Search

Because of the coronavirus disease (COVID-19) pandemic, graduate medical education programs adopted virtual interviews (VIs) as the default modality for the 2020 recruitment season. It is unknown whether VIs allowed applicants to effectively evaluate programs, and the best interview format for the future is unclear.ToAfter the National Residency Matching Program medical subspecialty match, an electronic survey was sent to 1,067 applicants to pulmonary and critical care medicine programs asking them to compare their fellowship VI experience with their residency in-person interview (IPI) experience.Three hundred six (29%) applicants responded to the survey, and 289 completed it (27%). There were 117 (40%) women and 146 (51%) White individuals. Most respondents believed that VIs hindered their ability to evaluate programs' culture, faculty-fellow relationships, location, facilities, and their own fit within the program. They believed they were able to evaluate the clinical experience, curriculum, and potential for academic development equally well compared with IPIs. The most helpful elements of VIs were the interview with the program director, meetings with the fellows, and interviews with faculty members. Less helpful elements included conference access, prerecorded program director presentations, virtual hospital and city tours, and video testimonials. One hundred twenty-three respondents (43%) chose VIs with an optional visit as their preferred future interview format, 85 (29%) chose IPIs, 54 (19%) wanted a choice between VIs and IPIs, and 27 (9%) chose VIs only.Most pulmonary and critical care medicine applicants preferred future interviews to include both VIs and the option of an in-person visit or interview. This study can assist programs in designing their future interview formats in a trainee-centric fashion.

Rationale Two distinct subphenotypes have been identified in acute respiratory distress syndrome (ARDS), but the presence of subgroups in ARDS associated with COVID-19 is unknown. The objective of this study was to identify clinically relevant, novel subgroups in COVID-19-related ARDS, and compare them to previously described ARDS subphenotypes. Methods Eligible participants were adults with COVID-19 and ARDS at Columbia University Irving Medical Center. Latent class analysis (LCA) was used to identify subgroups with baseline clinical, respiratory, and laboratory data serving as partitioning variables. A previously-developed machine learning model was used to classify patients as the hypoinflammatory and hyperinflammatory subphenotypes. Baseline characteristics and clinical outcomes were compared between subgroups. Heterogeneity of treatment effect (HTE) for corticosteroid-use in subgroups was tested. Measurements and Main Results From 3/2-4/30/2020, 483 patients with COVID-19-related ARDS met study criteria. A two-class LCA model best fit the population (p=0.0075). Class 2 (23%) had higher pro-inflammatory markers, troponin, creatinine and lactate, lower bicarbonate and lower blood pressure than Class 1 (77%). 90-day mortality was higher in Class 2 versus Class 1 (75% vs 48%; p

Background Competence in ultrasonography is essential for pulmonary and critical care medicine (PCCM) fellows, but little is known about fellow-reported barriers to acquiring this crucial skill during fellowship training. Research Question How do PCCM fellows acquire experience performing and interpreting ultrasonography during their training, what is their perspective on barriers to acquiring ultrasound expertise during fellowship, and what is their comfort with a range of ultrasound examinations? Study Design and Methods A 20-item survey including questions about procedural training and acquisition of ultrasound skills during PCCM fellowship was developed. The survey instrument was sent to PCCM fellowship program directors to distribute to their fellows at program directors’ discretion. Results Four hundred seventy-five responses were received. The most common method of learning ultrasonography was performing it independently at the bedside. Fellows reported that the greatest barrier to acquiring ultrasound skills was the lack of trained faculty experts, followed by lack of a formal curriculum. Fellow comfort was greatest with thoracic ultrasound and least with advanced cardiac ultrasound. Interpretation Significant barriers to ultrasound training during PCCM fellowship exist, and future educational efforts should address these barriers at both program and institutional levels.

Extracorporeal life support (ECLS) has a role in different types of respiratory failure including acute respiratory distress syndrome (ARDS), decompensated pulmonary hypertension, bridge to lung transplantation, and primary graft dysfunction after lung transplantation. ECLS in ARDS allows for lung-protective ventilation with the goal to reduce the risk of ventilator-induced lung injury. ECLS use in severe ARDS should be considered when conventional management strategies are not sufficient to safely support gas exchange. More research is needed to identify optimal mechanical ventilation during ECLS, weaning ECLS support, strategies for mobilization, sedation and anticoagulation, and long-term outcomes post-ECLS.

Background The prevalence of burnout and depressive symptoms is high among physician trainees. Research Question What is the burden of burnout and depressive symptoms among fellows training in pulmonary and critical care medicine (PCCM) and what are associated individual fellow, program, and institutional characteristics? Study Design and Methods We conducted a cross-sectional electronic survey of fellows enrolled in pulmonary, PCCM, and critical care medicine training programs in the United States to assess burnout and depressive symptoms. Burnout symptoms were measured using the Maslach Burnout Index two-item measure. The two-item Primary Care Evaluation of Mental Disorders Procedure was used to screen for depressive symptoms. For each of the two outcomes (burnout and depressive symptoms), we constructed three multivariate logistic regression models to assess individual fellow characteristics, program structure, and institutional polices associated with either burnout or depressive symptoms. Results Five hundred two of the 976 fellows who received the survey completed it—including both outcome measures—giving a response rate of 51%. Fifty percent of fellows showed positive results for either burnout or depressive symptoms, with 41% showing positive results for depressive symptoms, 32% showing positive results for burnout, and 23% showing positive results for both. Reporting a coverage system in the case of personal illness or emergency (adjusted OR [aOR], 0.44; 95% CI, 0.26-0.73) and access to mental health services (aOR, 0.14; 95% CI, 0.04-0.47) were associated with lower odds of burnout. Financial concern was associated with higher odds of depressive symptoms (aOR, 1.13; 95% CI, 1.05-1.22). Working more than 70 hours in an average clinical week and the burdens of electronic health record (EHR) documentation were associated with a higher odds of both burnout and depressive symptoms. Interpretation Given the high prevalence of burnout and depressive symptoms among fellows training in PCCM, an urgent need exists to identify solutions that address this public health crisis. Strategies such as providing an easily accessible coverage system, access to mental health resources, reducing EHR burden, addressing work hours, and addressing financial concerns among trainees may help to reduce burnout or depressive symptoms and should be studied further by the graduate medical education community.

