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Purpose To determine racial differences in intensive care unit (ICU) mortality outcomes among mechanically ventilated patients with severe coronavirus disease 2019 (COVID-19) infection in a safety net hospital. Methods We retrospectively analyzed a cohort of patients ≥ 18 years old with confirmed severe acute respiratory syndrome-CoV-2 disease associated respiratory failure who were treated with invasive mechanical ventilation and admitted to the ICU from May 1, 2020 – July 30 -2020 at Grady Memorial Hospital, Atlanta, Georgia – a safety net hospital. We evaluated the association between mortality and demographics, co-morbidities, inpatient laboratory, and radiological parameters. Results Among 181 critically ill mechanically ventilated African American patients treated at a safety net hospital, the mortality rate was 33%. On stratified analysis by race (Table 2), mortality rates were significantly higher in African Americans (39%) and Hispanics (26.3%), compared to Whites (18.9%). On multivariate regression, African Americans were 3 times more likely to die in the ICU compared to Whites (OR 3.1 95% CI 1.6 -5.5). Likewise, the likelihood of mortality was higher in Hispanics compared to Whites (OR 1.3 95% CI 1.0 -3.9). Conclusions Our study demonstrated a high ICU mortality rate in a cohort of mechanically ventilated patients with severe COVID-19 infection treated at a safety net hospital. African Americans and Hispanics had significantly higher risks of ICU mortality compared to Whites. These study findings further elucidate the disproportionately higher burden of COVID-19 infection in African Americans and Hispanics.

BACKGROUND There is limited data on the difference in the clinical characteristics and outcomes of patients with severe coronavirus disease 2019 (COVID-19) infection in the summer compared to the fall surge. AIM To compare the sociodemographic, clinical characteristics, and outcomes among mechanically ventilated patients with severe COVID-19 infection admitted to the intensive care unit (ICU) during the summer and fall surges in the year 2020. METHODS We included patients admitted to the ICU and treated with invasive mechanical ventilation for COVID-19 associated respiratory failure between April 1 and December 31, 2020. Patients were categorized into summer surge for ICU admissions between June 15, 2020, and August 15, 2020, and fall surge between October 15, 2020, and December 31, 2020. We compared patients' characteristics and outcomes using descriptive and inferential statistics. RESULTS A total of 220 patients were admitted to the Grady Memorial Hospital ICU and mechanically ventilated for COVID-19 associated hypoxemic respiratory failure during the period considered (125 during the summer surge and 95 during the fall surge). More women were admitted in the fall compared to summer (41.1% vs 36.8%, difference, 4.3%; 95%CI: 1.2, 7.5). Patients admitted in the fall had fewer comorbidities (chronic obstructive pulmonary disease, stroke, diabetes mellitus, obstructive sleep apnea and body mass index ≥ 35 kg/m2). Overall, patients in the fall had a lower ICU mortality rate (27.4% vs 38.4%, difference, -11.0; 95%CI: -6.4, -18.2), shorter length of stay on the mechanical ventilator (7 d vs 11 d, difference, 4 d; 95%CI: 2.1, 6.6) and shorter ICU length of stay (9 d vs 14 d, difference, 5 d; 95%CI: 2.7, 9.4). CONCLUSION Patients admitted with severe COVID-19 infection requiring mechanical ventilation had better outcomes in the fall than summer. This difference observed is likely attributable to a better understanding of the condition and advances in treatment strategies.

Introduction We surveyed a cohort of patients who recovered from severe SARS-CoV-2 infection to determine the COVID-19 vaccination rate. We also compared the willingness to accept COVID-19 vaccine before and after its availability to assess changes in perception and attitude towards vaccination. Materials and methods Recovered patients with severe hypoxemic respiratory failure from SARS-CoV-2 infection treated in the ICU at Grady Memorial Hospital, Atlanta, Georgia between April 1, 2020, and June 30, 2020 were followed up over a 1-year period to assess vaccine acceptability and acceptance rates, and changes in perception towards COVID-19 vaccination before and after vaccine availability. Results A total of 98 and 93 patients completed the initial and follow up surveys respectively. During the initial survey, 41% of the patients intended to receive vaccination, 46% responded they would not accept a vaccine against COVID-19 even if it were proven to be 'safe and effective 'and 13% undecided. During the follow up survey, 44% of the study cohort had received at least one dose of a COVID-19 vaccine. Major reasons provided by respondents for not accepting COVID-19 vaccine were lack of trust in the effectiveness of the vaccine, pharmaceutical companies, government, vaccine technology, fear of side effects and perceived immunity against COVID-19. Respondents were more likely to be vaccinated if recommended by their physicians (OR 6.4, 95% CI 2.8-8.3), employers (OR 2.5, 95% CI 1.9-5.8), and family and friends (OR 1.6, 95% CI 1.1-4.5). Conclusion We found a suboptimal COVID-19 vaccination rate in a cohort of patients who recovered from severe infection. COVID-19 vaccine information and recommendation by healthcare providers, employers, and family and friends may improve vaccination uptake.

BACKGROUND: Smokers manifest varied phenotypes of pulmonary impairment. RESEARCH QUESTION: Which pulmonary phenotypes are associated with coronary artery disease (CAD) in smokers? STUDY DESIGN AND METHODS: We analyzed data from the University of Pittsburgh COPD Specialized Center for Clinically Oriented Research (SCCOR) cohort (n = 481) and the Genetic Epidemiology of COPD (COPDGene) cohort (n = 2,580). Participants were current and former smokers with > 10 pack-years of tobacco exposure. Data from the two cohorts were analyzed separately because of methodologic differences. Lung hyperinflation was assessed by plethysmography in the SCCOR cohort and by inspiratory and expiratory CT scan lung volumes in the COPDGene cohort. Subclinical CAD was assessed as the coronary artery calcium score, whereas clinical CAD was defined as a self-reported history of CAD or myocardial infarction (MI). Analyses were performed in all smokers and then repeated in those with airflow obstruction (FEV(1) to FVC ratio, < 0.70). RESULTS: Pulmonary phenotypes, including airflow limitation, emphysema, lung hyperinflation, diffusion capacity, and radiographic measures of airway remodeling, showed weak to moderate correlations (r < 0.7) with each other. In multivariate models adjusted for pulmonary phenotypes and CAD risk factors, lung hyperinflation was the only phenotype associated with calcium score, history of clinical CAD, or history of MI (per 0.2 higher expiratory and inspiratory CT scan lung volume; coronary calcium: OR, 1.2; 95% CI, 1.1-1.5; P = .02; clinical CAD: OR, 1.6; 95% CI, 1.1-2.3; P = .01; and MI in COPDGene: OR, 1.7; 95% CI, 1.0-2.8; P = .05). FEV(1) and emphysema were associated with increased risk of CAD (P < .05) in models adjusted for CAD risk factors; however, these associations were attenuated on adjusting for lung hyperinflation. Results were the same in those with airflow obstruction and were present in both cohorts. INTERPRETATION: Lung hyperinflation is associated strongly with clinical and subclinical CAD in smokers, including those with airflow obstruction. After lung hyperinflation was accounted for, FEV(1) and emphysema no longer were associated with CAD. Subsequent studies should consider measuring lung hyperinflation and examining its mechanistic role in CAD in current and former smokers.

