BACKGROUND:Each year, millions of pulmonary nodules are identified incidentally or through lung cancer screening, and many involve biopsy to distinguish cancer from benign processes. Both navigational bronchoscopy and computed tomography-guided transthoracic needle biopsy are commonly used in patients undergoing biopsies of peripheral pulmonary nodules, but the relative diagnostic accuracy of these two approaches is unclear. METHODS:In this multicenter, randomized, parallel-group, noninferiority trial, we assigned patients with an intermediate-risk or high-risk peripheral pulmonary nodule measuring 10 to 30 mm in diameter to undergo navigational bronchoscopy or transthoracic needle biopsy at seven centers across the United States. The primary outcome was diagnostic accuracy, which was defined as the percentage of patients with biopsies that showed a specific diagnosis (cancer or a specific benign condition) that was confirmed to be accurate through 12 months of clinical follow-up (nonferiority margin, 10 percentage points). Secondary outcomes included procedural complications such as the occurrence of pneumothorax. RESULTS:Among the 234 patients included in the primary-outcome analysis (5 of whom were lost to follow-up), biopsy resulted in a specific diagnosis that was confirmed to be accurate through month 12 in 94 of 119 patients (79.0%) in the navigational bronchoscopy group and in 81 of 110 patients (73.6%) in the transthoracic needle biopsy group (absolute difference, 5.4 percentage points; 95% confidence interval, -6.5 to 17.2; P = 0.003 for noninferiority; P = 0.17 for superiority). Pneumothorax occurred in 4 of 121 patients (3.3%) in the navigational bronchoscopy group and in 32 of 113 patients (28.3%) in the transthoracic needle biopsy group and led to the placement of a chest tube, hospital admission, or both in 1 patient (0.8%) and 13 patients (11.5%), respectively. CONCLUSIONS:The diagnostic accuracy of navigational bronchoscopy was noninferior to that of transthoracic needle biopsy among patients with peripheral pulmonary nodules measuring 10 to 30 mm. (Funded by Medtronic and others; VERITAS ClinicalTrials.gov number, NCT04250194.).

BACKGROUND:Prior studies have found no differences in procedural chest discomfort for patients undergoing manual syringe aspiration or drainage with gravity after thoracentesis. However, whether gravity drainage could protect against chest pain due to the larger negative-pressure gradient generated by wall suction has not been investigated. RESEARCH QUESTION:Does wall suction drainage result in more chest discomfort compared with gravity drainage in patients undergoing large-volume thoracentesis? STUDY DESIGN AND METHODS:In this multicenter, single-blinded, randomized controlled trial, patients with large free-flowing effusions of ≥ 500 mL were assigned at a 1:1 ratio to wall suction or gravity drainage. Wall suction was performed with a suction system attached to the suction tubing and with vacuum pressure adjusted to full vacuum. Gravity drainage was performed with a drainage bag placed 100 cm below the catheter insertion site and connected via straight tubing. Patients rated chest discomfort on a 100-mm visual analog scale before, during, and after drainage. The primary outcome was postprocedural chest discomfort at 5 minutes. Secondary outcomes included measures of postprocedure chest discomfort, breathlessness, procedure time, volume of fluid drained, and complication rates. RESULTS:Of the 228 patients initially randomized, 221 were included in the final analysis. The primary outcome of procedural chest discomfort did not differ significantly between the groups (P = .08), nor did the secondary outcomes of postprocedural discomfort and dyspnea. Similar volumes were drained in both groups, but the procedure duration was longer in the gravity arm by approximately 3 minutes. No differences in rate of pneumothorax or reexpansion pulmonary edema were noted between the two groups. INTERPRETATION:Thoracentesis via wall suction and gravity drainage results in similar levels of procedural discomfort and dyspnea improvement. CLINICAL TRIAL REGISTRY:ClinicalTrials.gov; No.: NCT05131945; URL: www. CLINICALTRIALS:gov.

*Division of Allergy, Pulmonary and Critical Care Medicine Vanderbilt University Medical Center †Department of Thoracic Surgery, Vanderbilt University Medical Center ‡Veterans Affairs Medical Center, Nashville, TN This report has not been previously published, nor is it under consideration elsewhere. It was accepted for a brief presentation at the AABIP 2022 international meeting. L.R., R.J.L., F.M.: Study concept and design and drafting of the manuscript. L.R.: Acquisition of data. L.R. and R.J.L.: Analysis and interpretation of data. All authors participated in the critical revision of the manuscript for important intellectual content and provided final approval to submit this version of the manuscript and have agreed to be accountable for all aspects of the work. Disclosure: F.M. reports research funding (Medtronic) and consulting fees (Intuitive, Johnson & Johnson). The remaining authors have no conflicts of interest to declare. Correspondence: Robert J. Lentz, MD, Vanderbilt University Medical Center, Division of Allergy, Pulmonary & Critical Care, 1161 21st Avenue South, T-1218 MCN, Nashville, TN 37232-2650 (e-mail: [email protected]). Supplemental Digital Content is available for this article. Direct URL citations are provided in the HTML and PDF versions of this article on the journal's website, www.bronchology.com.

