (inner diameter >3 mm) of the lower lobe. The dogs' lung lobes were resected to evaluate histological and neuronal changes of the treated large airways and untreated small airways 12 weeks after BT. RESULTS: Patients receiving BT treatment had significant improvement in Asthma Control Questionnaire (ACQ) scores and significant reduction in asthma exacerbations. EB-OCT results demonstrated a notable increase in inner-airway area (Ai) and decrease in airway wall area percentage (Aw%) in both large (3rd-to 6th-generation) and small (7th-to 9th-generation) airways. Furthermore, the animal study showed a significant reduction in the amount of SM in BT-treated large airways but not in untreated small airways. Protein gene product 9.5 (PGP9.5)-positive nerves and muscarinic receptor 3 (M3 receptor) expression in large and small airways were both markedly decreased throughout the airway wall 12 weeks after BT treatment. CONCLUSIONS: BT significantly reduced nerves, but not SM, in small airways, which might shed light on the mechanism of lung denervation by BT.

Feasibility and Safety of Radiofrequency Ablation Guided by Bronchoscopic Transparenchymal Nodule Access in Canines.

BACKGROUND: The treatment of pulmonary malignancies remains a challenge. The efficacy and safety of bronchoscopic radiofrequency ablation (RFA) for the treatment of lung cancer are not well elucidated. OBJECTIVE: This study aimed to evaluate the feasibility and safety of RFA guided by bronchoscopic transparenchymal nodule access (BTPNA) in vivo. METHODS: In an attempt to determine the parameters of RFA, we first performed RFA in conjunction with automatic saline microperfusion in the lung in vitro with various ablation energy (10, 15, 20, 25, and 30 W) and ablation times (3, 5, 8, and 10 min). The correlation between ablated area and RFA parameter was recorded and analyzed. Further, we conducted a canine study with RFA by BTPNA in vivo, observing the ablation effect and morphological changes in the lung assessed by chest CT and histopathologic examination at various follow-up time points (1 day, n = 3; 30 days, n = 4; 90 days, n = 4). The related complications were also observed and recorded. RESULTS: More ablation energy, but not ablation time, induced a greater range of ablation area in the lung. Ablation energy applied with 15 W for 3 min served as the appropriate setting for pulmonary lesions ≤1 cm. RFA guided by BTPNA was performed in 11 canines with 100% success rate. Inflammation, congestion, and coagulation necrosis were observed after ablation, which could be repaired within 7 days; subsequently, granulation and fibrotic scar tissue developed after 30 days. No procedure-related complication occurred during the operation or in the follow-up periods. CONCLUSION: The novel RFA system and catheter in conjunction with automatic saline microperfusion present a safe and feasible modality in pulmonary parenchyma. RFA guided by BTPNA appears to be well established with an acceptable tolerance; it might further provide therapeutic benefit in pulmonary malignancies.

Postintubation Tracheal Stenosis Evaluated by Endobronchial Optical Coherence Tomography: A Canine Model Study.

BACKGROUND: The predictors and airway morphological changes during the development of postintubation tracheal stenosis (PITS) have not been well elucidated. OBJECTIVES: To elucidate the validation of endobronchial optical coherence tomography (EB-OCT) in assessing the airway morphological changes in PITS. METHODS: We performed oral endotracheal intubation in 12 beagles to establish the PITS model. EB-OCT was performed respectively before modeling and on the 1st, 7th, and 12th day after extubation in 9 canines, and was conducted consecutively in 3 canines during the development of PITS. Histological findings and the thickness and gray-scale value of the tracheal wall assessed by EB-OCT measurements were analyzed and compared. RESULTS: The tracheal wall edema, granulation tissue proliferation, cartilage destruction in PITS, and airway wall thickening detected by EB-OCT were in concordance with the histopathological measurements. The consecutive EB-OCT observation of the airway structure demonstrated the tracheal wall thickness significantly increased from 344.41 ± 44.19 µm before modeling to 796.67 ± 49.75 µm on the 9th day after modeling (p < 0.05). The airway wall gray-scale values assessed by EB-OCT decreased from 111.19 ± 14.71 before modeling to 74.96 ± 4.08 on the 9th day after modeling (p < 0.05). The gray-scale value was negatively correlated with the airway wall thickness (r = -0.945, p = 0.001). CONCLUSION: The EB-OCT imaging, in concordance with the histopathological finding, was validated for assessing the airway morphological changes during the development of PITS. The EB-OCT evaluation of cartilage damage and gray-scale value measurement might help predict the development and prognosis of PITS.

Incidence and Predictors of Tracheobronchial Tuberculosis in Pulmonary Tuberculosis: A Multicentre, Large-Scale and Prospective Study in Southern China.