Background Coronavirus disease (COVID-19) disproportionately affects African Americans, and they tend to experience more severe course and adverse outcomes. Using a simple and validated instrument of depression screening, we evaluated the incidence and severity of major depression among African American patients within 90 days of recovery from severe COVID-19-associated respiratory failure. Methods African American patients hospitalized and treated with invasive mechanical ventilation for COVID-19-associated respiratory failure in the intensive care unit (ICU) of Grady Memorial Hospital, Atlanta, between April 1, 2020, and June 30, 2020, were screened for depression within 90 days of hospital discharge using the validated patient health questionnaires (PHQ-2) and PHQ-9. Results A total of 73 patients completed the questionnaire. The median age was 52.5 years [IQR 44–65] and 65% were males. The most common comorbidities were hypertension (66%) and diabetes mellitus (51%). Forty-four percent of the patients had a diagnosis of major depressive disorder (MDD) based on their PHQ-9 questionnaire responses. The incidence of MDD was higher among females (69%, n=18/26) compared to males (29%, n=14/47), in patients > 75 years (66%) and those with multiple comorbidities (45%). Eighteen percent of the patients had moderate depression, while 15% and 22% had moderately severe and severe depression, respectively. Only 26% (n=7/27) of eligible patients were receiving treatment for depression at the time of this survey. Conclusion The incidence of depression in a cohort of African American patients without prior psychiatric conditions who recovered from severe COVID-19 infection was 44%. More than 70% of these patients were not receiving treatment for depression. Supplementary Information The online version contains supplementary material available at 10.1007/s40615-021-01034-3.

Background: The diagnosis of sarcoidosis is not standardized but is based on three major criteria: a compatible clinical presentation, finding nonnecrotizing granulomatous inflammation in one or more tissue samples, and the exclusion of alternative causes of granulomatous disease. There are no universally accepted measures to determine if each diagnostic criterion has been satisfied; therefore, the diagnosis of sarcoidosis is never fully secure. Methods: Systematic reviews and, when appropriate, meta-analyses were performed to summarize the best available evidence. The evidence was appraised using the Grading of Recommendations, Assessment, Development, and Evaluation approach and then discussed by a multidisciplinary panel. Recommendations for or against various diagnostic tests were formulated and graded after the expert panel weighed desirable and undesirable consequences, certainty of estimates, feasibility, and acceptability. Results: The clinical presentation, histopathology, and exclusion of alternative diagnoses were summarized. On the basis of the available evidence, the expert committee made 1 strong recommendation for baseline serum calcium testing, 13 conditional recommendations, and 1 best practice statement. All evidence was very low quality. Conclusions: The panel used systematic reviews of the evidence to inform clinical recommendations in favor of or against various diagnostic tests in patients with suspected or known sarcoidosis. The evidence and recommendations should be revisited as new evidence becomes available.

RATIONALE: Multiple studies have demonstrated an increased risk of chronic obstructive pulmonary disease (COPD) in heterozygous carriers of the AAT (alpha-1 antitrypsin) Z allele. However, it is not known if MZ subjects with COPD are phenotypically different from noncarriers (MM genotype) with COPD. OBJECTIVES: To assess if MZ subjects with COPD have different clinical features compared with MM subjects with COPD. METHODS: Genotypes of SERPINA1 were ascertained by using whole-genome sequencing data in three independent studies. We compared outcomes between MM subjects with COPD and MZ subjects with COPD in each study and combined the results in a meta-analysis. We performed longitudinal and survival analyses to compare outcomes in MM and MZ subjects with COPD over time. MEASUREMENTS AND MAIN RESULTS: We included 290 MZ subjects with COPD and 6,184 MM subjects with COPD across the three studies. MZ subjects had a lower FEV(1)% predicted and greater quantitative emphysema on chest computed tomography scans compared with MM subjects. In a meta-analysis, the FEV(1) was 3.9% lower (95% confidence interval [CI], −6.55% to −1.26%) and emphysema (the percentage of lung attenuation areas

Background Each July, teaching hospitals in the United States experience an influx of new resident and fellow physicians. It has been theorized that this occurrence may be associated with increased patient mortality, complication rates, and health care resource use, a phenomenon known as the “July effect.” Objective To assess the existence of a July effect in clinical outcomes of patients with acute respiratory distress syndrome (ARDS) receiving mechanical ventilation in the intensive care unit in US teaching hospitals. Methods The National Inpatient Sample database was queried for all adult patients with ARDS who received mechanical ventilation from 2012 to 2014. Using a multivariate difference-in-differences (DID) model, differences in mortality, ventilator-associated pneumonia, iatrogenic pneumothorax, central catheter–associated bloodstream infection, and Clostridium difficile infection were compared between teaching and nonteaching hospitals during April-May and July-August. Results There were 70 535 and 43 175 hospitalizations meeting study criteria in teaching and nonteaching hospitals, respectively. Multivariate analyses revealed no differential effect on the rates of all-cause inpatient mortality (DID, 0.66; 95% CI, −0.42 to 1.75), C difficile infection (DID, 0.29; 95% CI, −0.19 to 0.78), central catheter–associated bloodstream infection (DID, 0.14; 95% CI, −0.04 to 0.33), iatrogenic pneumothorax (DID, 0.00; 95% CI, −0.25 to 0.24), ventilator-associated pneumonia (DID, 0.22; 95% CI, −0.05 to 0.49), and any complication (DID, 0.60; 95% CI, −0.01 to 1.20) for July-August versus April-May in teaching hospitals compared with nonteaching hospitals. Conclusion This study did not show a differential July effect on mortality outcomes and complication rates in ARDS patients receiving mechanical ventilation in teaching hospitals compared with nonteaching hospitals.