Background:Lung nodule incidence is increasing. Many nodules require biopsy to discriminate between benign and malignant causes. The gold standard for minimally invasive biopsy, CT scan-guided transthoracic needle biopsy (CT-TTNB), has not been compared directly with navigational bronchoscopy, a method that recently has seen rapid technological innovation and is associated with improving diagnostic yield and lower complication rates. Current estimates of the diagnostic usefulness of both methods are based largely on noncomparative data with significant risk for selection, referral, and publication biases. Research Question:Is contemporary navigational bronchoscopy noninferior to CT scan-guided transthoracic needle biopsy for the diagnosis of indeterminate pulmonary nodules? Study Design and Methods:Navigation Endoscopy to Reach Indeterminate Lung Nodules vs Transthoracic Needle Aspiration, a Randomized Controlled Study, is a multicenter, 1:1 randomized, parallel-group trial designed to ascertain whether electromagnetic navigational bronchoscopy with integrated digital tomosynthesis is noninferior to CT-TTNB for the diagnosis of peripheral lung nodules 10 to 30 mm in diameter with before testing probability of malignancy of at least 10%. The primary end point is diagnostic accuracy through 12 months of follow-up. Secondary end points include diagnostic yield, complication rate, procedure duration, need for additional invasive diagnostic procedures, and radiation exposure. Results:This article describes the protocol and rationale for the Navigation Endoscopy to Reach Indeterminate Lung Nodules vs Transthoracic Needle Aspiration, a Randomized Controlled Study, designed to answer the study question. Interpretation:The results of this rigorously designed trial will provide high-quality data regarding the management of lung nodules, a common clinical entity that often represents the earliest and most treatable stage of lung cancer. Several design challenges are described. Notably, all nodules are reviewed centrally by an independent interventional pulmonology and radiology adjudication panel relying on prespecified exclusions to ensure enrolled nodules are amenable to sampling by both methods while protecting against selection bias favoring either method. Conservative diagnostic yield and accuracy definitions with prespecified criteria for what nonmalignant findings may be considered diagnostic were chosen to avoid inflation of estimates of diagnostic usefulness. Trial Registry:ClinicalTrials.gov; No.: NCT04250194; URL: www.clinicaltrials.gov.

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.

BACKGROUND: Combination intrapleural fibrinolytic and enzyme therapy (IET) has been established as a therapeutic option in pleural infection. Despite demonstrated efficacy, studies specifically designed and adequately powered to address complications are sparse. The safety profile, the effects of concurrent therapeutic anticoagulation, and the nature and extent of nonbleeding complications remain poorly defined. RESEARCH QUESTION: What is the bleeding complication risk associated with IET use in pleural infection? STUDY DESIGN AND METHODS: This was a multicenter, retrospective observational study conducted in 24 centers across the United States and the United Kingdom. Protocolized data collection for 1,851 patients treated with at least one dose of combination IET for pleural infection between January 2012 and May 2019 was undertaken. The primary outcome was the overall incidence of pleural bleeding defined using pre hoc criteria. RESULTS: Overall, pleural bleeding occurred in 76 of 1,833 patients (4.1%; 95% CI, 3.0%-5.0%). Using a half-dose regimen (tissue plasminogen activator, 5 mg) did not change this risk significantly (6/172 [3.5%]; P = .68). Therapeutic anticoagulation alongside IET was associated with increased bleeding rates (19/197 [9.6%]) compared with temporarily withholding anticoagulation before administration of IET (3/118 [2.6%]; P = .017). As well as systemic anticoagulation, increasing RAPID score, elevated serum urea, and platelets of < 100 x 109/L were associated with a significant increase in bleeding risk. However, only RAPID score and use of systemic anticoagulation were independently predictive. Apart from pain, non-bleeding complications were rare. INTERPRETATION: IET use in pleural infection confers a low overall bleeding risk. Increased rates of pleural bleeding are associated with concurrent use of anticoagulation but can be mitigated by withholding anticoagulation before IET. Concomitant administration of IET and therapeutic anticoagulation should be avoided. Parameters related to higher IET-related bleeding have been identified that may lead to altered risk thresholds for treatment.

