Programmed Death Ligand 1 Testing of Endobronchial Ultrasound–guided Transbronchial Needle Aspiration Samples Acquired For the Diagnosis and Staging of Non–Small Cell Lung Cancer Rationale: Immunotherapy has become an integral part of management in patients with advanced non–small cell lung cancer (NSCLC). Programmed death ligand 1 (PD-L1) expression in at least 50% of tumor cells on histologic samples has been correlated with improved efficacy of the immune checkpoint inhibitor pembrolizumab. A limited number of studies have examined the suitability of endobronchial ultrasound–guided transbronchial needle aspiration (EBUS-TBNA) specimens for assessment of PD-L1 status. Objective: We sought to examine the feasibility and results of PD-L1 testing performed on EBUS-TBNA samples acquired for the diagnosis and staging of NSCLC. Materials and Methods: Patients were identified from a prospectively maintained pathology database. Baseline characteristics were tabulated. Hematoxylin and eosin slides were reviewed to categorize cellularity between <100, 100 to 500, and >500 viable tumor cells. Samples were tested using Dako’s PD-L1 IHC 22C3 pharmDx kit, with a minimum of 100 viable tumor cells. For patients in whom additional tissue samples were available, the results of PD-L1 testing were compared. Results: PD-L1 testing was attempted on 120 EBUS-TBNA samples. The most common NSCLC subtype was adenocarcinoma (78%). Seventy-six specimens (63%) had a cellularity >500 tumor cells. Among 110 of 120 (92%) patients with an adequate endobronchial ultrasound (EBUS) sample, 53 of 110 (48.2%) had high PD-L1 expression, defined as a Tumor Proportion Score ≥50%. EBUS PD-L1 results were concordant with an available histologic sample in 14 of 18 patients (78%), with no false-negative results. Conclusion: PD-L1 testing was feasible in the majority of EBUS-TBNA samples acquired for the diagnosis and staging of NSCLC. Comparison of EBUS results with histologic samples revealed moderate concordance, with no false-negative results. Supported by Rossy Cancer Network Research Fund. Disclosure: A.V.G. was the recipient of an FRQS chercheur-boursier-clinicien award and holds a grant from the Rossy Cancer Network. H.W. reports personal fees from Pfizer, Merck, and AstraZeneca, outside the submitted work. P.-O.F. reports personal fees from AstraZeneca, Merck, and Pfizer, outside the submitted work. The remaning authors have no conflict of interest or other disclosures. Reprints: Anne V. Gonzalez, MD, MSc, Respiratory Epidemiology and Clinical Research Unit, McGill University Health Centre Research Institute, 5252 Boul. de Maisonneuve West, 3D.63, Montreal, QC, Canada H4A 3S5 (e-mail: anne.gonzalez@mcgill.ca). Received March 10, 2019 Accepted August 5, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Patient-controlled Sedation During Flexible Bronchoscopy: A Randomized Controlled Trial Background: Patient-controlled sedation (PCS) is a documented method for endoscopic procedures considered to facilitate early recovery. Limited data have been reported, however, on its use during flexible bronchoscopy (FB). Materials and Methods: This study hypothesized that PCS with propofol during FB would facilitate early recovery, with similar bronchoscopist and patient satisfaction compared with nurse-controlled sedation (NCS) with midazolam. A total of 150 patients were randomized 1:1:1 into a control group (premedication with morphine-scopolamine and NCS with midazolam), PCS-MS group (premedication with morphine-scopolamine and PCS with propofol), and PCS-G group (premedication with glycopyrronium and PCS with propofol). Results: The procedures included transbronchial biopsy, transbronchial needle aspiration, cryotherapy/biopsy, and/or multistation endobronchial ultrasound. FB duration values in median (range) were 40 (10 to 80), 39 (12 to 68), and 44 (10 to 82) minutes for the groups NCS, PCS-MS, and PCS-G, respectively. An overall 81% of the patients in the combined PCS groups were ready for discharge (modified Post Anaesthetic Discharge Scoring System, score 10) 2 hours after bronchoscopy compared with 40% in the control group (P<0.0001). Between PCS groups, 96% of the