Incremental Application of Positive End-Expiratory Pressure for the Evaluation of Atelectasis During RP-EBUS and Bronchoscopy (I-APPEAR).

BACKGROUND: CT-to-body divergence-described as the difference between preprocedural CT scans and intraprocedural lung architecture-is a significant barrier to improving diagnostic yield during navigational bronchoscopy. A major proposed contributor to CT-to-body divergence is the development of atelectasis, which can confound visualization of peripheral lung lesions via radial probe endobronchial ultrasound (RP-EBUS). High positive end-expiratory pressure (PEEP) ventilatory strategies have been used to decrease atelectasis, allowing the lesion to re-APPEAR on intraprocedure imaging. However, standardized PEEP levels may not be appropriate for all patients due to hemodynamic and ventilatory impacts. METHODS: We performed a multicenter, prospective observational study in which patients were imaged with RP-EBUS under general anesthesia to determine if subsegmental atelectasis would resolve as incremental increases in PEEP were applied. Resolution of atelectasis was based on the transition from a non-aerated pattern to an aerated appearance on RP-EBUS. RP-EBUS images were reviewed by 3 experienced operators to determine correlation. RESULTS: Forty-three patients underwent RP-EBUS examination following navigational bronchoscopy. Thirty-seven patients underwent incremental PEEP application and subsequent RP-EBUS imaging. Atelectasis was determined to have resolved in 33 patients (88.2%) following increased PEEP. The intraclass correlation coefficient between reviewers was 0.76. A recruitment maneuver was performed in 7 (16.3%) patients after atelectasis persisted at maximal PEEP. Atelectasis was not identified in the examined subsegments in 6 (10.8%) patients despite zero PEEP. CONCLUSION: RP-EBUS is an effective tool to monitor what pressure atelectasis within a lung segment has resolved with increasing levels of PEEP.

Severity of Atelectasis during Bronchoscopy: Descriptions of a New Grading System (AtelectasisSeverity Scoring System-"ASSESS") and At-Risk-Lung Zones.

Atelectasis during bronchoscopy under general anesthesia is very common and can have a detrimental effect on navigational and diagnostic outcomes. While the intraprocedural incidence and anatomic location have been previously described, the severity of atelectasis has not. We reviewed chest CT images of patients who developed atelectasis in the VESPA trial (Ventilatory Strategy to Prevent Atelectasis). By drawing boundaries at the posterior chest wall (A), the anterior aspect of the vertebral body (C), and mid-way between these two lines (B), we delineated at-risk lung zones 1, 2, and 3 (from posterior to anterior). An Atelectasis Severity Score System ("ASSESS") was created, classifying atelectasis as "mild" (zone 1), "moderate" (zones 1-2), and "severe" (zones 1-2-3). A total of 43 patients who developed atelectasis were included in this study. A total of 32 patients were in the control arm, and 11 were in the VESPA arm; 20 patients (47%) had mild atelectasis, 20 (47%) had moderate atelectasis, and 3 (6%) had severe atelectasis. A higher BMI was associated with increased odds (1.5 per 1 unit change; 95% CI, 1.10-2.04) (p = 0.0098), and VESPA was associated with decreased odds (0.05; 95% CI, 0.01-0.47) (p = 0.0080) of developing moderate to severe atelectasis. ASSESS is a simple method used to categorize intra-bronchoscopy atelectasis, which allows for a qualitative description of this phenomenon to be developed. In the VESPA trial, a higher BMI was not only associated with increased incidence but also increased severity of atelectasis, while VESPA had the opposite effect. Preventive strategies should be strongly considered in patients with risk factors for atelectasis who have lesions located in zones 1 and 2, but not in zone 3.

Review of the clinical outcomes of therapeutic bronchoscopy for central airway obstruction.

Central airway obstruction (CAO) is a debilitating condition with a significant impact on patient's quality of life and risk of hospitalization from respiratory failure. The causes of CAO can be both benign and malignant. Benign CAO may be idiopathic or secondary to other disease processes (infection, intubation, tracheostomy, etc.). Malignant central airway obstruction (MCAO) may occur in patients with primary lung malignancy as well as metastasis from other malignancies including renal cell, colon, and breast. In a cohort review, MCAO was found in up to 13% of patients with newly diagnosed lung cancer. The obstruction may occur either due to endoluminal disease, extrinsic compression, or a combination of both. Several bronchoscopic tools are available to manage such obstruction. Practice patterns and tools used to relieve CAO vary between institutions and may depend on physician preference, patient characteristics, emergency nature of the procedure, and nature of the obstruction. To quantify the effect and added value of such interventions, it is crucial to understand the clinical impact these interventions have on patients. The clinical impact of therapeutic bronchoscopy (TB) must then be weighed against the potential complications to justify its value. Early studies of TB for CAO included patients with both malignant and benign etiologies. The study population's heterogeneity makes it difficult to determine how TB affects clinical outcomes, as clinical outcomes are disease specific. The impact of TB for a MCAO may be different when compared to a benign CAO. Similarly, the clinical outcome of treating an idiopathic benign CAO may be different than that of a post tracheostomy airway obstruction. In this article, we will focus on the clinical outcomes of TB in MCAO. TB has been shown to have a clear impact on weaning from mechanical ventilation, dyspnea, health-related quality of life, survival and quality adjusted survival. The potential impact of TB on these outcomes should be weighed against the potential risk of complications. Understanding the factors associated with improved clinical outcomes will help physicians decide when and if TB is helpful. Future studies should focus on creating a decision analysis tool to further define decision thresholds.