Background:E-cigarette or vaping-use related acute lung injury (EVALI) is a spectrum of radiographic and histologic patterns consistent with acute to subacute lung injury. However, limited data exist characterizing bronchoalveolar lavage (BAL) findings. The goal of this study is to further define the pathologic findings from BAL and biopsy samples of subjects with EVALI across 7 institutions. Methods:A multicentered registry of patients admitted with EVALI who underwent flexible bronchoscopy with BAL+/-transbronchial biopsy from July 2019 to April 2021 was compiled for retrospective evaluation from 7 academic institutions throughout the United States. Radiographic and cytopathologic findings and frequencies were correlated with the substance vaped. Results:Data from 21 subjects (42.9% women) who were predominantly White (76.2%) with a median age of 25 years (range, 16 to 68) with EVALI were included in this study. Sixteen patients (76.2%) reported use of tetrahydrocannabinol; the remainder used nicotine. BAL was performed in 19 of the 21 subjects, and transbronchial lung biopsy was performed in 7 subjects. BAL findings revealed neutrophilic predominance (median, 59.5%, range, 3.1 to 98) in most cases. Ten BAL samples demonstrated pulmonary eosinophilia ranging from 0.2% to 49.1% with one subject suggesting a diagnosis of acute eosinophilic pneumonia associated with the use of e-cigarettes. Lipid-laden macrophages were noted in 10 of 15 reports (66.7%). Transbronchial biopsy most frequently demonstrated patterns of organizing pneumonia (57.1%). Conclusion:EVALI-associated BAL findings typically demonstrate a spectrum of nonspecific inflammatory changes, including neutrophilia, lipid-laden macrophages, and in some cases eosinophilia.

P ulmonary alveolar proteinosis (PAP) is a rare lung disease in which surfactant accumulates in alveolar macrophages and the distal airways, resulting in impaired gas exchange.1,2 For symptomatic patients, standard treatment is whole lung lavage to restore gas exchange.1,3 This procedure is performed under general anesthesia using a double-lumen endotracheal tube with single lung-ventilation.3,4 Warmed saline is instilled in the target lung in serial aliquots until the fluid return resembles normal lavage fluid.3 Consequently, this can take hours to perform, may be associated with hypoxemia during the procedure, and has therefore traditionally been performed as a staged procedure over multiple days (ie, 1 lung per procedure).3,4 However, some institutions have adopted techniques that allow for bilateral whole lung lavage to be performed sequentially in a single procedure, although this practice remains controversial. We describe a multicenter cohort of patients with PAP treated with bilateral whole lung lavag in a single procedural setting.

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.

TOPIC: Lung Cancer TYPE: Original Investigations PURPOSE: A number of predicting models have been developed to estimate the pretest probability of malignancy in indeterminate pulmonary nodules (IPN), but none are specifically calibrated for the patient population referred to lung nodule clinics for consideration of minimally invasive biopsy. We aimed to identify independent predictors associated with malignancy in this population. A prediction model based on these factors will inform shared decision making regarding this common clinical problem. METHODS: Consecutive patients who underwent electromagnetic navigational bronchoscopy (SuperDimension, Medtronic, Minneapolis, MN) for the diagnosis of peripheral lung lesions between 2017-2019 at a large tertiary referral center were retrospectively identified. Demographic, radiographic, and procedural factors were abstracted and verified by two physicians (KL and RJL). Two-year follow-up was documented for all nodules not diagnosed as malignant to confirm benign disease. Bronchoscopic biopsy was deemed diagnostic if lesional tissue was acquired during the procedure (defined as histological findings which convincingly explain the presence of a nodule) with no evidence of malignancy through two years in those nodules with initially benign pathology. Descriptive statistics were performed and Wilcoxon signed-rank and Pearson chi-square tests were used to compare diagnostic and nondiagnostic groups on continuous and categorical variables, respectively. RESULTS: A total of 450 lesions biopsied in 394 patients were included in the analysis. The median lesion size was 18 mm (IQR, 14-28). Mean age was 64 ±12 years, 44% were men, and 75% were current or former smokers. The prevalence of malignancy was 61% (276 of 450 lesions). Factors associated with malignancy were older age (mean 66 ± 11 vs. 61 ± 13 years, p <0.01), current or former smoker (OR 2.1, 95% CI 1.2 to 3.4, p = 0.01), nodule in upper lobe (OR 1.5, 95% CI 1.0 to 2.2, p = 0.03), spiculation of nodule edge (OR 2.7, 95% CI 1.8 to 4.0, p < 0.01), lobulation of nodule edge (OR 1.8, 95% CI 1.2 to 2.9, p <0.01), and presence of radiographic emphysema (OR 2.9, 95% CI 2.0 to 4.4, p < 0.01). Factors associated with benignity included in presence of multiple macronodules (OR 0.5, 95% CI 0.3 to 0.9, p = 0.01). CONCLUSIONS: The prevalence of malignancy in this cohort of patients referred to lung nodule clinic with subsequent diagnostic bronchoscopy was higher than screening populations but lower than those referred for resection. Existing models developed from screening cohorts or cohorts referred for resection are therefore likely to perform sub-optimally. CLINICAL IMPLICATIONS: These factors associated with malignancy will be used to create a predictive tool based on patient and nodule characteristics which will inform shared decision making in the lung nodule clinic. DISCLOSURES: No relevant relationships by Sameer Avasarala, source=Web Response No relevant relationships by Heidi Chen, source=Web Response No relevant relationships by Sheau-Chiann Chen, source=Web Response No relevant relationships by Joyce Johnson, source=Web Response No relevant relationships by James Katsis, source=Web Response No relevant relationships by Robert Lentz, source=Web Response No relevant relationships by Kaele Leonard, source=Web Response PI ofan investigator-initiated study relationship with Medtronic Please note: >$100000 by Fabien Maldonado, source=Web Response, value=Grant/Research Supportco-I on investigator-initiated studies relationship with Janssen Please note: $20001 - $100000 by Fabien Maldonado, source=Web Response, value=Grant/Research Support Removed 04/19/2021 by Fabien Maldonado, source=Web ResponsePI on investigator-initiated relationship with Erbe Please note: $5001 - $20000 by Fabien Maldonado, source=Web Response, value=Grant/Research Support Consulting relationship with Medtronic Please note: $5001 - $20000 by Fabien Maldonado, source=Web Response, value=Honorariaco-I industry-sponsored trial relationship with Lung Therapeutics Please note: $5001 - $20000 by Fabien Maldonado, source=Web Response, value=Grant/Research Supportspeaker relationship with Longitudinal lung nodule fellows program - Please note: $1001 - $5000 by Fabien Maldonado, source=Web Response, value=Honoraria Removed 04/19/2021 by Fabien Maldonado, source=Web Response Board of director member relationship with AABIP Please note: $1-$1000 by Fabien Maldonado, source=Web Response, value=Travel Consultant relationship with Medtronic/Covidien Please note: $1001 - $5000 by Otis Rickman, source=Web Response, value=Consulting fee Advisory Committee Member relationship with Olympus Please note: $1001 - $5000 by Otis Rickman, source=Web Response, value=Honoraria Removed 04/29/2021 by Otis Rickman, source=Web Response Consultant relationship with Intuitive Surgical Please note: $1001 - $5000 by Otis Rickman, source=Web Response, value=Consulting fee Removed 04/29/2021 by Otis Rickman, source=Web Response Consultant relationship with Auris Health Please note: $5001 - $20000 by Otis Rickman, source=Web Response, value=Consulting fee Removed 04/29/2021 by Otis Rickman, source=Web Response Advisory Committee Member relationship with Abbvie Please note: $1001 - $5000 by Otis Rickman, source=Web Response, value=Honoraria Removed 04/29/2021 by Otis Rickman, source=Web Response Clinical Trial relationship with Spiration Please note: $5001 - $20000 by Otis Rickman, source=Web Response, value=Grant/Research Support Removed 04/29/2021 by Otis Rickman, source=Web Response Clinical Trial relationship with Becton, Dickinson Please note: $5001 - $20000 by Otis Rickman, source=Web Response, value=Grant/Research Support Removed 04/29/2021 by Otis Rickman, source=Web Response No relevant relationships by Lance Roller, source=Web Response