PCS-G group patients were ready for discharge compared with 65% in the PCS-MS group (P=0.0002) at 2 hours. Bronchoscopists’ and patients’ satisfaction scores were high in all groups. Postdischarge quality scores showed no differences among the groups. Conclusion: PCS with propofol during FB is feasible, as it shortened recovery time without compromising procedure conditions for bronchoscopists or patients. A rapid postsedation stabilization of vital signs facilitates surveillance before the patient leaves the hospital. Supported by internal grants from Region of Östergötland, Sweden. Disclosure: There is no conflict of interest or other disclosures. Reprints: Benjamin Grossmann, PhD, Linköping University Hospital, Linko[Combining Diaeresis]ping S-581 85, Sweden (e-mail: benjamin.grossmann@regionostergotland.se). Received December 20, 2018 Accepted June 11, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Rigid Mini-Thoracoscopy Versus Semirigid Thoracoscopy in Undiagnosed Exudative Pleural Effusion: The MINT Randomized Controlled Trial Background: There is debate regarding the ideal instrument for medical thoracoscopy. The authors compared rigid mini-thoracoscopy with semirigid thoracoscopy for thoracoscopic pleural biopsy. Methods: Consecutive subjects with undiagnosed exudative pleural effusion were randomized (1:1 ratio) to mini-thoracoscopy or semirigid thoracoscopy groups. The primary objective was a comparison of the diagnostic yield of pleural biopsy. Key secondary outcomes were the comparison of sedative/analgesic dose, operator-rated and patient-rated pain on visual analog scale (VAS), operator-rated overall procedural satisfaction (VAS), pleural biopsy size, and complications between the groups. Results: Of the 88 screened subjects, 73 were randomized: 36 to mini-thoracoscopy and 37 to semirigid thoracoscopy. Diagnostic yield of pleural biopsy in the mini-thoracoscopy (69.4%) and semirigid thoracoscopy groups (81.1%) was similar on intention-to-treat analysis (P=0.25). Although the operator-rated overall procedure satisfaction scores were similar between groups (P=0.87), operator-rated pain [VAS (mean±SD), 43.5±16.7 vs. 31.7±15.8; P<0.001] and patient-rated pain (VAS, 41.9±17.3 vs. 32.1±16.5; P=0.02) scores were greater in the mini-thoracoscopy group. Mean dose of fentanyl and midazolam received was similar between the 2 groups (P=0.28 and 0.68, respectively). Biopsy size was larger in the mini-thoracoscopy group (16.1±4.5 vs. 8.3±2.9 mm; P<0.001). Three minor complications occurred in the mini-thoracoscopy group and 6 in the semirigid thoracoscopy group (P=0.11). There were no serious adverse events or procedure-related mortality. Conclusion: Diagnostic yield of rigid mini-thoracoscopy is not superior to semirigid thoracoscopy. Use of semirigid thoracoscope may provide greater patient comfort. S.B.: collected data, data analysis, prepared the manuscript. S.M. and P.T.: collected data and manuscript revision. D.J. and S.A.: reported the pathology specimens and revised the manuscript. V.H., A.M., P.M., G.C.K., and R.G.: study design and manuscript revision. R.M.P.: data analysis and manuscript revision. K.M.: conceived the study, study design, manuscript preparation, and revision of the manuscript. There is no conflict of interest or other disclosures. Reprints: Karan Madan, MD, DM, Department of Pulmonary, Critical Care and Sleep Medicine, All India Institute of Medical Sciences (AIIMS), Ansari Nagar, New Delhi 110029, India (e-mail: drkaranmadan@gmail.com). Received April 11, 2019 Accepted July 29, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Predictors of Intraprocedural Respiratory Bronchoscopy Complications Purpose: Sleep apnea can increase adverse outcomes during ambulatory surgery but not during gastrointestinal endoscopy. We hypothesize that STOP-BANG is associated with intraprocedural bronchoscopy respiratory complications. Materials and Methods: Consecutive patients undergoing bronchoscopy under moderate sedation were prospectively administered the STOP-BANG questionnaire. Participants were assessed for intraprocedural complications including hypoxemia (oxygen saturation≤85%), bradypnea (respiratory