Comparing modalities for risk assessment in patients with pulmonary lesions and nondiagnostic bronchoscopy for suspected lung cancer.

BACKGROUND: Bronchoscopy is commonly utilized for non-surgical sampling of indeterminant pulmonary lesions, but nondiagnostic procedures are common. Accurate assessment of the risk of malignancy is essential for decision making in these patients, yet we lack tools that perform well across this heterogeneous group of patients. We sought to evaluate the accuracy of three previously validated risk models and physician-assessed risk (PAR) in patients with a newly identified lung lesion undergoing bronchoscopy for suspected lung cancer where the result is nondiagnostic. METHODS: We performed an analysis of prospective data collected for the Percepta Bronchial Genomic Classifier Multicenter Registry. PAR and three previously validated risk models (Mayo Clinic, Veteran's Affairs, and Brock) were used to determine the probability of lung cancer (low, intermediate, or high) in 375 patients with pulmonary lesions who underwent bronchoscopy for possible lung cancer with nondiagnostic pathology. Results were compared to the actual adjudicated prevalence of malignancy in each pre-test risk group, determined with a minimum of 12 months follow up after bronchoscopy. RESULTS: PAR and the risk models performed poorly overall in the assessment of risk in this patient population. PAR most closely matched the observed prevalence of malignancy in patients at 12 months after bronchoscopy, but all modalities had a low area under the curve, and in all clinical models more than half of all the lesions labeled as high risk were truly or likely benign. The studied risk model calculators overestimate the risk of malignancy compared to PAR, particularly in the subset in older patients, irregularly bordered nodules, and masses > 3 cm. Overall, the risk models perform only slightly better when confined to lung nodules < 3 cm in this population. CONCLUSION: The currently available tools for the assessment of risk of malignancy perform suboptimally in patients with nondiagnostic findings following a bronchoscopic evaluation for lung cancer. More accurate and objective tools for risk assessment are needed. TRIAL REGISTRATION: not applicable.

Safety and diagnostic performance of pulmonologists performing electromagnetic guided percutaneous lung biopsy (SPiNperc).

BACKGROUND AND OBJECTIVE: Percutaneous lung biopsy for diagnostic sampling of peripheral lung nodules has been widely performed by interventional radiologists under computed tomography (CT) guidance. New technology allows pulmonologists to perform percutaneous lung biopsies using electromagnetic (EM) guided technology. With the adoption of this new technique, the safety, feasibility and diagnostic yield need to be explored. The goal of this study was to determine the safety, feasibility and diagnostic yield of EM-guided percutaneous lung biopsy performed by pulmonologists. METHODS: We conducted a retrospective, multicentre study of 129 EM-guided percutaneous lung biopsies that occurred between November 2013 and March 2017. The study consisted of seven academic and three community medical centres. RESULTS: The average age of participants was 65.6 years, BMI was 26.3 and 50.4% were females. The majority of lesions were in the right upper lobe (37.2%) and left upper lobe (31.8%). The mean size of the lesions was 27.31 mm and the average distance from the pleura was 13.2 mm. Practitioners averaged two fine-needle aspirates and five core biopsies per procedure. There were 23 (17.8%) pneumothoraces, of which 16 (12.4%) received small-bore chest tube placement. The diagnostic yield of percutaneous lung biopsy was 73.7%. When EM-guided bronchoscopic sampling was also performed during the same procedural encounter, the overall diagnostic yield increased to 81.1%. CONCLUSION: In this large multicentred series, the use of EM guidance for percutaneous lung biopsies was safe and feasible, with acceptable diagnostic yield in the hands of pulmonologists. A prospective multicentre trial to validate these findings is currently underway (NCT03338049).

Attenuated heme oxygenase-1 responses predispose the elderly to pulmonary nontuberculous mycobacterial infections.

