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).

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.

Safety and Feasibility of a Sheath Cryoprobe for Bronchoscopic Transbronchial Biopsy: The FROSTBITE Trial.

BACKGROUND: Bronchoscopic lung biopsy is typically performed using transbronchial forceps. However, this method is limited by small sample size and presence of crush artifact. Cryobiopsy offers the potential to overcome these limitations with larger artifact-free samples but has not been widely adopted due to concerns over increased rates of bleeding and pneumothorax. A new, smaller 1.1-mm cryoprobe has been developed that operates in a similar fashion to forceps, though the safety profile of this cryoprobe has not yet been prospectively studied. OBJECTIVE: The aim of this study was to investigate the safety of transbronchial biopsy using a novel 1.1-mm cryoprobe. METHODS: This prospective, single-arm study enrolled patients referred for transbronchial biopsy. All procedures were performed using the 1.1-mm cryoprobe with oversheath. The primary outcome was the composite of significant complications related to the cryobiopsy procedure (bleeding Grade ≥3, pneumothorax Grade ≥2, and respiratory failure). Bleeding and pneumothorax were graded according to previously published scales. RESULTS: Fifty participants from two academic medical centers underwent transbronchial cryobiopsy. Indications for biopsy included evaluation of lung transplant allograft (50%), diffuse lung disease (44%), and pulmonary parenchymal lesion (6%). There were two pneumothoraces (4%), neither of which required aspiration or chest tube placement. There were no Grade 3 or 4 bleeding events. Mild bleeding (Grade ≤2) was observed in 25 cases (50%). No complications occurred that met the a priori primary outcome of bleeding Grade ≥3, pneumothorax Grade ≥2, and respiratory failure. CONCLUSIONS: Transbronchial cryobiopsy using a 1.1-mm cryoprobe is feasible with an acceptable safety profile.

Comparing modalities for risk assessment in patients with pulmonary lesions and nondiagnostic bronchoscopy for suspected lung cancer.

BACKGROUND: Bronchoscopy is commonly utilized for non-surgical sampling of indeterminant pulmonary lesions, but nondiagnostic procedures are common. Accurate assessment of the risk of malignancy is essential for decision making in these patients, yet we lack tools that perform well across this heterogeneous group of patients. We sought to evaluate the accuracy of three previously validated risk models and physician-assessed risk (PAR) in patients with a newly identified lung lesion undergoing bronchoscopy for suspected lung cancer where the result is nondiagnostic. METHODS: We performed an analysis of prospective data collected for the Percepta Bronchial Genomic Classifier Multicenter Registry. PAR and three previously validated risk models (Mayo Clinic, Veteran's Affairs, and Brock) were used to determine the probability of lung cancer (low, intermediate, or high) in 375 patients with pulmonary lesions who underwent bronchoscopy for possible lung cancer with nondiagnostic pathology. Results were compared to the actual adjudicated prevalence of malignancy in each pre-test risk group, determined with a minimum of 12 months follow up after bronchoscopy. RESULTS: PAR and the risk models performed poorly overall in the assessment of risk in this patient population. PAR most closely matched the observed prevalence of malignancy in patients at 12 months after bronchoscopy, but all modalities had a low area under the curve, and in all clinical models more than half of all the lesions labeled as high risk were truly or likely benign. The studied risk model calculators overestimate the risk of malignancy compared to PAR, particularly in the subset in older patients, irregularly bordered nodules, and masses > 3 cm. Overall, the risk models perform only slightly better when confined to lung nodules < 3 cm in this population. CONCLUSION: The currently available tools for the assessment of risk of malignancy perform suboptimally in patients with nondiagnostic findings following a bronchoscopic evaluation for lung cancer. More accurate and objective tools for risk assessment are needed. TRIAL REGISTRATION: not applicable.

Interventional Pulmonology: The Role of Simulation Training and Competency-Based Evaluation.

