Effectiveness and safety of Argon Plasma Coagulation in patients with haemoptysis caused by an endobronchial malignancy.

BACKGROUND: Patients with central neoplasms and haemoptysis show low survival rates. Symptom control without recurrence 48 hours after bronchoscopic interventions may improve the prognosis of these patients. Bronchoscopic Argon Plasma Coagulation (APC) is a useful technique for endobronchial management of haemoptysis in patients with central malignancies. Nevertheless, limited data are available in the literature on its efficacy and safety and the main predictors of success are still unclear. MATERIALS AND METHODS: An observational, prospective, single-center cohort study was carried out to assess the efficacy (i.e. immediate bleeding cessation without recurrence during the following 48 hours) of bronchoscopic APC in the treatment of patients with haemoptysis caused by endobronchial malignancies and the main predictors of success. RESULTS: A total of 76 patients with median age 75 years (IQR: 65-79) were enrolled. 67 (88.2%) patients had bleeding cessation without recurrence 48 hours after bronchoscopic APC. A low rate of non-serious adverse events (5.3%) was recorded and a low (7.6%) recurrence rate of haemoptysis at 3.5 months after the procedure was also shown. No clinical, demographic and endoscopic variables related to a successful procedure at 48 hours were found. CONCLUSIONS: This study demonstrates that bronchoscopic APC is an effective procedure in the treatment of patients with haemoptysis caused by endobronchial malignancies, regardless of the clinical characteristics of the patients, the endoscopic and histological features of the neoplasm and the severity of the symptom. Furthermore, it shows a low rate of complications and long-term efficacy in bleeding control.

A Multicenter, Single-Arm, Prospective Trial Assessing the Diagnostic Yield of Electromagnetic Bronchoscopic and Transthoracic Navigation for Peripheral Pulmonary Nodules.

Rationale: Strict adherence to procedural protocols and diagnostic definitions is critical to understand the efficacy of new technologies. Electromagnetic navigational bronchoscopy (ENB) for lung nodule biopsy has been used for decades without a solid understanding of its efficacy, but offers the opportunity for simultaneous tissue acquisition via electromagnetic navigational transthoracic biopsy (EMN-TTNA) and staging via endobronchial ultrasound (EBUS). Objective: To evaluate the diagnostic yield of EBUS, ENB, and EMN-TTNA during a single procedure using a strict a priori definition of diagnostic yield with central pathology adjudication. Methods: A prospective, single-arm trial was conducted at eight centers enrolling participants with pulmonary nodules (<3 cm; without computed tomography [CT]- and/or positron emission tomography-positive mediastinal lymph nodes) who underwent a staged procedure with same-day CT, EBUS, ENB, and EMN-TTNA. The procedure was staged such that, when a diagnosis had been achieved via rapid on-site pathologic evaluation, the procedure was ended and subsequent biopsy modalities were not attempted. A study finding was diagnostic if an independent pathology core laboratory confirmed malignancy or a definitive benign finding. The primary endpoint was the diagnostic yield of the combination of CT, EBUS, ENB, and EMN-TTNA. Measurements and Main Results: A total of 160 participants at 8 centers with a mean nodule size of 18 ± 6 mm were enrolled. The diagnostic yield of the combined procedure was 59% (94 of 160; 95% confidence interval [CI], 51-66%). Nodule regression was found on same-day CT in 2.5% of cases (4 of 160; 95% CI, 0.69-6.3%), and EBUS confirmed malignancy in 7.1% of cases (11 of 156; 95% CI, 3.6-12%). The yield of ENB alone was 49% (74 of 150; 95% CI, 41-58%), that of EMN-TTNA alone was 27% (8 of 30; 95% CI, 12-46%), and that of ENB plus EMN-TTNA was 53% (79 of 150; 95% CI, 44-61%). Complications included a pneumothorax rate of 10% and a 2% bleeding rate. When EMN-TTNA was performed, the pneumothorax rate was 30%. Conclusions: The diagnostic yield for ENB is 49%, which increases to 59% with the addition of same-day CT, EBUS, and EMN-TTNA, lower than in prior reports in the literature. The high complication rate and low diagnostic yield of EMN-TTNA does not support its routine use. Clinical trial registered with www.clinicaltrials.gov (NCT03338049).

Sampling of Thoracic Lymph Nodes and Lung Lesions: Trends in Procedural Utilization.