An 80-Year-Old Woman With Dyspnea and a Lung Mass.

CASE PRESENTATION: An 84-year-old woman presented to the interventional pulmonary clinic for evaluation of a right middle lobe lung mass. Her medical history was notable for atrial fibrillation on rivaroxaban and recurrent bilateral breast cancer that had required multiple lumpectomies, radiation, and chemotherapy. She is a former smoker of five-pack years. She underwent a right and left heart catheterization at an outside facility 2 months prior to her presentation for evaluation of dyspnea that showed minimal coronary artery disease but elevated pulmonary artery pressures of 55/24 mm Hg. The procedure itself was complicated by hemoptysis that required hospital admission for observation. She underwent a chest radiography during her hospitalization (Fig 1) There was no recent imaging for comparison. She was seen by a pulmonologist as an outpatient and underwent bronchoscopy with BAL and bronchial brushing for concerns of malignancy. The results were not diagnostic. She was then referred to the interventional pulmonary service for further evaluation.

Ventilatory Strategy to Prevent Atelectasis During Bronchoscopy Under General Anesthesia: A Multicenter Randomized Controlled Trial (Ventilatory Strategy to Prevent Atelectasis -VESPA- Trial).

BACKGROUND: Atelectasis negatively influences peripheral bronchoscopy, increasing CT scan-body divergence, obscuring targets, and creating false-positive radial-probe endobronchial ultrasound (RP-EBUS) images. RESEARCH QUESTION: Can a ventilatory strategy reduce the incidence of atelectasis during bronchoscopy under general anesthesia? STUDY DESIGN AND METHODS: Randomized controlled study (1:1) in which patients undergoing bronchoscopy were randomized to receive standard ventilation (laryngeal mask airway, 100% Fio2, zero positive end-expiratory pressure [PEEP]) vs a ventilatory strategy to prevent atelectasis (VESPA) with endotracheal intubation followed by a recruitment maneuver, Fio2 titration (< 100%), and PEEP of 8 to 10 cm H2O. All patients underwent chest CT imaging and a survey for atelectasis with RP-EBUS bilaterally on bronchial segments 6, 9, and 10 after artificial airway insertion (time 1) and 20 to 30 min later (time 2). Chest CT scans were reviewed by a blinded chest radiologist. RP-EBUS images were assessed by three independent, blinded readers. The primary end point was the proportion of patients with any atelectasis (either unilateral or bilateral) at time 2 according to chest CT scan findings. RESULTS: Seventy-six patients were analyzed, 38 in each group. The proportion of patients with any atelectasis according to chest CT scan at time 2 was 84.2% (95% CI, 72.6%-95.8%) in the control group and 28.9% (95% CI, 15.4%-45.9%) in the VESPA group (P < .0001). The proportion of patients with bilateral atelectasis at time 2 was 71.1% (95% CI, 56.6%-85.5%) in the control group and 7.9% (95% CI, 1.7%-21.4%) in the VESPA group (P < .0001). At time 2, 3.84 ± 1.67 (mean ± SD) bronchial segments in the control group vs 1.21 ± 1.63 in the VESPA group were deemed atelectatic (P < .0001). No differences were found in the rate of complications. INTERPRETATION: VESPA significantly reduced the incidence of atelectasis, was well tolerated, and showed a sustained effect over time despite bronchoscopic nodal staging maneuvers. VESPA should be considered for bronchoscopy when atelectasis is to be avoided. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT04311723; URL: www. CLINICALTRIALS: gov.

Predicting Lymph Node Metastasis in Non-small Cell Lung Cancer: Prospective External and Temporal Validation of the HAL and HOMER Models.