BackgroundBody composition measures, specifically low weight or reduced muscle mass, are associated with mortality in COPD, but the effect of longitudinal body composition changes is undefined.Research questionIs the longitudinal loss of fat-free mass (FFM) associated with increased mortality, including in those with initially normal or elevated body composition metrics?Study design and methodsParticipants with complete data for at least one visit in the COPDGene study (n= 9,268) and the ECLIPSE study (n= 1,760) were included and monitored for 12 and 8 years, respectively. Pectoralis muscle area (PMA) was derived from thoracic CT scans and used as a proxy for FFM. A longitudinal mixed submodel for PMA and a Cox proportional hazards submodel for survival were fitted on a joint distribution, using a shared random intercept parameter and Markov chain Monte Carlo parameter estimation.ResultsBoth cohorts demonstrated a left-shifted distribution of baseline FFM, not reflected in BMI, and an increase in all-cause mortality risk associated with longitudinal loss of PMA. For each 1-cm2 PMA loss, mortality increased 3.1%(95%CI, 2.4%-3.7%; P< .001) in COPDGene, and 2.4%(95%CI, 0.9%-4.0%; P< .001) in ECLIPSE. Increased mortality risk was independent of enrollment values for BMI and disease severity [BODE (body mass, airflow obstruction, dyspnea, and exercise capacity) index quartiles] and was significant even in participants with initially greater than average PMA.InterpretationLongitudinal loss of PMA is associated with increased all-cause mortality, regardless of BMI or initial muscle mass. Consideration of novel screening tests and further research into mechanisms contributing to muscle decline may improve risk stratification and identify novel therapeutic targets in ever smokers.

The Genetic Epidemiology of COPD (COPDGene) study is a noninterventional, multicenter, longitudinal analysis of > 10,000 subjects, including smokers with a ≥ 10 pack-year history with and without COPD and healthy never smokers. The goal was to characterize disease-related phenotypes and explore associations with susceptibility genes. The subjects were extensively phenotyped with the use of comprehensive symptom and comorbidity questionnaires, spirometry, CT scans of the chest, and genetic and biomarker profiling. The objective of this review was to summarize the major advances in the clinical epidemiology of COPD from the first 10 years of the COPDGene study. We highlight the influence of age, sex, and race on the natural history of COPD, and the impact of comorbid conditions, chronic bronchitis, exacerbations, and asthma/COPD overlap.

Rationale: Increasing awareness of the prevalence and significance of Preserved Ratio Impaired Spirometry (PRISm), alternatively known as restrictive or Global Initiative for Chronic Obstructive Lu...

Introduction The mental health impact of COVID-19 infection on its survivors have been reported. African Americans are disproportionately affected by COVID-19 and more likely to experience severe outcomes relative to other ethnicities. We evaluated the incidence and severity of depression among African American patients within 90 days of recovery from severe COVID-19 infection. Methods We identified African American patients with severe SARS-CoV-2 infection who received invasive mechanical ventilation at the intensive care unit (ICU) of Grady Memorial Hospital, Atlanta, Georgia between May 1, 2020, and June 30, 2020. The patient health questionnaire (PHQ-9), a nine-item questionnaire used to assess depression, and its severity was administered to the patients within 30 to 90 days of hospital discharge. Patients with a history of psychiatric disorders were excluded. We categorized patients into major depressive disorder (MDD) diagnosis or other depression based on their responses. To assess severity, all patients were categorized into none or minimal, mild, moderate, moderately severe, and severe based on a score range of 0-27 on the PHQ-9. We calculated the number of patients on treatment for depression as a percentage of the total eligible for treatment based on their PHQ-9 scores. Data analysis was performed using R version 3.6.3 (R Foundation). Results A total of 73 patients completed the questionnaire. The median age of the participants was 52.5 years [IQR 44-65 years] and 65% were males. 44% of the patients had a diagnosis of MDD. The incidence of MDD was higher among females (69%, n=18/26) compared to males (29%, n=14/47), patients aged 55-74 years (60%, n=18/30), > 75 years (66%, n=4/6) compared to younger patients and patients with multiple co-morbidities (45%, n=28/62) compared to patients with only one or no co-morbidity (36%, n=4/11). 27 patients in the study were eligible for treatment based on a PHQ-9 score of at least 14 (moderate and moderately severe depression). However, only 7 of them were receiving some form of depression treatment. The remaining 74% (n=20/27) had not been screened for depression since hospital discharge (Figure 1). ConclusionOur study showed that at least 4 out of 10 African Americans without prior psychiatric illness, hospitalized in the ICU for severe COVID-19 infection will develop MDD within 90 days of discharge. 74% of treatment eligible patients in our study had not been evaluated by a medical professional and were not on any form of treatment.

Contains fulltext : 220761.pdf (Publisher’s version ) (Open Access) Rationale: The decades-long progression of chronic obstructive pulmonary disease (COPD) renders identifying different trajectories of disease progression challenging.Objectives: To identify subtypes of patients with COPD with distinct longitudinal progression patterns using a novel machine-learning tool called "Subtype and Stage Inference" (SuStaIn) and to evaluate the utility of SuStaIn for patient stratification in COPD.Methods: We applied SuStaIn to cross-sectional computed tomography imaging markers in 3,698 Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1-4 patients and 3,479 controls from the COPDGene (COPD Genetic Epidemiology) study to identify subtypes of patients with COPD. We confirmed the identified subtypes and progression patterns using ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) data. We assessed the utility of SuStaIn for patient stratification by comparing SuStaIn subtypes and stages at baseline with longitudinal follow-up data.Measurements and Main Results: We identified two trajectories of disease progression in COPD: a "Tissue-->Airway" subtype (n = 2,354, 70.4%), in which small airway dysfunction and emphysema precede large airway wall abnormalities, and an "Airway-->Tissue" subtype (n = 988, 29.6%), in which large airway wall abnormalities precede emphysema and small airway dysfunction. Subtypes were reproducible in ECLIPSE. Baseline stage in both subtypes correlated with future FEV1/FVC decline (r = -0.16 [P < 0.001] in the Tissue-->Airway group; r = -0.14 [P = 0.011] in the Airway-->Tissue group). SuStaIn placed 30% of smokers with normal lung function at elevated stages, suggesting imaging changes consistent with early COPD. Individuals with early changes were 2.5 times more likely to meet COPD diagnostic criteria at follow-up.Conclusions: We demonstrate two distinct patterns of disease progression in COPD using SuStaIn, likely representing different endotypes. One third of healthy smokers have detectable imaging changes, suggesting a new biomarker of "early COPD."