BACKGROUND: Advances in bronchoscopy have impacted the practice patterns in the sampling of thoracic lymph nodes and lung lesions. OBJECTIVES: The aim of the study was to study the trends in utilization of mediastinoscopy, transthoracic needle aspiration (TTNA), and bronchoscopic transbronchial sampling. METHODS: We conducted an analysis of patient claims for sampling of thoracic lymph nodes and lung lesions in the Medicare population and a sample of the commercial population between 2016 and 2020. We used Current Procedural Terminology codes to identify mediastinoscopy, TTNA, and bronchoscopic transbronchial sampling. Post-procedural pneumothorax rates were assessed by procedure type including subset analyses for patients with chronic obstructive pulmonary disease (COPD). RESULTS: Between 2016 and 2020, utilization of mediastinoscopy has decreased in both the Medicare and commercial populations (-47.3% and -65.4%, respectively), while linear endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA) has increased only in the Medicare population (+28.2%). Percutaneous lung biopsy claims dropped by -17.0% in the Medicare and -41.22% in the commercial population. The use of bronchoscopic TBNA and forceps biopsy declined in both populations, but the reliance on a combination of guided technology (radial EBUS-guided and navigation) grew in the Medicare and commercial populations (+76.3% and +25%). Rates of post-procedural pneumothorax were significantly higher following percutaneous biopsy compared to bronchoscopic transbronchial biopsy. CONCLUSIONS: Linear EBUS-guided sampling has surpassed mediastinoscopy as the technique for sampling thoracic lymph nodes. Transbronchial lung sampling is increasingly being performed with guidance technology. This trend is aligned with favorable rates of post-procedure pneumothorax for transbronchial biopsy.

Bronchoscopic Evaluation of a Steerable Needle for Simulated Tumor Targets in the Lung Periphery: A Feasibility Study (Bullseye).

BACKGROUND: Peripheral bronchoscopy is often performed to biopsy peripheral pulmonary lesions. Despite technological advancements to improve reach and access to the lung periphery, the diagnostic yield of peripheral bronchoscopy has been inconsistent, and challenging, particularly for lesions that are adjacent to peripheral bronchi. Current biopsy instruments are reliant on the catheter or scope to align properly with targeted lesions. OBJECTIVES: This study evaluates the feasibility of using a steerable biopsy needle to gain access to peripheral tumor targets in a cadaveric model. METHODS: Simulated tumor targets 10-30 mm in axial diameter were placed into human cadavers. Bronchoscopy was performed using a 4.2 mm OD flexible bronchoscope, CT-anatomic correlation, and multi-planar fluoroscopy for lesion localization. Once at the targeted location, a steerable needle was deployed and the needle position was determined to be in the central zone, peripheral zone, or outside of the lesion by cone beam CT imaging. If the needle position was within the lesion, a fiducial marker was deployed to mark the needle position, and the needle was articulated and/or rotated in an attempt to place another fiducial marker into a different location within the same lesion. If the needle was outside of the lesion, the bronchoscopist was provided with two additional attempts to gain access to the lesion. RESULTS: Fifteen tumor targets were placed with a mean lesion size of 20.4 mm. The majority of lesions were located in the upper lobes. One fiducial marker was placed in 93.3% of lesions and a second fiducial marker was successfully placed in 80% of lesions. A fiducial marker was placed within the central zone in 60% of lesions. CONCLUSION: The steerable needle was successfully placed within 93% of targeted lesions 10-30 mm in diameter in a cadaveric model, with the ability steer the instrument into another portion of the lesion in 80% of cases. The ability to steer and control needle positioning toward and within peripheral lesions may complement existing catheter and scope technology during peripheral diagnostic procedures.

Efficacy and safety of virtual bronchoscopic navigation with fused fluoroscopy and vessel mapping for access of pulmonary lesions.

BACKGROUND AND OBJECTIVE: Virtual bronchoscopic navigation (VBN) with fused fluoroscopy and vessel mapping provides a point of entry (POE) for puncturing airway wall to biopsy lesions. The study was designed to evaluate the safety and efficacy of this technology to diagnose peripheral pulmonary lesions. METHODS: It was a prospective, single-arm, multicentre study. Patients underwent lesions biopsy with the Archimedes® VBN System via a POE using one of the two techniques: (1) bronchoscopic transparenchymal nodule access (BTPNA) and (2) guided transbronchial needle aspiration (TBNA). Biopsy yield, sampling yield and diagnostic yield were mainly determined in lesions biopsy attempted. RESULTS: One hundred and thirty patients underwent anaesthesia and constituted the intention-to-treat population. One hundred and four patients with 114 lesions had biopsy attempted. Mean lesion size was 2.4 ± 1.13 cm. Sufficient tissue samples were obtained from 86 lesions with a biopsy yield of 75.4%. Nevertheless, sufficient samples for diagnosis based on histology ± cytology were obtained from 107 lesions with a sampling yield of 93.9%. Follow-up was conducted for more than 1 year, with a diagnostic yield of 75.4% and 72.8%, respectively, on high and low estimate with consideration of three lesions without follow-up. Two (1.9%) pneumothoraxes and one (1.0%) mild bleeding occurred. CONCLUSION: BTPNA and guided TBNA contribute to safe and effective sampling of peripheral pulmonary lesions. A relatively high biopsy yield was obtained independent of the presence or absence of a bronchus sign (BS), and high sampling yield and diagnostic yield were obtained independent of location, lesion size and presence or absence of a BS.