Medical education and training are becoming more complex endeavors as technological and research advancements lead to new tools and methods to care for patients. In recent years, there has been a paradigm shift in medical education to competency-based assessments. Another important recent development in medical education has been the increasing use of simulation-based learning for procedural training. Interventional pulmonology (IP) is a relatively young and rapidly evolving procedural-based subspecialty. There are several well-validated competency-based assessment tools available to measure training adequacy in many of the most commonly performed procedures in IP. These tools have been shown to improve learning curves and training outcomes. The extent of how widely these tools are being used in clinical and educational spheres, however, remains unclear. Moreover, several commonly performed procedures in IP have no or limited validation tools currently available. Standardized training using simulation has also been shown to lead to positive training outcomes as compared with more traditional training models. However, widespread adoption of simulators has been limited due to the cost and availability.

The future of interventional pulmonology.

Interventional pulmonology (IP) is a maturing subspecialty of pulmonary medicine focused on advanced diagnostic and therapeutic pulmonary and thoracic medical procedures for a variety of illnesses. This rapidly growing field requires highly specific knowledge and skill sets beyond its parent specialty. While the future of IP will continue to show growth, we postulate on a few upcoming technologies which may influence the field and discuss some of the challenges associated with growth in IP.

Interventional pulmonology in the pediatric population.

Endoscopic airway interventions within pediatric populations vary considerably. Some of this variance may be related to institutional experience, however, may also be limited by operator experience and available equipment. Previous reports of pediatric bronchoscopic interventional procedures have been identified within the surgical literature; however, newer reports have identified other specialties participating in the care of these patients. Here, we will provide a review of the current relevant medical literature, including an evidence-based review of advanced diagnostic and therapeutic bronchoscopic treatments within the pediatric population.

Comparative study of ex vivo probe-based confocal laser endomicroscopy and light microscopy in lung cancer diagnostics.

BACKGROUND AND OBJECTIVE: Probe-based confocal laser endoscopy (pCLE) allows for real-time non-invasive histological imaging via bronchoscopy. Interpreting CLE images and correlating with traditional histopathology remains challenging. We performed an ex vivo study to evaluate the correlation between light microscopy findings and pCLE imaging of primary lung carcinoma. METHODS: Post-lobectomy specimens for lung cancer nodules were examined ex vivo by pCLE. The examined areas were marked with brilliant green dye, and the surrounding tissues were stained by methylene blue dye. Lung tissue segments were resected and histopathological specimens were generated with 50-µm thickness from the marked areas and stained with haematoxylin and eosin. Pathologists and pulmonologists reviewed the images for correlating features. RESULTS: Eighteen lobectomy specimens from 18 different patients were collected. Three primary features were observed in all samples using pCLE in the cancer surroundings: alveolar dystelectasis with thickening of alveolar walls, alveolar edema and a large amount of macrophages. The stromal and parenchymal components of the studied subtypes of non-small-cell lung cancer differed from each other. The stromal component for all nine adenocarcinoma specimens had a highly fluorescent field penetrated by dark hollows. All six squamous cell carcinoma specimens had the stromal component appeared as 'biparously' branching, highly fluorescent fibres. No stromal component was observed in any small-cell carcinoma specimen, and at low power field, the cellular component was dominant with an observed light scattering pattern. CONCLUSIONS: pCLE can identify lung carcinoma in ex vivo samples. Certain light microscopy features of lung carcinoma can be visualized with pCLE.

Palliative interventional pulmonology procedures in the incarcerated population with cancer: a case series.

RATIONALE: Cancer is the second most common cause of death in incarcerated population and lung cancer is the most common cause of cancer death in this group. Inmates are excluded from most published surveys and research,thus the effectiveness of lung cancer palliation in this population is not known. OBJECTIVE: To report the feasibility and safety of palliative interventional pulmonary procedures in inmates with cancer. STUDY DESIGN: Retrospective review of registry data from a single center. MATERIALS AND METHODS: Inmate data on prospectively enrolled data registry (2009­2012) from the interventional pulmonology procedural registry at Virginia Commonwealth University was extracted and analyzed for safety and efficacy. Inmates with lung cancer and advanced malignancies with pleural or airway metastasis requiring airway debulking (mechanical/thermal), airway stenting, and tunneled pleural catheter (TPC) placement were included in the analysis. RESULTS: A total of 16 procedures were performed in 12 incarcerated patients. These included six TPC placements in six patients. Ten procedures were performed in seven patients with airway obstruction. These procedures included rigid and flexible bronchoscopy with mechanical (rigid and balloon dilation) and thermal (laser, argon plasma coagulation, and cautery) tumor debulking and dilation,airway stenting, and tracheostomy in one case. All six TPCpatients had immediate symptomatic relief and improved lung aeration on chest radiograph. Three of six patients had successful auto-pleurodesis. In the seven patients with airway obstruction, three patients reported symptomatic relief and one had resolution of post-obstructive pneumonia. No immediate- or long-term procedure-related complications were reported. CONCLUSION: Incarcerated patients with advanced malignancy may benefit from interventional pulmonology procedures with low complications. Palliative interventional pulmonology procedures in inmates should not be withheld solely on their incarceration status.

