The Lung Cancer Prediction Model "Stress Test": Assessment of Models' Performance in a High-Risk Prospective Pulmonary Nodule Cohort.

BACKGROUND: Pulmonary nodules represent a growing health care burden because of delayed diagnosis of malignant lesions and overtesting for benign processes. Clinical prediction models were developed to inform physician assessment of pretest probability of nodule malignancy but have not been validated in a high-risk cohort of nodules for which biopsy was ultimately performed. RESEARCH QUESTION: Do guideline-recommended prediction models sufficiently discriminate between benign and malignant nodules when applied to cases referred for biopsy by navigational bronchoscopy? STUDY DESIGN AND METHODS: We assembled a prospective cohort of 322 indeterminate pulmonary nodules in 282 patients referred to a tertiary medical center for diagnostic navigational bronchoscopy between 2017 and 2019. We calculated the probability of malignancy for each nodule using the Brock model, Mayo Clinic model, and Veterans Affairs (VA) model. On a subset of 168 patients who also had PET-CT scans before biopsy, we also calculated the probability of malignancy using the Herder model. The performance of the models was evaluated by calculating the area under the receiver operating characteristic curves (AUCs) for each model. RESULTS: The study cohort contained 185 malignant and 137 benign nodules (57% prevalence of malignancy). The malignant and benign cohorts were similar in terms of size, with a median longest diameter for benign and malignant nodules of 15 and 16 mm, respectively. The Brock model, Mayo Clinic model, and VA model showed similar performance in the entire cohort (Brock AUC, 0.70; 95% CI, 0.64-0.76; Mayo Clinic AUC, 0.70; 95% CI, 0.64-0.76; VA AUC, 0.67; 95% CI, 0.62-0.74). For 168 nodules with available PET-CT scans, the Herder model had an AUC of 0.77 (95% CI, 0.68-0.85). INTERPRETATION: Currently available clinical models provide insufficient discrimination between benign and malignant nodules in the common clinical scenario in which a patient is being referred for biopsy, especially when PET-CT scan information is not available.

Robotic versus Electromagnetic bronchoscopy for pulmonary LesIon AssessmeNT: the RELIANT pragmatic randomized trial.

BACKGROUND: Robotic-assisted bronchoscopy has recently emerged as an alternative to electromagnetic navigational bronchoscopy for the evaluation of peripheral pulmonary lesions. While robotic-assisted bronchoscopy is proposed to have several advantages, such as an easier learning curve, it is unclear if it has comparable diagnostic utility as electromagnetic navigational bronchoscopy. METHODS: Robotic versus Electromagnetic bronchoscopy for pulmonary LesIon AssessmeNT (RELIANT) is an investigator-initiated, single-center, open label, noninferiority, cluster randomized controlled trial conducted in two operating rooms at Vanderbilt University Medical Center. Each operating room (OR) is assigned to either robotic-assisted or electromagnetic navigational bronchoscopy each morning, with each OR day considered one cluster. All patients undergoing diagnostic bronchoscopy for evaluation of a peripheral pulmonary lesion in one of the two operating rooms are eligible. Schedulers, patients, and proceduralists are blinded to daily group allocations until randomization is revealed for each operating room each morning. The primary endpoint is the diagnostic yield defined as the proportion of cases yielding lesional tissue. Secondary and safety endpoints include procedure duration and procedural complications. Enrolment began on March 6, 2023, and will continue until 202 clusters have been accrued, with expected enrolment of approximately 400 patients by the time of completion in March of 2024. DISCUSSION: RELIANT is a pragmatic randomized controlled trial that will compare the diagnostic yield of the two most commonly used bronchoscopic approaches for sampling peripheral pulmonary lesions. This will be the first known cluster randomized pragmatic trial in the interventional pulmonology field and the first randomized controlled trial of robotic-assisted bronchoscopy. TRIAL REGISTRATION: ClinicalTrials.gov registration (NCT05705544) on January 30, 2023.

Spray Cryotherapy for Benign Large Airway Stenosis: A Multicenter Retrospective Cohort Study of Safety and Practice Patterns.

