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Rationale: Bronchoscopically collected cytology specimens are commonly used to obtain a diagnosis of cancer in patients with pulmonary lesions. However, the sensitivity of cytology is suboptimal, especially for peripheral lesions less than 2 cm in diameter. Objectives: We assessed the performance of a testing algorithm using cytology and fluorescence in situ hybridization (FISH) as part of clinical practice. Methods: Bronchial brushing specimens (n = 343) were obtained from patients undergoing bronchoscopy for indeterminate pulmonary lesions. Routine cytology was performed and specimens without a positive diagnosis (n = 294) were analyzed by FISH, using residual brushing material. Pathology-confirmed lung cancer or clinical/radiographic evidence of disease was considered diagnostic of malignancy. Measurements and Main Results: Routine cytology had a sensitivity and specificity of 41% (23 of 56) and 100% (45 of 45) for central lesions and 20% (26 of 133) and 100% (109 of 109) for peripheral nodules, respectively. FISH detected an additional 32% of lung cancers (18 central and 43 peripheral) not detectable by cytology alone, while producing false positive diagnoses in 22% (10 of 45) and 6% (6 of 109) benign central and peripheral lesions, respectively. In peripheral nodules, FISH detected (relative to routine cytology) an additional 44% (15 of 34) and 28% (25 of 91) of lung cancers less than 2 cm and 2 cm or more in size, respectively. A positive FISH result had a likelihood ratio of 1.45 and 5.87 for central and peripheral lesions and 3.44 and 15.38 for peripheral nodules less than 2 cm and 2 cm or more in size, respectively. Conclusions: FISH testing significantly increases the detection of lung cancer over routine cytology alone. It is especially useful for peripheral nodules. [ABSTRACT FROM AUTHOR]

Rationale: Acute lung injury (ALI) that develops 6 hours after transfusion (TRALI) is the leading cause of transfusion-related mortality. Several transfusion characteristics have been postulated as risk factors for TRALI, but the evidence is limited to retrospective studies.Objectives: To compare patient and transfusion risk factors between patients who do and do not develop ALI.Methods: In this prospective cohort study, consecutive transfused critically ill patients were closely observed for development of ALI. Donor samples were collected from the transfusion bags. Risk factors were compared between patients who developed ALI after transfusion and transfused control patients, matched by age, sex, and admission diagnosis.Measurements and Main Results: Seventy-four of 901 transfused patients developed ALI within 6 hours of transfusion (8%). Compared with transfused control subjects, patients with ALI were more likely to have sepsis (37 vs. 22%, P = 0.016) and a history of chronic alcohol abuse (37 vs. 18%, P = 0.006). When adjusted for patient characteristics, transfusion of plasma from female donors (odds ratio [OR], 5.09; 95% confidence interval [95% CI], 1.37-18.85) rather than male donors (OR, 1.60; 95% CI, 0.76 to 3.37), number of pregnancies among the donors (OR, 1.19; 95% CI, 1.05 to 1.34), number of donor units positive for anti-granulocyte antibodies (OR, 4.85; 95% CI, 1.32-17.86) and anti-HLA class II antibodies (OR, 3.08; 95% CI, 1.15-8.25), and concentration of lysophosphatidylcholine in the donor product (OR, 1.69; 95% CI, 1.10 to 2.59) were associated with the development of ALI.Conclusions: Both patient and transfusion risk factors determine the probability of ALI after transfusion. Transfusion factors represent attractive targets for the prevention of ALI. [ABSTRACT FROM AUTHOR]

N-butyl-2-cyanoacrylate, a tissue adhesive that polymerizes on contact with weak bases such as blood, is being used widely outside the United States to obliterate gastric varices. Embolization of this material can occur via portosystemic shunts. We report a case of pulmonary embolization of 2-octyl cyanoacrylate (an analogue of N-butyl-2-cyanoacrylate) that occurred after endoscopic injection therapy for gastric variceal bleeding. Cyanoacrylate embolism is difficult to diagnose with computed tomographic angiography because radiopaque emboli are masked by the contrast material. It is important to distinguish these emboli from conventional thromboemboli because "glue emboli" require only symptomatic treatment. Clinicians should have a high index of suspicion for embolism in the setting of tachycardia, chest pain, or hypoxia after a patient undergoes endoscopic injection therapy with cyanoacrylate glue for gastric variceal bleeding. The radiologist should be alerted so that the appropriate radiographic settings are used to make the diagnosis. [ABSTRACT FROM AUTHOR]

Sirolimus is an immunosuppressive medication used in transplant recipients. To our knowledge, we describe the third reported case of alveolar hemorrhage in association with sirolimus. Fever, dyspnea, hemoptysis, and lung infiltrates resolved rapidly with cessation of sirolimus therapy both initially and after reinstitution of the drug. Unlike previous reports, our patient had no evidence of lymphocytic alveolitis but rather marked macrophage hemosiderosis, suggesting that sirolimus pulmonary toxicity may manifest through 2 separate mechanisms. Our case highlights an uncommon but potentially lethal manifestation of sirolimus pulmonary toxicity. [ABSTRACT FROM AUTHOR]

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., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: F. M. reports research support from Medtronic and consulting fees from Johnson & Johnson and Intuitive Surgical. O. B. R. reports consulting fees from Medtronic, Noah, and Intuitive Surgical. None disclosed (K. M. L., S.-W. L., C. S. E., B. A. S., J. J., G. D., R. P., A. P. R., S. S., and R. J. L.)., (Copyright © 2023 American College of Chest Physicians. All rights reserved.)

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., (© 2024. The Author(s).)