rate<8), premature procedure cessation as well as the use of nonrebreather mask, bag-mask ventilation, jaw lift/chin tilt, nasal/oral airway, and naloxone administration. Associations were assessed via logistic regression. Least absolute shrinkage and selection operator was used for multivariable model variable selection. Results: The 223 participants—mean age 61.1±15.5 years, body mass index 25.4kg/m2 (interquartile range: 22.4 to 30.7), 50.7% female, and 45.3% inpatient—had a high rate of respiratory complications (37.7%). There were no associations between STOP-BANG score and respiratory complications [odds ratio (OR)=1.07, 95% confidence interval (CI): 0.92-1.25]. Asthma was protective in univariable models (OR=0.26, 95% CI: 0.04-0.98), whereas endobronchial ultrasound (OR=2.34, 95% CI: 1.35-4.10) and the number of procedure types (OR=1.24, 95% CI: 1.01-1.51) was associated with increased complications. The following factors were associated with respiratory complications in both multivariable and univariate analyses: increasing age (OR=1.28/decade, 95% CI: 1.03-1.61), baseline oxygen use per each liters per minute (OR=1.57, 95% CI: 1.21-2.09), and bronchoscopy duration (OR=1.20/10 min, 95% CI: 1.08-1.33). Conclusion: Bronchoscopy respiratory complications are common. STOP-BANG was not associated with increased immediate bronchoscopy complication risk. Increasing age, oxygen use, and bronchoscopy duration were associated with respiratory complications; increased vigilance in these circumstances may prevent complications. Supported by funds from the National Institutes of Health (NIH) National Heart Lung Blood Institute (NHLBI) T32 HL/NS 007913 Sleep Medicine Neurobiology and Epidemiology grant and the American Thoracic Society ASPIRE fellowship. The sponsors did not participate in the design or conduct of the study; collection, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript. Disclosure: K.P.S. receives research support from Inspire Medica Systems, and is a consultant for Galvani Bioelectronics, Jazz Pharmaceuticals, Sommetrics, and Seven Dreamers. The remaining authors there are no conflict of interest or other disclosures. Reprints: Anna M. May, MD, MS, Louis Stokes Cleveland VA Medical Center, Pulmonary 111J(W), 10701 East Boulevard, Cleveland, OH 44106 (e-mail: drannamay@gmail.com). Received April 5, 2019 Accepted July 26, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Combined Thoracoscopic Surgical Stapling and Endobronchial Valve Placement For Lung Volume Reduction With Incomplete Lobar Fissures: An Experimental Pilot Animal Study Background: In patients with severe emphysema and complete fissures, bronchoscopic lung volume reduction with valves reduces target lobe volume providing improvement in respiratory symptoms, lung function, quality of life, and exercise capacity. It is estimated that up to 88% of patients with emphysema have at least 1 incomplete interlobar fissure. The aim of this study was to evaluate the feasibility of creating a complete fissure with stapling via minimally invasive video-assisted thoracoscopic surgery (VATS) followed by bronchoscopic valve placement to induce lobar collapse in a swine model. Methods: Chest computed tomography (CT) scans were performed on 2 swine and at least 1 target incomplete fissure was identified. Both swine underwent VATS to complete the target fissure using a surgical stapler, followed by bronchoscopic placement of the Spiration endobronchial valves. A chest CT scan was performed immediately postprocedure. Follow-up bronchoscopy and CT scans were performed 2 weeks after the initial procedure prior to sacrifice. Results: Successful fissure completion was accomplished using VATS and confirmed at postmortem explanted lung gross examination. Flexible bronchoscopy 2 weeks following valve placement showed proper positioning of the valves. Effectiveness of combined procedures was confirmed by a chest CT scan that showed complete atelectasis of the target lobe at 2-week follow-up. There was no perioperative or postoperative morbidity or mortality. Conclusion: Combined minimally invasive VATS fissure stapling with bronchoscopic valve placement to induce lobar atelectasis