BACKGROUND: Patients with pulmonary tuberculosis (PTB) have a high risk of concomitant tracheobronchial tuberculosis (TBTB), which commonly causes severe complications such as tracheobronchial stenosis. The prevalence and predictors of TBTB in China remain unclear due to the lack of prospective and large-scale studies. OBJECTIVES: To investigate the incidence of TBTB in PTB patients in southern China, and elucidate the predictors of TBTB and related tracheobronchial stenosis. METHODS: We prospectively performed bronchoscopy in PTB patients to diagnose TBTB at four medical centres in southern China from September 2015 to August 2016. Clinical and epidemiological data were recorded and analysed to determine predictors of TBTB and related tracheobronchial stenosis. RESULTS: A total of 345 (23.9%) of the 1,442 PTB patients undergoing bronchoscopy were diagnosed with TBTB. Female sex (OR 2.53), age < 50 years (OR 1.88), living in urban (OR 2.19), diabetes (OR 1.84), coughing (OR 2.61), and symptoms ≥4 weeks (OR 1.66) were predictors of PTB concomitant with TBTB. About 59.7% TBTB patients developed tracheobronchial stenosis, of which 23.3% cases presented severe airway narrowing. Female sex (OR 2.27), age < 50 years (OR 2.11), shortness of breath (OR 1.97), and symptoms ≥4 weeks (OR 1.71) were predictors of TBTB-related tracheobronchial stenosis. CONCLUSIONS: About 23.9% of PTB patients undergoing bronchoscopy present with TBTB in Guangdong province, southern China. Young and middle-aged females with symptoms persisting for ≥4 weeks (the main predictors of TBTB and related tracheobronchial stenosis) should receive bronchoscopy immediately when diagnosed with PTB.

Breathing Hydrogen-Oxygen Mixture Decreases Inspiratory Effort in Patients with Tracheal Stenosis.

BACKGROUND: Hydrogen-oxygen mixture (H2-O2) may reduce airway resistance in patients with acute severe tracheal stenosis, yet data supporting the clinical use of H2-O2 are insufficient. OBJECTIVES: To evaluate the efficacy and safety of breathing H2-O2 in acute severe tracheal stenosis. METHODS: Thirty-five consecutive patients with severe acute tracheal stenosis were recruited in this prospective self-control study. Air, H2-O2 and O2 inhalation was given in 4 consecutive breathing steps: air for 15 min, H2-O2 (6 L per min, H2:O2 = 2: 1) for 15 min, oxygen (3 L per min) for 15 min, and H2-O2 for 120 min. The primary endpoint was inspiratory effort as assessed by diaphragm electromyography (EMGdi); the secondary endpoints were transdiaphragmatic pressure (Pdi), Borg score, vital signs, and impulse oscillometry (IOS). The concentration of H2 in the ambient environment was obtained with 12 monitors. Adverse reactions during the inhalation were recorded. RESULTS: The mean reduction in the EMGdi under H2-O2 was 10.53 ± 6.83%. The EMGdi significantly decreased during 2 H2-O2 inhalation steps (Steps 2 and 4) compared with air (Step 1) and O2 (Step 3) (52.95 ± 15.00 vs. 42.46 ± 13.90 vs. 53.20 ± 14.74 vs. 42.50 ± 14.12% for Steps 1 through 4, p < 0.05). The mean reduction in the Pdi under H2-O2 was 4.77 ± 3.51 cmH2O. Breathing H2-O2 significantly improved the Borg score and resistance parameters of IOS but not vital signs. No adverse reactions occurred. H2 was undetectable in the environment throughout the procedure. CONCLUSIONS: Breathing H2-O2 may reduce the inspiratory effort in patients with acute severe tracheal stenosis and can be used for this purpose safely.

[Refractory pulmonary alveolar proteinosis treated with inhaled granulocyte macrophage colony stimulating factor: a case report and review of the literatures].

OBJECTIVE: To observe the efficacy of granulocyte macrophage colony stimulating factor inhalation therapy for pulmonary alveolar proteinosis (PAP) patients and to improve the understanding of the therapy. METHODS: The clinical data of a patient with autoimmune PAP treated with inhaled granulocyte macrophage colony stimulating factor were described and the literatures were reviewed. RESULTS: This 70-year-old female patient was diagnosed with autoimmune PAP and had been treated with whole lung lavage for 10 times, but only achieved short-term symptomatic relief after each operation. Inhalation of granulocyte macrophage colony stimulating factor was then used after the recurrence of PAP, and a significant improvement in oxygenation and clinical symptoms were abserved. The patient remained stable 4 month after the therapy. CONCLUSION: Treatment with inhalation of granulocyte macrophage colony stimulating factor is safe, effective and economic for patients with PAP, and would be the first choice for the recurrence of autoimmune PAP after whole lung lavage.

