Kevin L. Kovitz

A Randomized Study of Endobronchial Valves for Advanced Emphysema

BACKGROUND Endobronchial valves that allow air to escape from a pulmonary lobe but not enter it can induce a reduction in lobar volume that may thereby improve lung function and exercise tolerance in patients with pulmonary hyperinflation related to advanced emphysema. METHODS We compared the safety and efficacy of endobronchial-valve therapy in patients with heterogeneous emphysema versus standard medical care. Efficacy end points were percent changes in the forced expiratory volume in 1 second (FEV1) and the 6-minute walk test on intention-to-treat analysis. We assessed safety on the basis of the rate of a composite of six major complications. RESULTS Of 321 enrolled patients, 220 were randomly assigned to receive endobronchial valves (EBV group) and 101 to receive standard medical care (control group). At 6 months, there was an increase of 4.3% in the FEV1 in the EBV group (an increase of 1.0 percentage point in the percent of the predicted value), as compared with a decrease of 2.5% in the control group (a decrease of 0.9 percentage point in the percent of the predicted value). Thus, there was a mean between-group difference of 6.8% in the FEV1 (P=0.005). Roughly similar between-group differences were observed for the 6-minute walk test. At 12 months, the rate of the complications composite was 10.3% in the EBV group versus 4.6% in the control group (P=0.17). At 90 days, in the EBV group, as compared with the control group, there were increased rates of exacerbation of chronic obstructive pulmonary disease (COPD) requiring hospitalization (7.9% vs. 1.1%, P=0.03) and hemoptysis (6.1% vs. 0%, P=0.01). The rate of pneumonia in the target lobe in the EBV group was 4.2% at 12 months. Greater radiographic evidence of emphysema heterogeneity and fissure completeness was associated with an enhanced response to treatment. CONCLUSIONS Endobronchial-valve treatment for advanced heterogeneous emphysema induced modest improvements in lung function, exercise tolerance, and symptoms at the cost of more frequent exacerbations of COPD, pneumonia, and hemoptysis after implantation. (Funded by Pulmonx; ClinicalTrials.gov number, NCT00129584.)

Design of the Endobronchial Valve for Emphysema Palliation Trial (VENT): a non-surgical method of lung volume reduction

BackgroundLung volume reduction surgery is effective at improving lung function, quality of life, and mortality in carefully selected individuals with advanced emphysema. Recently, less invasive bronchoscopic approaches have been designed to utilize these principles while avoiding the associated perioperative risks. The Endobronchial Valve for Emphysema PalliatioN Trial (VENT) posits that occlusion of a single pulmonary lobe through bronchoscopically placed Zephyr® endobronchial valves will effect significant improvements in lung function and exercise tolerance with an acceptable risk profile in advanced emphysema.MethodsThe trial design posted on Clinical trials.gov, on August 10, 2005 proposed an enrollment of 270 subjects. Inclusion criteria included: diagnosis of emphysema with forced expiratory volume in one second (FEV1) < 45% of predicted, hyperinflation (total lung capacity measured by body plethysmography > 100%; residual volume > 150% predicted), and heterogeneous emphysema defined using a quantitative chest computed tomography algorithm. Following standardized pulmonary rehabilitation, patients were randomized 2:1 to receive unilateral lobar placement of endobronchial valves plus optimal medical management or optimal medical management alone. The co-primary endpoint was the mean percent change in FEV1 and six minute walk distance at 180 days. Secondary end-points included mean percent change in St. Georges Respiratory Questionnaire score and the mean absolute changes in the maximal work load measured by cycle ergometry, dyspnea (mMRC) score, and total oxygen use per day. Per patient response rates in clinically significant improvement/maintenance of FEV1 and six minute walk distance and technical success rates of valve placement were recorded. Apriori response predictors based on quantitative CT and lung physiology were defined.ConclusionIf endobronchial valves improve FEV1 and health status with an acceptable safety profile in advanced emphysema, they would offer a novel intervention for this progressive and debilitating disease.Trial RegistrationClinicalTrials.gov: NCT00129584