BACKGROUND: Benign airway stenosis (BAS) represents a significant burden on patients, providers, and healthcare systems. Spray cryotherapy (SCT) has been proposed as an adjunctive treatment to reduce BAS recurrence. We sought to examine safety and practice variations of the latest SCT system when used for BAS. METHODS: We conducted a retrospective multicenter cohort study in seven academic institutions within the Interventional Pulmonary Outcomes Group. All patients who underwent at least one SCT session with a diagnosis of BAS at the time of procedure at these institutions were included. Demographics, procedure characteristics, and adverse events were captured through each center's procedural database and electronic health record. RESULTS: A total of 102 patients underwent 165 procedures involving SCT from 2013 to 2022. The most frequent etiology of BAS was iatrogenic (n = 36, 35%). In most cases, SCT was used prior to other standard BAS interventions (n = 125; 75%). The most frequent SCT actuation time per cycle was five seconds. Pneumothorax complicated four procedures, requiring tube thoracostomy in two. Significant post-SCT hypoxemia was noted in one case, with recovery by case conclusion and no long-term effects. There were no instances of air embolism, hemodynamic compromise, or procedural or in-hospital mortality. CONCLUSION: SCT as an adjunctive treatment for BAS was associated with a low rate of complications in this retrospective multicenter cohort study. SCT-related procedural aspects varied widely in examined cases, including actuation duration, number of actuations, and timing of actuations relative to other interventions.

Navigational Bronchoscopy versus Computed Tomography-guided Transthoracic Needle Biopsy for the Diagnosis of Indeterminate Lung Nodules: protocol and rationale for the VERITAS multicenter randomized trial.

Background: Lung nodule incidence is increasing. Many nodules require biopsy to discriminate between benign and malignant etiologies. The gold-standard for minimally invasive biopsy, computed tomography-guided transthoracic needle biopsy (CT-TTNB), has never been directly compared to navigational bronchoscopy, a modality which has recently seen rapid technological innovation and is associated with improving diagnostic yield and lower complication rate. Current estimates of the diagnostic utility of both modalities are based largely on non-comparative data with significant risk for selection, referral, and publication biases. Methods: The VERITAS trial (na V igation E ndoscopy to R each Indeterminate lung nodules versus T ransthoracic needle A spiration, a randomized controlled S tudy) is a multicenter, 1:1 randomized, parallel-group trial designed to ascertain whether electromagnetic navigational bronchoscopy with integrated digital tomosynthesis is noninferior to CT-TTNB for the diagnosis of peripheral lung nodules 10-30 mm in diameter with pre-test probability of malignancy of at least 10%. The primary endpoint is diagnostic accuracy through 12 months follow-up. Secondary endpoints include diagnostic yield, complication rate, procedure duration, need for additional invasive diagnostic procedures, and radiation exposure. Discussion: The results of this rigorously designed trial will provide high-quality data regarding the management of lung nodules, a common clinical entity which often represents the earliest and most treatable stage of lung cancer. Several design challenges are described. Notably, all nodules are centrally reviewed by an independent interventional pulmonology and radiology adjudication panel relying on pre-specified exclusions to ensure enrolled nodules are amenable to sampling by both modalities while simultaneously protecting against selection bias favoring either modality. Conservative diagnostic yield and accuracy definitions with pre-specified criteria for what non-malignant findings may be considered diagnostic were chosen to avoid inflation of estimates of diagnostic utility. Trial registration: ClinicalTrials.gov NCT04250194.

Diagnostic Yield vs Diagnostic Accuracy for Peripheral Lung Biopsy Evaluation: Evidence Supporting a Future Pragmatic End Point.

