Carla Lamb

Airway epithelial gene expression in the diagnostic evaluation of smokers with suspect lung cancer

Lung cancer is the leading cause of death from cancer in the US and the world. The high mortality rate (80–85% within 5 years) results, in part, from a lack of effective tools to diagnose the disease at an early stage. Given that cigarette smoke creates a field of injury throughout the airway, we sought to determine if gene expression in histologically normal large-airway epithelial cells obtained at bronchoscopy from smokers with suspicion of lung cancer could be used as a lung cancer biomarker. Using a training set (n = 77) and gene-expression profiles from Affymetrix HG-U133A microarrays, we identified an 80-gene biomarker that distinguishes smokers with and without lung cancer. We tested the biomarker on an independent test set (n = 52), with an accuracy of 83% (80% sensitive, 84% specific), and on an additional validation set independently obtained from five medical centers (n = 35). Our biomarker had ∼90% sensitivity for stage 1 cancer across all subjects. Combining cytopathology of lower airway cells obtained at bronchoscopy with the biomarker yielded 95% sensitivity and a 95% negative predictive value. These findings indicate that gene expression in cytologically normal large-airway epithelial cells can serve as a lung cancer biomarker, potentially owing to a cancer-specific airway-wide response to cigarette smoke.

Post tracheostomy and post intubation tracheal stenosis: Report of 31 cases and review of the literature

BackgroundSevere post tracheostomy (PT) and post intubation (PI) tracheal stenosis is an uncommon clinical entity that often requires interventional bronchoscopy before surgery is considered. We present our experience with severe PI and PT stenosis in regards to patient characteristics, possible risk factors, and therapy.MethodsWe conducted a retrospective chart review of 31 patients with PI and PT stenosis treated at Lahey Clinic over the past 8 years. Demographic characteristics, body mass index, co-morbidities, stenosis type and site, procedures performed and local treatments applied were recorded.ResultsThe most common profile of a patient with tracheal stenosis in our series was a female (75%), obese (66%) patient with a history of diabetes mellitus (35.4%), hypertension (51.6%), and cardiovascular disease (45.1%), who was a current smoker (38.7%). Eleven patients (PI group) had only oro-tracheal intubation (5.2 days of intubation) and developed web-like stenosis at the cuff site. Twenty patients (PT group) had undergone tracheostomy (54.5 days of intubation) and in 17 (85%) of them the stenosis appeared around the tracheal stoma. There was an average of 2.4 procedures performed per patient. Rigid bronchoscopy with Nd:YAG laser and dilatation (mechanical or balloon) were the preferred methods used. Only 1(3.2%) patient was sent to surgery for re-stenosis after multiple interventional bronchoscopy treatments.ConclusionWe have identified putative risk factors for the development of PI and PT stenosis. Differences in lesions characteristics and stenosis site were noted in our two patient groups. All patients underwent interventional bronchoscopy procedures as the first-line, and frequently the only treatment approach.

American College of Chest Physicians Consensus Statement on the Use of Topical Anesthesia, Analgesia, and Sedation During Flexible Bronchoscopy in Adult Patients

BACKGROUND Optimal performance of bronchoscopy requires patients comfort, physicians ease of execution, and minimal risk. There is currently a wide variation in the use of topical anesthesia, analgesia, and sedation during bronchoscopy. METHODS A panel of experts was convened by the American College of Chest Physicians Interventional/Chest Diagnostic Network. A literature search was conducted on MEDLINE from 1969 to 2009, and consensus was reached by the panel members after a comprehensive review of the data. Randomized controlled trials and prospective studies were given highest priority in building the consensus. RESULTS In the absence of contraindications, topical anesthesia, analgesia, and sedation are suggested in all patients undergoing bronchoscopy because of enhanced patient tolerance and satisfaction. Robust data suggest that anticholinergic agents, when administered prebronchoscopy, do not produce a clinically meaningful effect, and their use is discouraged. Lidocaine is the preferred topical anesthetic for bronchoscopy, given its short half life and wide margin of safety. The use of a combination of benzodiazepines and opiates is suggested because of their synergistic effects on patient tolerance during the procedure and the added antitussive properties of opioids. Propofol is an effective agent for sedation in bronchoscopy and can achieve similar sedation, amnesia, and patient tolerance when compared with the combined administration of benzodiazepines and opiates. CONCLUSIONS We suggest that all physicians performing bronchoscopy consider using topical anesthesia, analgesic and sedative agents, when feasible. The existing body of literature supports the safety and effectiveness of this approach when the proper agents are used in an appropriately selected patient population.

