Doreen J. Addrizzo-Harris

Physiologic Evaluation of the Patient With Lung Cancer Being Considered for Resectional Surgery: Diagnosis and Management of Lung Cancer, 3rd ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines

BACKGROUND This section of the guidelines is intended to provide an evidence-based approach to the preoperative physiologic assessment of a patient being considered for surgical resection of lung cancer. METHODS The current guidelines and medical literature applicable to this issue were identified by computerized search and were evaluated using standardized methods. Recommendations were framed using the approach described by the Guidelines Oversight Committee. RESULTS The preoperative physiologic assessment should begin with a cardiovascular evaluation and spirometry to measure the FEV1 and the diffusing capacity for carbon monoxide (Dlco). Predicted postoperative (PPO) lung functions should be calculated. If the % PPO FEV1 and % PPO Dlco values are both > 60%, the patient is considered at low risk of anatomic lung resection, and no further tests are indicated. If either the % PPO FEV1 or % PPO Dlco are within 60% and 30% predicted, a low technology exercise test should be performed as a screening test. If performance on the low technology exercise test is satisfactory (stair climbing altitude > 22 m or shuttle walk distance > 400 m), patients are regarded as at low risk of anatomic resection. A cardiopulmonary exercise test is indicated when the PPO FEV1 or PPO Dlco (or both) are < 30% or when the performance of the stair-climbing test or the shuttle walk test is not satisfactory. A peak oxygen consumption (V˙O2 peak) < 10 mL/kg/min or 35% predicted indicates a high risk of mortality and long-term disability for major anatomic resection. Conversely, a V˙O2 peak > 20 mL/kg/min or 75% predicted indicates a low risk. CONCLUSIONS A careful preoperative physiologic assessment is useful for identifying those patients at increased risk with standard lung cancer resection and for enabling an informed decision by the patient about the appropriate therapeutic approach to treating his or her lung cancer. This preoperative risk assessment must be placed in the context that surgery for early-stage lung cancer is the most effective currently available treatment of this disease.

Randomized Trial of Liposomal Amikacin for Inhalation in Nontuberculous Mycobacterial Lung Disease

Rationale: Lengthy, multidrug, toxic, and low‐efficacy regimens limit management of pulmonary nontuberculous mycobacterial disease. Objectives: In this phase II study, we investigated the efficacy and safety of liposomal amikacin for inhalation (LAI) in treatment‐refractory pulmonary nontuberculous mycobacterial (Mycobacterium avium complex [MAC] or Mycobacterium abscessus) disease. Methods: During the double‐blind phase, patients were randomly assigned to LAI (590 mg) or placebo once daily added to their multidrug regimen for 84 days. Both groups could receive open‐label LAI for 84 additional days. The primary endpoint was change from baseline to Day 84 on a semiquantitative mycobacterial growth scale. Other endpoints included sputum conversion, 6‐minute‐walk distance, and adverse events. Measurements and Main Results: The modified intention‐to‐treat population included 89 (LAI = 44; placebo = 45) patients. The average age of the sample was 59 years; 88% were female; 92% were white; and 80 and 59 patients completed study drug dosing during the double‐blind and open‐label phases, respectively. The primary endpoint was not achieved (P = 0.072); however, a greater proportion of the LAI group demonstrated at least one negative sputum culture (14 [32%] of 44 vs. 4 [9%] of 45; P = 0.006) and improvement in 6‐minute‐walk test (+20.6 m vs. −25.0 m; P = 0.017) at Day 84. A treatment effect was seen predominantly in patients without cystic fibrosis with MAC and was sustained 1 year after LAI. Most adverse events were respiratory, and in some patients it led to drug discontinuation. Conclusions: Although the primary endpoint was not reached, LAI added to a multidrug regimen produced improvements in sputum conversion and 6‐minute‐walk distance versus placebo with limited systemic toxicity in patients with refractory MAC lung disease. Further research in this area is needed. Clinical trial registered with www.clinicaltrials.gov (NCT01315236).

Methodology for development of guidelines for lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines.

BACKGROUND The objective was to develop high-quality and comprehensive evidence-based guidelines on the diagnosis and management of lung cancer. METHODS A carefully crafted panel of lung cancer experts, methodologists, and other specialists was assembled and reviewed for relevant conflicts of interest. The American College of Chest Physicians guideline methodology was used. Population, intervention, comparator, outcome (PICO)-based key questions and defined criteria for eligible studies were developed to inform the search strategies, subsequent evidence summaries, and recommendations. Research studies, systematic reviews, and meta-analyses, where they existed, were assessed for quality and summarized to inform the recommendations. RESULTS Each recommendation was developed with supporting evidence and the consensus of the writing committees. Controversial recommendations were identified for further consultation by the entire panel, with anonymous voting to achieve consensus. CONCLUSIONS The final recommendations can be trusted by health-care providers, patients, and other stakeholders since they are based on the current evidence in these areas and were developed with trustworthy processes for guideline development.