BACKGROUND: Two models, the Help with the Assessment of Adenopathy in Lung cancer (HAL) and Help with Oncologic Mediastinal Evaluation for Radiation (HOMER), were recently developed to estimate the probability of nodal disease in patients with non-small cell lung cancer (NSCLC) as determined by endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA). The objective of this study was to prospectively externally validate both models at multiple centers. RESEARCH QUESTION: Are the HAL and HOMER models valid across multiple centers? STUDY DESIGN AND METHODS: This multicenter prospective observational cohort study enrolled consecutive patients with PET-CT clinical-radiographic stages T1-3, N0-3, M0 NSCLC undergoing EBUS-TBNA staging. HOMER was used to predict the probability of N0 vs N1 vs N2 or N3 (N2|3) disease, and HAL was used to predict the probability of N2|3 (vs N0 or N1) disease. Model discrimination was assessed using the area under the receiver operating characteristics curve (ROC-AUC), and calibration was assessed using the Brier score, calibration plots, and the Hosmer-Lemeshow test. RESULTS: Thirteen centers enrolled 1,799 patients. HAL and HOMER demonstrated good discrimination: HAL ROC-AUC = 0.873 (95%CI, 0.856-0.891) and HOMER ROC-AUC = 0.837 (95%CI, 0.814-0.859) for predicting N1 disease or higher (N1|2|3) and 0.876 (95%CI, 0.855-0.897) for predicting N2|3 disease. Brier scores were 0.117 and 0.349, respectively. Calibration plots demonstrated good calibration for both models. For HAL, the difference between forecast and observed probability of N2|3 disease was +0.012; for HOMER, the difference for N1|2|3 was -0.018 and for N2|3 was +0.002. The Hosmer-Lemeshow test was significant for both models (P = .034 and .002), indicating a small but statistically significant calibration error. INTERPRETATION: HAL and HOMER demonstrated good discrimination and calibration in multiple centers. Although calibration error was present, the magnitude of the error is small, such that the models are informative.

Incidence and Location of Atelectasis Developed During Bronchoscopy Under General Anesthesia: The I-LOCATE Trial.

BACKGROUND: Despite the many advances in peripheral bronchoscopy, its diagnostic yield remains suboptimal. With the use of cone-beam CT imaging we have found atelectasis mimicking lung tumors or obscuring them when using radial-probe endobronchial ultrasound (RP-EBUS), but its incidence remains unknown. RESEARCH QUESTION: What are the incidence, anatomic location, and risk factors for developing atelectasis during bronchoscopy under general anesthesia? STUDY DESIGN AND METHODS: We performed a prospective observational study in which patients undergoing peripheral bronchoscopy under general anesthesia were subject to an atelectasis survey carried out by RP-EBUS under fluoroscopic guidance. The following dependent segments were evaluated: right bronchus 2 (RB2), RB6, RB9, and RB10; and left bronchus 2 (LB2), LB6, LB9, and LB10. Images were categorized either as aerated lung ("snowstorm" pattern) or as having a nonaerated/atelectatic pattern. Categorization was performed by three independent readers. RESULTS: Fifty-seven patients were enrolled. The overall intraclass correlation agreement among readers was 0.82 (95% CI, 0.71-0.89). Median time from anesthesia induction to atelectasis survey was 33 min (range, 3-94 min). Fifty-one patients (89%; 95% CI, 78%-96%) had atelectasis in at least one of the eight evaluated segments, 45 patients (79%) had atelectasis in at least three, 41 patients (72%) had atelectasis in at least four, 33 patients (58%) had atelectasis in at least five, and 18 patients (32%) had atelectasis in at least six segments. Right and left B6, B9, and B10 segments showed atelectasis in > 50% of patients. BMI and time to atelectasis survey were associated with increased odds of having more atelectatic segments (BMI: OR, 1.13 per unit change; 95% CI, 1.034-1.235; P = .007; time to survey: OR, 1.064 per minute; 95% CI, 1.025-1.105; P = .001). INTERPRETATION: The incidence of atelectasis developing during bronchoscopy under general anesthesia in dependent lung zones is high, and the number of atelectatic segments is greater with higher BMI and with longer time under anesthesia. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT03523689; URL: www.clinicaltrials.gov.

Complications following symptom-limited thoracentesis using suction.

BACKGROUND: Thoracentesis using suction is perceived to have increased risk of complications, including pneumothorax and re-expansion pulmonary oedema (REPO). Current guidelines recommend limiting drainage to 1.5 L to avoid REPO. Our purpose was to examine the incidence of complications with symptom-limited drainage of pleural fluid using suction and identify risk factors for REPO. METHODS: A retrospective cohort study of all adult patients who underwent symptom-limited thoracentesis using suction at our institution between January 1, 2004 and August 31, 2018 was performed, and a total of 10 344 thoracenteses were included. RESULTS: Pleural fluid ≥1.5 L was removed in 19% of the procedures. Thoracentesis was stopped due to chest discomfort (39%), complete drainage of fluid (37%) and persistent cough (13%). Pneumothorax based on chest radiography was detected in 3.98%, but only 0.28% required intervention. The incidence of REPO was 0.08%. The incidence of REPO increased with Eastern Cooperative Oncology Group performance status (ECOG PS) ≥3 compounded with ≥1.5 L (0.04-0.54%; 95% CI 0.13-2.06 L). Thoracentesis in those with ipsilateral mediastinal shift did not increase complications, but less fluid was removed (p<0.01). CONCLUSIONS: Symptom-limited thoracentesis using suction is safe even with large volumes. Pneumothorax requiring intervention and REPO are both rare. There were no increased procedural complications in those with ipsilateral mediastinal shift. REPO increased with poor ECOG PS and drainage ≥1.5 L. Symptom-limited drainage using suction without pleural manometry is safe.