Contains fulltext : 194255.pdf (Publisher’s version ) (Open Access) BACKGROUND: Emphysema has considerable variability in its regional distribution. Craniocaudal emphysema distribution is an important predictor of the response to lung volume reduction. However, there is little consensus regarding how to define upper lobe-predominant and lower lobe-predominant emphysema subtypes. Consequently, the clinical and genetic associations with these subtypes are poorly characterized. METHODS: We sought to identify subgroups characterized by upper-lobe or lower-lobe emphysema predominance and comparable amounts of total emphysema by analyzing data from 9,210 smokers without alpha-1-antitrypsin deficiency in the Genetic Epidemiology of COPD (COPDGene) cohort. CT densitometric emphysema was measured in each lung lobe. Random forest clustering was applied to lobar emphysema variables after regressing out the effects of total emphysema. Clusters were tested for association with clinical and imaging outcomes at baseline and at 5-year follow-up. Their associations with genetic variants were also compared. RESULTS: Three clusters were identified: minimal emphysema (n = 1,312), upper lobe-predominant emphysema (n = 905), and lower lobe-predominant emphysema (n = 796). Despite a similar amount of total emphysema, the lower-lobe group had more severe airflow obstruction at baseline and higher rates of metabolic syndrome compared with subjects with upper-lobe predominance. The group with upper-lobe predominance had greater 5-year progression of emphysema, gas trapping, and dyspnea. Differential associations with known COPD genetic risk variants were noted. CONCLUSIONS: Subgroups of smokers defined by upper-lobe or lower-lobe emphysema predominance exhibit different functional and radiological disease progression rates, and the upper-lobe predominant subtype shows evidence of association with known COPD genetic risk variants. These subgroups may be useful in the development of personalized treatments for COPD.

Background: Chronic obstructive pulmonary disease (COPD) remains a major cause of morbidity and mortality. Present-day diagnostic criteria are largely based solely on spirometric criteria. Accumulating evidence has identified a substantial number of individuals without spirometric evidence of COPD who suffer from respiratory symptoms and/or increased morbidity and mortality. There is a clear need for an expanded definition of COPD that is linked to physiologic, structural (computed tomography [CT]) and clinical evidence of disease. Using data from the COPD Genetic Epidemiology study (COPDGene(®)), we hypothesized that an integrated approach that includes environmental exposure, clinical symptoms, chest CT imaging and spirometry better defines disease and captures the likelihood of progression of respiratory obstruction and mortality. Methods: Four key disease characteristics – environmental exposure (cigarette smoking), clinical symptoms (dyspnea and/or chronic bronchitis), chest CT imaging abnormalities (emphysema, gas trapping and/or airway wall thickening), and abnormal spirometry – were evaluated in a group of 8784 current and former smokers who were participants in COPDGene(®) Phase 1. Using these 4 disease characteristics, 8 categories of participants were identified and evaluated for odds of spirometric disease progression (FEV(1) > 350 ml loss over 5 years), and the hazard ratio for all-cause mortality was examined. Results: Using smokers without symptoms, CT imaging abnormalities or airflow obstruction as the reference population, individuals were classified as Possible COPD, Probable COPD and Definite COPD. Current Global initiative for obstructive Lung Disease (GOLD) criteria would diagnose 4062 (46%) of the 8784 study participants with COPD. The proposed COPDGene(®) 2019 diagnostic criteria would add an additional 3144 participants. Under the new criteria, 82% of the 8784 study participants would be diagnosed with Possible, Probable or Definite COPD. These COPD groups showed increased risk of disease progression and mortality. Mortality increased in patients as the number of their COPD characteristics increased, with a maximum hazard ratio for all cause-mortality of 5.18 (95% confidence interval [CI]: 4.15–6.48) in those with all 4 disease characteristics. Conclusions: A substantial portion of smokers with respiratory symptoms and imaging abnormalities do not manifest spirometric obstruction as defined by population normals. These individuals are at significant risk of death and spirometric disease progression. We propose to redefine the diagnosis of COPD through an integrated approach using environmental exposure, clinical symptoms, CT imaging and spirometric criteria. These expanded criteria offer the potential to stimulate both current and future interventions that could slow or halt disease progression in patients before disability or irreversible lung structural changes develop.

Rationale: The American Thoracic Society (ATS)/European Respiratory Society defines a positive bronchodilator response (BDR) by a composite of BDR in either forced expiratory volume in 1 second (FEV(1)) and/or forced vital capacity (FVC) greater than or equal to 12% and 200 ml (ATS-BDR). We hypothesized that ATS-BDR components would be differentially associated with important chronic obstructive pulmonary disease (COPD) outcomes. Objectives: To examine whether ATS-BDR components are differentially associated with clinical, functional, and radiographic features in COPD. Methods: We included subjects with COPD enrolled in the COPDGene study. In the main analysis, we excluded subjects with self-reported asthma. We categorized BDR into the following: 1) No-BDR, no BDR in either FEV(1) or FVC; 2) FEV(1)-BDR, BDR in FEV(1) but no BDR in FVC; 3) FVC-BDR, BDR in FVC but no BDR in FEV(1); and 4) Combined-BDR, BDR in both FEV(1) and FVC. We constructed multivariable logistic, linear, zero-inflated negative binomial, and Cox hazards models to examine the association of BDR categories with symptoms, computed tomography findings, change in FEV(1) over time, respiratory exacerbations, and mortality. We also created models using the ATS BDR definition (ATS-BDR) as the main independent variable. Results: Of 3,340 COPD subjects included in the analysis, 1,083 (32.43%) had ATS-BDR, 182 (5.45%) had FEV(1)-BDR, 522 (15.63%) had FVC-BDR, and 379 (11.34%) had Combined-BDR. All BDR categories were associated with FEV(1) decline compared with No-BDR. Compared with No-BDR, both ATS-BDR and Combined-BDR were associated with higher functional residual capacity %predicted, greater internal perimeter of 10 mm, and greater 6-minute-walk distance. In contrast to ATS-BDR, Combined-BDR was independently associated with less emphysema (adjusted beta regression coefficient, −1.67; 95% confidence interval [CI], −2.68 to −0.65; P = 0.001), more frequent respiratory exacerbations (incidence rate ratio, 1.25; 95% CI, 1.03–1.50; P = 0.02) and severe exacerbations (incidence rate ratio, 1.34; 95% CI, 1.05–1.71; P = 0.02), and lower mortality (adjusted hazards ratio, 0.76; 95% CI, 0.58–0.99; P = 0.046). Sensitivity analysis that included subjects with self-reported history of asthma showed similar findings. Conclusions: BDR in both FEV(1) and FVC indicates a COPD phenotype with asthma-like characteristics, and provides clinically more meaningful information than current definitions of BDR.