BACKGROUND: Diagnostic yield and accuracy endpoints have been used inconsistently in the evaluation of advanced diagnostic bronchoscopy devices and techniques, limiting between-study comparisons. In addition, diagnostic accuracy can be adjudicated only after prolonged clinical follow-up, which delays reporting on the performance of novel devices. RESEARCH QUESTION: Will a conservative diagnostic yield definition result in few false-negative initial results to closely approximate diagnostic accuracy and represent a useful outcome for future studies of diagnostic utility? METHODS: Commonly used definitions of diagnostic yield were applied to a prospective data set of consecutive peripheral pulmonary lesions sampled by navigational bronchoscopy from 2017 to 2019. All consider malignancy to be diagnostic but differ in their classification of nonmalignant biopsy findings, which were subcategorized as specific benign, nonspecific benign, or normal lung. Diagnostic yield calculations were also compared with diagnostic accuracy, defined as the proportion of biopsy specimens deemed diagnostic by each definition that were confirmed accurate through 2 years of follow-up. RESULTS: A total of 450 biopsy specimens of lesions were analyzed. The prevalence of malignancy was 60.9% (274 of 450). On initial bronchoscopy pathology, there were 227 malignant diagnoses (50.4%), with a single false positive (0.4%). Among 104 biopsy specimens with specific benign findings, only two were false negative for malignancy (1.9%). There were 119 nonspecific benign biopsy specimens, with 46 false negatives for malignancy (38.7%). The discrepancy between diagnostic yield and accuracy was 0.7% for the conservative definition, which only considered malignant or specific benign findings as diagnostic. INTERPRETATION: A conservative diagnostic yield definition excluding nonspecific benign diagnoses closely approximated diagnostic accuracy through 2 years' follow-up, with a less than 1% discrepancy. Using this conservative yield definition may allow for dissemination of reliable diagnostic utility data without protracted delays needed for follow-up data in this era of rapid technological change in advanced diagnostic bronchoscopy.

Inter-rater reliability of a novel objective endpoint for benign central airway stenosis interventions: Segmentation-based volume rendering of computed tomography scans.

OBJECTIVES: To evaluate the reliability of a novel segmentation-based volume rendering approach for quantification of benign central airway obstruction (BCAO). DESIGN: A retrospective single-center cohort study. SETTING: Data were ascertained using electronic health records at a tertiary academic medical center in the United States. PARTICIPANTS AND INCLUSION: Patients with airway stenosis located within the trachea on two-dimensional (2D) computed tomography (CT) imaging and documentation of suspected benign etiology were included. Four readers with varying expertise in quantifying tracheal stenosis severity were selected to manually segment each CT using a volume rendering approach with the available free tools in the medical imaging viewing software OsiriX (Bernex, Switzerland). Three expert thoracic radiologists were recruited to quantify the same CTs using traditional subjective methods on a continuous and categorical scale. OUTCOME MEASURES: The interrater reliability for continuous variables was calculated by the intraclass correlation coefficient (ICC) using a two-way mixed model with 95% confidence intervals (CI). RESULTS: Thirty-eight patients met the inclusion criteria, and fifty CT scans were selected for measurement. The most common etiology of BCAO was iatrogenic in 22 patients (58%). There was an even distribution of chest and neck CT imaging within our cohort. The average ICC across all four readers for the volume rendering approach was 0.88 (95% CI, 0.84 to 0.93), suggesting good to excellent agreement. The average ICC for thoracic radiologists for subjective methods on the continuous scale was 0.38 (95% CI, 0.20 to 0.55), suggesting poor to fair agreement. The kappa for the categorical approach was 0.26, suggesting a slight to fair agreement amongst the raters. CONCLUSION: In this retrospective cohort study, agreement was good to excellent for raters with varying expertise in airway cross-sectional imaging using a novel segmentation-based volume rendering approach to quantify BCAO. This proposed measurement outperformed our expert thoracic radiologists using conventional subjective grading methods.

Robotic versus Electromagnetic Bronchoscopy for Pulmonary LesIon AssessmeNT: the RELIANT pragmatic randomized trial.

Background: Robotic assisted bronchoscopy has recently emerged as an alternative to electromagnetic navigational bronchoscopy for the evaluation of peripheral pulmonary lesions. While robotic assisted bronchoscopy is proposed to have several advantages, such as an easier learning curve, it is unclear if it has comparable diagnostic utility as electromagnetic navigational bronchoscopy. Methods: Robotic versus Electromagnetic Bronchoscopy for Pulmonary LesIon AssessmeNT (RELIANT) is an investigator-initiated, single-center, open label, noninferiority, cluster randomized controlled trial conducted in two operating rooms at Vanderbilt University Medical Center. Each operating room is assigned to either robotic assisted or electromagnetic navigational bronchoscopy each morning, with each OR day considered one cluster. All patients undergoing diagnostic bronchoscopy for evaluation of a peripheral pulmonary lesion in one of the two operating rooms are eligible. Schedulers, patients and proceduralists are blinded to daily group allocations until randomization is revealed for each operating room each morning. The primary endpoint is the diagnostic yield defined as the proportion of cases yielding lesional tissue. Secondary and safety endpoints include procedure duration and procedural complications. Enrolment began on March 6, 2023, and will continue until 202 clusters have been accrued, with expected enrolment of approximately 400 patients by the time of completion in March of 2024. Discussion: RELIANT is a pragmatic randomized controlled trial that will compare the diagnostic yield of the two most commonly used bronchoscopic approaches for sampling peripheral pulmonary lesions. This will be the first known cluster randomized pragmatic trial in the interventional pulmonology field and the first randomized controlled trial of robotic assisted bronchoscopy. Trial registration: ClinicalTrials.gov registration (NCT05705544) on January 30, 2023.