Accuracy of Pulmonary Nodule Sampling Using Robotic Assisted Bronchoscopy with Shape Sensing, Fluoroscopy, and Radial Endobronchial Ultrasound (The ACCURACY Study).

BACKGROUND: Despite recent advances in guided bronchoscopy, the yield of bronchoscopic biopsy of a peripheral pulmonary nodule (PPN) remains highly variable. OBJECTIVE: The aim of the study was to evaluate which features of robotic assisted bronchoscopy (RAB) contribute to a successful biopsy in a cadaver model. METHODS: A preclinical, prospective, single-blinded trial using a ventilated human cadaveric model assessed the successful puncture of implanted pulmonary nodules using various localization techniques with RAB. The different approaches included positioning the robotic catheter at predefined distances from the target nodule (<10 mm, 10-20 mm, 20-30 mm), bronchoscopist correction of divergence between the software virtual map and bronchoscopic view if observed, and impact of fluoroscopy and radial endobronchial ultrasound (rEBUS). The primary endpoint was a central target hit (defined as an inner 2/3 target puncture) verified by cone-beam computed tomography. RESULTS: Thirty-eight RAB procedures were performed to target 16 PPNs. Median nodule size was 16.2 mm. All targets were located in the outer 1/3 of the lung with a bronchus sign in 31.3%. Central target hit rates were improved when the robotic catheter tip was closer to the nodule (<10 mm 68%, 10-20 mm 66%, 20-30 mm 11%, p < 0.001). Multivariable analysis confirmed the strongest predictor of a central target hit was robotic catheter distance to nodule (OR 0.89 per increase in 1 mm, p < 0.001), independent of the presence of a bronchus sign, divergence or concentric rEBUS view. CONCLUSIONS: Utilizing a RAB platform, closer proximity of the robotic catheter to the target nodule results in an increase in peripheral nodule biopsy success.

Comparison of Forceps, Cryoprobe, and Thoracoscopic Lung Biopsy for the Diagnosis of Interstitial Lung Disease - The CHILL Study.

RATIONALE: Transbronchial lung cryobiopsy (TBLC) has emerged as a less invasive method to obtain a tissue diagnosis in patients with interstitial lung disease (ILD). The diagnostic yield of TBLC compared to surgical lung biopsy (SLB) remains uncertain. OBJECTIVES: The aim of this study was to determine the diagnostic accuracy of forceps transbronchial lung biopsy (TBLB) and TBLC compared to SLB when making the final diagnosis based on multidisciplinary discussion (MDD). METHODS: Patients enrolled in the study underwent sequential TBLB and TBLC followed immediately by SLB. De-identified cases, with blinding of the biopsy method, were reviewed by a blinded pathologist and then discussed at a multidisciplinary conference. MAIN RESULTS: Between August 2013 and October 2017, we enrolled 16 patients. The raw agreement between TBLC and SLB for the MDD final diagnosis was 68.75% with a Cohen's kappa of 0.6 (95% CI 0.39, 0.81). Raw agreement and Cohen's kappa of TBLB versus TBLC and TBLB versus SLB for the MDD final diagnosis were much lower (50%, 0.21 [95% CI 0, 0.42] and 18.75%, 0.08 [95% CI -0.03, 0.19], respectively). TBLC was associated with mild bleeding (grade 1 bleeding requiring suction to clear) in 56.2% of patients. CONCLUSIONS: In patients with ILD who have an uncertain type based on clinical and radiographic data and require tissue sampling to obtain a specific diagnosis, TBLC showed moderate correlation with SLB when making the diagnosis with MDD guidance. TBLB showed poor concordance with both TBLC and SLB MDD diagnoses.