Background: The Galaxy System (Noah Medical) is a novel robotic endoluminal platform using electromagnetic navigation combined with integrated tomosynthesis technology and augmented fluoroscopy. It provides intraprocedural imaging to correct computerized tomography (CT) to body divergence and novel confirmation of tool-in-lesion (TIL). The primary aim of this study was to assess the TIL accuracy of the robotic bronchoscope with integrated digital tomosynthesis and augmented fluoroscopy., Methods: Four operators conducted the experiment using 4 pigs. Each physician performed between 4 and 6 nodule biopsies for 20 simulated lung nodules with purple dye and a radio pacifier. Using Galaxy's "Tool-in-Lesion Tomography (TOMO+)" with augmented fluoroscopy, the physician navigated to the lung nodules, and a tool (needle) was placed into the lesion. TIL was defined by the needle in the lesion determined by cone-beam CT., Results: The lung nodule's average size was 16.3 ± 0.97 mm and was predominantly in the lower lobes (65%). All 4 operators successfully navigated to all (100%) of the lesions in an average of 3 minutes and 39 seconds. The median number of tomosynthesis sweeps was 3 and augmented fluoroscopy was utilized in most cases (17/20 or 85%). TIL after the final TOMO sweep was 95% (19/20) and tool-touch-lesion was 5% (1/20). Biopsy yielding purple pigmentation was also 100% (20/20)., Conclusion: The Galaxy System demonstrated successful digital TOMO confirmed TIL success in 95% (19/20) of lesions and tool-touch-lesion in 5% (1/20) as confirmed by cone-beam CT. Successful diagnostic yield was achieved in 100% (20/20) of lesions as confirmed by intralesional pigment acquisition., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

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., Competing Interests: Disclosure: O.B.R.: Consultant for STERIS endoscopy J.S.F. VIDA Diagnostics-multiple grants, consulting, stock options; Noah Medical – grants, consulting, stock options; Cook Medical – consulting; PPDI – DMC membership. For the remaining authors there are no conflict of interest or other disclosures., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Appropriate risk stratification of indeterminate pulmonary nodules (IPNs) is necessary to direct diagnostic evaluation. Currently available models were developed in populations with lower cancer prevalence than that seen in thoracic surgery and pulmonology clinics and usually do not allow for missing data. We updated and expanded the Thoracic Research Evaluation and Treatment (TREAT) model into a more generalized, robust approach for lung cancer prediction in patients referred for specialty evaluation., Research Question: Can clinic-level differences in nodule evaluation be incorporated to improve lung cancer prediction accuracy in patients seeking immediate specialty evaluation compared with currently available models?, Study Design and Methods: Clinical and radiographic data on patients with IPNs from six sites (N = 1,401) were collected retrospectively and divided into groups by clinical setting: pulmonary nodule clinic (n = 374; cancer prevalence, 42%), outpatient thoracic surgery clinic (n = 553; cancer prevalence, 73%), or inpatient surgical resection (n = 474; cancer prevalence, 90%). A new prediction model was developed using a missing data-driven pattern submodel approach. Discrimination and calibration were estimated with cross-validation and were compared with the original TREAT, Mayo Clinic, Herder, and Brock models. Reclassification was assessed with bias-corrected clinical net reclassification index and reclassification plots., Results: Two-thirds of patients had missing data; nodule growth and fluorodeoxyglucose-PET scan avidity were missing most frequently. The TREAT version 2.0 mean area under the receiver operating characteristic curve across missingness patterns was 0.85 compared with that of the original TREAT (0.80), Herder (0.73), Mayo Clinic (0.72), and Brock (0.68) models with improved calibration. The bias-corrected clinical net reclassification index was 0.23., Interpretation: The TREAT 2.0 model is more accurate and better calibrated for predicting lung cancer in high-risk IPNs than the Mayo, Herder, or Brock models. Nodule calculators such as TREAT 2.0 that account for varied lung cancer prevalence and that consider missing data may provide more accurate risk stratification for patients seeking evaluation at specialty nodule evaluation clinics., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: J. M. I. discloses grants from Guardant Health and GRAIL, prior support for meeting attendance from Intuitive Surgical, planned or issued patents with AstraZeneca and Roche Genentech, and stock or stock options from LumaCyte, LLC. L. T. V. has received consulting fees from Ambu A/S. F. M. receives consulting fees from Medtronic, Johnson & Johnson, and Intuitive and additionally received research funding from Medtronic. The disclosures listed did not have any relation to the content of this manuscript. None declared (C. M. G., M. E. S., V. F. W., A. W. M., M. C. A., C. M., J. C., S. R., O. B. R., R. P., E. S. L., J. C. N., J. D. B., S. A. D., E. L. G.)., (Published by Elsevier Inc.)

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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Ratwani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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., (© 2023 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

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., (Copyright © 2022 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Disclosure: There is no conflict of interest or other disclosures.

Background and Objective: Low and intermediate grade neuroendocrine tumors of the lung are uncommon malignancies representing 2% of all lung cancers. These are termed typical and atypical pulmonary carcinoid tumors. These can arise in the setting of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH). The presentation, workup, management and outcomes of patients with these tumors can overlap with more common lung cancers but differ in that many of these patients have a prolonged clinical course. The objective of this narrative review is to summarize the literature and provide evidence and expert-based algorithms for work up and treatment of pulmonary carcinoids and DIPNECH., Methods: A search of PubMed and Web of Science databases ending April 15, 2022, with the following keywords "lung carcinoid", "DIPNECH", "lung neuroendocrine," and "bronchopulmonary carcinoid"., Key Content and Findings: Pulmonary carcinoid tumors benefit from a multidisciplinary approach. Pre-treatment imaging with contrast-enhanced computed tomography, and DOTATATE positron emission tomography is required. Surgical resection is the gold standard for curative intent, and possibly including sublobar resections. Patients can recur or develop new primaries thus emphasizing the importance of surveillance; national guidelines recommend at least a 10-year follow up. A growing body of literature support the use of endobronchial therapy, with long responses documented. Systemic therapy consists of everolimus, somatostatin analogs, peptide receptor radionuclide therapy, and chemotherapy. Diffuse idiopathic pulmonary neuroendocrine tumor cell hyperplasia is rare, but series suggest somatostatin analogs may confer clinical benefit., Conclusions: Pulmonary carcinoid tumors and DIPNECH are rare. Despite lack of regulatory approvals for advanced disease, multiple options are available but should be sequenced according to the clinical status and disease biology. Each patient should be discussed in a multidisciplinary setting and clinical trials should be considered if available., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-22-415/coif). The authors have no conflicts of interest to declare. RAR serves as an unpaid editorial board member of Translational Lung Cancer Research from January 2022 to December 2023. RAR has been a consultant for Amgen, Ipsen Biopharmaceuticals, Novartis, Advanced Accelerator Applications, Curium Pharma, EMD Serono, Astra-Zeneca. He has also received research funding (to institution) from Merck & Co and Aadi Biosciences. He is also on the speaker bureaus for Ipsen Biopharmaceuticals and Astra-Zeneca. He is a member of the North American Neuroendocrine Tumor Society-Board of Directors. SD has been a consultant for Ipsen Biopharmaceuticals, Novartis, and TerSera. EAG has been a consultant for Astra-Zeneca and is on the speaker bureau for Intuitive Surgical and ASCO. The other authors have no conflicts of interest to declare., (2022 Translational Lung Cancer Research. All rights reserved.)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Lung cancer is the leading cause of cancer-related death worldwide and within the United States. Although evidence-based screening has been shown to reduce cancer-related mortality, the late-stage presentation remains common. Bronchoscopy has been proven to be an essential tool in the diagnosis and management of lung cancer. Basic and advanced diagnostic bronchoscopic techniques offer a minimally invasive modality for diagnosing and staging patients with lung cancer. In patients with malignant endotracheobronchial disease, therapeutic bronchoscopy (flexible or rigid) is a safe procedure that palliates symptoms such as dyspnea and hemoptysis. In this article, we review the various endobronchial tools and strategies essential for the management of lung cancer., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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., (© 2021 S. Karger AG, Basel.)