Pulmonary infections with nontuberculous mycobacteria (P-NTM), such as by Mycobacterium avium complex (M. avium), are increasingly found in the elderly, but the underlying mechanisms are unclear. Recent studies suggest that adaptive immunity is necessary, but not sufficient, for host defense against mycobacteria. Heme oxygenase-1 (HO-1) has been recognized as a critical modulator of granuloma formation and programmed cell death in mycobacterial infections. Old mice (18-21 mo) infected with M. avium had attenuated HO-1 response with diffuse inflammation, high burden of mycobacteria, poor granuloma formation, and decreased survival (45%), while young mice (4-6 mo) showed tight, well-defined granuloma, increased HO-1 expression, and increased survival (95%). To further test the role of HO-1 in increased susceptibility to P-NTM infections in the elderly, we used old and young HO-1+/+ and HO-1-/- mice. The transcriptional modulation of the JAK/STAT signaling pathway in HO-1-/- mice due to M. avium infection demonstrated similarities to infected wild-type old mice with upregulation of SOCS3 and inhibition of Bcl2. Higher expression of SOCS3 with downregulation of Bcl2 resulted in higher macrophage death via cellular necrosis. Finally, peripheral blood monocytes (PBMCs) from elderly patients with P-NTM also demonstrated attenuated HO-1 responses after M. avium stimulation and increased cell death due to cellular necrosis (9.69% ± 2.02) compared with apoptosis (4.75% ± 0.98). The augmented risk for P-NTM in the elderly is due, in part, to attenuated HO-1 responses, subsequent upregulation of SOCS3, and inhibition of Bcl2, leading to programmed cell death of macrophages, and sustained infection.

Survey of Clinical Knowledge and Procedural Readiness of Pulmonary Fellows to Start Interventional Pulmonary Fellowship: A Survey of Interventional Pulmonary Fellowship Directors.

BACKGROUND: Entry into the interventional pulmonary (IP) fellowship requires prerequisite training in pulmonary and critical care medicine (PCCM) fellowship in the United States. IP fellowship has become standardized, but the prerequisite training may be quite variable depending on the learner's exposure to IP during their PCCM fellowship. A survey study was conducted to identify potential foundational knowledge and/or skills gaps of new fellows entering IP fellowships. This may help both PCCM and IP fellowship directors to identify common knowledge gaps within PCCM training specific to IP. METHODS: Based on components of the ACGME's common program requirements for PCCM fellowships, a survey was developed and categorized into 5 domains: nonprocedural skills, didactic knowledge, diagnostic bronchoscopy, pleural procedures, and airway/percutaneous procedures. The survey was then sent to 42 IP fellowship directors after the content validity review and approval by the Association of Interventional Pulmonary Program Directors. RESULTS: The survey response rate was 88.1% (37/42). The overall mean scores in all 5 domains were perceived as below competent (<3). The highest mean domain was nonprocedural skills, and the lowest was airway/percutaneous procedures. Within the domains, there were 4/ 30 topics that were considered competent with a score of ≥3 as competent or higher; bronchoscopy lavage (mean: 3.5/5, SD: 0.87), interpersonal skills (mean: 3.03/5, SD: 0.76), thoracentesis (mean: 3.14/5, SD: 0.89), and ultrasound for pleural effusion (mean: 3.19/5, SD: 0.84). CONCLUSION: There are perceived gaps in PCCM training pertaining to IP fellowship readiness.

Interventional Pulmonary Fellowship Training: End of the Beginning.

Interventional pulmonology (IP) fellowship training has undergone increased popularity and growth. The Accreditation Council of Graduate Medical Education recently recognized IP medicine as a new subspecialty, which leads to new challenges and opportunities for a young subspecialty. Although the specialty-specific requirements are in progress, IP fellowship programs must plan ahead for the known common program requirements and anticipated accreditation process. The educational leadership in IP must identify and execute solutions to sustain continued excellence. This includes transitioning to a new regulatory environment with issues of funding new fellowships, keeping up to date with training/assessment of new procedures, and shaping the future through recruitment of talent to lead the young subspecialty.

A Longitudinal Study of Multimodal Bronchoscopy Training in Uganda.