Airway necrosis and granulation tissue formation caused by Rhizopus oryzae leading to severe upper airway obstruction: a case report.

Pulmonary Mucormycosis is a fatal infectious disease with high mortality rate. The occurrence of Mucormycosis is commonly related to the fungal virulence and the host's immunological defenses against pathogens. Mucormycosis infection and granulation tissue formation occurred in the upper airway was rarely reported. This patient was a 60-year-old male with diabetes mellitus, who was admitted to hospital due to progressive cough, sputum and dyspnea. High-resolution computed tomography (HRCT) and bronchoscopy revealed extensive tracheal mucosal necrosis, granulation tissue proliferation, and severe airway stenosis. The mucosal necrotic tissue was induced by the infection of Rhizopus Oryzae, confirmed by metagenomic next-generation sequencing (mNGS) in tissue biopsy. This patient was treated with the placement of a covered stent and local instillation of amphotericin B via bronchoscope. The tracheal mucosal necrosis was markedly alleviated, the symptoms of cough, shortness of breath, as well as exercise tolerance were significantly improved. The placement of airway stent and transbronchial microtube drip of amphotericin B could conduce to rapidly relieve the severe airway obstruction due to Mucormycosis infection.

The safety and effectiveness of the treatment of refractory post-intubation subglottic stenosis using short bronchial Dumon stent: a pilot study.

Background: Post-intubation subglottic stenosis (PI-SGS) is a fatal disease which could result in partial or complete narrowing of the airway. Although airway stenting is commonly used as an alternative treatment for PI-SGS patients unsuitable for surgery, complications including stent migration and excessive granulation tissue formation are frequently encountered. Additionally, tracheotomy is necessary in patients undergoing T-tube placement. Therefore, it is necessary to further enhance the effectiveness of airway stenting in refractory PI-SGS. In this study, we aimed to evaluate the safety and effectiveness of utilizing short bronchial Dumon (BD) stents in managing refractory PI-SGS. Methods: PI-SGS patients who were not suitable for surgery and in whom previous interventional treatments had proven ineffective were enrolled. Short BD stents were inserted via rigid bronchoscopy under general anesthesia. Complications and outcomes were assessed by follow-ups. Results: Fourteen patients were included and successful stent insertion was achieved in all cases. The median diameter and length of stents was 12 (0.25) and 33.5 (5) mm, respectively. During the 6-month follow-up period, complications were reported in five patients. Granulation tissue formation was the most frequently observed complication (4 in 14 patients, 28.57%), followed by stent migration (2 in 14 patients, 14.29%). Out of the total participants, 11 patients (78.57%) demonstrated good tolerance to the stent, while 3 (21.43%) required stent removal. Among these three patients, two finally underwent subsequent T-tube insertion after the removal. Twelve patients (85.71%) avoided the tracheotomy and T-tube insertion. Conclusions: The utilization of short BD stents appears to be a safe and effective approach for managing refractory PI-SGS. The complications and tolerability are acceptable.

Efficacy and Safety of Platelet-Rich Plasma on Bronchopleural Fistula: A Pilot Prospective Cohort Study.

INTRODUCTION: Bronchopleural fistula (BPF) is associated with high morbidity and mortality rates in patients undergoing pulmonary resections. Surgery, bronchoscopy, and conservative management have their limitations for small fistulas. Platelet-rich plasma (PRP) has regenerative properties, which might be efficient in enhancing tissue recovery and repairing small BPF. This study aimed to investigate efficacy and safety of PRP on BPF. METHODS: This is a pilot prospective cohort study. Patients whose fistulas smaller than 4mm were enrolled in this study, treated with PRP under bronchoscopy and followed up at 2 weeks and 4-6 weeks after the last PRP treatment. The cure rate, improvement rate and ineffectiveness rate were investigated. The severity of respiratory symptoms was evaluated by modified Medical Research Council dyspnea scale (mMRC) and COPD Assessment Test (CAT). The recurrence of fistula, new infection and mortality rate were examined. Adverse events were documented to explore the safety profile of PRP therapy. RESULTS: A total of 16 patients (mean age, 50.1 years) met the eligibility criteria. The median time from the first PRP treatment to the closure of the fistula was 12.0 (IQR 6.0, 21.5) days. Our findings indicate an effectiveness rate of 87.6%, with 68.8% of cure and 18.8% of improvement, along with significant improvement of respiratory symptoms evaluated by mMRC (P<0.001) and CAT (P<0.001). No recurrent of fistulas, newly developed infection, or death was observed. Adverse events of the procedure were most mild (82.6%) and temporary. CONCLUSIONS: PRP is a potential treatment for small BPF and is well tolerated.