The field of interventional pulmonology (IP) has grown from a fringe subspecialty utilized in only a few centers worldwide to a standard component in advanced medical centers. IP is increasingly recognized for its value in patient care and its ability to deliver minimally invasive and cost-effective diagnostics and treatments. This article will provide an in-depth review of advanced bronchoscopic technologies used by IP physicians focusing on pulmonary nodules. While most pulmonary nodules are benign, malignant nodules represent the earliest detectable manifestation of lung cancer. Lung cancer is the second most common and the deadliest cancer worldwide. Differentiating benign from malignant nodules is clinically challenging as these entities are often indistinguishable radiographically. Tissue biopsy is often required to discriminate benign from malignant nodule etiologies. A safe and accurate means of definitively differentiating benign from malignant nodules would be highly valuable for patients, and the medical system at large. This would translate into a greater number of early-stage cancer detections while reducing the burden of surgical resections for benign disease. There is little high-grade evidence to guide clinicians on optimal lung nodule tissue sampling modalities. The number of novel technologies available for this purpose has rapidly expanded over the last decade, making it difficult for clinicians to assess their efficacy. Unfortunately, there is a wide variety of methods used to determine the accuracy of these technologies, making comparisons across studies impossible. This paper will provide an in-depth review of available data regarding advanced bronchoscopic technologies.

Objectives: Practice patterns for the use of extracorporeal membrane oxygenation (ECMO) during high-risk airway interventions vary, and data are limited. We aim to characterize our recent experience using ECMO for procedural support during whole-lung lavage (WLL) and high-risk bronchoscopy for central airway obstruction (CAO)., Methods: We performed a retrospective cohort study of adults who received ECMO during WLL and high-risk bronchoscopy from 1 July 2018 to 30 March 2020. Our primary end point was successful completion of the intervention. Secondary end points included ECMO-associated complications and hospital survival., Results: Eight patients received venovenous ECMO for respiratory support during 9 interventions; 3 WLLs for pulmonary alveolar proteinosis were performed in 2 patients, and 6 patients underwent 6 bronchoscopic interventions for CAO. We initiated ECMO prior to the intervention in 8 cases and during the intervention in 1 case for respiratory decompensation. All 9 interventions were successfully completed. Median ECMO duration was 17.8 h (interquartile range, 15.9-26.6) for the pulmonary alveolar proteinosis group and 1.9 h (interquartile range, 1.4-8.1) for the CAO group. There was 1 cannula-associated deep vein thrombosis; there were no other ECMO complications. Seven patients (87.5%) and 4 (50.0%) patients survived to discharge and 1 year postintervention, respectively., Conclusions: Use of venovenous ECMO to facilitate high-risk airway interventions is safe and feasible. Planned preprocedural ECMO initiation may prevent avoidable respiratory emergencies and extend therapeutic airway interventions to patients otherwise considered too high-risk to treat. Guidelines are needed to inform the utilization of ECMO during high-risk bronchoscopy and other airway interventions., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: To examine whether social determinants of health (SDH) factors are associated with time to diagnosis, treatment selection, and time to recurrent surgical intervention in idiopathic subglottic stenosis (iSGS) patients., Methods: Adult patients with diagnosed iSGS were recruited prospectively (2015-2017) via clinical providers as part of the North American Airway Collaborative (NoAAC) and via an online iSGS support community on Facebook. Patient-specific SDH factors included highest educational attainment (self-reported), median household income (matched from home zip code via U.S. Census data), and number of close friends (self-reported) as a measure of social support. Main outcomes of interest were time to disease diagnosis (years from symptom onset), treatment selection (endoscopic dilation [ED] vs cricotracheal resection [CTR] vs endoscopic resection with adjuvant medical therapy [ERMT]), and time to recurrent surgical intervention (number of days from initial surgical procedure) as a surrogate for disease recurrence., Results: The total 810 participants were 98.5% female, 97.2% Caucasian, and had a median age of 50 years (IQR, 43-58). The cohort had a median household income of $62 307 (IQR, $50 345-$79 773), a median of 7 close friends (IQR, 4-10), and 64.7% of patients completed college or graduate school. Education, income, and number of friends were not associated with time to diagnosis via multivariable linear regression modeling. Univariable multinominal logistic regression demonstrated an association between education and income for selecting ED versus ERMT, but no associations were noted for CTR. No associations were noted for time to recurrent surgical procedure via Kaplan Meier modeling and Cox proportional hazards regression., Conclusions: Patient education, income, and social support were not associated with time to diagnosis or time to disease recurrence. This suggests additional patient, procedure, or disease-specific factors contribute to the observed variations in iSGS surgical outcomes.