A common, and often recurrent, complication of advanced neoplastic disease is a malignant pleural effusion (MPE) or paramalignant pleural effusion (PMPE). This complication imparts a significant burden, not only on quality of life and independence, but also on the health care system as well. Current guidelines recommend definitive management to palliate symptoms, including tunneled pleural catheter (TPC) use.1Feller-Kopman D.J. Reddy C.B. Decamp M.M. et al.Management of malignant pleural effusions: an official ATS/STS/STR clinical practice guideline.Am J Respir Crit Care Med. 2018; 198: 839-849Crossref PubMed Scopus (135) Google Scholar We aimed to assess temporal utilization of TPCs for definitive pleural palliation in patients with an MPE/PMPE in a large, international, multicenter population. We also aimed to identify differences in TPC treatment practices in patients with recent/current antineoplastic therapy vs without. We reviewed patients with a MPE/PMPE treated with a TPC between January 1, 2008, to December 31, 2015, from 12 sites (Swedish Cancer Institute, Duke University, Johns Hopkins, MD Anderson, University of North Carolina, Medical University of South Carolina, University of Utah, Vanderbilt University, Virginia Commonwealth University, Gloucestershire Royal Hospital, Thoraxklinik Heidelberg, University of Oxford). There were 57 exclusions from 1,364 patients: 43 cases with no laboratory data and 14 cases with a pleural infection at TPC insertion. All centers secured ethics committee approval (primary site: Swedish Institutional Review Board SWD5993S-16), individual consent was waived. Histocytologic proof of pleural space malignancy defined an MPE; a recurrent exudative pleural effusion with a histologically proven malignancy outside the pleural space defined a PMPE. Antineoplastic therapy was defined by systemic cytotoxic and/or biologic therapy given within the month preceding TPC insertion/during drainage. Duration of TPC management included TPC in situ duration for all individuals, including those who died with the TPC, those alive at review/lost to follow up, and those with TPC removal. Time to TPC removal included only patients who had TPC removal. Descriptive data were summarized by median (interquartile range [IQR]) for continuous and count (percentage) for categoric data. Data between groups were compared with the use of the Mann-Whitney U test and χ2 test. Groups were compared with the use of the Yates correction and Fisher exact test when appropriate. Kruskal-Wallis rank sum test was used to evaluate change in time to insertion temporally. Time to TPC removal from insertion was estimated with the use of cumulative incidence functions and competing risk regression that was adjusted for year of effusion diagnosis, which accounted for death as the competing risk event. Statistical significance was defined as P < .05. Statistical analyses were performed with R software (version 3.6.0; R Core Team 2019) and SPSS statistical software package (version 24.0; SPSS Inc., Chicago, IL). There were 1,307 patients. Median age at TPC insertion was 63 years (IQR, 54-72 years) and 57% (745/1,307) were women. Lung (36%; 468/1,307) and breast (20%; 265/1,307) cancer were the most frequently identified primary cancers. Sixty-three percent of them (822/1,307) underwent antineoplastic therapy. TPC use increased from 14 patients in 2008 to 244 in 2012, where its use leveled off (Fig 1). More than one-half of the patients (63%; 818/1,307) received antineoplastic therapy. Radiographic effusion diagnosis date was unknown for 27 patients; thus, for 1,280 patients, the median time to TPC insertion was 27 days (IQR, 11-71 days). There was no change in the time to insertion temporally, ranging from 19 (IQR, 10-83 days) to 42 days (IQR, 11-89 days; P = .058) (Table 1).Table 1Time to Tunneled Pleural Catheter Insertion and Duration of Tunneled Pleural Catheter ManagementTunneled Pleural CatheterOverallaExcluding 27 patients with no date of radiographic pleural effusion diagnosis.Year20082009201020112012201320142015Effusion diagnosis to insertion, median (interquartile range), d…n = 14n = 42n = 115n = 194n = 244n = 222n = 250n = 199Overall (N = 1,280)27 (11-71)35 (20-70)42 (11-89)19 (10-83)27 (8-68)27 (11-62)23 (10-55)34 (14-88)30 (11-93)Antineoplastic therapy (n = 807)28 (11-75)51 (26-416)56 (11-93)19 (11-109)26 (9-67)23 (8-61)20 (9-54)34 (14-91)40 (15-116)No antineoplastic therapy (n = 473)27 (12-66)33 (14-45)25 (11-87)22 (9-64)27 (7-69)31 (17-63)24 (13-68)34 (14-63)24 (8-67)Duration of management,bIncludes patients lost to follow up (no tunneled pleural catheter removal date or death date) and patients who died with the tunneled pleural catheter in situ. median (interquartile range), d…n = 14n = 44n = 121n = 197n = 251n = 230n = 251n = 199Overall (N = 1,307)55 (26-116)113 (80-226)50 (33-141)49 (30-96)47 (20-105)63 (29-122)56 (28-114)61 (29-132)52 (22-118)Antineoplastic therapy (n = 822)62 (31-131)179 (90-290)65 (40-170)49 (31-96)47 (24-106)71 (33-127)59 (32-122)69 (32-143)65 (30-153)No antineoplastic therapy (n = 485)45 (20-97)109 (80-187)44 (32-68)49 (23-98)46 (15-98)48 (20-106)47 (24-106)47 (22-107)35 (12-75)Time to removal from insertion,cIncludes only patients with tunneled pleural catheter removal dates. median (interquartile range), d…n = 6n = 14n = 54n = 83n = 132n = 89n = 114n = 73Overall (N = 565)50 (30-110)109 (84-226)105 (68-194)45 (34-85)44 (23-104)55 (33-102)50 (30-98)48 (30-103)62 (30-129)Antineoplastic therapy (n = 395)56 (33-119)112 (90-179)151 (72-199)43 (35-82)44 (24-98)63 (35-111)56 (32-108)55 (32-117)74 (35-136)No antineoplastic therapy (n = 170)43 (27-85)105 (95-166)68 (51-70)49 (30-94)52 (21-134)45 (28-64)40 (28-83)41 (28-59)38 (23-89)a Excluding 27 patients with no date of radiographic pleural effusion diagnosis.b Includes