Rapid Pleurodesis for Malignant Pleural Effusions: A Pilot Study

BACKGROUND Malignant pleural effusions (MPEs) affect > 150,000 people each year in the United States. Current palliative options include pleurodesis and placement of an indwelling catheter, each with its own associated benefits. This study was conducted to determine the safety, efficacy, and feasibility of a rapid pleurodesis protocol by combining medical thoracoscopy with talc pleurodesis and simultaneous placement of a tunneled pleural catheter (TPC) in patients with symptomatic MPE. METHODS Patients with recurrent, symptomatic MPEs underwent medical thoracoscopy with placement of a TPC and talc poudrage. The TPC was drained per protocol until the output was < 150 mL/d on two consecutive drainage attempts and then removed. Patients were followed for up to 6 months. RESULTS Between October 2005 and September 2009, 30 patients underwent the procedure. The median duration of hospitalization following the procedure was 1.79 days. All patients showed an improvement in dyspnea and quality of life. Pleurodesis was successful in 92% of patients, and the TPC was removed at a median of 7.54 days. Complications included fever (two patients), the need for TPC replacement (one patient), and empyema (one patient). CONCLUSION Rapid pleurodesis can be achieved safely by combining medical thoracoscopy and talc poudrage with simultaneous TPC placement. Both hospital length of stay and duration of TPC use can be reduced significantly as compared with historical controls of either procedure alone. Future randomized trials are needed to confirm these results.

Clinical Outcomes of Indwelling Pleural Catheter-Related Pleural Infections: An International Multicenter Study

BACKGROUND Indwelling pleural catheters (IPCs) offer effective control of malignant pleural effusions (MPEs). IPC-related infection is uncommon but remains a major concern. Individual IPC centers see few infections, and previous reports lack sufficient numbers and detail. This study combined the experience of 11 centers from North America, Europe, and Australia to describe the incidence, microbiology, management, and clinical outcomes of IPC-related pleural infection. METHODS This was a multicenter retrospective review of 1,021 patients with IPCs. All had confirmed MPE. RESULTS Only 50 patients (4.9%) developed an IPC-related pleural infection; most (94%) were successfully controlled with antibiotics (62% IV). One death (2%) directly resulted from the infection, whereas two patients (4%) had ongoing infectious symptoms when they died of cancer progression. Staphylococcus aureus was the causative organism in 48% of cases. Infections from gram-negative organisms were associated with an increased need for continuous antibiotics or death (60% vs 15% in gram-positive and 25% mixed infections, P = .02). The infections in the majority (54%) of cases were managed successfully without removing the IPC. Postinfection pleurodesis developed in 31 patients (62%), especially those infected with staphylococci (79% vs 45% with nonstaphylococcal infections, P = .04). CONCLUSIONS The incidence of IPC-related pleural infection was low. The overall mortality risk from pleural infection in patients treated with IPC was only 0.29%. Antibiotics should cover S aureus and gram-negative organisms until microbiology is confirmed. Postinfection pleurodesis is common and often allows removal of IPC. Heterogeneity in management is common, and future studies to define the optimal treatment strategies are needed.

Technical aspects of endobronchial ultrasound-guided transbronchial needle aspiration CHEST guideline and expert panel report

BACKGROUND Endobronchial ultrasound (EBUS) was introduced in the last decade, enabling real-time guidance of transbronchial needle aspiration (TBNA) of mediastinal and hilar structures and parabronchial lung masses. The many publications produced about EBUS-TBNA have led to a better understanding of the performance characteristics of this procedure. The goal of this document was to examine the current literature on the technical aspects of EBUS-TBNA as they relate to patient, technology, and proceduralist factors to provide evidence-based and expert guidance to clinicians. METHODS Rigorous methodology has been applied to provide a trustworthy evidence-based guideline and expert panel report. A group of approved panelists developed key clinical questions by using the PICO (population, intervention, comparator, and outcome) format that addressed specific topics on the technical aspects of EBUS-TBNA. MEDLINE (via PubMed) and the Cochrane Library were systematically searched for relevant literature, which was supplemented by manual searches. References were screened for inclusion, and well-recognized document evaluation tools were used to assess the quality of included studies, to extract meaningful data, and to grade the level of evidence to support each recommendation or suggestion. RESULTS Our systematic review and critical analysis of the literature on 15 PICO questions related to the technical aspects of EBUS-TBNA resulted in 12 statements: 7 evidence-based graded recommendations and 5 ungraded consensus-based statements. Three questions did not have sufficient evidence to generate a statement. CONCLUSIONS Evidence on the technical aspects of EBUS-TBNA varies in strength but is satisfactory in certain areas to guide clinicians on the best conditions to perform EBUS-guided tissue sampling. Additional research is needed to enhance our knowledge regarding the optimal performance of this effective procedure.