Background: The diagnostic yield of electromagnetic navigation bronchoscopy (ENB) is impacted by biopsy tool strategy and rapid on-site evaluation (ROSE) use. This analysis evaluates usage patterns, accuracy, and safety of tool strategy and ROSE in a multicenter study., Methods: NAVIGATE (NCT02410837) evaluates ENB using the superDimension navigation system (versions 6.3 to 7.1). The 1-year analysis included 1215 prospectively enrolled subjects at 29 United States sites. Included herein are 416 subjects who underwent ENB-aided biopsy of a single lung lesion positive for malignancy at 1 year. Use of a restricted number of tools (only biopsy forceps, standard cytology brush, and/or bronchoalveolar lavage) was compared with an extensive multimodal strategy (biopsy forceps, cytology brush, aspirating needle, triple needle cytology brush, needle-tipped cytology brush, core biopsy system, and bronchoalveolar lavage)., Results: Of malignant cases, 86.8% (361/416) of true positive diagnoses were obtained using extensive multimodal strategies. ROSE was used in 300/416 cases. The finding of malignancy by ROSE reduced the total number of tools used. A malignant ROSE call was obtained in 71% (212/300), most (88.7%; 188/212) by the first tool used (49.5% with aspirating needle, 20.2% with cytology brush, 17.0% with forceps). True positive rates were highest for the biopsy forceps (86.9%) and aspirating needle (86.6%). Use of extensive tool strategies did not increase the rates of pneumothorax (5.5% restricted, 2.8% extensive) or bronchopulmonary hemorrhage (3.6% restricted, 1.1% extensive)., Conclusion: These results suggest that extensive biopsy tool strategies, including the aspirating needle, may provide higher true positive rates for detecting lung cancer without increasing complications., Competing Interests: Disclosure: Dr E.E.F. reports consultant fees from Medtronic and Boston Scientific, and a research grant from Intuitive Surgical. Dr T.R.G. reports travel funds from Medtronic. Dr S.J.K. reports consultant fees from Medtronic. Dr G.P.L. reports consultant fees from Medtronic. H.L. and Dr J.S.M. are full-time employees of Medtronic. Dr A.K.M. reports consultant fees from Medtronic. Dr M.A.P. reports speaking, consulting, or research payments from Medtronic, Auris Health, BodyVision, Intuitive Surgical, Philips, Biodesix, AstraZeneca, Johnson and Johnson, Boehringer Ingelheim, United Therapeutics, Actelion, Inivata, and Boston Scientific. Dr O.B.R. reports consultant fees from Medtronic. Dr J.S. reports consultant fees from Somnoware Sleep Solutions. For the remaining authors there is no conflict of interest or other disclosures., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Indwelling pleural catheters (IPC) are effective at palliating benign and malignant pleural effusions (MPE). They have also been found to be cost effective from a third-party payor perspective. Little is known of the impact IPCs have on patient-centered quality of life outcomes such as financial burden and patient and caregiver burden. We performed a cross-sectional survey study evaluating the impact of IPCs on multiple patient and caregiver quality of life metrics., Methods: Patients ≥ 18 years old with an IPC in place for 2 months were eligible. Twenty patients were recruited over a 10-month period. Patients completed the CDC-Health Related Quality of Life (HRQOL)-4 and a HRQOL-financial questionnaire. The primary objective was to describe the socio-economic impact of IPCs. Demographic and IPC specific data were collected. Descriptive statistics were used., Results: The mean (SD) age was 64.3 (0.70). The indication was MPE in 19/20. All patients had medical insurance. Medicare or Medicaid (CMS) comprised 10/20 of payors. The median (IQR) copay for private insurers was $238.45 (72-875); 11/20 had additional costs related to the IPC; 4/20 had significant life changes after the IPC; 17/20 received assistance from a non-paid caregiver; 6/20 patients could not do activities because of the IPC and this negatively impacted QOL in 3/6 of those patients., Conclusion: Patients with IPCs may experience negative life consequences, incur additional medical expenses, and require assistance from a non-paid caregiver. Activities may be negatively impacted by IPC. Discussion of alternative means of symptom palliation and pleurodesis would be beneficial.

Background: Major airway bleeding is the most feared complication of transbronchial cryobiopsy (TBC). Radial endobronchial ultrasound (REBUS) has been used to assess the peripheral lung, primarily to identify pulmonary nodules, and also peripheral blood vessels. Using REBUS-guided TBC to avoid peripheral vasculature might reduce bleeding risk. This prospective randomized double-blind pilot trial was designed to investigate the feasibility of study procedures and inform the power calculation and clinical significance of a future large randomized trial., Methods: Consecutive TBCs were randomized to be performed with or without REBUS guidance in the same patient. A nonblinded operator obtained each biopsy while a blinded second operator managed the bleeding after each biopsy and determined when hemostasis had been obtained. Feasibility of study procedures and the ability to recruit patients were of primary interest. Time to hemostasis after each biopsy was also examined., Results: Forty TBCs were performed in 10 patients (4 biopsies per patient) over an enrollment period of 6 months. The time to control bleeding between biopsies was not statistically different between intervention and control arms [-14.3 (-120.1 to 92.0) s, P=0.7878]. Mean bleeding time was 139.4±59.895 seconds (REBUS 132.25± 89.305 s, non-REBUS 146.55±82.043 s). A trend towards the decreased grade of bleeding and less need for additional interventions was observed with REBUS use, but this difference did not reach statistical significance in this pilot investigation., Conclusion: Our findings suggest that REBUS-guided TBC is feasible. We did not observe any statistically significant difference in time to hemostasis or bleeding grade in this pilot study., Competing Interests: Disclosure: F.M. reports grants from ERBE research funding outside the submitted work. The remaining authors declare that there is no conflict of interest or other disclosures., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