Background: Flexible bronchoscopy is an essential tool in diagnosing and managing pulmonary diseases. However, there is limited capacity for bronchoscopy in low and middle income countries (LMICs). In 2019, a pilot program for flexible bronchoscopy training was launched for local physicians in Kampala, Uganda. We then conducted a follow up multimodal bronchoscopy course after 2 years. Objective: The aim of this study is to assess a longitudinal multimodal bronchoscopy training in an LMIC setting. Methods: A multimodal follow up curriculum was developed with pulmonologists from Uganda and the United States. The training was delivered to Ugandan providers who attended previous bronchoscopy training and new participants. The training included a prepared curriculum consisting of lectures, simulations, and deliberate practice-based proctoring. A 12-question multiple-choice exam was administered at the beginning and end of the course, assessing knowledge. Procedural competency was measured using a validated assessment tool called the BSTAT (Bronchoscopic Skills and Tasks Assessment Tool). Results were analyzed to evaluate the retention of knowledge among those who took part in previous training and the efficacy of the follow-up curriculum for participants without previous training. Results: Among the participants who attended didactic training in 2022 (11), mean exam scores were improved after training, from 43.9 (standard deviation [SD], 11.3) to 59.8 (SD, 16.1) (mean difference [MD], +15.9; SD, 13.9; P = 0.008), but were lower compared with post didactic scores in 2019: 90.8 (SD, 6.1; MD, -31; P < 0.0001). Participants who completed BSTAT assessments (8) had mean scores similar in 2019 and 2022, at 72.1 and 75.2, respectively (MD, 3.1; P = 0.38). Conclusion: This study provides an example of how a longitudinal multimodal bronchoscopy curriculum can improve competency and proficiency for local physicians in an LMIC.

A Multicenter Study Assessing Interventional Pulmonary Fellow Competency in Electromagnetic Navigation Bronchoscopy.

Background: Current medical society guidelines recommend a procedural number for obtaining electromagnetic navigational bronchoscopy (ENB) competency and for institutional volume for training. Objective: To assess learning curves and estimate the number of ENB procedures for interventional pulmonology (IP) fellows to reach competency. Methods: We conducted a prospective multicenter study of IP fellows in the United States learning ENB. A tool previously validated in a similar population was used to assess IP fellows by their local faculty and two blinded independent reviewers using virtual recording of the procedure. Competency was determined by performing three consecutive procedures with a competency score on the assessment tool. Procedural time, faculty global rating scale, and periprocedural complications were also recorded. Results: A total of 184 ENB procedures were available for review with assessment of 26 IP fellows at 16 medical centers. There was a high correlation between the two blinded independent observers (rho = 0.8776). There was substantial agreement for determination of procedural competency between the faculty assessment and blinded reviewers (kappa = 0.7074; confidence interval, 0.5667-0.8482). The number of procedures for reaching competency for ENB bronchoscopy was determined (median, 4; mean, 5; standard deviation, 3.83). There was a wide variation in the number of procedures to reach competency, ranging from 2 to 15 procedures. There were six periprocedural complications reported, four (one pneumomediastinum, three pneumothorax) of which occurred before reaching competence and two pneumothoraces after achieving competence. Conclusion: There is a wide variation in acquiring competency for ENB among IP fellows. Virtual competency assessment has a potential role but needs further studies.

Bleeding Risk With Combination Intrapleural Fibrinolytic and Enzyme Therapy in Pleural Infection: An International, Multicenter, Retrospective Cohort Study.

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 × 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.

Managing complications of percutaneous tracheostomy and gastrostomy.

Percutaneous tracheostomy and gastrostomy are some of the most commonly performed procedures at bedside in the intensive care unit. While they are generally considered safe, they can be associated with numerous short and long-term complications, many of which can occur long after their placement and cause significant morbidity. Performers of these procedures should possess a comprehensive understanding of procedural indications and contraindications, and know how to recognize and manage complications that may arise. In this review, we highlight complications of percutaneous tracheostomy and describe strategies for their prevention and management, with a special focus on post-tracheostomy tracheal stenosis. Other complications reviewed include bleeding, pneumothorax and subcutaneous emphysema, posterior wall injury, tube displacement, tracheomalacia, tracheoinominate artery fistula, tracheo-esophageal fistula, and stomal cellulitis. Gastrostomy complications and their management are also discussed including bleeding, internal organ injury, necrotizing fasciitis, aspiration pneumonia, buried bumper syndrome, tumor seeding, wound infection, tube displacement, peristomal leakage, and gastric outlet obstruction. In light of the potentially serious outcomes associated with complications of percutaneous tracheostomy and gastrostomy, the emphasis should be placed on risk-reduction strategies to minimize morbidity and mortality. We therefore present detailed pragmatic and comprehensive checklists to serve as a reference for clinicians involved in performing these procedures.

Predictors of In-Hospital Death in Patients with Lung Cancer Admitted for Acute Radiation Pneumonitis: A Healthcare Cost and Utilization Project (HCUP) Analysis.