Variable Learning Curve of Basic Rigid Bronchoscopy in Trainees.

BACKGROUND: Despite increased use of rigid bronchoscopy (RB) for therapeutic indications and recommendations from professional societies to use performance-based competency, an assessment tool has not been utilized to measure the competency of trainees to perform RB in clinical settings. OBJECTIVES: The aim of the study was to evaluate a previously developed assessment tool - Rigid Bronchoscopy Tool for Assessment of Skills and Competence (RIGID-TASC) - for determining the RB learning curve of interventional pulmonary (IP) trainees in the clinical setting and explore the variability of learning curve of trainees. METHODS: IP fellows at 4 institutions were enrolled. After preclinical simulation training, all RBs performed in patients were scored by faculty using RIGID-TASC until competency threshold was achieved. Competency threshold was defined as unassisted RB intubation and navigation through the central airways on 3 consecutive patients at the first attempt with a minimum score of 89. A regression-based model was devised to construct and compare the learning curves. RESULTS: Twelve IP fellows performed 178 RBs. Trainees reached the competency threshold between 5 and 24 RBs, with a median of 15 RBs (95% CI, 6-21). There were differences among trainees in learning curve parameters including starting point, slope, and inflection point, as demonstrated by the curve-fitting model. Subtasks that required the highest number of procedures (median = 10) to gain competency included ability to intubate at the first attempt and intubation time of <60 s. CONCLUSIONS: Trainees acquire RB skills at a variable pace, and RIGID-TASC can be used to assess learning curve of IP trainees in clinical settings.

Interventional Bronchoscopy.

For over 150 years, bronchoscopy, especially flexible bronchoscopy, has been a mainstay for airway inspection, the diagnosis of airway lesions, therapeutic aspiration of airway secretions, and transbronchial biopsy to diagnose parenchymal lung disorders. Its utility for the diagnosis of peripheral pulmonary nodules and therapeutic treatments besides aspiration of airway secretions, however, has been limited. Challenges to the wider use of flexible bronchoscopy have included difficulty in navigating to the lung periphery, the avoidance of vasculature structures when performing diagnostic biopsies, and the ability to biopsy a lesion under direct visualization. The last 10-15 years have seen major advances in thoracic imaging, navigational platforms to direct the bronchoscopist to lung lesions, and the ability to visualize lesions during biopsy. Moreover, multiple new techniques have either become recently available or are currently being investigated to treat a broad range of airway and lung parenchymal diseases, such as asthma, emphysema, and chronic bronchitis, or to alleviate recurrent exacerbations. New bronchoscopic therapies are also being investigated to not only diagnose, but possibly treat, malignant peripheral lung nodules. As a result, flexible bronchoscopy is now able to provide a new and expanding armamentarium of diagnostic and therapeutic tools to treat patients with a variety of lung diseases. This State-of-the-Art review succinctly reviews these techniques and provides clinicians an organized approach to their role in the diagnosis and treatment of a range of lung diseases.

Management of Immunotherapy-Related Toxicities, Version 1.2019.

The aim of the NCCN Guidelines for Management of Immunotherapy-Related Toxicities is to provide guidance on the management of immune-related adverse events resulting from cancer immunotherapy. The NCCN Management of Immunotherapy-Related Toxicities Panel is an interdisciplinary group of representatives from NCCN Member Institutions and ASCO, consisting of medical and hematologic oncologists with expertise in a wide array of disease sites, and experts from the fields of dermatology, gastroenterology, neuro-oncology, nephrology, emergency medicine, cardiology, oncology nursing, and patient advocacy. Several panel representatives are members of the Society for Immunotherapy of Cancer (SITC). The initial version of the NCCN Guidelines was designed in general alignment with recommendations published by ASCO and SITC. The content featured in this issue is an excerpt of the recommendations for managing toxicity related to immune checkpoint blockade and a review of existing evidence. For the full version of the NCCN Guidelines, including recommendations for managing toxicities related to chimeric antigen receptor T-cell therapy, visit NCCN.org.

Management of Malignant Pleural Effusions. An Official ATS/STS/STR Clinical Practice Guideline.