Rationale: Studies suggest a pathogenic role of endothelial dysfunction in chronic obstructive lung disease (COPD). Omega-3 (n-3) polyunsaturated fatty acid (PUFA) supplementation improves endothelial function in other diseases but has not been examined in COPD. Objective: We hypothesized that n-3 PUFA supplementation would improve systemic endothelial function in COPD. We performed a pilot randomized, placebo-controlled, double-blind, phase 2 superiority trial (NCT00835289). Methods: Adults with moderate and severe stable COPD (79% with emphysema on computed tomography [CT]) were randomized to high-dose fish oil capsules or placebo daily for 6 months. The primary endpoint was percentage change in brachial artery flow-mediated dilation (FMD) from baseline to 6 months. Secondary endpoints included peripheral arterial tonometry, endothelial microparticles (EMPs), 6-minute walk distance, respiratory symptoms, and pulmonary function. Results: Thirty-three of 40 randomized participants completed all measurements. Change in FMD after 6 months did not differ between the fish oil and placebo arms (-1.1%, 95% CI -5.0—2.9, p=0.59). CD31(+) EMPs increased in the fish oil arm (0.9%, 95% CI 0.1—1.7, p=0.04). More participants in the fish oil arm reported at least a 4-point improvement in the St George’s Respiratory Questionnaire (SGRQ) compared to placebo (8 versus 1; p=0.01). There were no significant changes in other secondary endpoints. There were 4 serious adverse events determined to be unrelated to the study (3 in the fish oil arm and 1 in the placebo arm). Conclusion: Randomization to n-3 PUFAs for 6 months did not change systemic endothelial function in COPD. Changes in EMPs and SGRQ suggest n-3 PUFAs might have biologic and clinical effects that warrant further investigation.

The coronavirus pandemic forced the Association of Pulmonary and Critical Care Medicine Program Directors to change the 2020 annual conference to a virtual format with relatively short notice. Using the experience of the planning committee and survey feedback from attendees, we describe the steps taken to implement a virtual conference and lessons learned in the process. The lessons described include frequent and concise communication, establishment of roles within a discrete production team, preparing speakers with a protocolized training session, active moderation of the chat box, using interactive polling and online documents to improve interactivity, a shorter agenda with more frequent breaks, encouraging "virtual happy hours" to connect with colleagues, and establishing facilitators for breakout rooms.

Background: All applicants to accredited training programs must write a personal statement as part of the application process. This may provoke anxiety on the part of the applicant and can result i...

RATIONALE: Communities of color are bearing a disproportionate burden of coronavirus disease 2019 (COVID-19) morbidity and mortality. Social determinants of health have resulted in higher prevalence and severity of COVID-19 among minority groups. Published work on COVID-19 disparities has focused on higher transmission, hospitalization, and mortality risk among people of color, but studies on disparities in the post-acute care setting are scarce. Our aim was to identify socioeconomic disparities in health resource utilization after hospital discharge. METHODS: This was a retrospective study. We identified adult patients who were hospitalized at CUIMC or the Allen Hospital from March 1st through April 30th 2020, had a positive RT-PCR for severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), developed severe hypoxemic respiratory failure requiring invasive mechanical ventilation, and were successfully discharged from the hospital without need for ventilator support. Patients who received a tracheostomy and were weaned off the ventilator prior to discharge were included. Exclusion criteria included transfer from or to another institution, prior tracheostomy, in-hospital death, and discharge with a ventilator. RESULTS: We identified 195 patients meeting inclusion criteria. The median age was 59 (IQR 47-67), and 135 (66.5%) were men. There were 25 (12.8%) patients who were uninsured and 116 (59.5%) patients who had public insurance. There were 121 (62%) Hispanic, 34 (17%) Black, and 18 (9%) White patients. Uninsured patients within our cohort were more likely to be Hispanic and Spanish-speaking (p=0.027;p