BACKGROUND: Radiation pneumonitis (RP) is a dose-limiting and potentially fatal toxicity of thoracic radiotherapy most often seen in patients treated for primary lung cancer. The purpose of this study was to identify predictors of in-hospital death among lung cancer patients admitted for acute RP in the Healthcare Cost and Utilization Project (HCUP) database. MATERIALS AND METHODS: The HCUP National Inpatient Sample database was queried from 2012 through 2016 to capture adult lung cancer patients admitted to the hospital with a principal diagnosis of acute RP. Multivariate logistic regression modeling and χ2 tests were used to determine predictors of in-hospital death. RESULTS: Of the 882 patients with lung cancer admitted for RP, 67 patients (7.6%) died during the hospitalization and 90 patients (10.2%) required mechanical ventilation. Of those requiring mechanical ventilation, 38 patients (42.2%) died. The average age at hospitalization was 70.4 years (range, 35-90). Of those factors associated with death on univariate analysis, interstitial lung disease (odds ratio [OR] = 6.14; 95% confidence interval [CI], 1.9-19.4; P = .002), pulmonary hypertension (OR = 3.1; 95% CI, 1.6-6.2; P = .001), diabetes mellitus (OR = 2.0; 95% CI, 1.1-3.3; P = .013), and more affluent Zip Code (OR = 1.9; 95% CI, 1.1-3.2; P = .021) remained statistically significant on multivariate logistic regression. CONCLUSION: In the largest reported cohort of patients with lung cancer hospitalized with a principal diagnosis of acute RP, the presence of interstitial lung disease, pulmonary hypertension, diabetes mellitus, and more affluent Zip Code were associated with in-hospital death. Comorbid diagnoses may be useful for risk-stratified management of inpatients with RP.

Tracheotomy in the SARS-CoV-2 pandemic.

The severe acute respiratory syndrome (SARS)-CoV-2 pandemic continues to produce a large number of patients with chronic respiratory failure and ventilator dependence. As such, surgeons will be called upon to perform tracheotomy for a subset of these chronically intubated patients. As seen during the SARS and the SARS-CoV-2 outbreaks, aerosol-generating procedures (AGP) have been associated with higher rates of infection of medical personnel and potential acceleration of viral dissemination throughout the medical center. Therefore, a thoughtful approach to tracheotomy (and other AGPs) is imperative and maintaining traditional management norms may be unsuitable or even potentially harmful. We sought to review the existing evidence informing best practices and then develop straightforward guidelines for tracheotomy during the SARS-CoV-2 pandemic. This communication is the product of those efforts and is based on national and international experience with the current SARS-CoV-2 pandemic and the SARS epidemic of 2002/2003.

Impact of Video Game Cross-Training on Learning Bronchoscopy. A Pilot Randomized Controlled Trial.

Background: Video game playing requires many of the same skill sets as medical procedures such as bronchoscopy. These include visual-spatial awareness, rapid decision making, and psychomotor skills. The role of video game cross-training on learning bronchoscopy is unknown. Objective: We studied the association of baseline video gaming experience with, and the impact of short-term video game playing on, visual-spatial awareness and acquisition of basic bronchoscopic skills among medical trainees. Methods: Bronchoscopy-naive medical trainees underwent formal didactic and hands-on instruction on basic bronchoscopy, along with a baseline assessment measuring bronchoscopic and visual-spatial skills. Half of the subjects were subsequently randomized to playing a videogame (Rocket League) for 8 weeks. All participants returned at 4 weeks for a refresher course and at 8 weeks for a final assessment. Results: Thirty subjects completed the study, 16 of them in the intervention arm who all met the minimum video game playing time requirement. At baseline, video game players had significantly lower airway collision rates (6.82 collisions/min vs. 11.64 collisions/min; P = 0.02) and higher scores on the Purdue Visual Spatial Test: Visualization of Rotations test (27.5 vs. 23.54; P = 0.04). At completion, the intervention group had no significant differences in airway collisions, bronchoscopy time, or Bronchoscopy Skills and Tasks Assessment Tool scores. There was moderate correlation between airway collision rate and mean Purdue Visual Spatial Test: Visualization of Rotations score (Spearman's rho, -0.59; P < 0.001). Conclusion: At baseline, learners with former video game-playing experience have higher visual-spatial awareness and fewer airway collisions. The impact of video game playing as an aid to simulation-based bronchoscopic education is uncertain.

Indications and complications of rigid bronchoscopy.