Robotic Bronchoscopy: Review of Three Systems.

Robotic bronchoscopy (RB) has been shown to improve access to smaller and more peripheral lung lesions, while simultaneously staging the mediastinum. Pre-clinical studies demonstrated extremely high diagnostic yields, but real-world RB yields have yet to fully matched up in prospective studies. Despite this, RB technology has rapidly evolved and has great potential for lung-cancer diagnosis and even treatment. In this article, we review the historical and present challenges with RB in order to compare three RB systems.

Interventional Pulmonary Fellowship Training: End of the Beginning.

Interventional pulmonology (IP) fellowship training has undergone increased popularity and growth. The Accreditation Council of Graduate Medical Education recently recognized IP medicine as a new subspecialty, which leads to new challenges and opportunities for a young subspecialty. Although the specialty-specific requirements are in progress, IP fellowship programs must plan ahead for the known common program requirements and anticipated accreditation process. The educational leadership in IP must identify and execute solutions to sustain continued excellence. This includes transitioning to a new regulatory environment with issues of funding new fellowships, keeping up to date with training/assessment of new procedures, and shaping the future through recruitment of talent to lead the young subspecialty.

A Longitudinal Study of Multimodal Bronchoscopy Training in Uganda.

Background: Flexible bronchoscopy is an essential tool in diagnosing and managing pulmonary diseases. However, there is limited capacity for bronchoscopy in low and middle income countries (LMICs). In 2019, a pilot program for flexible bronchoscopy training was launched for local physicians in Kampala, Uganda. We then conducted a follow up multimodal bronchoscopy course after 2 years. Objective: The aim of this study is to assess a longitudinal multimodal bronchoscopy training in an LMIC setting. Methods: A multimodal follow up curriculum was developed with pulmonologists from Uganda and the United States. The training was delivered to Ugandan providers who attended previous bronchoscopy training and new participants. The training included a prepared curriculum consisting of lectures, simulations, and deliberate practice-based proctoring. A 12-question multiple-choice exam was administered at the beginning and end of the course, assessing knowledge. Procedural competency was measured using a validated assessment tool called the BSTAT (Bronchoscopic Skills and Tasks Assessment Tool). Results were analyzed to evaluate the retention of knowledge among those who took part in previous training and the efficacy of the follow-up curriculum for participants without previous training. Results: Among the participants who attended didactic training in 2022 (11), mean exam scores were improved after training, from 43.9 (standard deviation [SD], 11.3) to 59.8 (SD, 16.1) (mean difference [MD], +15.9; SD, 13.9; P = 0.008), but were lower compared with post didactic scores in 2019: 90.8 (SD, 6.1; MD, -31; P < 0.0001). Participants who completed BSTAT assessments (8) had mean scores similar in 2019 and 2022, at 72.1 and 75.2, respectively (MD, 3.1; P = 0.38). Conclusion: This study provides an example of how a longitudinal multimodal bronchoscopy curriculum can improve competency and proficiency for local physicians in an LMIC.

Bronchoscopy in Patients With Known or Suspected COVID-19: Results From the Global Pandemic SARS-CoV-2 Bronchoscopy Database (GPS-BD).