Background: Pulmonary and critical care medicine (PCCM) fellowship requires a high degree of medical knowledge and procedural competency. Gaps in fellowship readiness can result in significant trainee anxiety related to starting fellowship training. Objective: To improve fellowship readiness and alleviate anxiety for PCCM-bound trainees by improving confidence in procedural skills and cognitive domains. Methods: Medical educators within the American Thoracic Society developed a national resident boot camp (RBC) to provide an immersive, experiential training program for physicians entering PCCM fellowships. The RBC curriculum is a 2-day course designed to build procedural skills, medical knowledge, and clinical confidence through high-fidelity simulation and active learning methodology. Separate programs for adult and pediatric providers run concurrently to provide unique training objectives targeted to their learners’ needs. Trainee assessments include multiple-choice pre- and post-RBC knowledge tests and confidence assessments, which are scored on a four-point Likert scale, for specific PCCM-related procedural and cognitive skills. Learners also evaluate course material and educator effectiveness, which guide modifications of future RBC programs and provide feedback for individual educators, respectively. Results: The American Thoracic Society RBC was implemented in 2014 and has grown annually to include 132 trainees and more than 100 faculty members. Mean knowledge test scores for participants in the 2019 RBC adult program increased from 55% (±14% SD) on the pretest to 72% (±11% SD; P

Competence in ultrasonography is essential for pulmonary and critical care medicine (PCCM) fellows, but little is known about fellow-reported barriers to acquiring this crucial skill during fellowship training.How do PCCM fellows acquire experience performing and interpreting ultrasonography during their training, what is their perspective on barriers to acquiring ultrasound expertise during fellowship, and what is their comfort with a range of ultrasound examinations?A 20-item survey including questions about procedural training and acquisition of ultrasound skills during PCCM fellowship was developed. The survey instrument was sent to PCCM fellowship program directors to distribute to their fellows at program directors' discretion.Four hundred seventy-five responses were received. The most common method of learning ultrasonography was performing it independently at the bedside. Fellows reported that the greatest barrier to acquiring ultrasound skills was the lack of trained faculty experts, followed by lack of a formal curriculum. Fellow comfort was greatest with thoracic ultrasound and least with advanced cardiac ultrasound.Significant barriers to ultrasound training during PCCM fellowship exist, and future educational efforts should address these barriers at both program and institutional levels.

The prevalence of burnout and depressive symptoms is high among physician trainees.What is the burden of burnout and depressive symptoms among fellows training in pulmonary and critical care medicine (PCCM) and what are associated individual fellow, program, and institutional characteristics?We conducted a cross-sectional electronic survey of fellows enrolled in pulmonary, PCCM, and critical care medicine training programs in the United States to assess burnout and depressive symptoms. Burnout symptoms were measured using the Maslach Burnout Index two-item measure. The two-item Primary Care Evaluation of Mental Disorders Procedure was used to screen for depressive symptoms. For each of the two outcomes (burnout and depressive symptoms), we constructed three multivariate logistic regression models to assess individual fellow characteristics, program structure, and institutional polices associated with either burnout or depressive symptoms.Five hundred two of the 976 fellows who received the survey completed it-including both outcome measures-giving a response rate of 51%. Fifty percent of fellows showed positive results for either burnout or depressive symptoms, with 41% showing positive results for depressive symptoms, 32% showing positive results for burnout, and 23% showing positive results for both. Reporting a coverage system in the case of personal illness or emergency (adjusted OR [aOR], 0.44; 95% CI, 0.26-0.73) and access to mental health services (aOR, 0.14; 95% CI, 0.04-0.47) were associated with lower odds of burnout. Financial concern was associated with higher odds of depressive symptoms (aOR, 1.13; 95% CI, 1.05-1.22). Working more than 70 hours in an average clinical week and the burdens of electronic health record (EHR) documentation were associated with a higher odds of both burnout and depressive symptoms.Given the high prevalence of burnout and depressive symptoms among fellows training in PCCM, an urgent need exists to identify solutions that address this public health crisis. Strategies such as providing an easily accessible coverage system, access to mental health resources, reducing EHR burden, addressing work hours, and addressing financial concerns among trainees may help to reduce burnout or depressive symptoms and should be studied further by the graduate medical education community.

Chronic obstructive pulmonary disease (COPD), diagnosed by reduced lung function, is a leading cause of morbidity and mortality. We performed whole genome sequence (WGS) analysis of lung function and COPD in a multi-ethnic sample of 11,497 participants from population- and family-based studies, and 8499 individuals from COPD-enriched studies in the NHLBI Trans-Omics for Precision Medicine (TOPMed) Program. We identify at genome-wide significance 10 known GWAS loci and 22 distinct, previously unreported loci, including two common variant signals from stratified analysis of African Americans. Four novel common variants within the regions of PIAS1, RGN (two variants) and FTO show evidence of replication in the UK Biobank (European ancestry n ~ 320,000), while colocalization analyses leveraging multi-omic data from GTEx and TOPMed identify potential molecular mechanisms underlying four of the 22 novel loci. Our study demonstrates the value of performing WGS analyses and multi-omic follow-up in cohorts of diverse ancestry., Chronic obstructive pulmonary disease is a leading cause of morbidity and mortality. Here, the authors analyse whole genome sequence data and find new loci associated with lung function and COPD.

Background: The progression of clinical manifestations in patients with coronavirus disease 2019 (COVID-19) highlights the need to account for symptom duration at the time of hospital presentation in decision-making algorithms. Methods: We performed a nested case–control analysis of 4103 adult patients with COVID-19 and at least 28 days of follow-up who presented to a New York City medical center. Multivariable logistic regression and classification and regression tree (CART) analysis were used to identify predictors of poor outcome. Results: Patients presenting to the hospital earlier in their disease course were older, had more comorbidities, and a greater proportion decompensated (&lt, 4 days, 41%, 4–8 days, 31%, &gt, 8 days, 26%). The first recorded oxygen delivery method was the most important predictor of decompensation overall in CART analysis. In patients with symptoms for &lt, 4, 4–8, and &gt, 8 days, requiring at least non-rebreather, age ≥ 63 years, and neutrophil/lymphocyte ratio ≥ 5.1, requiring at least non-rebreather, IL-6 ≥ 24.7 pg/mL, and D-dimer ≥ 2.4 µg/mL, and IL-6 ≥ 64.3 pg/mL, requiring non-rebreather, and CRP ≥ 152.5 mg/mL in predictive models were independently associated with poor outcome, respectively. Conclusion: Symptom duration in tandem with initial clinical and laboratory markers can be used to identify patients with COVID-19 at increased risk for poor outcomes.