Background: Chronic obstructive pulmonary disease (COPD) remains a major cause of morbidity and mortality. Present-day diagnostic criteria are largely based solely on spirometric criteria. Accumulating evidence has identified a substantial number of individuals without spirometric evidence of COPD who suffer from respiratory symptoms and/or increased morbidity and mortality. There is a clear need for an expanded definition of COPD that is linked to physiologic, structural (computed tomography [CT]) and clinical evidence of disease. Using data from the COPD Genetic Epidemiology study (COPDGene®), we hypothesized that an integrated approach that includes environmental exposure, clinical symptoms, chest CT imaging and spirometry better defines disease and captures the likelihood of progression of respiratory obstruction and mortality. Methods: Four key disease characteristics – environmental exposure (cigarette smoking), clinical symptoms (dyspnea and/or chronic bronchitis), chest CT imaging abnormalities (emphysema, gas trapping and/or airway wall thickening), and abnormal spirometry – were evaluated in a group of 8784 current and former smokers who were participants in COPDGene® Phase 1. Using these 4 disease characteristics, 8 categories of participants were identified and evaluated for odds of spirometric disease progression (FEV1 > 350 ml loss over 5 years), and the hazard ratio for all-cause mortality was examined. Results: Using smokers without symptoms, CT imaging abnormalities or airflow obstruction as the reference population, individuals were classified as Possible COPD, Probable COPD and Definite COPD. Current Global initiative for obstructive Lung Disease (GOLD) criteria would diagnose 4062 (46%) of the 8784 study participants with COPD. The proposed COPDGene® 2019 diagnostic criteria would add an additional 3144 participants. Under the new criteria, 82% of the 8784 study participants would be diagnosed with Possible, Probable or Definite COPD. These COPD groups showed increased risk of disease progression and mortality. Mortality increased in patients as the number of their COPD characteristics increased, with a maximum hazard ratio for all cause-mortality of 5.18 (95% confidence interval [CI]: 4.15–6.48) in those with all 4 disease characteristics. Conclusions: A substantial portion of smokers with respiratory symptoms and imaging abnormalities do not manifest spirometric obstruction as defined by population normals. These individuals are at significant risk of death and spirometric disease progression. We propose to redefine the diagnosis of COPD through an integrated approach using environmental exposure, clinical symptoms, CT imaging and spirometric criteria. These expanded criteria offer the potential to stimulate both current and future interventions that could slow or halt disease progression in patients before disability or irreversible lung structural changes develop.

Background Chronic bronchitis (CB) increases risk of COPD exacerbations. We have shown that the St. George's Respiratory Questionnaire (SGRQ) CB definition identifies patients with a similar clinical phenotype as classically defined CB. Whether the SGRQ CB definition is a predictor of future COPD exacerbations is unknown. Methods We analyzed 7,557 smokers with normal spirometry and Global Initiative for Chronic Obstructive Lung Disease stage 1-4 COPD in the Genetic Epidemiology of COPD study with longitudinal follow-up data on exacerbations. Subjects were divided into classic CB+ or classic CB–, using the classic definition. In addition, subjects were divided into SGRQ CB+ or SGRQ CB–. Exacerbation frequency and severe exacerbation frequency were determined in each group. Multivariable linear regressions were performed for exacerbation frequency with either classic CB or SGRQ CB and relevant covariates. Results There were 1,434 classic CB+ subjects and 2,290 SGRQ CB+ subjects. The classic CB+ group had a greater exacerbation frequency compared with the classic CB– group (0.69 ± 1.26 vs 0.36 ± 0.90 exacerbations per patient per year; P Conclusions The SGRQ CB definition identified more subjects at risk for future exacerbations than the classic CB definition. SGRQ CB was at least a similar if not better predictor of future exacerbations than classic CB.

INTRODUCTION: Hospitalization and mortality rates from COVID-19 infection are disproportionately higher in African Americans compared to non-Hispanic whites It is unclear if recovery from COVID-19 infection confers longterm immunity Therefore, a COVID-19 vaccine is urgently needed to potentially end the pandemic However, the uptake of COVID-19 vaccine when it becomes available will be important to effectively curb the spread of the infection Historically, African American adults are less likely than non- Hispanic white adults to receive influenza, pneumococcal, and HPV vaccine We evaluated the potential uptake rate of COVID-19 vaccine among African American patients who recovered from severe COVID-19 infection METHODS: African American patients that were hospitalized with severe COVID-19 infection in the medical ICU of Grady Memorial Hospital, Atlanta between April 1, 2020, and June 30, 2020, were asked to participate in the study after recovery and discharge from the hospital All participants completed a questionnaire over the phone on their likelihood to accept the COVID-19 vaccine and factors impacting their decisions Co-morbidities were extracted from the patients' charts in the electronic medical record system MS Excel 2019 and R programming language were used for data management and analyses respectively RESULTS: 48 patients completed the survey 62% were males and the median age was 71 5 (interquartile range, 67-76;range, 29 - 77 years) 66% of the patients irrespective of co-morbidities stated they will not receive the COVID-19 vaccine when it is available Reasons provided by participants for declining COVID-19 vaccination included fear of vaccinerelated side effects (61%), distrust of the pharmaceutical companies that make vaccines (58%), and uncertainty that the vaccine will be effective (42%) 75% of the participants stated they will be more likely to accept the vaccine if recommended by their primary care physicians or specialists Only 8% stated they will accept the vaccine based on information from TV/radio ads or the internet CONCLUSIONS: Direct recommendation of the COVID-19 vaccine by medical providers and focused education around the reasons highlighted in our study for potentially declining vaccination may improve vaccination coverage in this vulnerable population

Spirometric Volumes and Breathlessness Across Levels of Airflow Limitation : The COPDGene Study.