Diagnostic Yield of Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration: Results of the AQuIRE Bronchoscopy Registry

BACKGROUND New transbronchial needle aspiration (TBNA) technologies have been developed, but their clinical effectiveness and determinants of diagnostic yield have not been quantified. Prospective data are needed to determine risk-adjusted diagnostic yield. METHODS We prospectively enrolled patients undergoing TBNA of mediastinal lymph nodes in the American College of Chest Physicians Quality Improvement Registry, Evaluation, and Education (AQuIRE) multicenter database and recorded clinical, procedural, and provider information. All clinical decisions, including type of TBNA used (conventional vs endobronchial ultrasound-guided), were made by the attending bronchoscopist. The primary outcome was obtaining a specific diagnosis. RESULTS We enrolled 891 patients at six hospitals. Most procedures (95%) were performed with ultrasound guidance. A specific diagnosis was made in 447 cases. Unadjusted diagnostic yields were 37% to 54% for different hospitals, with significant between-hospital heterogeneity (P = .0001). Diagnostic yield was associated with annual hospital TBNA volume (OR, 1.003; 95% CI, 1.000-1.006; P = .037), smoking (OR, 1.55; 95% CI, 1.02-2.34; P = .042), biopsy of more than two sites (OR, 0.57; 95% CI, 0.38-0.85; P = .015), lymph node size (reference > 1-2 cm, ≤ 1 cm: OR, 0.51; 95% CI, 0.34-0.77; P = .003; > 2-3 cm: OR, 2.49; 95% CI, 1.61-3.85; P < .001; and > 3 cm: OR, 3.61; 95% CI, 2.17-6.00; P < .001), and positive PET scan (OR, 3.12; 95% CI, 1.39-7.01; P = .018). Biopsy was performed on more and smaller nodes at high-volume hospitals (P < .0001). CONCLUSIONS To our knowledge, this is the first bronchoscopy study of risk-adjusted diagnostic yields on a hospital-level basis. High-volume hospitals were associated with high diagnostic yields. This study also demonstrates the value of procedural registries as a quality improvement tool. A larger number and variety of participating hospitals is needed to verify these results and to further investigate other determinants of diagnostic yield.

Diagnostic Yield and Complications of Bronchoscopy for Peripheral Lung Lesions. Results of the AQuIRE Registry.

RATIONALE Advanced bronchoscopy techniques such as electromagnetic navigation (EMN) have been studied in clinical trials, but there are no randomized studies comparing EMN with standard bronchoscopy. OBJECTIVES To measure and identify the determinants of diagnostic yield for bronchoscopy in patients with peripheral lung lesions. Secondary outcomes included diagnostic yield of different sampling techniques, complications, and practice pattern variations. METHODS We used the AQuIRE (ACCP Quality Improvement Registry, Evaluation, and Education) registry to conduct a multicenter study of consecutive patients who underwent transbronchial biopsy (TBBx) for evaluation of peripheral lesions. MEASUREMENTS AND MAIN RESULTS Fifteen centers with 22 physicians enrolled 581 patients. Of the 581 patients, 312 (53.7%) had a diagnostic bronchoscopy. Unadjusted for other factors, the diagnostic yield was 63.7% when no radial endobronchial ultrasound (r-EBUS) and no EMN were used, 57.0% with r-EBUS alone, 38.5% with EMN alone, and 47.1% with EMN combined with r-EBUS. In multivariate analysis, peripheral transbronchial needle aspiration (TBNA), larger lesion size, nonupper lobe location, and tobacco use were associated with increased diagnostic yield, whereas EMN was associated with lower diagnostic yield. Peripheral TBNA was used in 16.4% of cases. TBNA was diagnostic, whereas TBBx was nondiagnostic in 9.5% of cases in which both were performed. Complications occurred in 13 (2.2%) patients, and pneumothorax occurred in 10 (1.7%) patients. There were significant differences between centers and physicians in terms of case selection, sampling methods, and anesthesia. Medical center diagnostic yields ranged from 33 to 73% (P = 0.16). CONCLUSIONS Peripheral TBNA improved diagnostic yield for peripheral lesions but was underused. The diagnostic yields of EMN and r-EBUS were lower than expected, even after adjustment.