Interventional pulmonology (IP) is a rapidly evolving subspecialty of pulmonary medicine. In the last 10 years, formal IP fellowships have increased substantially in number from five to now > 30. The vast majority of IP fellowship trainees are selected through the National Resident Matching Program, and validated in-service and certification examinations for IP exist. Practice standards and training guidelines for IP fellowship programs have been published; however, considerable variability in the environment, curriculum, and experience offered by the various fellowship programs remains, and there is currently no formal accreditation process in place to standardize IP fellowship training. Recognizing the need for more uniform training across the various fellowship programs, a multisociety accreditation committee was formed with the intent to establish common accreditation standards for all IP fellowship programs in the United States. This article provides a summary of those standards and can serve as an accreditation template for training programs and their offices of graduate medical education as they move through the accreditation process.

Nearly 100 loci have been identified for pulmonary function, almost exclusively in studies of European ancestry populations. We extend previous research by meta-analyzing genome-wide association studies of 1000 Genomes imputed variants in relation to pulmonary function in a multiethnic population of 90,715 individuals of European (N = 60,552), African (N = 8429), Asian (N = 9959), and Hispanic/Latino (N = 11,775) ethnicities. We identify over 50 additional loci at genome-wide significance in ancestry-specific or multiethnic meta-analyses. Using recent fine-mapping methods incorporating functional annotation, gene expression, and differences in linkage disequilibrium between ethnicities, we further shed light on potential causal variants and genes at known and newly identified loci. Several of the novel genes encode proteins with predicted or established drug targets, including KCNK2 and CDK12. Our study highlights the utility of multiethnic and integrative genomics approaches to extend existing knowledge of the genetics of lung function and clinical relevance of implicated loci., Supported in part by the Intramural Research Program of the National Institutes of Health, NIEHS. Infrastructure for the CHARGE Consortium is supported in part by the National Heart, Lung, and Blood Institute Grant R01HL105756

Lung function and chronic obstructive pulmonary disease (COPD) are heritable traits. Genome-wide association studies (GWAS) have identified numerous pulmonary function and COPD loci, primarily in cohorts of European ancestry.Perform a GWAS of COPD phenotypes in Hispanic/Latino populations to identify loci not previously detected in European populations.GWAS of lung function and COPD in Hispanic/Latino participants from a population-based cohort. We performed replication studies of novel loci in independent studies.Among 11,822 Hispanic/Latino participants, we identified eight novel signals; three replicated in independent populations of European Ancestry. A novel locus for FEVWe identified novel signals for lung function and COPD in a Hispanic/Latino cohort. Including admixed populations when performing genetic studies may identify variants contributing to genetic etiologies of COPD.

This paper outlines specific tips for those applying to pulmonary and/or critical care medicine fellowship training in the United States using the PAIR-Match steps: preparation, application, interview, ranking, and match. Preparation for fellowship begins long before the application process with an assessment of one's long-term goals (to the extent that these are known). The cornerstone of the application is the curriculum vitae, which should highlight applicants' pulmonary and critical care-related experiences and scholarly work. Applicants should obtain letters of recommendation from faculty members who know them well and can write a letter that speaks to their strengths in clinical, scholarly, or leadership areas. The personal statement is an opportunity to share experiences not otherwise shared in the application and is an opportunity to explain any breaks in training or performance lapses. When selecting programs to which they will apply, applicants should pay close attention to the areas of education and curriculum, clinical experience, scholarly opportunity, and personal factors. Preparing for interviews should include a review of the program at which one is interviewing and development of relevant questions regarding details of the program. The interview day is the applicant's opportunity to see the "personality" of the program by meeting with the program director, faculty, and current fellows and to assess whether the program is a good fit for their goals. Applicants should only rank those programs they are willing to attend, in order of preference; they should be aware that the match process is binding.