BACKGROUND: This Guideline, a collaborative effort from the American Thoracic Society, Society of Thoracic Surgeons, and Society of Thoracic Radiology, aims to provide evidence-based recommendations to guide contemporary management of patients with a malignant pleural effusion (MPE). METHODS: A multidisciplinary panel developed seven questions using the PICO (Population, Intervention, Comparator, and Outcomes) format. The GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach and the Evidence to Decision framework was applied to each question. Recommendations were formulated, discussed, and approved by the entire panel. RESULTS: The panel made weak recommendations in favor of: 1) using ultrasound to guide pleural interventions; 2) not performing pleural interventions in asymptomatic patients with MPE; 3) using either an indwelling pleural catheter (IPC) or chemical pleurodesis in symptomatic patients with MPE and suspected expandable lung; 4) performing large-volume thoracentesis to assess symptomatic response and lung expansion; 5) using either talc poudrage or talc slurry for chemical pleurodesis; 6) using IPC instead of chemical pleurodesis in patients with nonexpandable lung or failed pleurodesis; and 7) treating IPC-associated infections with antibiotics and not removing the catheter. CONCLUSIONS: These recommendations, based on the best available evidence, can guide management of patients with MPE and improve patient outcomes.

A Multicenter Randomized Controlled Trial of Zephyr Endobronchial Valve Treatment in Heterogeneous Emphysema (LIBERATE).

RATIONALE: This is the first multicenter randomized controlled trial to evaluate the effectiveness and safety of Zephyr Endobronchial Valve (EBV) in patients with little to no collateral ventilation out to 12 months. OBJECTIVES: To evaluate the effectiveness and safety of Zephyr EBV in heterogeneous emphysema with little to no collateral ventilation in the treated lobe. METHODS: Subjects were enrolled with a 2:1 randomization (EBV/standard of care [SoC]) at 24 sites. Primary outcome at 12 months was the ΔEBV-SoC of subjects with a post-bronchodilator FEV1 improvement from baseline of greater than or equal to 15%. Secondary endpoints included absolute changes in post-bronchodilator FEV1, 6-minute-walk distance, and St. George's Respiratory Questionnaire scores. MEASUREMENTS AND MAIN RESULTS: A total of 190 subjects (128 EBV and 62 SoC) were randomized. At 12 months, 47.7% EBV and 16.8% SoC subjects had a ΔFEV1 greater than or equal to 15% (P < 0.001). ΔEBV-SoC at 12 months was statistically and clinically significant: for FEV1, 0.106 L (P < 0.001); 6-minute-walk distance, +39.31 m (P = 0.002); and St. George's Respiratory Questionnaire, -7.05 points (P = 0.004). Significant ΔEBV-SoC were also observed in hyperinflation (residual volume, -522 ml; P < 0.001), modified Medical Research Council Dyspnea Scale (-0.8 points; P < 0.001), and the BODE (body mass index, airflow obstruction, dyspnea, and exercise capacity) index (-1.2 points). Pneumothorax was the most common serious adverse event in the treatment period (procedure to 45 d), in 34/128 (26.6%) of EBV subjects. Four deaths occurred in the EBV group during this phase, and one each in the EBV and SoC groups between 46 days and 12 months. CONCLUSIONS: Zephyr EBV provides clinically meaningful benefits in lung function, exercise tolerance, dyspnea, and quality of life out to at least 12 months, with an acceptable safety profile in patients with little or no collateral ventilation in the target lobe. Clinical trial registered with www.clinicaltrials.gov (NCT 01796392).

Clinical and radiographic predictors of successful therapeutic bronchoscopy for the relief of malignant central airway obstruction.

BACKGROUND: Malignant central airway obstruction (CAO) occurs in approximately 20-30% of patients with lung cancer and is associated with debilitating symptoms and poor prognosis. Multimodality therapeutic bronchoscopy can relieve malignant CAO, though carries risk. Evidence to guide clinicians regarding which patients may benefit from such interventions is sparse. We aimed to assess the clinical and radiographic predictors associated with therapeutic bronchoscopy success in relieving malignant CAO. METHODS: We reviewed all cases of therapeutic bronchoscopy performed for malignant CAO at our institution from January 2010-February 2017. Therapeutic bronchoscopy success was defined as establishing airway patency of > 50%. Patient demographics and baseline characteristics, oncology history, degree of airway obstruction, procedural interventions, and complications were compared between successful and unsuccessful groups. Univariate and multivariate logistic regression identified the significant clinical and radiographic predictors for therapeutic success. The corresponding simple and conditional odds ratio were calculated. A time-to-event analysis with Kaplan-Meier plots was performed to estimate overall survival. RESULTS: During the study period, 301 therapeutic bronchoscopies were performed; 44 (14.6%) were considered unsuccessful. Factors associated with success included never vs current smoking status (OR 5.36, 95% CI:1.45-19.74, p = 0.010), patent distal airway on CT imaging (OR 15.11, 95% CI:2.98-45.83, p < 0.0001) and patent distal airway visualized during bronchoscopy (OR 10.77, 95% CI:3.63-31.95, p < 0.001) in univariate analysis. Along with patent distal airway on CT imaging, increased time from radiographic finding to therapeutic bronchoscopy was associated with lower odds of success in multivariate analysis (OR 0.96, 95% CI:0.92-1.00, p = 0.048). Median survival was longer in the successful group (10.2 months, 95% CI:4.8-20.2) compared to the unsuccessful group (6.1 months, 95% CI:2.1-10.8, log rank p = 0.015). CONCLUSIONS: Predictors associated with successful therapeutic bronchoscopy for malignant CAO include distal patent airway visualized on CT scan and during bronchoscopy. Odds of success are higher in non-smokers, and with decreased time from radiographic finding of CAO to intervention.