Continuing medical education effect on physician knowledge application and psychomotor skills: effectiveness of continuing medical education: American College of Chest Physicians Evidence-Based Educational Guidelines.

BACKGROUND Recommendations for optimizing continuing medical education (CME) effectiveness in improving physician application of knowledge and psychomotor skills are needed to guide the development of processes that effect physician change and improve patient care. METHODS The guideline panel reviewed evidence tables and a comprehensive review of the effectiveness of CME developed by The Johns Hopkins Evidence-based Practice Center for the Agency for Healthcare Research and Quality (AHRQ Evidence Report). The panel considered studies relevant to the effect of CME on physician knowledge application and psychomotor skill development. From the 136 studies identified in the systematic review, 15 articles, 12 addressing physician application of knowledge and 3 addressing psychomotor skills, were identified and reviewed. Recommendations for optimizing CME were developed using the American College of Chest Physicians guideline grading system. RESULTS The preponderance of evidence demonstrated improvement in physician application of knowledge with CME. The quality of evidence did not allow specific recommendations regarding optimal media or educational techniques or the effectiveness of CME in improving psychomotor skills. CONCLUSIONS CME is effective in improving physician application of knowledge. Multiple exposures and longer durations of CME are recommended to optimize educational outcomes.

Multisociety task force recommendations of competencies in Pulmonary and Critical Care Medicine.

RATIONALE Numerous accrediting organizations are calling for competency-based medical education that would help define specific specialties and serve as a foundation for ongoing assessment throughout a practitioners career. Pulmonary Medicine and Critical Care Medicine are two distinct subspecialties, yet many individual physicians have expertise in both because of overlapping content. Establishing specific competencies for these subspecialties identifies educational goals for trainees and guides practitioners through their lifelong learning. OBJECTIVES To define specific competencies for graduates of fellowships in Pulmonary Medicine and Internal Medicine-based Critical Care. METHODS A Task Force composed of representatives from key stakeholder societies convened to identify and define specific competencies for both disciplines. Beginning with a detailed list of existing competencies from diverse sources, the Task Force categorized each item into one of six core competency headings. Each individual item was reviewed by committee members individually, in group meetings, and conference calls. Nominal group methods were used for most items to retain the views and opinions of the minority perspective. Controversial items underwent additional whole group discussions with iterative modified-Delphi techniques. Consensus was ultimately determined by a simple majority vote. MEASUREMENTS AND MAIN RESULTS The Task Force identified and defined 327 specific competencies for Internal Medicine-based Critical Care and 276 for Pulmonary Medicine, each with a designation as either: (1) relevant, but competency is not essential or (2) competency essential to the specialty. CONCLUSIONS Specific competencies in Pulmonary and Critical Care Medicine can be identified and defined using a multisociety collaborative approach. These recommendations serve as a starting point and set the stage for future modification to facilitate maximum quality of care as the specialties evolve.

CT Scan Screening for Lung Cancer: Risk Factors for Nodules and Malignancy in a High-Risk Urban Cohort

Background Low-dose computed tomography (CT) for lung cancer screening can reduce lung cancer mortality. The National Lung Screening Trial reported a 20% reduction in lung cancer mortality in high-risk smokers. However, CT scanning is extremely sensitive and detects non-calcified nodules (NCNs) in 24–50% of subjects, suggesting an unacceptably high false-positive rate. We hypothesized that by reviewing demographic, clinical and nodule characteristics, we could identify risk factors associated with the presence of nodules on screening CT, and with the probability that a NCN was malignant. Methods We performed a longitudinal lung cancer biomarker discovery trial (NYU LCBC) that included low-dose CT-screening of high-risk individuals over 50 years of age, with more than 20 pack-year smoking histories, living in an urban setting, and with a potential for asbestos exposure. We used case-control studies to identify risk factors associated with the presence of nodules (n = 625) versus no nodules (n = 557), and lung cancer patients (n = 30) versus benign nodules (n = 128). Results The NYU LCBC followed 1182 study subjects prospectively over a 10-year period. We found 52% to have NCNs >4 mm on their baseline screen. Most of the nodules were stable, and 9.7% of solid and 26.2% of sub-solid nodules resolved. We diagnosed 30 lung cancers, 26 stage I. Three patients had synchronous primary lung cancers or multifocal disease. Thus, there were 33 lung cancers: 10 incident, and 23 prevalent. A sub-group of the prevalent group were stable for a prolonged period prior to diagnosis. These were all stage I at diagnosis and 12/13 were adenocarcinomas. Conclusions NCNs are common among CT-screened high-risk subjects and can often be managed conservatively. Risk factors for malignancy included increasing age, size and number of nodules, reduced FEV1 and FVC, and increased pack-years smoking. A sub-group of screen-detected cancers are slow-growing and may contribute to over-diagnosis and lead-time biases.