BACKGROUND:Eosinophilic airway inflammation in patients with chronic obstructive pulmonary disease (COPD) is associated with exacerbations and responsivity to steroids, suggesting potential shared mechanisms with eosinophilic asthma. However, there is no consistent blood eosinophil count that has been used to define the increased exacerbation risk. OBJECTIVE:We sought to investigate blood eosinophil counts associated with exacerbation risk in patients with COPD. METHODS:Blood eosinophil counts and exacerbation risk were analyzed in patients with moderate-to-severe COPD by using 2 independent studies of former and current smokers with longitudinal data. The Genetic Epidemiology of COPD (COPDGene) study was analyzed for discovery (n=1,553), and the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study was analyzed for validation (n=1,895). Asubset of the ECLIPSE study subjects were used to assess the stability of blood eosinophil counts over time. RESULTS:COPD exacerbation risk increased with higher eosinophil counts. An eosinophil count threshold of 300cells/μL or greater showed adjusted incidence rate ratios for exacerbations of 1.32 in the COPDGene study (95% CI, 1.10-1.63). The cutoff of 300cells/μL or greater was validated for prospective risk of exacerbation in the ECLIPSE study, with adjusted incidence rate ratios of 1.22 (95% CI, 1.06-1.41) using 3-year follow-up data. Stratified analysis confirmed that the increased exacerbation risk associated with an eosinophil count of 300cells/μL or greater was driven by subjects with a history of frequent exacerbations in both the COPDGene and ECLIPSE studies. CONCLUSIONS:Patients with moderate-to-severe COPD and blood eosinophil counts of 300cells/μL or greater had an increased risk exacerbations in the COPDGene study, which was prospectively validated in the ECLIPSE study.

The heritability of chronic obstructive pulmonary disease (COPD) cannot be fully explained by recognized genetic risk factors identified as achieving genome-wide significance. In addition, the combined contribution of genetic variation to COPD risk has not been fully explored. We sought to determine: (1) whether studies of variants from previous studies of COPD or lung function in a larger sample could identify additional associated variants, particularly for severe COPD; and (2) the impact of genetic risk scores on COPD. We genotyped 3,346 single-nucleotide polymorphisms (SNPs) in 2,588 cases (1,803 severe COPD) and 1,782 control subjects from four cohorts, and performed association testing with COPD, combining these results with existing genotyping data from 6,633 cases (3,497 severe COPD) and 5,704 control subjects. In addition, we developed genetic risk scores from SNPs associated with lung function and COPD and tested their discriminatory power for COPD-related measures. We identified significant associations between SNPs near PPIC (P = 1.28 X 10(-8)) and PPP4R4/SERPINA1 (P = 1.01 X 10(-8)) and severe COPD; the latter association may be driven by recognized variants in SERPINA1. Genetic risk scores based on SNPs previously associated with COPD and lung function had a modest ability to discriminate COPD (area under the curve, similar to 0.6), and accounted for a mean 0.9-1.9% lower forced expiratory volume in 1 second percent predicted for each additional risk allele. In a large genetic association analysis, we identified associations with severe COPD near PPIC and SERPINA1. A risk score based on combining genetic variants had modest, but significant, effects on risk of COPD and lung function.

Introduction Multimorbidity, the presence of 2 or more chronic conditions, frequently affects people with chronic obstructive pulmonary disease (COPD). Many have high-cost, highly complex conditions that have a substantial impact on state Medicaid programs. We quantified the cost of Medicaid-insured patients with COPD co-diagnosed with other chronic disorders. Methods We used nationally representative Medicaid claims data to analyze the impact of comorbidities (other chronic conditions) on the disease burden, emergency department (ED) use, hospitalizations, and total health care costs among 291,978 adult COPD patients. We measured the prevalence of common conditions and their influence on COPD-related and non-COPD-related resource use by using the Elixhauser Comorbidity Index. Elixhauser comorbidity counts were clustered from 0 to 7 or more. We performed multivariable logistic regression to determine the odds of ED visits by Elixhauser scores adjusting for age, sex, race/ethnicity, and residence. Results Acute care, hospital bed days, and total Medicaid-reimbursed costs increased as the number of comorbidities increased. ED visits unrelated to COPD were more common than visits for COPD, especially in patients self-identified as black or African American (designated black). Hypertension, diabetes, affective disorders, hyperlipidemia, and asthma were the most prevalent comorbid disorders. Substance abuse, congestive heart failure, and asthma were commonly associated with ED visits for COPD. Female sex was associated with COPD-related and non-COPD-related ED visits. Conclusion Comorbidities markedly increased health services use among people with COPD insured with Medicaid, although ED visits in this study were predominantly unrelated to COPD. Achieving excellence in clinical practice with optimal clinical and economic outcomes requires a whole-person approach to the patient and a multidisciplinary health care team.

RationaleThe demographic, physiological, and computed tomography (CT) features associated with pneumothorax in smokers with and without chronic obstructive pulmonary disease (COPD) are not clearly defined.ObjectivesWe evaluated the hypothesis that pneumothorax in smokers is associated with male sex, tall and thin stature, airflow obstruction, and increased total and subpleural emphysema.MethodsThe study included smokers with and without COPD from the COPDGene Study, with quantitative chest CT analysis. Pleural-based emphysema was assessed on the basis of local histogram measures of emphysema. Pneumothorax history was defined by subject self-report.Measurements and main resultsPneumothorax was reported in 286 (3.2%) of 9,062 participants. In all participants, risk of prior pneumothorax was significantly higher in men (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.08-2.22) and non-Hispanic white subjects (OR, 1.90; 95% CI, 1.34-2.69). Risk of prior pneumothorax was associated with increased percent CT emphysema in all participants and participants with COPD (OR, 1.04 for each 1% increase in emphysema; 95% CI, 1.03-1.06). Increased pleural-based emphysema was independently associated with risk of past pneumothorax in all participants (OR, 1.05 for each 1% increase; 95% CI, 1.01-1.10). In smokers with normal spirometry, risk of past pneumothorax was associated with non-Hispanic white race and lifetime smoking intensity (OR, 1.20 for every 10 pack-years; 95% CI, 1.09-1.33).ConclusionsAmong smokers, pneumothorax is associated with male sex, non-Hispanic white race, and increased percentage of total and subpleural CT emphysema. Pneumothorax was not independently associated with height or lung function, even in participants with COPD. Clinical trial registered with www.clinicaltrials.gov (NCT00608764).