Randomized Trial of Pleural Fluid Drainage Frequency in Patients with Malignant Pleural Effusions. The ASAP Trial.

RATIONALE: Patients with malignant pleural effusions have significant dyspnea and shortened life expectancy. Indwelling pleural catheters allow patients to drain pleural fluid at home and can lead to autopleurodesis. The optimal drainage frequency to achieve autopleurodesis and freedom from catheter has not been determined. OBJECTIVES: To determine whether an aggressive daily drainage strategy is superior to the current standard every other day drainage of pleural fluid in achieving autopleurodesis. METHODS: Patients were randomized to either an aggressive drainage (daily drainage; n = 73) or standard drainage (every other day drainage; n = 76) of pleural fluid via a tunneled pleural catheter. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the incidence of autopleurodesis following the placement of the indwelling pleural catheters. The rate of autopleurodesis, defined as complete or partial response based on symptomatic and radiographic changes, was greater in the aggressive drainage arm than the standard drainage arm (47% vs. 24%, respectively; P = 0.003). Median time to autopleurodesis was shorter in the aggressive arm (54 d; 95% confidence interval, 34-83) as compared with the standard arm (90 d; 95% confidence interval, 70 to nonestimable). Rate of adverse events, quality of life, and patient satisfaction were not significantly different between the two arms. CONCLUSIONS: Among patients with malignant pleural effusion, daily drainage of pleural fluid via an indwelling pleural catheter led to a higher rate of autopleurodesis and faster time to liberty from catheter. Clinical trial registered with www.clinicaltrials.gov (NCT 00978939).

Electromagnetic navigation bronchoscopy to access lung lesions in 1,000 subjects: first results of the prospective, multicenter NAVIGATE study.

BACKGROUND: Electromagnetic navigation bronchoscopy (ENB) is an image-guided, minimally invasive approach that uses a flexible catheter to access pulmonary lesions. METHODS: NAVIGATE is a prospective, multicenter study of the superDimension™ navigation system. A prespecified 1-month interim analysis of the first 1,000 primary cohort subjects enrolled at 29 sites in the United States and Europe is described. Enrollment and 24-month follow-up are ongoing. RESULTS: ENB index procedures were conducted for lung lesion biopsy (n = 964), fiducial marker placement (n = 210), pleural dye marking (n = 17), and/or lymph node biopsy (n = 334; primarily endobronchial ultrasound-guided). Lesions were in the peripheral/middle lung thirds in 92.7%, 49.7% were <20 mm, and 48.4% had a bronchus sign. Radial EBUS was used in 54.3% (543/1,000 subjects) and general anesthesia in 79.7% (797/1,000). Among the 964 subjects (1,129 lesions) undergoing lung lesion biopsy, navigation was completed and tissue was obtained in 94.4% (910/964). Based on final pathology results, ENB-aided samples were read as malignant in 417/910 (45.8%) subjects and non-malignant in 372/910 (40.9%) subjects. An additional 121/910 (13.3%) were read as inconclusive. One-month follow-up in this interim analysis is not sufficient to calculate the true negative rate or diagnostic yield. Tissue adequacy for genetic testing was 80.0% (56 of 70 lesions sent for testing). The ENB-related pneumothorax rate was 4.9% (49/1,000) overall and 3.2% (32/1,000) CTCAE Grade ≥2 (primary endpoint). The ENB-related Grade ≥2 bronchopulmonary hemorrhage and Grade ≥4 respiratory failure rates were 1.0 and 0.6%, respectively. CONCLUSIONS: One-month results of the first 1,000 subjects enrolled demonstrate low adverse event rates in a generalizable population across diverse practice settings. Continued enrollment and follow-up are required to calculate the true negative rate and delineate the patient, lesion, and procedural factors contributing to diagnostic yield. TRIAL REGISTRATION: ClinicalTrials.gov NCT02410837 . Registered 31 March 2015.