patients lost to follow up (no tunneled pleural catheter removal date or death date) and patients who died with the tunneled pleural catheter in situ.c Includes only patients with tunneled pleural catheter removal dates. Open table in a new tab There was also no delay in the median time to insertion in those patients with recent/current antineoplastic therapy (28 days; IQR, 11-75 days) compared with those without (27 days; IQR, 12-66 days; P = .950). After we controlled for the year of effusion diagnosis, the conclusion remained the same (P = .584). There was no difference in infection rate temporally (range, 4-14%; P = .707). Of the 1,307 patients, 43% (565 patients) had TPC removal; 48% (623 patients) died with their TPC in situ, and 9% (119 patients) were alive/lost to follow up. Median duration of TPC management was 55 days (IQR, 26-116 days). The median duration from TPC insertion to removal was 50 days (IQR, 30-110 days). There was no change in time to removal temporally, ranging from 44 days (IQR, 23-104 days) to 109 days (IQR, 84-226; P = .351) (Table 1). The rate of TPC removal was higher in patients with recent/current antineoplastic therapy (48%; 395/822 patients) compared with those without (35%; 170/485 patients; P < .001). When we accounted for the competing event of death, the probability of TPC removal was higher in patients with recent/current antineoplastic therapy compared with those without (P = .005). After we controlled for the year of effusion diagnosis, the conclusion remained the same (P = .004). In this large, international, multicenter study, we identified TPC palliation initially to have increased annually and subsequently plateaued. We also identified it to be prevalent in patients with recent/current antineoplastic therapy. Time to insertion was 1 month, with no temporal change overall or delay in patients with recent/current antineoplastic therapy. Duration of TPC management was 2 months with no temporal change; one-half of the patients had their TPC removed, with removal being more frequent in patients with recent/current antineoplastic therapy. Our findings are consistent with published literature, where a report identified a five-fold increase in TPC use from 2009 to 2010.2Suzuki K. Servais E.L. Rizk N.P. et al.Palliation and pleurodesis in malignant pleural effusion: the role for tunneled pleural catheters.J Thorac Oncol. 2011; 6: 762-767Abstract Full Text Full Text PDF PubMed Scopus (63) Google Scholar However, this was a single institution study over a limited period, whereas our study covers a prolonged period and demonstrates an early increase in TPC use with a plateau. Our included data are from highly experienced centers and demonstrate widespread acceptance of TPC use; however, findings may differ in lower volume centers with less experienced personnel. In contrast to a previous study that identified that only 24% of patients received a definitive procedure after MPE recurrence after initial thoracentesis during 2007 to 2011, we identified time to definitive management to be a month.3Ost D.E. Niu J. Zhao H. Grosu H.B. Giordano S.H. Quality gaps and comparative effectiveness of management strategies for recurrent malignant pleural effusions.Chest. 2018; 153: 339-348Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar This may suggest a shift, with definitive pleural palliation now being at the forefront of physician's management plans. Management durations (27-56 days) and removal rates (26%-58%) were similar to published studies.2Suzuki K. Servais E.L. Rizk N.P. et al.Palliation and pleurodesis in malignant pleural effusion: the role for tunneled pleural catheters.J Thorac Oncol. 2011; 6: 762-767Abstract Full Text Full Text PDF PubMed Scopus (63) Google Scholar,4Van Meter M.E.M. McKee K.Y. Kohlwes R.J. Efficacy and safety of tunneled pleural catheters in adults with malignant pleural effusions: a systematic review.J Gen Intern Med. 2011; 26: 70-76Crossref PubMed Scopus (189) Google Scholar, 5Tremblay A. Michaud G. Single-center experience with 250 tunnelled pleural catheter insertions for malignant pleural effusion.Chest. 2006; 129: 362-368Abstract Full Text Full Text PDF PubMed Scopus (299) Google Scholar, 6Warren W.H. Kalimi R. Khodadadian L.M. Kim A.W. Management of malignant pleural effusions using the pleurx catheter.Ann Thorac Surg. 2008; 85: 1049-1055Abstract Full Text Full Text PDF PubMed Scopus (109) Google Scholar The novel finding of TPCs being more frequently removed in patients with recent/current antineoplastic therapy may possibly be due to antineoplastic therapy promoting pleurodesis and/or prolonging survival. Increased TPC use in patients with MPE/PMPEs, if considered a surrogate for increased definitive pleural palliation, is encouraging; however, the finding of a plateau suggests that continued focus on pleural palliation is required. In those patients with recent/current antineoplastic therapy, timing of palliation requires further study to maximize symptomatic benefit. Author contributions: C. L. W. is the guarantor of the paper, taking responsibility for the integrity of the work as a whole, from inception to published article. C. L. W., C. R. G., N. M. R., and J. A. G. contributed substantially to the study design, data collection, data analysis, data interpretation and writing of the manuscript. S. C., J. A. A., M. K. A., R. A., B. T. B., K. R. D., A. D., H. B. G., F. J. F. H., H. J. L., J. E. L., F. M., D. E. O., N. J. P., C. B. R., L. J. R., T. M. S., S. S., H. S., J. T., M. M. W., A. N. W., and L. B. Y. contributed substantially to the data collection, data analysis, data interpretation, and writing of the manuscript. Role of sponsors: The sponsor had no role in the design of the study, the collection and analysis of the data, or the preparation of the manuscript.

