Training in interventional pulmonology: a leap into the future.

PURPOSE OF REVIEW: This review holds significant relevance and is timely; as of June 2022, the United States Accreditation Council of Graduate Medical Education (ACGME) formally recognized interventional pulmonary medicine as a novel subspecialty with a unique fellowship training program pathway beyond Pulmonary and Critical Care Medicine. This recognition stands as a culmination of extensive efforts spanning decades, aimed at establishing a specialized training program for interventional pulmonary medicine beyond traditional Pulmonary and Critical Care Fellowship in the United States. Globally, there are apprenticeship models in non-US programs with ongoing efforts to further standardize training in interventional pulmonary medicine. It underscores the progressive evolution and innovative nature inherent to this subspecialty, signifying a distinctive leap forward in medical education and practice, which calls for further inventive development of training tools and standardized educational delivery. RECENT FINDINGS: Newly discovered insights from the recent literature review will highlight methodologies of procedural education and innovative training approaches. These findings will underscore the significance of standardized curriculum development within the field as well as ongoing challenges. SUMMARY: Identifying and addressing future challenges in integrating new technologies into clinical education and broadening the educational scope of trainees in this newly recognized subspecialty is crucial for enhancing competency. The implications of moving toward a more standardized process, creating new clinical pathways with research, and adopting emerging minimally invasive technologies aim to impact patient outcomes in both nonmalignant and malignant thoracic diseases. This progressive shift is redefining the specialty, moving beyond specific procedures, and pivoting towards a more distinct educational pathway. Such a transformation will lead to more diverse, comprehensive, and evidence-based driven patient care delivery.

Performance of a new single-use bronchoscope versus a marketed single-use comparator: a bench study.

BACKGROUND: Single-use flexible bronchoscopes eliminate cross contamination from reusable bronchoscopes and are cost-effective in a number of clinical settings. The present bench study aimed to compare the performance of a new single-use bronchoscope (Boston Scientific EXALT Model B) to a marketed single-use comparator (Ambu aScope 4), each in slim, regular and large diameters. METHODS: Three bronchoscopy tasks were performed: water suction and visualization, "mucus" mass (synthetic mucoid mixture) suctioned in 30 s, and "mucus" plug (thicker mucoid mixture) suction. Suction ability, task completion times, and subjective ratings of visualization and overall performance on a scale of one to 10 (best) were compared. All bronchoscopy tasks were completed by 15 physicians representing diversity in specialization including pulmonary, interventional pulmonary, critical care, anesthesia, and thoracic surgery. Each physician utilized the six bronchoscope versions with block randomization by bronchoscope and task. RESULTS: Aspirated mean mass of "mucus" using EXALT Model B Regular was comparable to that for an aScope 4 Large (41.8 ± 8.3 g vs. 41.5 ± 5.7 g respectively, p = 0.914). In comparisons of scopes with the same outer diameter, the aspirated mean mass by weight of water and "mucus" was significantly greater for EXALT Model B than for aScope 4 (p < 0.001 for all three diameters). Mean ratings for visualization attributes were significantly better for EXALT Model B compared to aScope 4 (p-value range 0.001-0.029). CONCLUSION: A new single-use bronchoscope provided strong suction capability and visualization compared to same-diameter marketed single-use comparators in a bench model simulation.

Variable Learning Curve of Basic Rigid Bronchoscopy in Trainees.

BACKGROUND: Despite increased use of rigid bronchoscopy (RB) for therapeutic indications and recommendations from professional societies to use performance-based competency, an assessment tool has not been utilized to measure the competency of trainees to perform RB in clinical settings. OBJECTIVES: The aim of the study was to evaluate a previously developed assessment tool - Rigid Bronchoscopy Tool for Assessment of Skills and Competence (RIGID-TASC) - for determining the RB learning curve of interventional pulmonary (IP) trainees in the clinical setting and explore the variability of learning curve of trainees. METHODS: IP fellows at 4 institutions were enrolled. After preclinical simulation training, all RBs performed in patients were scored by faculty using RIGID-TASC until competency threshold was achieved. Competency threshold was defined as unassisted RB intubation and navigation through the central airways on 3 consecutive patients at the first attempt with a minimum score of 89. A regression-based model was devised to construct and compare the learning curves. RESULTS: Twelve IP fellows performed 178 RBs. Trainees reached the competency threshold between 5 and 24 RBs, with a median of 15 RBs (95% CI, 6-21). There were differences among trainees in learning curve parameters including starting point, slope, and inflection point, as demonstrated by the curve-fitting model. Subtasks that required the highest number of procedures (median = 10) to gain competency included ability to intubate at the first attempt and intubation time of <60 s. CONCLUSIONS: Trainees acquire RB skills at a variable pace, and RIGID-TASC can be used to assess learning curve of IP trainees in clinical settings.