There are over 200,000 new cases of lung cancer diagnosed annually in the United States resulting in nearly 150,000 deaths, making lung cancer the most lethal of all forms of cancer. Only 1 in 6 lung cancers are diagnosed at an early stage an over half are diagnosed with distant metastasis. Despite advances in screening and treatment, the 5-year survival rate for all lung cancers remains low, around 20%. The advent of effective lung cancer screening with low-dose computed tomography has started to shift diagnosis to earlier stages. Screening, along with the ever-increasing use of chest CT, have led to an exponential increase in the detection of indeterminate lung nodules. For many nodules, effective diagnosis relies on invasive tissue sample collection. Advances in bronchoscopic technology have allowed for safe and increasingly effective tissue diagnosis of these nodules; however, inconsistencies across studies evaluating diagnostic yield remain. This review will provide an overview of the advanced bronchoscopic technologies currently in wide use, the quality of data supporting their use, some of the perceived weaknesses and strengths of each technology, and introduce promising emerging diagnostic platforms poised to advance the field. Ultimately, quality comparative research is needed to accurately characterize the diagnostic test performance of currently available bronchoscopic platforms, improve the efficacy of bronchoscopy-generated diagnostic yields while maintaining, their strong safety profile., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd.2020.02.36). The series “Novel Diagnostic Techniques for Lung Cancer” was commissioned by the editorial office without any funding or sponsorship. RJL served as an unpaid Guest Editor for the series. FM served as the unpaid Guest Editor of the series and serves as an unpaid editorial member of Journal of Thoracic Disease from Aug 2019 to Jul 2021. FM reports grants and personal fees from Medtronic and personal fees from Erbe, outside the submitted work. OBR reports grants and personal fees from Medtronic, personal fees from Olympus America, personal fees from Auris, personal fees from Intuitive, personal fees from VERAN, outside the submitted work. JMK has no other conflicts of interest to declare., (2020 Journal of Thoracic Disease. All rights reserved.)

Background: Transbronchial cryobiopsy (TBC) is increasingly recognized as a potential alternative to surgical lung biopsy (SLB) for the diagnosis of interstitial lung disease (ILD). The goal of this analysis was to examine the literature on TBC as it relates to diagnostic utility and safety to provide evidence-based and expert guidance to clinicians., Methods: Approved panelists developed key questions regarding the diagnostic utility and safety of TBC for the evaluation of ILD using the PICO (Population, Intervention, Comparator, Outcome) format. MEDLINE (via PubMed) and the Cochrane Library were systematically searched for relevant literature, which was supplemented by manual searches. References were screened for inclusion, and vetted evaluation tools were used to assess the quality of included studies, to extract data, and to grade the level of evidence supporting each recommendation or statement. Graded recommendations and ungraded consensus-based statements were drafted and voted on using a modified Delphi technique to achieve consensus., Results: The systematic review and critical analysis of the literature based on four PICO questions resulted in six statements: two evidence-based graded recommendations and four ungraded consensus-based statements., Conclusions: Evidence of the utility and safety of TBC for the diagnosis of ILD is limited but suggests TBC is safer than SLB, and its contribution to the diagnosis obtained via multidisciplinary discussion is comparable to that of SLB, although the histological diagnostic yield appears higher with SLB (approximately 80% for TBC vs 95% for SLB). Additional research is needed to enhance knowledge regarding utility and safety of TBC, its role in the diagnostic algorithm of ILD, and the impact of technical aspects of the procedure on diagnostic yield and safety., (Copyright © 2019 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Thoracentesis can be accomplished by active aspiration or drainage with gravity. This trial investigated whether gravity drainage could protect against negative pressure-related complications such as chest discomfort, re-expansion pulmonary edema, or pneumothorax compared with active aspiration., Methods: This prospective, multicenter, single-blind, randomized controlled trial allocated patients with large free-flowing effusions estimated ≥ 500 mL 1:1 to undergo active aspiration or gravity drainage. Patients rated chest discomfort on 100-mm visual analog scales prior to, during, and following drainage. Thoracentesis was halted at complete evacuation or for persistent chest discomfort, intractable cough, or other complication. The primary outcome was overall procedural chest discomfort scored 5 min following the procedure. Secondary outcomes included measures of discomfort and breathlessness through 48 h postprocedure., Results: A total of 142 patients were randomized to undergo treatment, with 140 in the final analysis. Groups did not differ for the primary outcome (mean visual analog scale score difference, 5.3 mm; 95% CI, -2.4 to 13.0; P = .17). Secondary outcomes of discomfort and dyspnea did not differ between groups. Comparable volumes were drained in both groups, but the procedure duration was significantly longer in the gravity arm (mean difference, 7.4 min; 95% CI, 10.2 to 4.6; P < .001). There were no serious complications., Conclusions: Thoracentesis via active aspiration and gravity drainage are both safe and result in comparable levels of procedural comfort and dyspnea improvement. Active aspiration requires less total procedural time., Trial Registry: ClinicalTrials.gov; No.: NCT03591952; URL: www.clinicaltrials.gov., (Copyright © 2019 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

New robotic systems have recently emerged to assist with peripheral lung access, but a robotic system for rigid bronchoscopy has yet to be developed. We describe a new robotic system that can deliver thin robotic manipulators through the ports of standard rigid bronchoscopes. The manipulators bend and elongate to provide maneuverability of surgical tools at the endoscope tip, without endoscope motion. We describe an initial feasibility study on the use of this system to bronchoscopically treat a central airway obstruction (CAO). CAO is prevalent and can be life-threatening in patients with large tumors, and conventional rigid bronchoscopic treatments place patients at risk of complications including broken teeth, neck trauma and damage to oropharyngeal structures due to significant forces induced by bronchoscope tilting and manipulation. In this study, we used an ex vivo ovine airway model to demonstrate the ability of a physician using the robotic system to efficiently remove tissue and restore the airway. Pre- and post-operative CT scans showed that the robot was able to reduce the degree of airway obstruction stenosis from 75 to 14% on average for five CAO resections performed in an ex vivo animal model. Using cadaver experiments, we demonstrated the potential of the robotic system to substantially reduce the intraoperative forces applied to the patient's head and neck (from 80.6 to 4.1 N). These preliminary results illustrate that CAO removal is feasible with our new rigid bronchoscopy robot system, and that this approach has the potential to reduce forces applied to the patient due to bronchoscope angulation, and thereby reduce the risk of complications encountered during CAO surgery.