A Prediction Model to Help with Oncologic Mediastinal Evaluation for Radiation: HOMER.

Rationale: When stereotactic ablative radiotherapy is an option for patients with non-small cell lung cancer (NSCLC), distinguishing between N0, N1, and N2 or N3 (N2|3) disease is important.Objectives: To develop a prediction model for estimating the probability of N0, N1, and N2|3 disease.Methods: Consecutive patients with clinical-radiographic stage T1 to T3, N0 to N3, and M0 NSCLC who underwent endobronchial ultrasound-guided staging from a single center were included. Multivariate ordinal logistic regression analysis was used to predict the presence of N0, N1, or N2|3 disease. Temporal validation used consecutive patients from 3 years later at the same center. External validation used three other hospitals.Measurements and Main Results: In the model development cohort (n = 633), younger age, central location, adenocarcinoma, and higher positron emission tomography-computed tomography nodal stage were associated with a higher probability of having advanced nodal disease. Areas under the receiver operating characteristic curve (AUCs) were 0.84 and 0.86 for predicting N1 or higher (vs. N0) disease and N2|3 (vs. N0 or N1) disease, respectively. Model fit was acceptable (Hosmer-Lemeshow, P = 0.960; Brier score, 0.36). In the temporal validation cohort (n = 473), AUCs were 0.86 and 0.88. Model fit was acceptable (Hosmer-Lemeshow, P = 0.172; Brier score, 0.30). In the external validation cohort (n = 722), AUCs were 0.86 and 0.88 but required calibration (Hosmer-Lemeshow, P < 0.001; Brier score, 0.38). Calibration using the general calibration method resulted in acceptable model fit (Hosmer-Lemeshow, P = 0.094; Brier score, 0.34).Conclusions: This prediction model can estimate the probability of N0, N1, and N2|3 disease in patients with NSCLC. The model has the potential to facilitate decision-making in patients with NSCLC when stereotactic ablative radiotherapy is an option.

Chronic Cough in a 70-Year-Old Woman.

CASE PRESENTATION: A 70-year-old lifelong nonsmoking woman with a past medical history of hypertension was referred to the respiratory clinic for evaluation of chronic cough. She presented with a 5-month history of dry cough, night sweats, fatigue, and a 4.5-kg weight loss. Her cough tended to be worse while lying flat. She denied having shortness of breath, chest pain, wheeze, or hemoptysis. She was taking amlodipine for her blood pressure as well as omeprazole for indigestion. She denied having any reflux symptoms or heartburn. She worked as a receptionist for an optician. She did not have any pets at home and had no family history of asthma or allergic conditions. She had not been abroad recently.

Centrally located lung cancer and risk of occult nodal disease: an objective evaluation of multiple definitions of tumour centrality with dedicated imaging software.

INTRODUCTION: Current guidelines recommend invasive mediastinal staging in patients with centrally located radiographic stage T1N0M0 nonsmall cell lung cancer (NSCLC). The lack of a specific definition of a central tumour has resulted in discrepancies among guidelines and heterogeneity in practice patterns. METHODS: Our objective was to study specific definitions of tumour centrality and their association with occult nodal disease. Pre-operative chest computed tomography scans from patients with clinical (c) T1N0M0 NSCLC were processed with a dedicated software system that divides the lungs in thirds following vertical and concentric lines. This software accurately assigns tumours to a specific third based both on the location of the centre of the tumour and its most medial aspect, creating eight possible definitions of central tumours. RESULTS: 607 patients were included in our study. Surgery was performed for 596 tumours (98%). The overall pathological (p) N disease was: 504 (83%) N0, 56 (9%) N1, 47 (8%) N2 and no N3. The prevalence of N2 disease remained relatively low regardless of tumour location. Central tumours were associated with upstaging from cN0 to any N (pN1/pN2). Two definitions were associated with upstaging to any N: concentric lines, inner one-third, centre of the tumour (OR 3.91, 95% CI 1.85-8.26; p<0.001) and concentric lines, inner two-thirds, most medial aspect of the tumour (OR 1.91, 95% CI 1.23-2.97; p=0.004). CONCLUSIONS: We objectively identified two specific definitions of central tumours. While the rate of occult mediastinal disease was relatively low regardless of tumour location, central tumours were associated with upstaging from cN0 to any N.