appears safe and feasible in the swine model. Future research in humans using a combined procedure is needed to confirm safety and clinical efficacy. A.M. and F.K. contributed equally. Supported by Olympus Respiratory America. A.M.: is the guarantor of the content of the manuscript, including the data and analysis, and participated in data analysis, manuscript writing, and manuscript review. F.K., D.A.: participated in data analysis, manuscript writing, and manuscript review. L.D.V., S.G.: participated in data analysis, data collection and manuscript review; A.A., M.P., A.C.: participated in manuscript review. Disclosure: A.M., F.K., and M.P. are educational consultants for Olympus. For the remaining authors there is no conflict of interest or other disclosures. Reprints: Adnan Majid, MD, FCCP, Section of Interventional Pulmonology, Beth Israel Deaconess Medical Center, Harvard Medical School, 185 Pilgrim Road, Deaconess-201, Boston, MA 02215 (e-mail: amajid@bidmc.harvard.edu). Received March 26, 2019 Accepted July 17, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Physician Practice Patterns for Performing Thoracentesis in Patients Taking Anticoagulant Medications Background: Patients undergoing thoracentesis often have comorbid conditions or take medications that potentially put them at higher bleeding risk. Direct oral anticoagulant (DOAC) use has also increased significantly. There are no published guidelines or consensus on when to perform thoracentesis in patients on anticoagulants. Recent studies support the safety of a more liberal approach for thoracentesis among patients with coagulopathy. Methods: We conducted a survey to ascertain the practices of physicians regarding thoracentesis in patients with increased bleeding risk. The survey was administered to the email distribution lists of the American Association of Bronchology and Interventional Pulmonology and of the American Thoracic Society. Results: The survey was completed by 256 attending physicians. Most of them were general pulmonologists practicing at academic medical centers. Most of them would perform a thoracentesis in patients receiving acetylsalicylic acid or prophylactic doses of unfractionated heparin or low molecular weight heparin (96%, 89%, and 88%, respectively). Half of the respondents would perform a thoracentesis in patients on antiplatelet medications (clopidogrel and ticagrelor, 51%; ticlopidine, 53%). A minority would perform thoracentesis in patients on direct oral anticoagulants or infused thrombin inhibitors (19% and 12%, respectively). The only subgroup that had a higher proclivity for performing thoracentesis without holding medications were attending physicians practicing for under 10 years. Relative to noninterventional pulmonologists, there were no significant differences in the responses of interventional pulmonologists. Conclusion: There was variation in the practice patterns of attending physicians in performing thoracentesis in patients with elevated bleeding risk. Further data and guidelines regarding the safety of thoracentesis in these patients are needed. E.M.D. and J.T.P.: had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. E.M.D., T.E.M., M.A.P., and J.T.P.: contributed equally and substantially to the study design, data analysis and interpretation, and the writing of the manuscript. K.L.B.A.: contributed with data analysis, figures, and writing of the manuscript. T.E.M. and K.L.B.A. were supported by Yale Program on Aging, Claude D. Pepper Older Americans Independence Center (P30 AG021342). Disclosure: There is no conflict of interest or other disclosures.. Reprints: Erin M. DeBiasi, MD, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510 (e-mail: erin.debiasi@yale.edu). Received February 27, 2019 Accepted July 3, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Pleural Fluid Cytokine Levels at Baseline and Over Time are Associated With Time to IPC Removal: An Exploratory Study Background: The behavior of pleural fluid cytokine (PFCs) levels and their association with pleurodesis after indwelling pleural catheter (IPC) placement is unknown. Objective: A prospective exploratory study was conducted to obtain