Quantitative Pectoralis Muscle Area is Associated with the Development of Lung Cancer in a Large Lung Cancer Screening Cohort.

BACKGROUND: Studies have demonstrated an inverse relationship between body mass index (BMI) and the risk of developing lung cancer. We conducted a retrospective cohort study evaluating baseline quantitative computed tomography (CT) measurements of body composition, specifically muscle and fat area in a large CT lung screening cohort (CTLS). We hypothesized that quantitative measurements of baseline body composition may aid in risk stratification for lung cancer. METHODS: Patients who underwent baseline CTLS between January 1st, 2012 and September 30th, 2014 and who had an in-network primary care physician were included. All patients met NCCN Guidelines eligibility criteria for CTLS. Quantitative measurements of pectoralis muscle area (PMA) and subcutaneous fat area (SFA) were performed on a single axial slice of the CT above the aortic arch with the Chest Imaging Platform Workstation software. Cox multivariable proportional hazards model for cancer was adjusted for variables with a univariate p < 0.2. Data were dichotomized by sex and then combined to account for baseline differences between sexes. RESULTS: One thousand six hundred and ninety six patients were included in this study. A total of 79 (4.7%) patients developed lung cancer. There was an association between the 25th percentile of PMA and the development of lung cancer [HR 1.71 (1.07, 2.75), p < 0.025] after adjusting for age, BMI, qualitative emphysema, qualitative coronary artery calcification, and baseline Lung-RADS® score. CONCLUSIONS: Quantitative assessment of PMA on baseline CTLS was associated with the development of lung cancer. Quantitative PMA has the potential to be incorporated as a variable in future lung cancer risk models.

Improving Lung Function in Severe Heterogenous Emphysema with the Spiration Valve System (EMPROVE). A Multicenter, Open-Label Randomized Controlled Clinical Trial.

Rationale: Less invasive, nonsurgical approaches are needed to treat severe emphysema.Objectives: To evaluate the effectiveness and safety of the Spiration Valve System (SVS) versus optimal medical management.Methods: In this multicenter, open-label, randomized, controlled trial, subjects aged 40 years or older with severe, heterogeneous emphysema were randomized 2:1 to SVS with medical management (treatment) or medical management alone (control).Measurements and Main Results: The primary efficacy outcome was the difference in mean FEV1 from baseline to 6 months. Secondary effectiveness outcomes included: difference in FEV1 responder rates, target lobe volume reduction, hyperinflation, health status, dyspnea, and exercise capacity. The primary safety outcome was the incidence of composite thoracic serious adverse events. All analyses were conducted by determining the 95% Bayesian credible intervals (BCIs) for the difference between treatment and control arms. Between October 2013 and May 2017, 172 participants (53.5% male; mean age, 67.4 yr) were randomized to treatment (n = 113) or control (n = 59). Mean FEV1 showed statistically significant improvements between the treatment and control groups-between-group difference at 6 and 12 months, respectively, of 0.101 L (95% BCI, 0.060-0.141) and 0.099 L (95% BCI, 0.048-0.151). At 6 months, the treatment group had statistically significant improvements in all secondary endpoints except 6-minute-walk distance. Composite thoracic serious adverse event incidence through 6 months was greater in the treatment group (31.0% vs. 11.9%), primarily due to a 12.4% incidence of serious pneumothorax.Conclusions: In patients with severe heterogeneous emphysema, the SVS shows significant improvement in multiple efficacy outcomes, with an acceptable safety profile.Clinical trial registered with www.clinicaltrials.gov (NCT01812447).

Pleurodesis.