Importance: Surgical treatment comparisons in rare diseases are difficult secondary to the geographic distribution of patients. Fortunately, emerging technologies offer promise to reduce these barriers for research., Objective: To prospectively compare the outcomes of the 3 most common surgical approaches for idiopathic subglottic stenosis (iSGS), a rare airway disease., Design, Setting, and Participants: In this international, prospective, 3-year multicenter cohort study, 810 patients with untreated, newly diagnosed, or previously treated iSGS were enrolled after undergoing a surgical procedure (endoscopic dilation [ED], endoscopic resection with adjuvant medical therapy [ERMT], or cricotracheal resection [CTR]). Patients were recruited from clinician practices in the North American Airway Collaborative and an online iSGS community on Facebook., Main Outcomes and Measures: The primary end point was days from initial surgical procedure to recurrent surgical procedure. Secondary end points included quality of life using the Clinical COPD (chronic obstructive pulmonary disease) Questionnaire (CCQ), Voice Handicap Index-10 (VHI-10), Eating Assessment Test-10 (EAT-10), the 12-Item Short-Form Version 2 (SF-12v2), and postoperative complications., Results: Of 810 patients in this cohort, 798 (98.5%) were female and 787 (97.2%) were white, with a median age of 50 years (interquartile range, 43-58 years). Index surgical procedures were ED (n = 603; 74.4%), ERMT (n = 121; 14.9%), and CTR (n = 86; 10.6%). Overall, 185 patients (22.8%) had a recurrent surgical procedure during the 3-year study, but recurrence differed by modality (CTR, 1 patient [1.2%]; ERMT, 15 [12.4%]; and ED, 169 [28.0%]). Weighted, propensity score-matched, Cox proportional hazards regression models showed ED was inferior to ERMT (hazard ratio [HR], 3.16; 95% CI, 1.8-5.5). Among successfully treated patients without recurrence, those treated with CTR had the best CCQ (0.75 points) and SF-12v2 (54 points) scores and worst VHI-10 score (13 points) 360 days after enrollment as well as the greatest perioperative risk., Conclusions and Relevance: In this cohort study of 810 patients with iSGS, endoscopic dilation, the most popular surgical approach for iSGS, was associated with a higher recurrence rate compared with other procedures. Cricotracheal resection offered the most durable results but showed the greatest perioperative risk and the worst long-term voice outcomes. Endoscopic resection with medical therapy was associated with better disease control compared with ED and had minimal association with vocal function. These results may be used to inform individual patient treatment decision-making.

Introduction: Electromagnetic navigation bronchoscopy (ENB)-guided pleural dye marking is useful to localize small peripheral pulmonary nodules for sublobar resection., Objective: To report findings on the use of ENB-guided dye marking among participants in the NAVIGATE study., Methods: NAVIGATE is a prospective, multicentre, global and observational cohort study of ENB use in patients with lung lesions. The current subgroup report is a prespecified 1-month interim analysis of ENB-guided pleural dye marking in the NAVIGATE United States cohort., Results: The full United States cohort includes 1215 subjects from 29 sites (April 2015 to August 2016). Among those, 23 subjects (24 lesions) from seven sites underwent dye marking in preparation for surgical resection. ENB was conducted for dye marking alone in nine subjects while 14 underwent dye marking concurrent with lung lesion biopsy, lymph node biopsy and/or fiducial marker placement. The median nodule size was 10 mm (range 4-22) and 83.3% were <20 mm in diameter. Most lesions (95.5%) were located in the peripheral third of the lung, at a median of 3.0 mm from the pleura. The median ENB-specific procedure time was 11.5 minutes (range 4-38). The median time from dye marking to resection was 0.5 hours (range 0.3-24). Dye marking was adequate for surgical resection in 91.3%. Surgical biopsies were malignant in 75% (18/24)., Conclusion: In this study, ENB-guided dye marking to localize lung lesions for surgery was safe, accurate and versatile. More information is needed about surgical practice patterns and the utility of localization procedures., (© 2019 John Wiley & Sons Ltd.)