An Approach to Interventional Pulmonary Fellowship Training

Interventional pulmonology continues to be a specialty that is experiencing an evolution of new technologies, with an emphasis on multidisciplinary care. The diversity and application of these procedures in patients with more complex conditions is leading to the need for more specific recommendations in training within this area. As patient safety and outcomes-based measures of clinical practice and procedures are in the forefront, the need for standardization in procedural training in high-volume centers of excellence beyond pulmonary and critical care fellowships must be considered. Other procedure-based specialties have developed such training programs, with structured curricula to enhance patient safety and outcomes, develop validated metrics for competency assessment of trainees, improve trainee education, and further advance the field by fostering research.

Therapeutic Bronchoscopy for Malignant Central Airway Obstruction: Success Rates and Impact on Dyspnea and Quality of Life

BACKGROUND There is significant variation between physicians in terms of how they perform therapeutic bronchoscopy, but there are few data on whether these differences impact effectiveness. METHODS This was a multicenter registry study of patients undergoing therapeutic bronchoscopy for malignant central airway obstruction. The primary outcome was technical success, defined as reopening the airway lumen to > 50% of normal. Secondary outcomes were dyspnea as measured by the Borg score and health-related quality of life (HRQOL) as measured by the SF-6D. RESULTS Fifteen centers performed 1,115 procedures on 947 patients. Technical success was achieved in 93% of procedures. Center success rates ranged from 90% to 98% (P = .02). Endobronchial obstruction and stent placement were associated with success, whereas American Society of Anesthesiology (ASA) score > 3, renal failure, primary lung cancer, left mainstem disease, and tracheoesophageal fistula were associated with failure. Clinically significant improvements in dyspnea occurred in 90 of 187 patients measured (48%). Greater baseline dyspnea was associated with greater improvements in dyspnea, whereas smoking, having multiple cancers, and lobar obstruction were associated with smaller improvements. Clinically significant improvements in HRQOL occurred in 76 of 183 patients measured (42%). Greater baseline dyspnea was associated with greater improvements in HRQOL, and lobar obstruction was associated with smaller improvements. CONCLUSIONS Technical success rates were high overall, with the highest success rates associated with stent placement and endobronchial obstruction. Therapeutic bronchoscopy should not be withheld from patients based solely on an assessment of risk, since patients with the most dyspnea and lowest functional status benefitted the most.

Concomitant weekly docetaxel, cisplatin and radiation therapy in locally advanced non-small cell lung cancer: a dose finding study

The optimal dose of weekly docetaxel in combination with cisplatin and concomitant thoracic radiation therapy (XRT) in patients with locally advanced non-small cell lung cancer (NSCLC) is not well defined. The purpose of this study was to define the maximal tolerated dose (MTD) of docetaxel in this combination. Eligible patients had unresectable stage IIIA or IIIB NSCLC without pleural effusion. Treatment consisted of cisplatin 25 mg/m(2) plus docetaxel weekly and concomitant standard XRT for a total of 60 Gy at 200 cGy/fraction/day 5 times weekly for 6 weeks. The starting dose of docetaxel in the first cohort was 15 mg/m(2)/week. This dose was escalated by 5 mg/m(2) per cohort of 3 patients. No intrapatient dose escalation was allowed. The doses of cisplatin and XRT were not escalated. A total of 23 patients were enrolled, and 19 patients were evaluable for analysis. The first cohort (docetaxel 15 mg/m(2)/week) completed treatment without any Grade 3 or 4 toxicities. The second cohort (docetaxel 20 mg/m(2)/week) was expanded to 6 patients because of Grade 3 cough observed in 1 patient. One of 5 patients experienced Grade 3 esophagitis at the docetaxel 25 mg/m(2)/week dose level. Dose limiting toxicity consisting of Grade 3 esophagitis was reached in 4 of 5 patients receiving docetaxel at 30 mg/m(2)/week. This study determined the MTD of weekly docetaxel to be 25 mg/m(2) when combined with cisplatin 25 mg/m(2) and radiation therapy for locally advanced NSCLC. Further evaluation of this regimen in a phase II trial is underway.

