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.

Predictors of Severe Bleeding During Endobronchial Biopsy: Experience of 537 Cases Background: Endobronchial biopsy (EBB) remains the standard procedure for evaluating endobronchial lesions visualized during flexible bronchoscopy. However, the predictors of bleeding and its impact on the diagnostic yield of EBB remains unknown. Methods: This was a retrospective study of subjects who underwent EBB for suspected neoplastic endobronchial lesion. We noted the demographic details, radiology, bronchoscopy findings (vascularity and location of the lesion), and the procedural details. Immediately after EBB, the bronchoscopist recorded the severity of bleed as none, mild, moderate, or severe (requiring instillation of cold saline/topical adrenaline or tamponade to control bleed). We assessed the diagnostic yield of EBB, the incidence and predictors of severe bleeding. Results: A total of 537 subjects with a mean age of 59.7 years (84.2% males) were included. On histopathology, malignancy was confirmed in 429 (85.8%) subjects. Severe bleeding occurred in 45 (8%) subjects. On a multivariate logistic regression analysis, bronchoscopic appearance of increased vascularity [odds ratio (95% confidence interval), 2.68 (1.38-5.19)] and the central location of the tumor [odds ratio (95% confidence interval), 3.01 (1.52-5.96)] were independent predictors of severe bleeding during EBB. Severe bleeding led to significantly lesser median number of biopsies (4 vs. 6, P=0.001) obtained, and a higher proportion of nondiagnostic biopsies (20% vs. 7.1%, P=0.004). Conclusion: Severe bleeding during EBB was associated with a decrease in the number of biopsies obtained and a lower diagnostic yield. A centrally located and vascular-appearing lesion on bronchoscopy predicted severe bleeding. V.M. and B.R. contributed equally to the manuscript and are the joint first authors. 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, Sector-12, Chandigarh, 160012, India (e-mail: agarwal.ritesh@outlook.in). Received October 29, 2018 Accepted March 4, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Incidence of Bleeding Complications With Flexible Bronchoscopy in Cancer Patients With Thrombocytopenia Background: Bronchoscopy is a safe procedure, but current guidelines recommend transfusion for platelets <20 K/μL. Studies of bronchoscopy in thrombocytopenia are limited. Objectives: Our objective was to evaluate the incidence of bleeding with flexible bronchoscopy in those with thrombocytopenia especially those <20 K/μL. Method: We performed a retrospective review of all flexible bronchoscopies between June 1, 2008 and December 31, 2010. Biopsies and therapeutic procedures were excluded. The χ2, Fisher exact, and Rank-sum test were conducted to evaluate associations of clinically significant bleeding. Results: There were 1711 patients who underwent 2053 flexible bronchoscopies. Cancer diagnosis included hematologic (61.3%) and solid organ malignancy (34.9%). Half of the bronchoscopies had moderate to severe thrombocytopenia (<100 K/μL) with the following ranges: 14.7% with 50 to <100 K/μL, 20.6% with 20 to <50 K/μL, 10.6% with 10 to <20 K/μL, 4.1% with <10 K/μL. Platelet transfusion was given in 90.6% of those with platelets <10 K/μL and 55.5% of those with platelets 10 to <20 K/μL. The nasal route for bronchoscopy was used in 92.4%. Bleeding complication rate however was 1.1% (0.2% major) and not affected by platelets. Conclusion: Bronchoscopy with lavage can be safely performed without platelet transfusion in those with platelets of ≥10 K/μL. In the absence of nasal bleeding, trauma, or deformity, the nasal route can be used for bronchoscopy. S.A.F.: had full access to the all of the data in the study and takes responsibility for the integrity of the data and accuracy of the data analysis, including and especially any adverse effects. S.A.F., C.A.J., T.H., S.J., and L.B.: contributed substantially to the study design, data collection, data analysis and interpretation, and the writing of the manuscript. S.A.H., R.C.M., H.B.G., D.D.B., V.R.S., and G.A.E.: contributed to the performance of procedures, data analysis and interpretation, review and editing of the manuscript. B.M.F.: contributed to the data analysis and interpretation, and review and editing of the manuscript. Supported in part by the National Institutes of Health through MD Anderson’s Cancer Center Support Grant (CA016672). Disclosure: There is no conflict of interest or other disclosures. Reprints: Saadia A. Faiz, MD, Department of Pulmonary Medicine, Unit 1462, The University of Texas MD Anderson Cancer Center, P.O. Box 301402, Houston, TX 77030-1402 (e-mail: safaiz@mdanderson.org). Received November 3, 2018 Accepted February 28, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