INTRODUCTION: Rigid bronchoscopy is an invaluable tool for the management of airway disorders and an essential skill for an interventional pulmonologist. Since its introduction in the late 19th century, it has remained an important technique for the management of central airway obstruction, foreign body aspiration and massive hemoptysis. Areas covered: This article will review the history, indications, contraindication, technique and complications of rigid bronchoscopy. We will also briefly discuss the methods of anesthesia and ventilation and finally our perspective on the future of rigid bronchoscopy. Expert commentary: Although the rise of flexible bronchoscopy in the 1960s led to a decline in the use of rigid bronchoscopy, the last two decades have witnessed resurgence in its popularity. We anticipate that it will remain an important tool used by interventional pulmonologists for decades to come. We suggest that interventional pulmonologists must have training and develop expertise in this technique.

Pleural mesothelial cells in pleural and lung diseases.

During development, the mesoderm maintains a complex relationship with the developing endoderm giving rise to the mature lung. Pleural mesothelial cells (PMCs) derived from the mesoderm play a key role during the development of the lung. The pleural mesothelium differentiates to give rise to the endothelium and smooth muscle cells via epithelial-to-mesenchymal transition (EMT). An aberrant recapitulation of such developmental pathways can play an important role in the pathogenesis of disease processes such as idiopathic pulmonary fibrosis (IPF). The PMC is the central component of the immune responses of the pleura. When exposed to noxious stimuli, it demonstrates innate immune responses such as Toll-like receptor (TLR) recognition of pathogen associated molecular patterns as well as causes the release of several cytokines to activate adaptive immune responses. Development of pleural effusions occurs due to an imbalance in the dynamic interaction between junctional proteins, n-cadherin and ß-catenin, and phosphorylation of adherens junctions between PMCs, which is caused in part by vascular endothelial growth factor (VEGF) released by PMCs. PMCs play an important role in defense mechanisms against bacterial and mycobacterial pleural infections, and in pathogenesis of malignant pleural effusion, asbestos related pleural disease and malignant pleural mesothelioma. PMCs also play a key role in the resolution of inflammation, which can occur with or without fibrosis. Fibrosis occurs as a result of disordered fibrin turnover and due to the effects of cytokines such as transforming growth factor-ß, platelet-derived growth factor (PDGF), and basic fibroblast growth factor; which are released by PMCs. Recent studies have demonstrated a role for PMCs in the pathogenesis of IPF suggesting their potential as a cellular biomarker of disease activity and as a possible therapeutic target. Pleural-based therapies targeting PMCs for treatment of IPF and other lung diseases need further exploration.

Heme oxygenase-1 protects corexit 9500A-induced respiratory epithelial injury across species.

The effects of Corexit 9500A (CE) on respiratory epithelial surfaces of terrestrial mammals and marine animals are largely unknown. This study investigated the role of CE-induced heme oxygenase-1 (HO-1), a cytoprotective enzyme with anti-apoptotic and antioxidant activity, in human bronchial airway epithelium and the gills of exposed aquatic animals. We evaluated CE-mediated alterations in human airway epithelial cells, mice lungs and gills from zebrafish and blue crabs. Our results demonstrated that CE induced an increase in gill epithelial edema and human epithelial monolayer permeability, suggesting an acute injury caused by CE exposure. CE induced the expression of HO-1 as well as C-reactive protein (CRP) and NADPH oxidase 4 (NOX4), which are associated with ROS production. Importantly, CE induced caspase-3 activation and subsequent apoptosis of epithelial cells. The expression of the intercellular junctional proteins, such as tight junction proteins occludin, zonula occludens (ZO-1), ZO-2 and adherens junctional proteins E-cadherin and Focal Adhesion Kinase (FAK), were remarkably inhibited by CE, suggesting that these proteins are involved in CE-induced increased permeability and subsequent apoptosis. The cytoskeletal protein F-actin was also disrupted by CE. Treatment with carbon monoxide releasing molecule-2 (CORM-2) significantly inhibited CE-induced ROS production, while the addition of HO-1 inhibitor, significantly increased CE-induced ROS production and apoptosis, suggesting a protective role of HO-1 or its reaction product, CO, in CE-induced apoptosis. Using HO-1 knockout mice, we further demonstrated that HO-1 protected against CE-induced inflammation and cellular apoptosis and corrected CE-mediated inhibition of E-cadherin and FAK. These observations suggest that CE activates CRP and NOX4-mediated ROS production, alters permeability by inhibition of junctional proteins, and leads to caspase-3 dependent apoptosis of epithelial cells, while HO-1 and its reaction products protect against oxidative stress and apoptosis.