Safety and utility of indwelling pleural catheters in lung transplant recipients.

INTRODUCTION: The safety and efficacy of indwelling pleural catheters (IPCs) in lung allograft recipients is under-reported. METHODS: We performed a multicenter, retrospective analysis between 1/1/2010 and 6/1/2022 of consecutive IPCs placed in lung transplant recipients. Outcomes included incidence of infectious and non-infectious complications and rate of auto-pleurodesis. RESULTS: Seventy-one IPCs placed in 61 lung transplant patients at eight centers were included. The most common indication for IPC placement was recurrent post-operative effusion. IPCs were placed at a median of 59 days (IQR 40-203) post-transplant and remained for 43 days (IQR 25-88). There was a total of eight (11%) complications. Infection occurred in five patients (7%); four had empyema and one had a catheter tract infection. IPCs did not cause death or critical illness in our cohort. Auto-pleurodesis leading to the removal of the IPC occurred in 63 (89%) instances. None of the patients in this cohort required subsequent surgical decortication. CONCLUSIONS: The use of IPCs in lung transplant patients was associated with an infectious complication rate comparable to other populations previously studied. A high rate of auto-pleurodesis was observed. This work suggests that IPCs may be considered for the management of recurrent pleural effusions in lung allograft recipients.

Comparative Treatment Outcomes for Idiopathic Subglottic Stenosis: 5-Year Update.

The North American Airway Collaborative (NoAAC) previously published a 3-year multi-institutional prospective cohort study showing variation in treatment effectiveness between 3 primary surgical techniques for idiopathic subglottic stenosis (iSGS). In this report, we update these findings to include 5 years of data evaluating treatment effectiveness. Patients in the NoAAC cohort were re-enrolled for 2 additional years and followed using the prespecified published protocol. Consistent with prior data, prospective observation of 487 iSGS patients for 5 years showed treatment effectiveness differed by modality. Cricotracheal resection maintained the lowest rate of recurrent operation (5%), followed by endoscopic resection with adjuvant medical therapy (30%) and endoscopic dilation (50%). These data support the initial observations and continue to provide value to providers and patients navigating longitudinal decision-making. Level of evidence: 2-prospective cohort study.

Shape-Sensing Robotic-Assisted Bronchoscopy vs Digital Tomosynthesis-Corrected Electromagnetic Navigation Bronchoscopy: A Comparative Cohort Study of Diagnostic Performance.

BACKGROUND: Electromagnetic navigational bronchoscopy has been the dominant bronchoscopic technology for targeting small peripheral lesions and now includes digital tomosynthesis-electromagnetic navigational bronchoscopy (DT-ENB), allowing near-real-time intraprocedural nodule visualization. Shape-sensing robotic-assisted bronchoscopy (ssRAB), with improved catheter stability and articulation recently became available. Although the diagnostic performance of these two methods seems higher than that of legacy systems, data remain limited. We sought to compare the diagnostic yield of these two novel platforms after their introduction at our institution. RESEARCH QUESTION: Does the diagnostic yield of ssRAB differ significantly from that of DT-ENB in patients undergoing biopsy of peripheral pulmonary lesions (PPLs)? STUDY DESIGN AND METHODS: This retrospective comparative cohort study analyzed prospectively collected data on consecutive procedures performed with DT-ENB and ssRAB in their first 6 months of use at our institution. Biopsies were considered diagnostic if histopathologic analysis revealed malignancy or specific benign features that readily explained the presence of a PPL. Nonspecific inflammation, normal lung or airway, and atypia not diagnostic of malignancy were considered nondiagnostic. RESULTS: SSRAB was used to biopsy 143 PPLs in 133 patients and DT-ENB was used to biopsy 197 PPLs in 170 patients. Diagnostic yield was 77% for ssRAB (110 of 143 PPLs) and 80% (158 of 197 PPLs) for DT-ENB (OR, 0.8; 95% CI, 0.5-1.4; P = .4). Median lesion diameters were 17 and 19 mm, respectively. No difference in diagnostic yield was found after adjustment for lesion size, bronchus sign, peripheral vs middle third location, and sex. Pneumothorax complicated 1.5% of ssRAB and 1.8% of DT-ENB procedures (P = .86). INTERPRETATION: SSRAB and DT-ENB showed comparable diagnostic yields and safety profiles in this comparative cohort study.