Identification of an autoantibody panel to separate lung cancer from smokers and nonsmokers

BackgroundSera from lung cancer patients contain autoantibodies that react with tumor associated antigens (TAAs) that reflect genetic over-expression, mutation, or other anomalies of cell cycle, growth, signaling, and metabolism pathways.MethodsWe performed immunoassays to detect autoantibodies to ten tumor associated antigens (TAAs) selected on the basis of previous studies showing that they had preferential specificity for certain cancers. Sera examined were from lung cancer patients (22); smokers with ground-glass opacities (GGOs) (46), benign solid nodules (55), or normal CTs (35); and normal non-smokers (36). Logistic regression models based on the antibody biomarker levels among the high risk and lung cancer groups were developed to identify the combinations of biomarkers that predict lung cancer in these cohorts.ResultsStatistically significant differences in the distributions of each of the biomarkers were identified among all five groups. Using Receiver Operating Characteristic (ROC) curves based on age, c-myc, Cyclin A, Cyclin B1, Cyclin D1, CDK2, and survivin, we obtained a sensitivity = 81% and specificity = 97% for the classification of cancer vs smokers(no nodules, solid nodules, or GGO) and correctly predicted 31/36 healthy controls as noncancer.ConclusionA pattern of autoantibody reactivity to TAAs may distinguish patients with lung cancer versus smokers with normal CTs, stable solid nodules, ground glass opacities, or normal healthy never smokers.

Adult Bronchoscopy Training: Current State and Suggestions for the Future: CHEST Expert Panel Report

BACKGROUND The determination of competency of trainees in programs performing bronchoscopy is quite variable. Some programs provide didactic lectures with hands-on supervision, other programs incorporate advanced simulation centers, whereas others have a checklist approach. Although no single method has been proven best, the variability alone suggests that outcomes are variable. Program directors and certifying bodies need guidance to create standards for training programs. Little well-developed literature on the topic exists. METHODS To provide credible and trustworthy guidance, rigorous methodology has been applied to create this bronchoscopy consensus training statement. All panelists were vetted and approved by the CHEST Guidelines Oversight Committee. Each topic group drafted questions in a PICO (population, intervention, comparator, outcome) format. MEDLINE data through PubMed and the Cochrane Library were systematically searched. Manual searches also supplemented the searches. All gathered references were screened for consideration based on inclusion criteria, and all statements were designated as an Ungraded Consensus-Based Statement. RESULTS We suggest that professional societies move from a volume-based certification system to skill acquisition and knowledge-based competency assessment for trainees. Bronchoscopy training programs should incorporate multiple tools, including simulation. We suggest that ongoing quality and process improvement systems be introduced and that certifying agencies move from a volume-based certification system to skill acquisition and knowledge-based competency assessment for trainees. We also suggest that assessment of skill maintenance and improvement in practice be evaluated regularly with ongoing quality and process improvement systems after initial skill acquisition. CONCLUSIONS The current methods used for bronchoscopy competency in training programs are variable. We suggest that professional societies and certifying agencies move from a volume- based certification system to a standardized skill acquisition and knowledge-based competency assessment for pulmonary and thoracic surgery trainees.

Mechanisms of colchicine effect in the treatment of asbestosis and idiopathic pulmonary fibrosis.

AbstractThe objective of this study was to evaluate the mechanisms of colchicine action in pulmonary fibrosis. The study included 10 patients with pulmonary fibrosis (idiopathic pulmonary fibrosis 5, asbestosis 4, and scleroderma 1) who had been admitted to Bellevue Hospital Center, a tertiary care public hospital in New York City. We administered colchicine 0.6 mg orally for 12 weeks to patients with pulmonary fibrosis. Symptoms, high resolution CT scans, pulmonary function tests, and bronchoalveolar lavage parameters were compared prior to and after treatment. Results showed declines in dyspnea index, selective improvement in several CT scans, but no statistically significant change in BAL cells, cytokines, fibronectin, or hydroxyproline. However, there was a decline in hydroxyproline in the BAL fluid in 8/10 patients. We concluded that colchicine has a mild antifibrotic effect which may be in inhibiting collagen formation since there was no effect on the inflammation that accompanies fibrosis.

Entrustable Professional activities and curricular milestones for fellowship training in pulmonary and critical care medicine: Executive summary from the multi-society working group

Assessment of graduate medical trainee progress via the accomplishment of competency milestones is an important element of the Next Accreditation System of the Accreditation Council for Graduate Medical Education. This article summarizes the findings of a multisociety working group that was tasked with creating the entrustable professional activities and curricular milestones for fellowship training in pulmonary medicine, critical care medicine, and combined programs. Using the Delphi process, experienced medical educators from the American College of Chest Physicians, American Thoracic Society, Society of Critical Care Medicine, and Association of Pulmonary and Critical Care Medicine Program Directors reached consensus on the detailed curricular content and expected skill set of graduates of these programs. These are now available to trainees and program directors for the purposes of curriculum design, review, and trainee assessment.