Symptomatic pleural disease, specifically malignant pleural effusion, refractory benign pleural effusion, and pneumothoraces are common diseases that often require therapeutic interventions. The spectrum of management strategies often includes selection of a chemical pleurodesis agent administered in combination with an indwelling pleural catheter or chest tube.Additionally, there is a role for minimally invasive techniques which include medical thoracoscopy or more advanced video-assisted thoracoscopic approaches. Ongoing clinical trials continue to evolve best practices regarding the optimal sclerosant agents and procedural approaches in the management of these diseases.

Randomized Trial of Pleural Fluid Drainage Frequency in Patients with Malignant Pleural Effusions. The ASAP Trial.

RATIONALE: Patients with malignant pleural effusions have significant dyspnea and shortened life expectancy. Indwelling pleural catheters allow patients to drain pleural fluid at home and can lead to autopleurodesis. The optimal drainage frequency to achieve autopleurodesis and freedom from catheter has not been determined. OBJECTIVES: To determine whether an aggressive daily drainage strategy is superior to the current standard every other day drainage of pleural fluid in achieving autopleurodesis. METHODS: Patients were randomized to either an aggressive drainage (daily drainage; n = 73) or standard drainage (every other day drainage; n = 76) of pleural fluid via a tunneled pleural catheter. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the incidence of autopleurodesis following the placement of the indwelling pleural catheters. The rate of autopleurodesis, defined as complete or partial response based on symptomatic and radiographic changes, was greater in the aggressive drainage arm than the standard drainage arm (47% vs. 24%, respectively; P = 0.003). Median time to autopleurodesis was shorter in the aggressive arm (54 d; 95% confidence interval, 34-83) as compared with the standard arm (90 d; 95% confidence interval, 70 to nonestimable). Rate of adverse events, quality of life, and patient satisfaction were not significantly different between the two arms. CONCLUSIONS: Among patients with malignant pleural effusion, daily drainage of pleural fluid via an indwelling pleural catheter led to a higher rate of autopleurodesis and faster time to liberty from catheter. Clinical trial registered with www.clinicaltrials.gov (NCT 00978939).

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.

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 approximately 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.

A Nasal Swab Classifier to Evaluate the Probability of Lung Cancer in Patients With Pulmonary Nodules.

BACKGROUND: Accurate assessment of the probability of lung cancer (pCA) is critical in patients with pulmonary nodules (PNs) to help guide decision-making. We sought to validate a clinical-genomic classifier developed using whole-transcriptome sequencing of nasal epithelial cells from patients with a PN ≤ 30 mm who smoke or have previously smoked. RESEARCH QUESTION: Can the pCA in individuals with a PN and a history of smoking be predicted by a classifier that uses clinical factors and genomic data from nasal epithelial cells obtained by cytologic brushing? STUDY DESIGN AND METHODS: Machine learning was used to train a classifier using genomic and clinical features on 1,120 patients with PNs labeled as benign or malignant established by a final diagnosis or a minimum of 12 months of radiographic surveillance. The classifier was designed to yield low-, intermediate-, and high-risk categories. The classifier was validated in an independent set of 312 patients, including 63 patients with a prior history of cancer (other than lung cancer), comparing the classifier prediction with the known clinical outcome. RESULTS: In the primary validation set, sensitivity and specificity for low-risk classification were 96% and 42%, whereas sensitivity and specificity for high-risk classification was 58% and 90%, respectively. Sensitivity was similar across stages of non-small cell lung cancer, independent of subtype. Performance compared favorably with clinical-only risk models. Analysis of 63 patients with prior cancer showed similar performance as did subanalyses of patients with light vs heavy smoking burden and those eligible for lung cancer screening vs those who were not. INTERPRETATION: The nasal classifier provides an accurate assessment of pCA in individuals with a PN ≤ 30 mm who smoke or have previously smoked. Classifier-guided decision-making could lead to fewer diagnostic procedures in patients without cancer and more timely treatment in patients with lung cancer.

Determination of 35 cell surface antigen levels in malignant pleural effusions identifies CD24 as a marker of disseminated tumor cells.