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.

RATIONALE Patients with malignant/paramalignant pleural effusions (MPE/PMPEs) may have tunneled pleural catheter (TPC) management withheld due to infection concerns from immunosuppression associated with antineoplastic therapy. OBJECTIVE To determine the rate of infections related to TPC use and to determine the relationship to antineoplastic therapy, immune system competency and overall survival (OS)? METHODS We performed an international, multi-institutional study of MPE/PMPE patients undergoing TPC management from 2008-2016. Patients were stratified by whether or not they underwent antineoplastic therapy and/or were immunocompromised or not. Cumulative incidence functions and multivariable competing risk regression analyses were performed to identify independent predictors of TPC-related infection. Kaplan-Meier method and multivariable Cox proportional-hazards modeling were performed to examine for independent effects on OS. RESULTS A total of 1,408 TPCs were placed in 1,318 patients. Patients had a high frequency of overlap between antineoplastic therapy and an immunocompromised state (75-83%). No difference in the overall (6-7%), deep pleural (3-5%) or superficial (3-4%) TPC-related infection rates between subsets of patients stratified by antineoplastic therapy or immune status was observed. The median time to infection was 41 (interquartile range: 19-87) days following TPC insertion. Multivariable competing risk analyses demonstrated longer TPC duration was associated with a higher risk of TPC-related infection [subdistribution hazard ratio (95% CI): 1.03 (1.00-1.06), p=0.028]. Cox proportional-hazards analysis showed antineoplastic therapy was associated with better OS [hazard ratio (95% CI): 0.84 (0.73-0.97), p=0.015]. CONCLUSION The risk of TPC-related infection does not appear to be increased by antineoplastic therapy use or an immunocompromised state. The overall rates of infection are low and comparable to immunocompetent patients with no relevant antineoplastic therapy. These results support TPC palliation for MPE/PMPE regardless of plans for antineoplastic therapy.