BACKGROUND: Amid the Coronavirus Disease 2019 (COVID-19) pandemic, the benefits and risks of bronchoscopy remain uncertain. This study was designed to characterize bronchoscopy-related practice patterns, diagnostic yields, and adverse events involving patients with known or suspected COVID-19. METHODS: An online survey tool retrospectively queried bronchoscopists about their experiences with patients with known or suspected COVID-19 between March 20 and August 20, 2020. Collected data comprised the Global Pandemic SARS-CoV-2 Bronchoscopy Database (GPS-BD). All bronchoscopists and patients were anonymous with no direct investigator-to-respondent contact. RESULTS: Bronchoscopy procedures involving 289 patients from 26 countries were analyzed. One-half of patients had known COVID-19. Most (82%) had at least 1 pre-existing comorbidity, 80% had at least 1 organ failure, 51% were critically ill, and 37% were intubated at the time of the procedure. Bronchoscopy was performed with diagnostic intent in 166 (57%) patients, yielding a diagnosis in 86 (52%). and management changes in 80 (48%). Bronchoscopy was performed with therapeutic intent in 71 (25%) patients, mostly for secretion clearance (87%). Complications attributed to bronchoscopy or significant clinical decline within 12 hours of the procedure occurred in 24 (8%) cases, with 1 death. CONCLUSION: Results from this international database provide a widely generalizable characterization of the benefits and risks of bronchoscopy in patients with known or suspected COVID-19. Bronchoscopy in this setting has reasonable clinical benefit, with diagnosis and/or management change resulting from about half of the diagnostic cases. However, it is not without risk, especially in patients with limited physiological reserve.

Clinical validation and utility of Percepta GSC for the evaluation of lung cancer.

The Percepta Genomic Sequencing Classifier (GSC) was developed to up-classify as well as down-classify the risk of malignancy for lung lesions when bronchoscopy is non-diagnostic. We evaluated the performance of Percepta GSC in risk re-classification of indeterminate lung lesions. This multicenter study included individuals who currently or formerly smoked undergoing bronchoscopy for suspected lung cancer from the AEGIS I/ II cohorts and the Percepta Registry. The classifier was measured in normal-appearing bronchial epithelium from bronchial brushings. The sensitivity, specificity, and predictive values were calculated using predefined thresholds. The ability of the classifier to decrease unnecessary invasive procedures was estimated. A set of 412 patients were included in the validation (prevalence of malignancy was 39.6%). Overall, 29% of intermediate-risk lung lesions were down-classified to low-risk with a 91.0% negative predictive value (NPV) and 12.2% of intermediate-risk lesions were up-classified to high-risk with a 65.4% positive predictive value (PPV). In addition, 54.5% of low-risk lesions were down-classified to very low risk with >99% NPV and 27.3% of high-risk lesions were up-classified to very high risk with a 91.5% PPV. If the classifier results were used in nodule management, 50% of patients with benign lesions and 29% of patients with malignant lesions undergoing additional invasive procedures could have avoided these procedures. The Percepta GSC is highly accurate as both a rule-out and rule-in test. This high accuracy of risk re-classification may lead to improved management of lung lesions.

A Multicenter Study Assessing Interventional Pulmonary Fellow Competency in Electromagnetic Navigation Bronchoscopy.

Background: Current medical society guidelines recommend a procedural number for obtaining electromagnetic navigational bronchoscopy (ENB) competency and for institutional volume for training. Objective: To assess learning curves and estimate the number of ENB procedures for interventional pulmonology (IP) fellows to reach competency. Methods: We conducted a prospective multicenter study of IP fellows in the United States learning ENB. A tool previously validated in a similar population was used to assess IP fellows by their local faculty and two blinded independent reviewers using virtual recording of the procedure. Competency was determined by performing three consecutive procedures with a competency score on the assessment tool. Procedural time, faculty global rating scale, and periprocedural complications were also recorded. Results: A total of 184 ENB procedures were available for review with assessment of 26 IP fellows at 16 medical centers. There was a high correlation between the two blinded independent observers (rho = 0.8776). There was substantial agreement for determination of procedural competency between the faculty assessment and blinded reviewers (kappa = 0.7074; confidence interval, 0.5667-0.8482). The number of procedures for reaching competency for ENB bronchoscopy was determined (median, 4; mean, 5; standard deviation, 3.83). There was a wide variation in the number of procedures to reach competency, ranging from 2 to 15 procedures. There were six periprocedural complications reported, four (one pneumomediastinum, three pneumothorax) of which occurred before reaching competence and two pneumothoraces after achieving competence. Conclusion: There is a wide variation in acquiring competency for ENB among IP fellows. Virtual competency assessment has a potential role but needs further studies.