Investigate the prevalence, risk factors and impact of continuous EEG (cEEG) abnormalities on mortality through the 1-year follow-up period in patients with severe sepsis. Prospective, single-center, observational study of consecutive patients admitted with severe sepsis to the Medical ICU at an academic medical center. A total of 98 patients with 100 episodes of severe sepsis were included; 49 patients (50%) were female, median age was 60 (IQR 52–74), the median non-neuro APACHE II score was 23.5 (IQR 18–28) and median non-neuro SOFA score was 8 (IQR 6–11). Twenty-five episodes had periodic discharges (PD), of which 11 had nonconvulsive seizures (NCS). No patient had NCS without PD. Prior neurological history was associated with a higher risk of PD or NCS (45 vs. 17%; CI 1.53–10.43), while the non-neuro APACHE II, non-neuro SOFA, severity of cardiovascular shock and presence of sedation during cEEG were associated with a lower risk of PD or NCS. Clinical seizures before cEEG were associated with a higher risk of nonconvulsive status epilepticus (24 vs. 6%; CI 1.42–19.94) while the non-neuro APACHE II and non-neuro SOFA scores were associated with a lower risk. Lack of EEG reactivity was present in 28% of episodes. In the survival analysis, a lack of EEG reactivity was associated with higher 1-year mortality [mean survival time 3.3 (95% CI 1.8–4.9) vs. 7.5 (6.4–8.7) months; p = 0.002] but the presence of PD or NCS was not [mean survival time 3.3 (95% CI 1.8–4.9) vs. 7.5 (6.4–8.7) months; p = 0.592]. Lack of reactivity was more frequent in patients on continuous sedation during cEEG. In patients with available 1-year data (34% of the episodes), 82% had good functional outcome (mRS ≤ 3, n = 27). There were no significant predictors of functional outcome, late cognition, and no patient with complete follow-up data developed late seizure or new epilepsy. NCS and PD are common in patients with severe sepsis and altered mental status. They were less frequent among the most severely sick patients and were not associated with outcome in this study. Lack of EEG reactivity was more frequent in patients on continuous sedation and was associated with mortality up to 1 year after discharge. Larger studies are needed to confirm these findings in a broader population and to further evaluate long-term cognitive outcome, risk of late seizure and epilepsy.

Rationale: Genome-wide association studies (GWAS) of chronic obstructive pulmonary disease (COPD) have identified disease-susceptibility loci, mostly in subjects of European descent.Objectives: We hypothesized that by studying Hispanic populations we would be able to identify unique loci that contribute to COPD pathogenesis in Hispanics but remain undetected in GWAS of non-Hispanic populations.Methods: We conducted a metaanalysis of two GWAS of COPD in independent cohorts of Hispanics in Costa Rica and the United States (Multi-Ethnic Study of Atherosclerosis [MESA]). We performed a replication study of the top single-nucleotide polymorphisms in an independent Hispanic cohort in New Mexico (the Lovelace Smokers Cohort). We also attempted to replicate prior findings from genome-wide studies in non-Hispanic populations in Hispanic cohorts.Measurements and Main Results: We found no genomewide significant association with COPD in our metaanalysis of Costa Rica and MESA. After combining the top results from this metaanalysis with those from our replication study in the Lovelace Smokers Cohort, we identified two single-nucleotide polymorphisms approaching genome-wide significance for an association with COPD. The first (rs858249, combined P value = 6.1 X 10(-8)) is near the genes KLHL7 and NUPL2 on chromosome 7. The second (rs286499, combined P value = 8.4 X 10(-8)) is located in an intron of DLG2. The two most significant single-nucleotide polymorphisms in FAM13A from a previous genome-wide study in non-Hispanics were associated with COPD in Hispanics.Conclusions: We have identified two novel loci (in or near the genes KLHL7/NUPL2 and DLG2) that may play a role in COPD pathogenesis in Hispanic populations.

Nearly 100 loci have been identified for pulmonary function, almost exclusively in studies of European ancestry populations. We extend previous research by meta-analyzing genome-wide association studies of 1000 Genomes imputed variants in relation to pulmonary function in a multiethnic population of 90,715 individuals of European (N=60,552), African (N=8,429), Asian (N=9,959), and Hispanic/Latino (N=11,775) ethnicities. We identified over 50 novel loci at genome-wide significance in ancestry-specific and/or multiethnic meta-analyses. Recent fine mapping methods incorporating functional annotation, gene expression, and/or differences in linkage disequilibrium between ethnicities identified potential causal variants and genes at known and newly identified loci. Sixteen of the novel genes encode proteins with predicted or established drug targets, including KCNK2 and CDK12.

Background: Over 90 regions of the genome have been associated with lung function to date, many of which have also been implicated in chronic obstructive pulmonary disease. Methods: We carried out meta-analyses of exome array data and three lung function measures: forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and the ratio of FEV1 to FVC (FEV1/FVC). These analyses by the SpiroMeta and CHARGE consortia included 60,749 individuals of European ancestry from 23 studies, and 7,721 individuals of African Ancestry from 5 studies in the discovery stage, with follow-up in up to 111,556 independent individuals. Results: We identified significant (P-7) associations with six SNPs: a nonsynonymous variant in RPAP1, which is predicted to be damaging, three intronic SNPs (SEC24C, CASC17 and UQCC1) and two intergenic SNPs near to LY86 and FGF10. Expression quantitative trait loci analyses found evidence for regulation of gene expression at three signals and implicated several genes, including TYRO3 and PLAU. Conclusions: Further interrogation of these loci could provide greater understanding of the determinants of lung function and pulmonary disease.

Wellness is critical to physicians in training and the general physician workforce. At present, physicians in general and especially intensive care unit physicians are experiencing high rates of depression and burnout. The prevalence of burnout is greatest in resident and fellow trainees. The Accreditation Council for Graduate Medical Education has recognized the importance of physician wellness by proposing Common Program Requirements that pertain to trainee and faculty well-being. Several individual-focused, organizational, and structural strategies have been described in the literature as helpful in decreasing burnout. Successful implementation of a trainee wellness program requires institutional resources and collaborative efforts between the institution, leadership, faculty, and trainees. To ensure the greatest effect in reducing burnout, training programs and institutions should create programs that intervene at both the organizational and individual levels. Additional steps to implement a trainee wellness program include the following: (1) establish support from institutional and divisional leadership; (2) create a wellness committee; (3) perform a needs assessment; (4) assess trainee wellness and burnout; (5) perform targeted interventions; and (6) routinely reassess trainee wellness and burnout. More research is needed to identify and refine strategies that improve wellness and decrease burnout among physicians and trainees. As a community, we must take on the challenge of improving wellness among physicians for the benefit of our trainees, ourselves, and our patients.

Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P

Extracorporeal membrane oxygenation (ECMO) can serve as a bridge to recovery in cases of acute reversible illness, a bridge to transplantation in circumstances of irreversible cardiac or respiratory failure, a bridge to ventricular assist device therapy in select cases of cardiac failure, or a bridge to decision when the prognosis remains uncertain. Recent advances in ECMO technology that allow for prolonged support with decreased complications, the development of mobile ECMO teams, the rapidity of initiation, and the growing body of evidence, much of which remains controversial, have led to a significant increase in the use of ECMO worldwide. This increasing use of a technology that is not a destination device in itself introduces many ethical dilemmas specific to this technology. In this article, we explore some of the ethical issues inherent in the decisions surrounding the initiation and withdrawal of ECMO by raising key questions and providing a framework for clinicians. We will address extracorporeal cardiopulmonary resuscitation, the inability to bridge a patient to transplant or recovery--the so-called "bridge to nowhere"--and the significance of resuscitation preferences in the setting of continual extracorporeal circulatory support.

Extracorporeal membrane oxygenation (ECMO) may be used to support patients with severe hypoxemic respiratory failure refractory to conventional mechanical ventilation. However, because systemic anticoagulation is generally required to maintain circuit patency, severe bleeding is often seen as a contraindication to ECMO. We describe our center's experience with four patients who received ECMO for refractory hypoxemic respiratory failure due to diffuse alveolar hemorrhage (DAH), a condition for which anticoagulation is typically contraindicated, and provide a review of the literature. The mean age was 35.8 ± 16.4 years. The mean pre-ECMO PaO2 to FIO2 ratio was 52.3 ± 9.4 mm Hg. All patients were treated with continuous infusions of heparin with a goal-activated partial thromboplastin time between 40 and 60 seconds (mean, 47.4 ± 11.6 seconds). All four subjects (100%) survived to decannulation, and three subjects (75%) survived to discharge. The results from this case series, along with previously published data, suggest that ECMO is a reasonable management option for patients with DAH-associated severe, refractory hypoxemic respiratory failure. This is especially true in the era of modern ECMO technology where lower levels of anticoagulation are able to maintain circuit patency while minimizing bleeding risk.

Acute exacerbations of chronic obstructive pulmonary disease (COPD) requiring invasive mechanical ventilation (IMV) are associated with significant morbidity and mortality. Extracorporeal carbon dioxide removal (ECCO₂R) may facilitate extubation and ambulation in these patients and potentially improve outcomes.We assessed the feasibility of achieving early extubation and ambulation in subjects requiring IMV for exacerbations of COPD using single-site ECCO₂R.Five subjects with exacerbations of COPD with uncompensated hypercapnia requiring IMV were enrolled in this single-center, prospective, feasibility trial using a protocol of ECCO₂R, extubation, and physical rehabilitation. The primary endpoint was extubation within 72 hours of starting ECCO₂R.Mean preintubation pH and PaCO₂ were 7.23 ± 0.05 and 81.6 ± 15.9 mm Hg, respectively. All subjects met the primary endpoint (median duration, 4 h; range, 1.5-21.5 h). Mean duration of extracorporeal support was 193.0 ± 76.5 hours. Mean time to ambulation after extracorporeal initiation was 29.4 ± 12.6 hours. Mean maximal ambulation on extracorporeal support was 302 feet (range, 70-600). Four subjects were discharged home, and one underwent planned lung transplantation. Two minor bleeding complications occurred. There were no complications from mobilization on extracorporeal support.ECCO₂R facilitates early extubation and ambulation in exacerbations of COPD requiring IMV and has the potential to serve as a new paradigm for the management of a select group of patients. Rigorous clinical trials are needed to corroborate these results and to investigate the effect on long-term outcomes and cost effectiveness over conventional management.

Chronic obstructive pulmonary disease (COPD) is linked to cardiovascular disease; however, there are few studies on the associations of cardiovascular genes with COPD. We assessed the association of lung function with 2,100 genes selected for cardiovascular diseases among 20,077 European-Americans and 6,900 African-Americans. We performed replication of significant loci in the other racial group and an independent consortium of Europeans, tested the associations of significant loci with percent emphysema, and examined gene expression in an independent sample. We then tested the association of a related lipid biomarker with FEV1/FVC and percent emphysema. We identified one new polymorphism for FEV1/FVC (rs805301) in European-Americans (p=1.3×10−6) and a second (rs707974) in the combined European-American and African-American analysis (p=1.38×10−7). Both SNPs flank the gene for apolipoprotein M (apoM), a component of HDL. Both replicated in an independent cohort. SNPs in a second gene related to apoM and HDL, PCSK9 , were associated with FEV1/FVC among African-Americans. rs707974 was associated with percent emphysema among European-Americans and African-Americans, and APOM expression was related to FEV1/FVC and percent emphysema. Higher HDL levels were associated with lower FEV1/FVC and greater percent emphysema. These findings suggest a novel role for the APOM/HDL pathway in the pathogenesis of COPD and emphysema.