An official American Thoracic Society/American College of Chest Physicians policy statement: implementation of low-dose computed tomography lung cancer screening programs in clinical practice.

RATIONALE Annual low-radiation-dose computed tomography (LDCT) screening for lung cancer has been shown to reduce lung cancer mortality among high-risk individuals and is now recommended by multiple organizations. However, LDCT screening is complex, and implementation requires careful planning to ensure benefits outweigh harms. Little guidance has been provided for sites wishing to develop and implement lung cancer screening programs. OBJECTIVES To promote successful implementation of comprehensive LDCT screening programs that are safe, effective, and sustainable. METHODS The American Thoracic Society (ATS) and American College of Chest Physicians (ACCP) convened a committee with expertise in lung cancer screening, pulmonary nodule evaluation, and implementation science. The committee reviewed the evidence from systematic reviews, clinical practice guidelines, surveys, and the experience of early-adopting LDCT screening programs and summarized potential strategies to implement LDCT screening programs successfully. MEASUREMENTS AND MAIN RESULTS We address steps that sites should consider during the main three phases of developing an LDCT screening program: planning, implementation, and maintenance. We present multiple strategies to implement the nine core elements of comprehensive lung cancer screening programs enumerated in a recent ACCP/ATS statement, which will allow sites to select the strategy that best fits with their local context and workflow patterns. Although we do not comment on cost-effectiveness of LDCT screening, we outline the necessary costs associated with starting and sustaining a high-quality LDCT screening program. CONCLUSIONS Following the strategies delineated in this policy statement may help sites to develop comprehensive LDCT screening programs that are safe and effective.

Endobronchial Ultrasound Skills and Tasks Assessment Tool Assessing the Validity Evidence for a Test of Endobronchial Ultrasound-guided Transbronchial Needle Aspiration Operator Skill

RATIONALE Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is becoming standard of care for the sampling of mediastinal adenopathy. The need for a safe, effective, accurate procedure makes EBUS-TBNA ideal for mastery training and testing. OBJECTIVES The Endobronchial Ultrasound Skills and Tasks Assessment Tool (EBUS-STAT) was created as an objective competency-oriented assessment tool of EBUS-TBNA skills and knowledge. This study demonstrates the reliability and validity evidence of this tool. METHODS The EBUS-STAT objectively scores the EBUS-TBNA operators skills, including atraumatic airway introduction and navigation, ultrasound image acquisition and optimization, identification of mediastinal nodal and vascular structures, EBUS-TBNA sampling, and recognition of EBUS/computed tomography images of mediastinal structures. It can be administered at the bedside or using combination of low- and high-fidelity simulation platforms. Two independent testers administered the EBUS-STAT to 24 operators at three levels of EBUS-TBNA experience (8 beginners, 8 intermediates, and 8 experienced) at three institutions; operators were also asked to self-assess their skills. Scores were analyzed for intertester reliability, correlation with prior EBUS-TBNA experience, and association with self-assessments. MEASUREMENTS AND MAIN RESULTS Intertester reliability between testers was very high (r = 0.9991, P < 0.00005). Mean EBUS-STAT scores for beginner, intermediate, and experienced groups, respectively, were 31.1, 74.9, and 93.6 out of 100 (F(2,21) = 118.6, P < 0.0001). Groups were nonoverlapping: post hoc tests showed each group differed significantly from the others (P < 0.001). Self-assessments corresponded closely to actual EBUS-STAT scores (r(2) = 0.81, P < 0.001). CONCLUSIONS The EBUS-STAT can be used to reliably and objectively score and classify EBUS-TBNA operators from novice to expert. Its use to assess and document the acquisition of knowledge and skill is a step toward the goal of mastery training in EBUS-TBNA.

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.

Initial experience with a free, high-volume, low-dose CT lung cancer screening program.

The National Lung Screening Trial demonstrated a significant mortality benefit for patients at high risk for lung cancer undergoing serial low-dose CT. Currently, the National Comprehensive Cancer Network and several United States-based professional associations recommend CT Lung screening for high-risk patients. In the absence of established reimbursement, the authors modeled and implemented a free low-dose CT lung cancer screening program to provide equitable access to all eligible patients. Elements of the program reported in this article include a decentralized referral network, centralized program coordination, structured reporting, and a patient data management system. The experience and initial results observed in this clinical setting closely match the performance metrics of the National Lung Screening Trial with regard to cancer detection and incidental findings rates. To eliminate health care disparities a vigorous lobbying effort will be needed to expedite reimbursement and make CT lung screening equally available to all patients at high-risk.