Pilot randomized study comparing two techniques of airway anaesthesia during curvilinear probe endobronchial ultrasound bronchoscopy (CP-EBUS).

BACKGROUND AND OBJECTIVE: This study evaluates two different techniques for topically anaesthetizing the airway with lidocaine during curvilinear probe endobronchial ultrasound bronchoscopy (CP-EBUS): standard injection through the working channel and spray catheter application. METHODS: This was a randomized, non-blinded, single-centre pilot study. Patients with plans for CP-EBUS under moderate sedation were enrolled. All patients received nebulized lidocaine followed by posterior oropharyngeal lidocaine via atomizer and a cotton ball swab using McGill forceps. Patients were then randomly assigned to lidocaine administration using spray catheter instillation or direct application through the working channel. Lidocaine was administered in a uniform fashion by a single investigator throughout the study. The primary end-point was the number of significant coughing episodes in the first 30 min of bronchoscopy. Other end-points included lidocaine and intravenous sedation medication dosage; severe coughing session; and number of transbronchial needle aspirations. RESULTS: Forty patients were included in the study: 20 patients in each group. The median numbers of coughing episodes in the first 30 min were 1 (spray catheter group) and 2 (standard injection group) (P < 0.004). Six patients in the standard installation group experienced severe coughing sessions, while there was none in the spray catheter group (P = 0.02). There were no statistical differences between the groups in the dosage of lidocaine or intravenous sedation medications used. There were a greater number of transbronchial needle aspirations performed in the spray catheter group (P = 0.008). CONCLUSIONS: Lidocaine delivery via the spray catheter reduced the number of significant coughing episodes compared with standard working channel injection during CP-EBUS. Larger studies are needed to confirm these exploratory findings.

Training in interventional pulmonology: the European and US perspective.

As the breadth of interventional pulmonology continues to expand, training in this discipline gains further importance. Interventional pulmonology training in the USA and Europe has common roots and similar concepts; however, there are variations in its delivery. We discuss the similarities, differences, challenges and goals of interventional pulmonology training in both continents. Collaboration and exchange of experiences between the USA and Europe are fundamental to entering the new era of competency/mastery training to implement a multidimensional approach to procedure-related education.

Malignant Pleural Effusions.

Malignant pleural effusions have a significant burden on patients and the health care system. Diagnosis is typically via thoracentesis, although other times more invasive procedures are required. Management centers around relief of dyspnea and patient quality of life and can be done via serial thoracentesis, indwelling pleural catheter, or pleurodesis. This article focuses on the diagnosis and management of malignant pleural effusion.

A Pilot Program Assessing Bronchoscopy Training and Program Initiation in a Low-income Country.

BACKGROUND: Flexible bronchoscopy is an essential procedure for the evaluation and management of the pulmonary disease. However, this technology and related training is not available in many low-middle income countries (LMICs). We conducted a pilot training program for flexible bronchoscopy in Uganda. METHODS: A multimodal curriculum was developed with pulmonologists from Uganda and the United States. The training included an online distance learning management system for video content, simulation, just-in-time training, and deliberate practice via clinical proctoring. Procedural standards and a de novo bronchoscopy suite were concurrently developed. Competency was assessed using the Bronchoscopic Skills and Tasks Assessment Tool written examination and the Ontario Bronchoscopy Assessment Tool. RESULTS: We trained 3 pulmonary physicians with no prior experience in flexible bronchoscopy. Three bronchoscopies with bronchoalveolar lavage were performed during the training and an additional 11 cases were performed posttraining. All 3 Ugandan physicians had an increase in their written Bronchoscopic Skills and Tasks Assessment Tool and Ontario Bronchoscopy Assessment Tool in the competent range (P<0.05). All bronchoscopies were successfully completed, adequate samples were obtained, and there were no procedure-related complications. CONCLUSION: Bronchoscopy implementation in LMICs is feasible, but requires competency-based training. Further studies are needed to validate this curriculum in LMICs, including the use of this type of curriculum for more complicated bronchoscopic procedures.