Many targets have been identified in solid tumors for antibody therapy but it is less clear what surface antigens may be most commonly expressed on disseminated tumor cells. Using malignant pleural effusions as a source of disseminated tumor cells, we compared a panel of 35 antigens for their cancer specificity, antigen abundance and functional significance. These antigens have been previously implicated in cancer metastasis and fall into four categories: (i) cancer stem cell, (ii) epithelial-mesenchymal transition, (iii) metastatic signature of in vivo selection and (iv) tyrosine kinase receptors. We determined the antigen density of all 35 antigens on the cell surface by flow cytometry, which ranges from 3 × 10(3) -7 × 10(6) copies per cell. Comparison between the malignant and benign pleural effusions enabled us to determine the antigens specific for cancer. We further chose six antigens and examined the correlation between their expression levels and tumor formation in immunocompromised mice. We concluded that CD24 is one of the few antigens that could simultaneously meet all three criteria of an ideal target. It was specifically and abundantly expressed in malignant pleural effusions; CD24(high) tumor cells formed tumors in mice at a faster rate than CD24(low) tumor cells, and shRNA-mediated knockdown of CD24 in HT29 cells confirmed a functional requirement for CD24 in the colonization of the lung. Concomitant consideration of antigen abundance, specificity and functional importance can help identify potentially useful markers for disseminated tumor cells.

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 operator's 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.

Innovation in rigid bronchoscopy-past, present, and future.

German laryngologist Gustav Killian performed the first "Direkte Bronchoskopie" using a rigid bronchoscope to extract a foreign airway body from the right main bronchus over a hundred years ago, transforming the practice of respiratory medicine. The procedure instantaneously became popular throughout the world. Chevalier Jackson Sr from the United States further advanced the instrument, technique, safety, and application. In the 1960s, Professors Harold H. Hopkins and N.S. Kapany introduced optical rods as well as fiberoptics that led Karl Storz to develop the cold light system improving endoluminal illumination, achievements that ushered in the modern era of flexible endoscopy. Several diagnostic and therapeutic procedures became possible such as transbronchial needle biopsy, transbronchial lung biopsy, airway electrosurgery, or cryotherapy. Dr. Jean-François Dumon from France advanced the use of Nd-YAG laser in the endobronchial tree and created the dedicated Dumon silicone stent introducing the whole new field of interventional pulmonology (IP). This major milestone revitalized interest in rigid bronchoscopy (RB). Now, advancements are being made in stenting, instrumentation, and education. RB robotic technology advancements are currently anticipated and can potentially revolutionize the practice of pulmonary medicine. In this review, we describe some of the most substantial advances related to RB from its beginning to the modern era.

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.

Interventional Pulmonology Productivity, Compensation, and Practice Benchmarks: The AABIP 2022 Report.

BACKGROUND: Interventional pulmonology (IP) is a growing field that has not yet been recognized by the American Board of Medical Specialties or incorporated into national benchmark organizations. As a result, there is a lack of data on IP practice patterns, physicians' compensation and productivity targets. METHODS: We sent an anonymous survey to 647 current or past physician members of the AABIP. Domains included demographics, training background, academic rank, practice settings, work relative value unit (wRVU) targets, salary, and career satisfaction. RESULTS: The response rate to the survey was 28.3%; 17.8% were female. The median salary for IP faculty in academic institutions was $320,000 for assistant professors, $338,000 for associate professors, and $350,000 for full professors. Salaries were lower for women than for men in academic practice, even after adjusting for the number of years in practice (mean salary difference after adjustment $57,175, 95% CI: $19,585-$94,764, P =0.003). The median salary for private practice was higher at $428,000. Among respondents that used wRVU targets, the median targets for academic and private practice were 5500 and 6300, respectively. The majority of IP physicians are satisfied with their career choice. CONCLUSIONS: Productivity targets in IP are used less than half the time, and when they are used, they are set in line with the lower wRVU of IP procedures. IP compensation is higher than that of general pulmonary medicine, as reported by national benchmark associations. In academic practices, gender differences in salaries were found.