A 50-year-old man was admitted to the intensive care unit with respiratory failure and shock after suffering a massive overdose of amlodipine, lisinopril and hydrochlorothiazide. Despite mechanical ventilation, vasopressors, calcium gluconate, hyperinsulinemia-euglycemia therapy, methylene blue and intravenous fat emulsion, the patient’s respiratory and hemodynamic status deteriorated. Venoarterial extracorporeal membrane oxygenation (ECMO) was initiated to provide cardiopulmonary support in the setting of profound respiratory failure and refractory shock. The patient was placed on ECMO 19 hours after arrival to the hospital, after which vasopressor and ventilatory requirements decreased significantly. The patient was decannulated from ECMO after 8 days and was discharged home after a 56-day hospitalization. Early institution of ECMO should be considered for the management of respiratory failure and refractory shock in the setting of calcium channel blocker overdose when medical therapies are insufficient.

Pulmonary arterial hypertension (PAH) is a disease with significant morbidity and mortality, particularly during an acute decompensation. We describe a single-center experience of three patients with severe Group 1 PAH, refractory to targeted medical therapy, in which an extubated, nonsedated, extracorporeal membrane oxygenation (ECMO) strategy with an upper-body configuration was used as a bridge to recovery or lung transplantation. All three patients were extubated within 24 hours of ECMO initiation. Two patients were successfully bridged to lung transplantation, and the other patient was optimized on targeted PAH therapy with subsequent recovery from an acute decompensation. The upper-body ECMO configuration allowed for daily physical therapy, including one patient, who would otherwise have been unsuitable for transplantation, ambulating over 850 meters daily. This series demonstrates the feasibility of using ECMO to bridge PAH patients to recovery or transplantation while avoiding the complications of immobility and invasive mechanical ventilation.

Interventional pulmonology (IP) is a rapidly evolving subspecialty of pulmonary medicine. In the last 10 years, formal IP fellowships have increased substantially in number from five to now30. The vast majority of IP fellowship trainees are selected through the National Resident Matching Program, and validated in-service and certification examinations for IP exist. Practice standards and training guidelines for IP fellowship programs have been published; however, considerable variability in the environment, curriculum, and experience offered by the various fellowship programs remains, and there is currently no formal accreditation process in place to standardize IP fellowship training. Recognizing the need for more uniform training across the various fellowship programs, a multisociety accreditation committee was formed with the intent to establish common accreditation standards for all IP fellowship programs in the United States. This article provides a summary of those standards and can serve as an accreditation template for training programs and their offices of graduate medical education as they move through the accreditation process.

Introduction: COPD is a major cause of morbidity and mortality, yet risk factors in the general population beyond smoking are poorly defined. HDL particles contain ceramides that cause emphysema in mice; higher HDL-C and HDL-related genes are associated with radiographic emphysema and lower lung function. Aims: To test associations of HDL-C with decline in lung function in the general population. Methods: Six US population-based cohorts of adults were harmonized and pooled. Pre-bronchodilator spirometry was measured repeatedly following ATS/ERS guidelines. HDL-C was measured by enzymatic methods. Mixed models with cohort-specific covariance structure were adjusted for baseline age, sex, race/ethnicity, pack-years, hypertension, LDL and total cholesterol, cohort, and time-varying height, weight, and smoking status. Results: Among 32,350 adults with longitudinal spirometry measures (mean age 49±19 years, 45% never smokers, 25% obese, 14% with airflow limitation, median 2 measures), mean HDL-C was 1.4±0.4 mmol/L. The mean rate of FEV 1 decline was 29.2±0.1 mL/year. In adjusted models, higher HDL-C was associated with a greater rate of decline in FEV 1 (P 1 /FVC (P 1 (P Conclusions: Higher levels of HDL-C were associated with more rapid decline in lung function in a large US population-based sample of adults.

RATIONALE: Genome-wide association studies (GWAS) have identified loci influencing lung function, but fewer genes influencing chronic obstructive pulmonary disease (COPD) are known.OBJECTIVES: Perform meta-analyses of GWAS for airflow obstruction, a key pathophysiologic characteristic of COPD assessed by spirometry, in population-based cohorts examining all participants, ever smokers, never smokers, asthma-free participants, and more severe cases.METHODS: Fifteen cohorts were studied for discovery (3,368 affected; 29,507 unaffected), and a population-based family study and a meta-analysis of case-control studies were used for replication and regional follow-up (3,837 cases; 4,479 control subjects). Airflow obstruction was defined as FEV(1) and its ratio to FVC (FEV(1)/FVC) both less than their respective lower limits of normal as determined by published reference equations.MEASUREMENTS AND MAIN RESULTS: The discovery meta-analyses identified one region on chromosome 15q25.1 meeting genome-wide significance in ever smokers that includes AGPHD1, IREB2, and CHRNA5/CHRNA3 genes. The region was also modestly associated among never smokers. Gene expression studies confirmed the presence of CHRNA5/3 in lung, airway smooth muscle, and bronchial epithelial cells. A single-nucleotide polymorphism in HTR4, a gene previously related to FEV(1)/FVC, achieved genome-wide statistical significance in combined meta-analysis. Top single-nucleotide polymorphisms in ADAM19, RARB, PPAP2B, and ADAMTS19 were nominally replicated in the COPD meta-analysis.CONCLUSIONS: These results suggest an important role for the CHRNA5/3 region as a genetic risk factor for airflow obstruction that may be independent of smoking and implicate the HTR4 gene in the etiology of airflow obstruction.