BACKGROUND The risk factors for acute episodes of respiratory disease in current and former smokers who do not have COPD are unknown. METHODS Eight thousand two hundred forty-six non-Hispanic white and black current and former smokers in the Genetic Epidemiology of COPD (COPDGene) cohort had longitudinal follow-up (LFU) every 6 months to determine acute respiratory episodes requiring antibiotics or systemic corticosteroids, an ED visit, or hospitalization. Negative binomial regression was used to determine the factors associated with acute respiratory episodes. A Cox proportional hazards model was used to determine adjusted hazard ratios (HRs) for time to first episode and an acute episode of respiratory disease risk score. RESULTS At enrollment, 4,442 subjects did not have COPD, 658 had mild COPD, and 3,146 had moderate or worse COPD. Nine thousand three hundred three acute episodes of respiratory disease and 2,707 hospitalizations were reported in LFU (3,044 acute episodes of respiratory disease and 827 hospitalizations in those without COPD). Major predictors included acute episodes of respiratory disease in year prior to enrollment (HR, 1.20; 95% CI, 1.15-1.24 per exacerbation), airflow obstruction (HR, 0.94; 95% CI, 0.91-0.96 per 10% change in % predicted FEV 1 ), and poor health-related quality of life (HR, 1.07; 95% CI, 1.06-1.08 for each 4-unit increase in St. George's Respiratory Questionnaire score). Risks were similar for those with and without COPD. CONCLUSIONS Although acute episode of respiratory disease rates are higher in subjects with COPD, risk factors are similar, and at a population level, there are more episodes in smokers without COPD.

The value of quantitative CT (QCT) to identify chronic obstructive pulmonary disease (COPD) phenotypes is increasingly appreciated. The authors hypothesised that QCT-defined emphysema and airway abnormalities relate to St George's Respiratory Questionnaire (SGRQ) and Body-Mass Index, Airflow Obstruction, Dyspnea and Exercise Capacity Index (BODE).1200 COPDGene subjects meeting Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria for COPD with QCT analysis were included. Total lung emphysema was measured using the density mask technique with a -950 Hounsfield unit threshold. An automated programme measured mean wall thickness (WT), wall area percentage (WA%) and 10 mm lumenal perimeter (pi10) in six segmental bronchi. Separate multivariate analyses examined the relative influence of airway measures and emphysema on SGRQ and BODE.In separate models predicting SGRQ score, a 1 unit SD increase in each airway measure predicted higher SGRQ scores (for WT, 1.90 points higher, p=0.002; for WA%, 1.52 points higher, p=0.02; for pi10, 2.83 points higher p0.001). The comparable increase in SGRQ for a 1 unit SD increase in emphysema percentage in these models was relatively weaker, significant only in the pi10 model (for emphysema percentage, 1.45 points higher, p=0.01). In separate models predicting BODE, a 1 unit SD increase in each airway measure predicted higher BODE scores (for WT, 1.07-fold increase, p0.001; for WA%, 1.20-fold increase, p0.001; for pi10, 1.16-fold increase, p0.001). In these models, emphysema more strongly influenced BODE (range 1.24-1.26-fold increase, p0.001).Emphysema and airway disease both relate to clinically important parameters. The relative influence of airway disease is greater for SGRQ; the relative influence of emphysema is greater for BODE.

The purposes of this study were: to describe chest CT findings in normal nonsmoking controls and cigarette smokers with and without COPD; to compare the prevalence of CT abnormalities with severity of COPD; and to evaluate concordance between visual and quantitative chest CT (QCT) scoring. Methods: Volumetric inspiratory and expiratory CT scans of 294 subjects, including normal non-smokers, smokers without COPD, and smokers with GOLD Stage I-IV COPD, were scored at a multi-reader workshop using a standardized worksheet. There were 58 observers (33 pulmonologists, 25 radiologists); each scan was scored by 9-11 observers. Interobserver agreement was calculated using kappa statistic. Median score of visual observations was compared with QCT measurements. Results: Interobserver agreement was moderate for the presence or absence of emphysema and for the presence of panlobular emphysema; fair for the presence of centrilobular, paraseptal, and bullous emphysema subtypes and for the presence of bronchial wall thickening; and poor for gas trapping, centrilobular nodularity, mosaic attenuation, and bronchial dilation. Agreement was similar for radiologists and pulmonologists. The prevalence on CT readings of most abnormalities (e.g. emphysema, bronchial wall thickening, mosaic attenuation, expiratory gas trapping) increased significantly with greater COPD severity, while the prevalence of centrilobular nodularity decreased. Concordances between visual scoring and quantitative scoring of emphysema, gas trapping and airway wall thickening were 75%, 87% and 65%, respectively. Conclusions: Despite substantial interobserver variation, visual assessment of chest CT scans in cigarette smokers provides information regarding lung disease severity; visual scoring may be complementary to quantitative evaluation.