preliminary data on PFC levels after IPC placement. Methods: The PFC panel consisted of 4 cytokines [interleukin -8 (IL-8), vascular endothelial growth factor, total (but not activated) transforming growth factor betas, and basic fibroblast growth factor], measured across 5 time points (T0: insertion; T1: 24 to 48 h; T2: 72 to 96 h; T3: 1 wk; and T4: 2 wk). Profile plots were used to identify patterns of change of PFC levels. Correlation matrices for each PFC over time were computed, and area under the curve (AUC) categories were used to compare the cumulative incidence of IPC removal. Auto pleurodesis was defined as elective catheter removal because of decreased drainage within 90 days of insertion. Results: A total of 22 patients provided complete data. Except for IL-8, the majority of PFCs demonstrated strong positive correlations across measurement time points. Patients with high AUCs for IL-8, basic fibroblast growth factor, and vascular endothelial growth factor had a higher cumulative incidence of IPC removal by 90 days than did patients with low AUCs. Conclusion: This is the first study to evaluate longitudinal changes of pleural cytokine levels with respect to the likelihood of IPC removal and provide early evidence that the cytokine profile may be associated with the outcome of pleurodesis induced by IPCs. However, this is an exploratory study and further studies are needed to assess if these findings can be validated in further studies. I.I.W. and H.B.G.: were principal investigator and was responsible for study design, analysis, management, writing, and editing. W.L. and X.T.: were responsible for pleural fluid processing. R.C., and G.A.E.: were responsible for data collection, study oversight, analysis, and writing. S.M., R.C., J.D.M., C.R., L.Y., D.S., M.S., J.J., D.O., M.R.V., M.H., N.G., L.N., A.M.H., L.B., S.F., D.B., R.C., G.E., V.S., and A.S.: performed the procedures and helped with data collection, data entry, study oversight, analysis, and writing. Disclosure: There is no conflict of interest or other disclosures. Reprints: Horiana B. Grosu, MD, Department of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, Unit 1462, 1515 Holcombe Blvd, Houston, TX 77030 (e-mail: hbgrosu@mdanderson.org). Received November 1, 2018 Accepted April 15, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Diagnostic Utility and Safety of Endobronchial Ultrasound–guided Transbronchial Needle Aspiration in the Elderly Background: There is limited evidence regarding the effect of age on the specimen adequacy, positivity rate of specimen on cytology (PR), and safety of endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA). The aim of this study was to investigate the utility of EBUS-TBNA in the elderly. Methods: This was a retrospective study of subjects who underwent EBUS-TBNA. We compare the specimen adequacy, PR, and the incidence of complications in the elderly (age 65 y and above) versus the younger subjects (age younger than 65 y). A multivariate logistic regression analysis was performed to identify the factors affecting the diagnostic yield. Results: Of the 1816 subjects, 258 (14.2%) were elderly. The specimen adequacy was similar between the old and the young (93.5% vs. 96.3%, P=0.053). The PR in the elderly (48.8%) was lower (P<0.001) than the younger subjects (66.7%). Among those with a definite diagnosis made on EBUS-TBNA, 55.4% of the older subjects had malignancy, while 82.4% of the young had granulomatous disorders. The incidence of complications was similar in the 2 groups (3.9% vs. 4.4%, P=0.87). The specimen adequacy, PR and complications were also similar among the different age groups within the older population (65 to 69, 70 to 74, 75 to 79, and 80 y and above). On multivariate logistic regression analysis, older age, the number of lymph nodes sampled, the lymph node size, and needle reuse influenced the PR. Conclusion: EBUS-TBNA appears to have a similar specimen adequacy and safety but a lower PR in the elderly as compared with the younger individuals. S.D.: involved in patient management, statistical analysis, drafted and revised the manuscript. I.S.S., N.G., K.T.P., and A.N.A.: involved in patient management, revised the manuscript. R.A.: conceived the idea, involved in patient management, revised the manuscript. Disclosure: There is no conflict of interest or other disclosures. Reprints: Ritesh Agarwal, MD, DM, Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India (e-mail: agarwal.ritesh@outlook.in). Received December 18, 2018 Accepted April 29, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