This article details the pros, cons, challenges/pitfalls, and elements required for the successful conduct of multicenter randomized trials, with specific focus on trials related to pleural diseases. Several networks dedicated to the multicenter study of important pleural conditions have developed, yielding practice-changing studies in pleural disease. This review describes the importance of multicenter trials, major elements required for the conduct of such trials, and lessons learned from the ongoing development of the Interventional Pulmonary Outcomes Group, a consortium of interventional pulmonologists dedicated to advancing diagnostic and management strategies in pleural, pulmonary parenchymal, and airway disease by generating high-quality multicenter evidence.

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.

This article details the pros, cons, challenges/pitfalls, and elements required for the successful conduct of multicenter randomized trials, with specific focus on trials related to pleural diseases. Several networks dedicated to the multicenter study of important pleural conditions have developed, yielding practice-changing studies in pleural disease. This review describes the importance of multicenter trials, major elements required for the conduct of such trials, and lessons learned from the ongoing development of the Interventional Pulmonary Outcomes Group, a consortium of interventional pulmonologists dedicated to advancing diagnostic and management strategies in pleural, pulmonary parenchymal, and airway disease by generating high-quality multicenter evidence.

BACKGROUND:Navigational bronchoscopy is commonly used to sample lung nodules, with a better safety profile but lower diagnostic yield than computerized tomography-guided transthoracic needle biopsy. The addition of digital tomosynthesis to electromagnetic navigation, using intraprocedural images obtained from a C-arm fluoroscope to identify target lesion location and update navigational guidance, may improve diagnostic yield.METHODS:Consecutive bronchoscopies using tomosynthesis-assisted fluoroscopic electromagnetic navigational bronchoscopy (F-ENB) at a single institution over a 1-year period were included. The primary outcome was diagnostic yield. A bronchoscopy was defined as diagnostic if pathologic examination revealed malignancy or specific histological findings indicative of lesional sampling with confirmatory 6-month follow-up for benign lesions.RESULTS:A total of 324 patients with 363 nodules underwent F-ENB between April 25, 2018 and April 29, 2019. The average nodule size was 1.9±1.1 cm, 65% of the nodules were located in the peripheral third of the lung. A bronchus sign was present in 24% of cases. Of the 363 nodules, 299 (82.4%) had lesional findings. At 6-month follow-up, among these 299 nodules, 6 were found to be false negatives and 12 nodules were lost to follow-up. Considering all nodules lost to follow-up as false negatives, the 6-month diagnostic yield was 77.4%. Pneumothorax complicated 8 (2.5%) of cases. There was 1 episode of respiratory failure.CONCLUSION:This retrospective study suggests the diagnostic yield of F-ENB may exceed that of traditional ENB. Future prospective and comparative studies are needed to confirm these promising data.