The Impact of an Interventional Pulmonary Program on Nontherapeutic Lung Resections Background: Pulmonary resection can concurrently diagnose and treat known or suspected lung cancer, but is not without risk. Benign resection rates range widely (9% to 40%). We evaluated the impact of an Interventional Pulmonology (IP) program and dedicated Pulmonary Nodule Clinic on surgical benign resection rates at a single institution. Methods: An IP program was initiated in August 2010 that offered advanced diagnostic techniques and a dedicated Pulmonary Nodule Clinic was opened in August 2013. We retrospectively reviewed all patients who underwent resection for known or suspected lung cancer between 2005 and 2015 at our tertiary referral hospital. Demographics, preoperative tissue diagnoses, surgical procedure, final pathology, and staging were collected. Quarterly benign resection rates were calculated and plotted on a statistical quality control chart (P-Chart) to determine the impact of the IP program and Pulmonary Nodule Clinic on benign resection rates over time. Results: Of 1112 resections, 209 (19%) were benign. Variation in quarterly benign resection rates decreased after introduction of the IP program in 2010, and a significant (P<0.05) sustained decrease in the quarterly benign resection rate occurred after introduction of the pulmonary nodule clinic in 2013 to a new baseline of 12% compared with 24% before 2010. After introduction of the IP program, mean quarterly preoperative tissue diagnostic rates increased from 45% to 58% (P<0.01). Conclusion: Integration of an IP program employing advanced diagnostic bronchoscopic techniques has improved preoperative diagnostic rates of suspicious pulmonary nodules and in combination with a pulmonary nodule clinic has resulted in fewer benign resections. Disclosure: There is no conflict of interest or other disclosures. Reprints: Eric L. Grogan, MD, MPH, FACS, Department of Thoracic Surgery, 609 Oxford House, 1313 21st Ave. South, Nashville, TN 37232 (e-mail: eric.grogan@VUMC.org). Received October 29, 2018 Accepted March 4, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

A Single-Center Case Series Describing Tracheobronchial Bonastent Implantation Background: The Bonastent is one of the newest self-expanding metallic tracheobronchial prostheses being used in the central airways. Experience with this stent is limited; there is a gap in literature. We report herein a case series of Bonastent implantation across a variety of tracheobronchial pathologies. Methods: All adult patients who had a Bonastent implanted within the tracheobronchial tree between November 2017 through May 2018 were included in this case series. Data were derived from a combination of sources: electronic medical records and a Research Electronic Data Capture–based bronchoscopy registry. Demographic, procedural, and short-term outcome data were collected for each patient. Results: Thirteen Bonastents were implanted in 11 patients during the observational period. Seven patients were male (64%); the mean age was 62.2 years. The most common indication was nonmalignant airway obstruction in a transplanted lung (n=6, 56%). Over half of all stents (n=8) were implanted in the bronchus intermedius. Three patients (27%) had clinically significant obstruction from their Bonastent. Conclusion: The Bonastent is the newest self-expanding metallic endotracheobronchial stent on the market. Like any other stent, it has its advantages and drawbacks. Interestingly, we noted 3 instances of tissue ingrowth through the covered portion of the stent. Larger studies with a longer follow-up periods are needed to assess long-term efficacy and safety of this relatively novel stent. Disclosure: There is no conflict of interest or other disclosures. Reprints: Sameer K. Avasarala, MD, A90, 9500 Euclid Avenue, Cleveland, OH, 44195 (e-mail: avasars@ccf.org). Received October 27, 2018 Accepted January 3, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.