Background Cigarette smoking is a major risk factor for chronic obstructive pulmonary disease (COPD) and COPD severity. Previous genome-wide association studies (GWAS) have identified numerous single nucleotide polymorphisms (SNPs) associated with the number of cigarettes smoked per day (CPD) and a dopamine beta-hydroxylase (DBH) locus associated with smoking cessation in multiple populations. Objective To identify SNPs associated with lifetime average and current CPD, age at smoking initiation, and smoking cessation in patients with COPD. Methods GWAS were conducted in four independent cohorts encompassing 3441 ever-smoking patients with COPD (Global Initiative for Obstructive Lung Disease stage II or higher). Untyped SNPs were imputed using the HapMap (phase II) panel. Results from all cohorts were meta-analysed. Results Several SNPs near the HLA region on chromosome 6p21 and in an intergenic region on chromosome 2q21 showed associations with age at smoking initiation, both with the lowest p=2x10(-7). No SNPs were associated with lifetime average CPD, current CPD or smoking cessation with p

Although COPD is associated with significant health-related quality-of-life (HRQL) impairment, factors influencing HRQL in patients with COPD are not well understood, particularly in African Americans. We hypothesized that HRQL in COPD differs by race and sought to identify factors associated with those differences.We analyzed 224 African American and 1,049 Caucasian subjects with COPD enrolled in the COPDGene (Genetic Epidemiology of COPD) Study whose conditions were classified as GOLD (Global Initiative for Chronic Obstructive Lung Disease) stages I to IV. HRQL and symptoms were compared using the St. George Respiratory Questionnaire (SGRQ) and the modified Medical Research Council Dyspnea (MMRC) scale. We constructed a mixed-effects linear regression model for SGRQ score.African Americans were younger and reported fewer pack-years of smoking, more current smoking, and less attained education than Caucasians; MMRC scores were higher (P = .02) as were SGRQ scores (mean score difference, 8.4; P.001). In a general linear model of SGRQ total score after adjusting for factors such as age, sex, and pack-years of smoking, SGRQ total score was similar for African Americans and Caucasians who reported no COPD exacerbations in the prior year. However, for subjects with exacerbations, SGRQ total score was increased to a greater relative extent for African Americans than for Caucasians (1.89 points for each exacerbation, P = .006). For hospitalized exacerbations, the effect on SGRQ total score also was greater for African Americans (4.19 points, P = .04). Furthermore, a larger percentage of African Americans reported having had at least one exacerbation that required hospitalization in the prior year (32% vs 16%, P.001).In analyses that account for other variables that affect quality of life, HRQL is similar for African Americans and Caucasians with COPD without exacerbations but worse for African Americans who experience exacerbations, particularly hospitalized exacerbations.

Sarcoidosis disease expression differs along racial/ethnic lines and black race has been cited as a poor prognostic factor. Besides genetic, healthcare, and socioeconomic factors, comorbid illnesses may influence sarcoidosis disease expression. We set out to investigate the association between comorbid illnesses and chest radiographic severity in a population of African-American sarcoidosis patients. The study was designed as a retrospective database analysis. The hospital and outpatient databases of the Grady Health System were searched to capture adult patients between November 1999 and December 2003 with the ICD-9 codes of 135 or 519.8, along with all associated secondary and tertiary diagnostic codes. Patient electronic pathology and radiographic reports were reviewed for tissue biopsies showing noncaseating granulomas and for chest radiographic Scadding stage. A total of 165 African-American patients were identified (64% female, 43 +/- 10 years old). Ninety percent (149/165) had comorbid illnesses. The most frequent chronic comorbid illnesses were hypertension (39%), diabetes mellitus (19%), anemia (19%), asthma (15%), gastroesophageal reflux disease (15%), depression (13%), and heart failure (10%). Females had increased frequency and clustering of chronic illnesses. Chest radiographic stages were more severe in patients with anemia, depression, and those less than 40 years old. Males, within each chronic illnesses category, had more severe CXR stages compared to females; however, significance was not achieved. We concluded that most adult patients with sarcoidosis have comorbid illnesses and these, in addition to gender differences, may influence sarcoidosis disease expression. Screening for comorbid illnesses should be an important aspect of sarcoidosis patient management.

Sarcoidosis is a multisystem granulomatous disease of unknown cause that occurs worldwide. The clinical expression of sarcoidosis varies by race. These racial differences may be the result of genetic and socioeconomic factors. Many of these genetic associations are race-specific in that they are found in either African Americans or whites but not both. Socioeconomic differences may also explain the racial disparities between African American and white patients with sarcoidosis. Finally, the phenotypic differences be-tween races may relate to an interaction between genetics and socioeconomic factors. The influences of genetics and socioeconomic status on the development and phenotypic expression of sarcoidosis will be better understood as the mechanisms of disease development are uncovered.

The catastrophic antiphospholipid syndrome (CAPS) defines a subgroup of patients with antiphospholipid syndrome who develop a fulminant clinical course with widespread microvascular thrombosis associated with elevated levels of anticardiolipin, or a positive lupus anticoagulant. The pathophysiology of CAPS appears to cause a clinical picture similar to the systemic inflammatory response syndrome, and the resulting tissue ischemia and necrosis have been associated with rapid demise and significant mortality. Precipitating factors include infections, surgical procedures, trauma, pregnancy/fetal demise, reduction/withdrawal of anticoagulation, and lupus flares. Organ involvement and manifestations include acute respiratory distress syndrome, congestive heart failure, malignant hypertension, acute renal failure, adrenal failure, coma or seizures, bowel or splenic infractions, livedo reticularis, and digital ischemia causing ulcerations or extremity gangrene. The differential diagnosis of CAPS includes thrombotic thrombocytopenic purpura, heparin-induced thrombocytopenia, disseminated intravascular coagulation, and hereditary thrombophilia. Several treatment modalities have been used, but anticoagulation and immunosuppressive therapy with steroids appear to be associated with decreased mortality.

After early experience with perioperative bleeding in sequential single-lung transplant recipients, aprotinin was introduced in an attempt to reduce this complication and the attendant morbidity. Records of sequential single-lung transplantations (n = 33) performed between January 1989 and November 1991 were reviewed to assess the impact of aprotinin on perioperative blood loss and blood product requirements. Recipients were divided according to whether or not they required cardiopulmonary bypass. In patients requiring cardiopulmonary bypass (n = 15), mean estimated postoperative blood loss was 3,000 +/- 500 mL in those who did not receive aprotinin (n = 4) compared with 1,177 +/- 253 mL in those who received aprotinin (n = 11) (p0.05). An average of 8.0 +/- 0.7 units of packed red blood cells were administered to patients not receiving aprotinin compared with 3.1 +/- 0.7 units to those who received aprotinin (p0.05). Requirements for fresh frozen plasma were similar in each group. There were no differences in blood loss or blood product replacement in the group not undergoing cardiopulmonary bypass (n = 18). Therefore, we conclude that aprotinin decreases postoperative blood loss and blood product requirements in patients undergoing sequential single-lung transplantation under cardiopulmonary bypass.