Background: In patients with non-expandable lung, removal of pleural fluid can result in excessively negative pleural pressure, which is associated with chest discomfort, pneumothorax, and re-expansion pulmonary oedema. Pleural manometry is widely used to safeguard against pressure-related complications during thoracentesis despite little evidence to support the approach. We investigated whether monitoring of pleural pressure with manometry during thoracentesis could protect against complications compared with assessment of symptoms alone., Methods: We did a prospective randomised single-blind trial involving patients with large pleural effusions at two academic medical centres in, Nashville, TN, and Baltimore, MD, USA. Eligible patients were adults with free-flowing effusions estimated to be at least 0·5 L who could remain seated throughout the procedure. Patients were randomly assigned 1:1 to receive thoracentesis guided by symptoms only (control) or by symptoms plus manometry at timepoints based on volume drained. The randomisation schedule was computer generated, used permuted blocks of four and six, and was stratified by participating institution. Patients, who were masked to study-group assignment, were asked to rate chest discomfort on 100 mm visual analogue scales before, during, and after drainage. In both groups drainage was discontinued before complete evacuation of pleural fluid if patients developed persistent chest discomfort, intractable cough, or other complications. In the manometry group, an additional criterion for stopping was if end-expiratory pleural pressure was lower than -20 cm H 2 O or declined by more than 10 cm H 2 O between two measurements to a value less than or equal to -10 cm H 2 O. The primary outcome was overall chest discomfort from before the start to after the procedure measured by patients 5 min after the end of drainage. Analysis was by modified intention to treat (ie, included all patients with any procedure or outcome data). This trial is registered with ClinicalTrials.gov, number NCT02677883., Findings: Between March 4, 2016, and Sept 8, 2017, 191 patients were screened, of whom 128 were randomly assigned treatment and 124 were included in the final analysis (62 in each group). Four patients were excluded because of manometer malfunction (n=2), inability to access effusion due to pleural tumour burden (n=1), and inability to remain seated (n=1). Groups did not differ for the primary outcome (mean difference in chest discomfort score 2·4 mm, 95% CI -5·7 to 10·5, p=0·56). Six (10%) of 62 patients in the control group had asymptomatic pneumothorax ex vacuo compared with none in the manometry group (p=0·01). No serious complications occurred in either group., Interpretation: Measurement of pleural pressure by manometry during large-volume thoracentesis does not alter procedure-related chest discomfort. Our findings do not support the routine use of this approach., Funding: Centurion Medical Products., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introduction: Electromagnetic navigation bronchoscopy (ENB) is a minimally invasive technology that guides endoscopic tools to pulmonary lesions. ENB has been evaluated primarily in small, single-center studies; thus, the diagnostic yield in a generalizable setting is unknown., Methods: NAVIGATE is a prospective, multicenter, cohort study that evaluated ENB using the superDimension navigation system (Medtronic, Minneapolis, Minnesota). In this United States cohort analysis, 1215 consecutive subjects were enrolled at 29 academic and community sites from April 2015 to August 2016., Results: The median lesion size was 20.0 mm. Fluoroscopy was used in 91% of cases (lesions visible in 60%) and radial endobronchial ultrasound in 57%. The median ENB planning time was 5 minutes; the ENB-specific procedure time was 25 minutes. Among 1157 subjects undergoing ENB-guided biopsy, 94% (1092 of 1157) had navigation completed and tissue obtained. Follow-up was completed in 99% of subjects at 1 month and 80% at 12 months. The 12-month diagnostic yield was 73%. Pathology results of the ENB-aided tissue samples showed malignancy in 44% (484 of 1092). Sensitivity, specificity, positive predictive value, and negative predictive value for malignancy were 69%, 100%, 100%, and 56%, respectively. ENB-related Common Terminology Criteria for Adverse Events grade 2 or higher pneumothoraces (requiring admission or chest tube placement) occurred in 2.9%. The ENB-related Common Terminology Criteria for Adverse Events grade 2 or higher bronchopulmonary hemorrhage and grade 4 or higher respiratory failure rates were 1.5% and 0.7%, respectively., Conclusions: NAVIGATE shows that an ENB-aided diagnosis can be obtained in approximately three-quarters of evaluable patients across a generalizable cohort based on prospective 12-month follow-up in a pragmatic setting with a low procedural complication rate., (Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Background: Electromagnetic navigation bronchoscopy (ENB) aids in the localization of lung lesions for biopsy and/or to guide fiducial or dye marking for stereotactic radiation or surgical localization. This study assessed ENB safety in patients with chronic obstructive pulmonary disease (COPD) and/or poor lung function., Methods: NAVIGATE is a prospective, multicenter, observational study of ENB. This substudy analyzed the 1-month follow-up of the first 1000 enrolled subjects. COPD was determined by medical history. Pulmonary function testing (PFT) results were collected if available within 30 days of the procedure. Procedure-related complications were captured., Results: The analysis included 448 subjects with COPD and 541 without COPD (COPD data missing in 11). One-month follow-up was completed in 93.3%. Subjects with COPD tended to be older, male, and have history of tobacco exposure, asthma, and recent pneumonia. Nodule size, location, and procedure time were similar between groups. There was no statistically significant difference in the procedure-related composite complication rate between groups (7.4% with COPD, 7.8% without COPD, P=0.90). Common Terminology Criteria for Adverse Events scale grade ≥2 pneumothorax was not different between groups (2.7% with COPD, 3.7% without COPD, P=0.47). COPD was not a significant multivariate predictor of complications. Severity of forced expiratory volume in 1 second (FEV1) or diffusing capacity of the lung for carbon monoxide impairment was not associated with increased composite procedure-related complications (ppFEV1 P=0.66, ppDLCO P=0.36)., Conclusion: In this analysis, complication rates following ENB procedures were not increased in patients with COPD or poor pulmonary function. Because pneumothorax risk is not elevated, ENB may be the preferred method to biopsy peripheral lung lesions in patients with COPD and/or poor pulmonary function testing.

Background: Mucoepidermoid carcinoma of the trachea is a rare pediatric malignancy that presents unique challenges in diagnosis, operative management, and surveillance., Methods and Results: We present a 17-year-old girl with primary tracheal mucoepidermoid carcinoma presenting in acute respiratory distress due to near-total occlusion of the tracheal airway. An algorithmic approach to preoperative planning was developed to evaluate and remove the tumor endoscopically without compromising oxygenation. After initial palliative resection, endobronchial ultrasound was uniquely applied to evaluate depth of tumor invasion, and subsequent tracheal resection with primary anastomosis was performed as curative treatment., Conclusion: Removal of distal tracheal masses can be performed safely with the implementation of an algorithmic approach to tumor visualization and resection. Endobronchial ultrasound can be used to evaluate the extent of tumor invasion and plan for definitive resection., (© 2018 Wiley Periodicals, Inc.)

Importance: Clinicians rely heavily on fluorodeoxyglucose F18-labeled positron emission tomography (FDG-PET) imaging to evaluate lung nodules suspicious for cancer. We evaluated the performance of FDG-PET for the diagnosis of malignancy in differing populations with varying cancer prevalence., Objective: To determine the performance of FDG-PET/computed tomography (CT) in diagnosing lung malignancy across different populations with varying cancer prevalence., Design, Setting, and Participants: Multicenter retrospective cohort study at 6 academic medical centers and 1 Veterans Affairs facility that comprised a total of 1188 patients with known or suspected lung cancer from 7 different cohorts from 2005 to 2015., Exposures: 18F fluorodeoxyglucose PET/CT imaging., Main Outcome and Measures: Final diagnosis of cancer or benign disease was determined by pathological tissue diagnosis or at least 18 months of stable radiographic follow-up., Results: Most patients were male smokers older than 60 years. Overall cancer prevalence was 81% (range by cohort, 50%-95%). The median nodule size was 22 mm (interquartile range, 15-33 mm). Positron emission tomography/CT sensitivity and specificity were 90.1% (95% CI, 88.1%-91.9%) and 39.8% (95% CI, 33.4%-46.5%), respectively. False-positive PET scans occurred in 136 of 1188 patients. Positive predictive value and negative predictive value were 86.4% (95% CI, 84.2%-88.5%) and 48.7% (95% CI, 41.3%-56.1%), respectively. On logistic regression, larger nodule size and higher population cancer prevalence were both significantly associated with PET accuracy (odds ratio, 1.027; 95% CI, 1.015-1.040 and odds ratio, 1.030; 95% CI, 1.021-1.040, respectively). As the Mayo Clinic model-predicted probability of cancer increased, the sensitivity and positive predictive value of PET/CT imaging increased, whereas the specificity and negative predictive value dropped., Conclusions and Relevance: High false-positive rates were observed across a range of cancer prevalence. Normal PET/CT scans were not found to be reliable indicators of the absence of disease in patients with a high probability of lung cancer. In this population, aggressive tissue acquisition should be prioritized using a comprehensive lung nodule program that emphasizes advanced tissue acquisition techniques such as CT-guided fine-needle aspiration, navigational bronchoscopy, and endobronchial ultrasonography.