[The cause and efficacy of benign tracheal stenosis].

OBJECTIVE: To analysis the causes of benign tracheal stenosis and evaluate the curative effect of intraluminal bronchoscopic treatment. METHODS: 158 patients with benign tracheal stenosis in our hospital from September 2005 to September 2012 were collected to retrospectively analysis the causes and clinic features of tracheal stenosis. Interventional treatments through bronchoscopy were used to treat the benign tracheal stenosis and the curative effects were evaluated. RESULTS: 158 cases of benign tracheal stenosis were recruited to our study, 69.6% of them were young and middle-aged. The main causes of benign tracheal stenosis were as follows: secondary to postintubation or tracheotomy in 61.4% (97/158), tuberculosis in 16% (26/158), benign tumor in 5.1% (8/158) and other 27 cases. 94.3% patients improved in symptoms with alleviation immediately after bronchoscopic treatment, the average tracheal diameter increased form (4.22 ± 2.06) mm to (10.16 ± 2.99) mm (t = 21.48, P < 0.01), dyspnea index decreased from 2.29 ± 0.75 to 0.63 ± 0.67 (t = 19.85, P < 0.01). The recurrence rate in 1 and 3 month after interventional treatment were 38.3% and 26.8%, respectively. CONCLUSION: The cases of benign tracheal stenosis were increasing year by year. The most common cause of benign tracheal stenosis was postintubation and tracheotomy. Interventional treatments through bronchoscopy is effective in treating benign tracheal stenosis, but repeated interventional procedures may be required to maintain the favorable long-term effects.

Multiple Lung Cavity Lesions, Thoracic Wall Abscess and Vertebral Destruction Caused by Streptococcus constellatus Infection: A Case Report.

Disseminated infection caused by Streptococcus constellatus was seldom occurred. We reported a case of Streptococcus constellatus infection, presenting as multiple pulmonary cavities, thoracic wall abscess and vertebral destruction. The 37-year-old male had recurrent fever, chest wall swelling and pain, and lower limb numbness, he had weak physical condition and previously suffered from poorly controlled diabetes and severe periodontal disease for 3 years. Definite diagnosis of Streptococcus constellatus infection was made by metagenomic next­generation sequencing (mNGS) in abscess drainage fluid. Systemic antibiotics and thoracic wall drainage were given, and the pulmonary cavity and the thoracic intermuscular abscess were significantly decreased. Few to no study reported the disseminated infection (pulmonary cavities, thoracic wall abscess and vertebral destruction) caused by Streptococcus constellatus. This case report highlighted the importance of mNGS for accurate diagnosis, as well as the timely drainage and antibiotics for effective treatment of Streptococcus constellatus infection.

Endobronchial optical coherence tomography or computed tomography for evaluating progression of bronchiectasis.

Background: The early radiological signs of progression in bronchiectasis remain unclear. The objective of the present study was to compare endobronchial optical coherence tomography (EB-OCT) and chest computed tomography (CT) for the evaluation of radiological progression of bronchiectasis via stratification of the presence (TW+) or absence (TW-) of thickened-walled bronchioles surrounding dilated bronchi in patients with bronchiectasis based on CT, and determine the risk factors. Methods: In this prospective cohort study, we performed both chest CT and EB-OCT at baseline and 5-year follow-up, to compare changes in airway calibre metrics. We evaluated bacterial microbiology, sputum matrix metalloproteinase-9 levels and free neutrophil elastase activity at baseline. We compared clinical characteristics and airway calibre metrics between the TW+ and TW- groups. We ascertained radiological progression at 5 years via CT and EB-OCT. Results: We recruited 75 patients between 2014 and 2017. At baseline, EB-OCT metrics (mean luminal diameter (p=0.017), inner airway area (p=0.005) and airway wall area (p=0.009) of seventh- to ninth-generation bronchioles) were significantly greater in the TW+ group than in the TW-group. Meanwhile, EB-OCT did not reveal bronchiole dilatation (compared with the same segment of normal bronchioles) surrounding nondilated bronchi on CT in the TW- group. At 5 years, 53.1% of patients in the TW+ group progressed to have bronchiectasis measured with EB-OCT, compared with only 3.3% in TW- group (p<0.05). 34 patients in the TW+ group demonstrated marked dilatation of medium-sized and small airways. Higher baseline neutrophil elastase activity and TW+ bronchioles on CT predicted progression of bronchiectasis. Conclusion: Thickened-walled bronchioles surrounding the dilated bronchi, identified with EB-OCT, indicates progression of bronchiectasis.