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.

Association between terminal pleural elastance and radiographic lung re-expansion after therapeutic thoracentesis in patients with symptomatic pleural effusion: a post-hoc analysis of a randomised trial.

OBJECTIVES: Recurrent symptomatic effusions can be durably managed with pleurodesis or placement of indwelling pleural catheters. Recent pleurodesis trials have largely relied on lung re-expansion on post-thoracentesis radiograph as an inclusion criterion rather than pleural elastance as determined by manometry, which is an important predictor of successful pleurodesis. We investigated the association between lung re-expansion on post-pleural drainage chest imaging and pleural physiology, with particular attention to pleural elastance over the final 200 mL aspirated. DESIGN: Post-hoc analysis of a recent randomised trial. SETTING AND PARTICIPANTS: Post-results analysis of 61 subjects at least 18 years old with symptomatic pleural effusions estimated to be at least of 0.5 L in volume allocated to manometry-guided therapeutic thoracentesis in a recent randomised trial conducted at two major university hospitals in the USA. PRIMARY OUTCOME MEASURES: The primary outcome was concordance of radiographic with normal terminal pleural elastance over the final 200 mL aspirated. We label this terminal elastance 'visceral pleural recoil', or the tendency of the maximally expanded lung to withdraw from the chest wall. RESULTS: Post-thoracentesis chest radiograph and thoracic ultrasound indicated successful lung re-expansion in 69% and 56% of cases, respectively. Despite successful radiographic lung re-expansion, visceral pleural recoil was abnormal in 71% of subjects expandable by radiograph and 77% expandable by ultrasound. The sensitivity and positive predictive value of radiographic lung re-expansion for normal visceral pleural recoil were 44% and 24%, respectively. CONCLUSION: Radiographic lung re-expansion by post-thoracentesis chest radiograph or thoracic ultrasound is a poor surrogate for normal terminal pleural elastance. Clinical management of patients with recurrent symptomatic pleural effusions guided by manometry rather than post-thoracentesis imaging might produce better outcomes, which should be investigated by future clinical trials. TRIAL REGISTRATION NUMBER: NCT02677883; Post-results.

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.

Sight Unseen: Diagnostic Yield and Safety Outcomes of a Novel Multimodality Navigation Bronchoscopy Platform with Real-Time Target Acquisition.

BACKGROUND: Several advanced bronchoscopy platforms are currently available, but the clinical data supporting their use vary. Electromagnetic navigation bronchoscopy (ENB) remains the dominant technology; it is limited by its reliance on preoperative computed tomography, which only approximates patient anatomy during the procedure. Recently, ENB was enhanced with the (1) addition of digital tomosynthesis-based navigation correction, (2) improvements in planning algorithms, and (3) continuous real-time guidance (Illumisite™; Medtronic, Minneapolis, MN, USA). There are currently no clinical data on the diagnostic yield and safety profile of this system. OBJECTIVES: The primary objective of this study is to describe the diagnostic yield of the first 100 pulmonary parenchymal lesions sampled using the multimodality navigation bronchoscopy (MNB) platform. The secondary objective is to describe safety. METHODS: In this single-center prospective observational study, a database was maintained to track patient, procedural, and outcome data for the first 100 consecutive lesions sampled using the MNB platform at an academic quaternary referral center. Descriptive statistics and univariate and multivariate analyses are reported. RESULTS: The overall diagnostic yield of samples acquired was 79% (79/100). In the cohort where digital tomosynthesis was used, the diagnostic yield was 83% (69/83). Sensitivity for malignancy was 71% (52/73). Overall complication rates were low: pneumothorax (n = 3, 3%) and bleeding requiring intervention (n = 2, 2%). There were no procedural-related hospital admissions. CONCLUSIONS: The MNB system performed favorably. Platform superiority cannot be established without future prospective and comparative studies.