Design of a prospective, multicenter, global, cohort study of electromagnetic navigation bronchoscopy.

BACKGROUND: Electromagnetic navigation bronchoscopy (ENB) procedures allow physicians to access peripheral lung lesions beyond the reach of conventional bronchoscopy. However, published research is primarily limited to small, single-center studies using previous-generation ENB software. The impact of user experience, patient factors, and lesion/procedural characteristics remains largely unexplored in a large, multicenter study. METHODS/DESIGN: NAVIGATE (Clinical Evaluation of superDimension™ Navigation System for Electromagnetic Navigation Bronchoscopy) is a prospective, multicenter, global, cohort study. The study aims to enroll up to 2,500 consecutive subjects presenting for evaluation of lung lesions utilizing the ENB procedure at up to 75 clinical sites in the United States, Europe, and Asia. Subjects will be assessed at baseline, at the time of procedure, and at 1, 12, and 24 months post-procedure. The pre-test probability of malignancy will be determined for peripheral lung nodules. Endpoints include procedure-related adverse events, including pneumothorax, bronchopulmonary hemorrhage, and respiratory failure, as well as quality of life, and subject satisfaction. Diagnostic yield and accuracy, repeat biopsy rate, tissue adequacy for genetic testing, and stage at diagnosis will be reported for biopsy procedures. Complementary technologies, such as fluoroscopy and endobronchial ultrasound, will be explored. Success rates of fiducial marker placement, dye marking, and lymph node biopsies will be captured when applicable. Subgroup analyses based on geography, demographics, investigator experience, and lesion and procedure characteristics are planned. DISCUSSION: Study enrollment began in April 2015. As of February 19, 2016, 500 subjects had been enrolled at 23 clinical sites with enrollment ongoing. NAVIGATE will be the largest prospective, multicenter clinical study on ENB procedures to date and will provide real-world experience data on the utility of the ENB procedure in a broad range of clinical scenarios. TRIAL REGISTRATION: ClinicalTrials.gov NCT02410837 . Registered 31 March 2015.

Endogenous pneumoconiosis: Analytical scanning electron microscopic analysis of a case.

Pneumoconiosis is often considered a disease of the lung initiated by exposure to dust or other airborne particles, resulting in injury to the lungs. The term "endogenous pneumoconiosis" has been used in the literature to describe the deposition of compounds on the elastic fibers of the lung, usually in the setting of cardiac failure. In the case we present here, the patient aspirated a foreign body resulting in damage to the lung tissue and subsequent deposition of endogenous compounds on the elastic fibers of the pulmonary parenchyma and vasculature. We determined the composition of this mineral and mapped the distribution of elements using a combination of backscattered electron microscopy and energy dispersive spectrometry.

Effect of Endobronchial Coils vs Usual Care on Exercise Tolerance in Patients With Severe Emphysema: The RENEW Randomized Clinical Trial.