Comparison of Sample Adequacy and Diagnostic Yield of the 21-G and 25-G EBUS TBNA Needles.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS TBNA) of mediastinal lymphadenopathy has been shown to be equivalent and possibly even superior to mediastinoscopy. Since the original dedicated 22-G aspiration needle, 21-G, 25-G, and recently 19-G needles have been introduced. Smaller needles may be more flexible and adept at accessing more difficult nodes, and may have less blood contamination compared with larger needles. PATIENTS AND METHODS: This is a prospective observational study of 50 consecutive patients who underwent endobronchial ultrasound-guided transbronchial needle aspiration with a 21-G needle and a 25-G needle for a total of 100 biopsies. The study slides were examined by a dedicated lung cytopathologist, who was blinded to the needle size used for each slide. Demographic data, and lymph node size were recorded. Comparisons between the 2 needles with regards to sample adequacy and diagnostic yield was performed using the McNemar test for dichotomous variables and marginal homogeneity test for nondichotomous variables since samples were related. RESULTS: The majority of lymph nodes (96%) were at least >1 cm. Adequate specimens were obtained in 78% of cases with the 21-G needle and 86% of cases with 25-G needle (P-value=0.424). The overall diagnostic yield was 74% and 80% with the 21-G needle and 25-G needle, respectively (P-value=0.607). CONCLUSION: Our study demonstrates that the there is no difference in terms of specimen adequacy and diagnostic yield when the 25-G needle is compared with the 21-G needle.

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.

Bronchial Thermoplasty in Patients With Severe Asthma at 5 Years: The Post-FDA Approval Clinical Trial Evaluating Bronchial Thermoplasty in Severe Persistent Asthma Study.

BACKGROUND: Bronchial thermoplasty is a device-based treatment for subjects ≥ 18 years of age with severe asthma poorly controlled with inhaled corticosteroids and long-acting beta-agonists. The Post-FDA Approval Clinical Trial Evaluating Bronchial Thermoplasty in Severe Persistent Asthma (PAS2) study collected data on patients with severe asthma undergoing this procedure. RESEARCH QUESTION: What are the 5-year efficacy and safety results in patients with severe asthma who have undergone bronchial thermoplasty? STUDY DESIGN AND METHODS: This was a prospective, open-label, observational, multicenter study conducted in the United States and Canada. Subjects 18 to 65 years of age who were taking inhaled corticosteroids ≥ 1,000 µg/d (beclomethasone or equivalent) and long-acting beta-agonists ≥ 80 µg/d (salmeterol or equivalent) were included. Severe exacerbations, hospitalization, ED visits, and medication usage were evaluated for the 12 months prior to and at years 1 through 5 posttreatment. Spirometry was evaluated at baseline and at years 1 through 5 posttreatment. RESULTS: A total of 284 subjects were enrolled at 27 centers; 227 subjects (80%) completed 5 years of follow-up. By year 5 posttreatment, the proportion of subjects with severe exacerbations, ED visits, and hospitalizations was 42.7%, 7.9%, and 4.8%, respectively, compared with 77.8%, 29.4%, and 16.1% in the 12 months prior to treatment. The proportion of subjects on maintenance oral corticosteroids decreased from 19.4% at baseline to 9.7% at 5 years. Analyses of subgroups based on baseline clinical and biomarker characteristics revealed a statistically significant clinical improvement among all subgroups. INTERPRETATION: Five years after treatment, subjects experienced decreases in severe exacerbations, hospitalizations, ED visits, and corticosteroid exposure. All subgroups demonstrated clinically significant improvement, suggesting that bronchial thermoplasty improves asthma control in different asthma phenotypes. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT01350336; URL: www. CLINICALTRIALS: gov.

Torsades de pointes in SARS-CoV-2 (COVID-19) pneumonia: medicine reconciliation and careful monitoring of QTc interval may help prevent cardiac complications.

Hydroxychloroquine has been widely prescribed to treat patients with COVID-19 pneumonia. A 73-year-0ld woman with COVID-19 pneumonia was treated with dexamethasone and hydroxychloroquine. Her home medications, citalopram and donepezil, were continued. The ECG prior to starting hydroxychloroquine showed normal sinus rhythm with prolonged corrected QT (QTc) of 497 ms, due to citalopram and donepezil therapy. Repeat ECG on days 3 and 4 of hydroxychloroquine therapy showed significantly prolonged QTc of 557 ms and 538 ms, respectively, despite normal serum electrolytes. All QT-prolonging medications including hydroxychloroquine were discontinued on day 4; however, she suffered a transient torsades de pointes lasting for about 15 s, which resolved before any intervention. QTc improved to 477 ms, after discontinuation of QT-prolonging medications. The patient had QTc prolongation and torsades de pointes due to therapy with multiple QT-prolonging medications. Medicine reconciliation and careful monitoring of QTc may help prevent cardiac complications in patients with COVID-19 treated with hydroxychloroquine.