TOPIC: Procedures TYPE: Original Investigations PURPOSE: Navigational bronchoscopy has evolved over the past decade and now includes near-real time lesion visualization and system re-calibration to mitigate computed tomography (CT)-body divergence. Our aim was to identify independent predictors of successful bronchoscopic biopsy of peripheral lung lesions using a contemporary navigational bronchoscopy platform. A model based on these predictive factors indicating the likelihood of a diagnostic bronchoscopy will better inform shared-decision making during indeterminate pulmonary nodule (IPN) workup. METHODS: Consecutive patients who underwent electromagnetic navigational bronchoscopy (SuperDimension, Medtronic, Minneapolis, MN) for the diagnosis of peripheral lung lesions between 2017-2019 at a large tertiary referral center were retrospectively identified. Demographic, radiographic, and procedural factors were abstracted and verified by two physicians (KL and RJL). Two-year follow-up was documented for all nodules not diagnosed as malignant to confirm benign disease. Bronchoscopic biopsy was deemed diagnostic if lesional tissue was acquired during the procedure (defined as histological findings which convincingly explain the presence of a nodule) with no evidence of malignancy through two years in those nodules with initially benign pathology. Descriptive statistics were performed and Wilcoxon signed-rank and Pearson chi-square tests were used to compare diagnostic and nondiagnostic groups on continuous and categorical variables, respectively. RESULTS: A total of 461 lesions biopsied in 400 patients were included in the analysis. The median lesion size was 18 mm (IQR, 14-28). Bronchoscopy successfully recovered lesional tissue in 328/461 (71%). The prevalence of malignancy was 60% (276 of 461 lesions). Digital tomosynthesis correction was used in 49% of the cases. Factors associated with a diagnostic bronchoscopy included larger nodule size (median diameter 20 vs. 16 mm), upper lobe location (OR 1.5, 95% CI 1.0 to 2.3, p = 0.04), spiculated edges (OR 2.2, 95% CI 1.5 to 3.4, p < 0.01), current inpatient status (OR 7.2, 95% CI 1.7 to 30.4, p = 0.01), use of a paralytic agent (OR 2.2, 95% CI 1.2 to 4.1, p = 0.02), transbronchial needle aspiration (TBNA) as the initial biopsy technique (OR 3.6, 95% CI 1.1 to 11.5, p = 0.03), concentric radial endobronchial ultrasound signature (OR 5.6, 95% CI 2.9 to 10.9, p < 0.01), and performance of six or more TBNA passes (OR 4.2, 95% CI 1.3 to 13.0, p = 0.01). Factors associated with nondiagnostic bronchoscopy included uniformly smooth nodule borders (OR 0.47, 95% CI 0.22 to 0.97, p = 0.04) and development of pneumothorax (OR 0.34, 95% CI 0.11 to 1.0, p = 0.05). CONCLUSIONS: We identified and internally validated independent predicting variables associated with successful bronchoscopy using a contemporary navigational bronchoscopy platform for the diagnosis of indeterminate pulmonary nodules. CLINICAL IMPLICATIONS: We are now in the process of developing a prediction tool using these independent predictors and plan to validate it on an ongoing multicenter randomized controlled trial (ClinicalTrials.gov Identifier: NCT04250194). If validated, this tool will inform shared-decision making about nodule management in the lung nodule clinic. DISCLOSURES: No relevant relationships by Sameer Avasarala, source=Web Response No relevant relationships by Heidi Chen, source=Web Response No relevant relationships by Sheau-Chiann Chen, source=Web Response No relevant relationships by Joyce Johnson, source=Web Response No relevant relationships by James Katsis, source=Web Response No relevant relationships by Robert Lentz, source=Web Response No relevant relationships by Kaele Leonard, source=Web Response PI ofan investigator-initiated study relationship with Medtronic Please note: >$100000 by Fabien Maldonado, source=Web Response, value=Grant/Research Supportco-I on investigator-initiated studies relationship with Janssen Please note: $20001 - $100000 by Fabien Maldonado, source=Web Response, value=Grant/Research Support Removed 04/19/2021 by Fabien Maldonado, source=Web Response PI on investigator-initiated relationship with Erbe Please note: $5001 - $20000 by Fabien Maldonado, source=Web Response, value=Grant/Research Support Consulting relationship with Medtronic Please note: $5001 - $20000 by Fabien Maldonado, source=Web Response, value=Honorariaco-I industry-sponsored trial relationship with Lung Therapeutics Please note: $5001 - $20000 by Fabien Maldonado, source=Web Response, value=Grant/Research Supportspeaker relationship with Longitudinal lung nodule fellows program - Please note: $1001 - $5000 by Fabien Maldonado, source=Web Response, value=Honoraria Removed 04/19/2021 by Fabien Maldonado, source=Web Response Board of director member relationship with AABIP Please note: $1-$1000 by Fabien Maldonado, source=Web Response, value=Travel Consultant relationship with Medtronic/Covidien Please note: $1001 - $5000 by Otis Rickman, source=Web Response, value=Consulting fee Advisory Committee Member relationship with Olympus Please note: $1001 - $5000 by Otis Rickman, source=Web Response, value=Honoraria Removed 04/29/2021 by Otis Rickman, source=Web Response Consultant relationship with Intuitive Surgical Please note: $1001 - $5000 by Otis Rickman, source=Web Response, value=Consulting fee Removed 04/29/2021 by Otis Rickman, source=Web Response Consultant relationship with Auris Health Please note: $5001 - $20000 by Otis Rickman, source=Web Response, value=Consulting fee Removed 04/29/2021 by Otis Rickman, source=Web Response Advisory Committee Member relationship with Abbvie Please note: $1001 - $5000 by Otis Rickman, source=Web Response, value=Honoraria Removed 04/29/2021 by Otis Rickman, source=Web Response Clinical Trial relationship with Spiration Please note: $5001 - $20000 by Otis Rickman, source=Web Response, value=Grant/Research Support Removed 04/29/2021 by Otis Rickman, source=Web Response Clinical Trial relationship with Becton, Dickinson Please note: $5001 - $20000 by Otis Rickman, source=Web Response, value=Grant/Research Support Removed 04/29/2021 by Otis Rickman, source=Web Response No relevant relationships by Lance Roller, source=Web Response