Complications following therapeutic bronchoscopy for malignant central airway obstruction: Results of the AQuIRE registry

BACKGROUND There are significant variations in how therapeutic bronchoscopy for malignant airway obstruction is performed. Relatively few studies have compared how these approaches affect the incidence of complications. METHODS We used the American College of Chest Physicians (CHEST) Quality Improvement Registry, Evaluation, and Education (AQuIRE) program registry to conduct a multicenter study of patients undergoing therapeutic bronchoscopy for malignant central airway obstruction. The primary outcome was the incidence of complications. Secondary outcomes were incidence of bleeding, hypoxemia, respiratory failure, adverse events, escalation in level of care, and 30-day mortality. RESULTS Fifteen centers performed 1,115 procedures on 947 patients. There were significant differences among centers in the type of anesthesia (moderate vs deep or general anesthesia, P < .001), use of rigid bronchoscopy (P < .001), type of ventilation (jet vs volume cycled, P < .001), and frequency of stent use (P < .001). The overall complication rate was 3.9%, but significant variation was found among centers (range, 0.9%-11.7%; P = .002). Risk factors for complications were urgent and emergent procedures, American Society of Anesthesiologists (ASA) score > 3, redo therapeutic bronchoscopy, and moderate sedation. The 30-day mortality was 14.8%; mortality varied among centers (range, 7.7%-20.2%, P = .02). Risk factors for 30-day mortality included Zubrod score > 1, ASA score > 3, intrinsic or mixed obstruction, and stent placement. CONCLUSIONS Use of moderate sedation and stents varies significantly among centers. These factors are associated with increased complications and 30-day mortality, respectively.

Endobronchial Valve Placement and Balloon Occlusion for Persistent Air Leak: Procedure Overview and New Current Procedural Terminology Codes for 2013

Unidirectional endobronchial valves, originally studied for potential treatment of emphysema, have emerged as a useful intervention for patients with persistent air leak from the lung. The procedure is accomplished via bronchoscopy in a patient who already has a chest tube in place for management of the air leak. It uses an occluding balloon to determine the specific airway(s) leading to the leak by impact on airflow and subsequent placement of removable valve(s) in one or more segment or subsegments to decrease flow across the leak to allow for healing of the fistula. Specific US Food and Drug Administration-approved criteria for placement and removal of these valves via a Humanitarian Device Exemption are discussed along with reported outcomes. Current Procedural Terminology codes effective for 2013 that are specific to the procedure are reviewed.

Simulation for Skills-based Education in Pulmonary and Critical Care Medicine

The clinical practice of pulmonary and critical care medicine requires procedural competence in many technical domains, including vascular access, airway management, basic and advanced bronchoscopy, pleural procedures, and critical care ultrasonography. Simulation provides opportunities for standardized training and assessment in procedures without placing patients at undue risk. A growing body of literature supports the use and effectiveness of low-fidelity and high-fidelity simulators for procedural training and assessment. In this manuscript by the Skills-based Working Group of the American Thoracic Society Education Committee, we describe the background, available technology, and current evidence related to simulation-based skills training within pulmonary and critical care medicine. We outline working group recommendations for key procedural domains.