Background: Initial reports of transbronchial cryobiopsy for diffuse parenchymal lung disease (DPLD) suggest the diagnostic yield approaches that of surgical lung biopsy (SLB) with an excellent safety profile. Centers performing cryobiopsy differ significantly in procedure technique; an optimal technique minimizing complications but still capable of diagnosing a wide range of DPLDs has not been established. We evaluated our practice of flexible bronchoscopic cryobiopsy in a primarily outpatient setting for patients who required a tissue diagnosis for DPLD of uncertain etiology., Methods: Consecutive patients with indeterminate DPLD who underwent bronchoscopic cryobiopsy at a large academic medical center from January 2012 to August 2015 were retrospectively analyzed. Rates of confident histopathologic diagnosis, confident multidisciplinary consensus diagnosis, management change, and complications were determined., Results: One hundred four cases were identified. Confident histopathologic diagnoses were established in 44% (46/104) and confident multidisciplinary consensus diagnoses in 68% (71/104). Usual interstitial pneumonia (19/104) and idiopathic pulmonary fibrosis (22/104) were the most common histopathologic and consensus diagnoses, respectively. Five subjects proceeded to SLB after cryobiopsy which was diagnostic in 3. Results of cryobiopsies changed management in 70% (73/104). Complications occurred in 8 cases with no death., Conclusions: Cryobiopsy during outpatient flexible bronchoscopy facilitated confident multidisciplinary consensus diagnosis of DPLD in more than two thirds of cases, and appears sufficient to establish the histopathologic diagnosis of usual interstitial pneumonia, with a complication rate that compares favorably to that reported for SLB.

Tracheobronchial foreign body (FB) aspiration is an uncommon but potentially life-threatening event in adults. Symptoms typically consist of a choking event followed by cough and dyspnea, however, these findings are inconsistent and symptoms may mimic more chronic lung diseases such as asthma or chronic obstructive pulmonary disease. Chest radiography and computed tomography can provide information regarding the location and characteristics of foreign bodies and aid in diagnosis. Bronchoscopy remains the gold standard for diagnosis and management of FB aspiration. The authors describe the typical clinical presentation, diagnostic evaluation, and bronchoscopic management of foreign bodies in adult airways with a focus on bronchoscopic techniques and potential complications of FB extraction., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Transbronchial lung biopsy with a cryoprobe, or cryobiopsy, is a promising new bronchoscopic biopsy technique capable of obtaining larger and better-preserved samples than previously possible using traditional biopsy forceps. Over two dozen case series and several small randomized trials are now available describing experiences with this technique, largely for the diagnosis of diffuse parenchymal lung disease (DPLD), in which the reported diagnostic yield is typically 70% to 80%. Cryobiopsy technique varies widely between centers and this predominantly single center-based retrospective literature heterogeneously defines diagnostic yield and complications, limiting the degree to which this technique can be compared between centers or to surgical lung biopsy (SLB). This review explores the broad range of cryobiopsy techniques currently in use, their rationale, the current state of the literature, and suggestions for the direction of future study into this promising but unproven procedure., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Objectives/hypothesis: Idiopathic subglottic stenosis (iSGS) is a rare and potentially life-threatening disease marked by recurrent and progressive airway obstruction frequently requiring repeated surgery to stabilize the airway. Unknown etiology and low disease prevalence have limited the ability to characterize the natural history of iSGS and resulted in variability in surgical management. It is uncertain how this variation relates to clinical outcomes., Study Design: Medical record abstraction., Methods: Utilizing an international, multi-institutional collaborative, we collected retrospective data on patient characteristics, treatment, and clinical outcomes. We investigated variation between and within open and endoscopic treatment approaches and assessed therapeutic outcomes; specifically, disease recurrence and need for tracheostomy at last follow-up., Results: Strikingly, 479 iSGS patients across 10 participating centers were nearly exclusively female (98%, 95% confidence interval [CI], 96.1-99.6), Caucasian (95%, 95% CI, 92.2-98.8), and otherwise healthy (mean age-adjusted Charlson Comorbidity Index 1.5; 95% CI, 1.44-1.69). The patients presented at a mean age of 50 years (95% CI, 48.8-51.1). A total of 80.2% were managed endoscopically, whereas 19.8% underwent open reconstruction. Endoscopic surgery had a significantly higher rate of disease recurrence than the open approach (chi(2) = 4.09, P = 0.043). Tracheostomy was avoided in 97% of patients irrespective of surgical approach (95% CI, 94.5-99.8). Interestingly, there were outliers in rates of disease recurrence between centers using similar treatment approaches., Conclusion: Idiopathic subglottic stenosis patients are surprisingly homogeneous. The heterogeneity of treatment approaches and the observed outliers in disease recurrence rates between centers raises the potential for improved clinical outcomes through a detailed understanding of the processes of care., Level of Evidence: 4. Laryngoscope, 126:1390-1396, 2016., (© 2015 The American Laryngological, Rhinological and Otological Society, Inc.)