IMPORTANCE: Preliminary clinical trials have demonstrated that endobronchial coils compress emphysematous lung tissue and may improve lung function, exercise tolerance, and symptoms in patients with emphysema and severe lung hyperinflation. OBJECTIVE: To determine the effectiveness and safety of endobronchial coil treatment. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial conducted among 315 patients with emphysema and severe air trapping recruited from 21 North American and 5 European sites from December 2012 through November 2015. INTERVENTIONS: Participants were randomly assigned to continue usual care alone (guideline based, including pulmonary rehabilitation and bronchodilators; n = 157) vs usual care plus bilateral coil treatment (n = 158) involving 2 sequential procedures 4 months apart in which 10 to 14 coils were bronchoscopically placed in a single lobe of each lung. MAIN OUTCOMES AND MEASURES: The primary effectiveness outcome was difference in absolute change in 6-minute-walk distance between baseline and 12 months (minimal clinically important difference [MCID], 25 m). Secondary end points included the difference between groups in 6-minute walk distance responder rate, absolute change in quality of life using the St George's Respiratory Questionnaire (MCID, 4) and change in forced expiratory volume in the first second (FEV1; MCID, 10%). The primary safety analysis compared the proportion of participants experiencing at least 1 of 7 prespecified major complications. RESULTS: Among 315 participants (mean age, 64 years; 52% women), 90% completed the 12-month follow-up. Median change in 6-minute walk distance at 12 months was 10.3 m with coil treatment vs -7.6 m with usual care, with a between-group difference of 14.6 m (Hodges-Lehmann 97.5% CI, 0.4 m to ∞; 1-sided P = .02). Improvement of at least 25 m occurred in 40.0% of patients in the coil group vs 26.9% with usual care (odds ratio, 1.8 [97.5% CI, 1.1 to ∞]; unadjusted between-group difference, 11.8% [97.5% CI, 1.0% to ∞]; 1-sided P = .01). The between-group difference in median change in FEV1 was 7.0% (97.5% CI, 3.4% to ∞; 1-sided P < .001), and the between-group St George's Respiratory Questionnaire score improved -8.9 points (97.5% CI, -∞ to -6.3 points; 1-sided P < .001), each favoring the coil group. Major complications (including pneumonia requiring hospitalization and other potentially life-threatening or fatal events) occurred in 34.8% of coil participants vs 19.1% of usual care (P = .002). Other serious adverse events including pneumonia (20% coil vs 4.5% usual care) and pneumothorax (9.7% vs 0.6%, respectively) occurred more frequently in the coil group. CONCLUSIONS AND RELEVANCE: Among patients with emphysema and severe hyperinflation treated for 12 months, the use of endobronchial coils compared with usual care resulted in an improvement in median exercise tolerance that was modest and of uncertain clinical importance, with a higher likelihood of major complications. Further follow-up is needed to assess long-term effects on health outcomes. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01608490.

A randomised trial of lung sealant versus medical therapy for advanced emphysema.

Uncontrolled pilot studies demonstrated promising results of endoscopic lung volume reduction using emphysematous lung sealant (ELS) in patients with advanced, upper lobe predominant emphysema. We aimed to evaluate the safety and efficacy of ELS in a randomised controlled setting.Patients were randomised to ELS plus medical treatment or medical treatment alone. Despite early termination for business reasons and inability to assess the primary 12-month end-point, 95 out of 300 patients were successfully randomised, providing sufficient data for 3- and 6-month analysis.57 patients (34 treatment and 23 control) had efficacy results at 3 months; 34 (21 treatment and 13 control) at 6 months. In the treatment group, 3-month lung function, dyspnoea, and quality of life improved significantly from baseline when compared to control. Improvements persisted at 6 months with >50% of treated patients experiencing clinically important improvements, including some whose lung function improved by >100%. 44% of treated patients experienced adverse events requiring hospitalisation (2.5-fold more than control, p=0.01), with two deaths in the treated cohort. Treatment responders tended to be those experiencing respiratory adverse events.Despite early termination, results show that minimally invasive ELS may be efficacious, yet significant risks (probably inflammatory) limit its current utility.

Therapeutic bronchoscopy improves spirometry, quality of life, and survival in central airway obstruction.

BACKGROUND: Central airway obstruction (CAO) occurs in patients with primary or metastatic lung malignancy and nonmalignant pulmonary disorders and results in significant adverse effects on respiratory function and quality of life. OBJECTIVES: The objective of this study was to assess the effect of therapeutic bronchoscopic interventions on spirometry, dyspnea, quality of life, and survival in patients with CAO. METHODS: We prospectively studied patients who underwent therapeutic rigid bronchoscopy for CAO. Spirometry, San Diego Shortness of Breath questionnaire (SOBQ), and SF-36 questionnaire responses were obtained before the procedure and at follow-up 6-8 weeks after the procedure. RESULTS: Fifty-three patients (24 malignant and 29 nonmalignant CAO), who underwent successful rigid bronchoscopic intervention, were enrolled. Airway stent placement and various debulking techniques including mechanical debridement and heat therapy were used. After bronchoscopy, there was a significant increase in forced vital capacity (2.2 ± 0.91 l before, 2.7 ± 0.80 l after, p = 0.009) and forced expiratory volume at 1 s (1.4 ± 0.60 l before, 1.8 ± 0.67 l after, p = 0.002). The SOBQ score improved from 55.8 ± 30.1 before the procedure to 37.9 ± 27.25 after the procedure (p = 0.002). In the SF-36, there was an improvement in almost all domains, with statistically significant improvement seen in several domains. Benefits were seen independent of the etiology of CAO, site of intervention or stent placement. The patients with malignant CAO, in whom airway patency could not be achieved, had a poor survival. CONCLUSIONS: Alleviation of CAO with therapeutic rigid bronchoscopy results in improvement in spirometry, shortness of breath, quality of life, and survival.