A Single Center Experience of Feasibility of a Novel Self-Expanding Metallic Airway Stent (Bonastent): A Case Study Background: Central airway obstruction (CAO) is defined as obstruction of the airway lumen in the trachea or mainstem bronchi, most commonly due to primary or metastatic malignancy; and is classified as extraluminal, endoluminal, or mixed. The majority of malignant CAO are advanced stage and require a multimodality palliative approach, including stent placement. We describe a retrospective review of a novel self-expandable metallic stent, the Bonastent; a fully covered, nitinol-braided airway stent which conforms to airway tortuosity without loss of diameter in the management of CAO. Methods: We performed a retrospective chart review of patients with CAO who underwent Bonastent placement at a single center between February 2017 and March 2018. Ease of stent placement, short-term complications (within 24 h of stent placement) and long-term complications (within 3 mo of stent placement) were recorded. Results: Eleven patients were identified, reviewed and included in the study. Thirteen stents in 11 patients were placed for predominantly malignant CAO. One patient had a short-term complication of stent migration. Four patients had long-term complications; of which 3 patients had in-stent mucus impaction requiring bronchoscopy. In our study, the stent-related complication rates were comparable to the reported literature. Conclusion: In our experience, Bonastent is an easy to use option which adds to the armamentarium of the self-expandable metallic stent to treat malignant CAO. Disclosure: There is no conflict of interest or other disclosures. Reprints: Priyanka Makkar, MD, Section of Interventional Pulmonology, Pulmonary Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10022 (e-mail: makkarp@mskcc.org). Received October 4, 2018 Accepted April 15, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Ambulatory Iodopovidone Instillation Via Indwelling Pleural Catheters For Malignant Pleural Effusions Malignant pleural effusions’ (MPEs) treatment goals focus on optimizing the quality of life and decreasing time spent in health care facilities in this patient population with limited life expectancy. Numerous pleural palliation options and combination of these exist and continue to undergo studies to identify safe, superior and ideally patient-centered care. We report a cohort of 13 patients with symptomatic MPE managed with iodopovidone intrapleural instillation via an indwelling pleural catheter (IPC) in the ambulatory setting. Successful complete pleurodesis was achieved in 10 of 13 (76.9%) patients at a median time of 5 days with IPC removal at a median of 16 days. Two patient obtained partial pleurodesis with IPC removal, 1 required IPC reinsertion due to symptom recurrence. Complications were limited to intraprocedural pain in 4 patients (31%). Iodopovidone pleurodesis via IPC may represent a safe, feasible, and effective ambulatory-based option for pleural palliation in MPE. I.M.: conceptualization and study design, provision of patients and performed procedures, manuscript drafting, critical review, and approval of the final manuscript. P.H.: collection, assembly of data, data analysis and interpretation, manuscript drafting, critical review, and approval of the final manuscript. Disclosure: There is no conflict of interest or other disclosures. Reprints: Ismael Matus MD, FCCP, Thoracic Surgery and Interventional Pulmonology Service, Helen F. Graham Cancer Center and Research Institute, Christiana Care Health System, 4701 Ogletown-Stanton Road, Suite 2100, Newark, DE 19713 (e-mail: ismael.matus@christianacare.org). Received November 8, 2018 Accepted April 11, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.