Chronic obstructive pulmonary disease (COPD) is defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) as a disease state characterized by airflow limitation that is not fully reversible (1). Cigarette smoking is the most important risk factor for the development of COPD. Although the dose-response relationship between cigarette smoking and pulmonary function is well-established, there is considerable variability in the reduction in FEV1 among smokers with similar smoking exposures (2, 3). The low percentage of variance in pulmonary function explained by smoking suggests that there could be genetic differences in susceptibility to the effects of cigarette smoking (4, 5). In addition to genetic factors, other environmental determinants such as indoor biomass smoke exposure can be important risk factors for COPD (6). A small percentage of COPD patients (estimated at 1-2%) inherit severe alpha-1 antitrypsin (AAT) deficiency, which proves that genetic factors can in-fluence COPD susceptibility. The discovery of AAT deficiency was a major factor in the development of the Protease-Antiprotease Hypothesis for COPD, which has been one of the prevailing models of disease pathogenesis for more than 40 years. With the substantial impact of AAT deficiency on our understanding of COPD pathogenesis, it was natural to hope that the identification of other COPD susceptibility genes would lead to similar novel insights into COPD. Until recently, however, progress in the identification of additional genetic risk factors for COPD has been slow. To facilitate the development of such research, a meeting of COPD genetics investigators was held on July 13-14,2010 in Boston. The goals of the meeting were: To review the current state of COPD genetics research; To discuss existing study populations for COPD genetics research throughout the world; To consider opportunities for collaborations between different COPD research groups through an International COPD Genetics Consortium; To recognize challenges in building COPD genetics collaborations and to discuss them openly; and, To develop a framework for future collaborative studies. Current status of COPD genetics research Many candidate gene association studies have been performed over the past 40 years, but the results have been largely inconsistent. These inconsistencies likely relate to a variety of methodological issues, including small sample sizes, variable definitions of case and control groups, failure to adjust for multiple statistical testing, and inadequate adjustments for population stratification and smoking exposure. Most of the studies describing COPD-associated polymorphisms were performed in White populations (7). A meta-analysis of 20 polymorphisms in 12 candidate genes involved in the protease-antiprotease balance and several an-tioxidant pathways showed that, after combining independent studies, many of these candidate genes had no association with COPD (8). Another factor likely impeding the progress of identifying COPD susceptibility genes is the lack of accurate phenotypic characterization of this complex and heterogeneous disease. Airflow limitation determined by spirometry has been the most common approach to classify and monitor the disease. Structural changes of the lung including emphysema and small airway obstruction are the primary processes that affect lung function (9), but they are not easily discernable with the simple spirometric measures commonly used for phe-notyping COPD. Recent advances in characterizing pathologic changes such as emphysema and remodeling of the small and large airways by quantitative analyses of image data from multidetector computed tomography (CT), together with physiological testing, have been helpful to differentiate COPD phenotypes (emphysema-predominant, airway-predominant, or mixed)(10). Study populations that have chest CT data may help to better identify COPD-associated genetic variations (11). Other potentially relevant COPD phenotypes, such as cachexia and low exercise capacity, have not been widely analyzed in COPD genetic studies. Perhaps the greatest problem in the candidate gene era of COPD genetic studies was improper candidate gene selection, which reflects our limited understanding of COPD pathogenesis. However, the application of genome-wide association studies (GWAS), which provide an unbiased and comprehensive search throughout the genome for common susceptibility loci, has changed the landscape of COPD genetics. Based on GWAS, three genetic loci have been unequivocally associated with COPD susceptibility, located on chromosome 4 near the HHIP gene, on chromosome 4 in the FAM13A gene, and on chromosome 15 in a block of genes which contains several components of the nicotinic acetyl-choline receptor as well as the IREB2 gene. In 2009, a series of studies provided convincing support for these three genetic loci in COPD susceptibility. Pillai and colleagues found genome-wide significant associations of the CHRNA3/CHRNA5/IREB2 region to COPD (12). DeMeo and colleagues performed gene expression studies of normal vs. COPD lung tissues followed by genetic association analysis of COPD (13), suggesting that at least one of the key COPD genetic determinants in the chromosome 15 GWAS region was IREB2. In the Framingham Heart Study (14), the HHIP region was associated with FEV1/FVC at genome-wide significance with replication of the effect on FEV1/FVC demonstrated in an independent sample drawn from the Family Heart Study, and this same region nearly reached genome-wide significance with COPD susceptibility in the Pillai paper (12). Recently, two papers published in Nature Genetics from large general population samples have provided strong support for the association of HHIP SNPs with FEV1/FVC (15, 16). One of these articles, from the CHARGE Consortium, also found evidence for association of FEV1/FVC with the FAM13A locus (15), which has been strongly associated with COPD susceptibility (17). Moreover, several case-control studies from other European populations have replicated these findings by confirming significant associations to the chromosome 15q25 locus (CHRNA3/CHRNA5/IREB2) (18, 19), chromosome 4q31 locus (HHIP) (20, 21), and chromosome 4q22 locus (FAM13 A) (22). Thus, the frustration of inconsistent genetic association results in COPD from the beginning of the last decade has been replaced by optimism regarding the likely importance of the IREB2/CHRNA3/CHRNA5, HHIP, and FAM13A loci in COPD susceptibility.