@article{pmid33904771,

title = {Association between Cardiorespiratory Fitness and Bronchiectasis at CT: A Long-term Population-based Study of Healthy Young Adults Aged 18-30 Years in the CARDIA Study},

author = {Alejandro A Diaz and Laura A Colangelo and Yuka Okajima and Andrew Yen and Marc A Sala and Mark T Dransfield and Gregory Tino and James C Ross and Raúl San José Estépar and George R Washko and Ravi Kalhan},

doi = {10.1148/radiol.2021203874},

issn = {1527-1315},

year  = {2021},

date = {2021-07-01},

journal = {Radiology},

volume = {300},

number = {1},

pages = {190--196},

abstract = {Background Protective factors against the risk of bronchiectasis are unknown. A high level of cardiorespiratory fitness is associated with a lower risk of chronic obstructive pulmonary disease. But whether fitness relates to bronchiectasis remains, to the knowledge of the authors, unknown. Purpose To examine the association between cardiorespiratory fitness and bronchiectasis. Materials and Methods This was a secondary analysis of a prospective observational study: the Coronary Artery Risk Development in Young Adults cohort (from 1985-1986 [year 0] to 2015-2016 [year 30]). During a 30-year period, healthy participants (age at enrollment 18-30 years) underwent treadmill exercise testing at year 0 and year 20 visits. Cardiorespiratory fitness was determined according to the treadmill exercise duration. The 20-year difference in cardiorespiratory fitness was used as the fitness measurement. At year 25, chest CT was performed to assess bronchiectasis and was used as the primary outcome. Multivariable logistic models were performed to determine the association between cardiorespiratory fitness changes and bronchiectasis. Results Of 2177 selected participants (at year 0: mean age, 25 years ± 4 [standard deviation]; 1224 women), 209 (9.6%) had bronchiectasis at year 25. After adjusting for age, race-sex group, study site, body mass index, pack-years smoked, history of tuberculosis, pneumonia, asthma and myocardial infarction, peak lung function, and cardiorespiratory fitness at baseline, preservation of cardiorespiratory fitness was associated with lower odds of bronchiectasis at CT at year 25 (per 1-minute-longer treadmill duration from year 0 to year 20: odds ratio [OR], 0.88; 95% CI: 0.80, 0.98;  = .02). A consistent strong association was found when cough and phlegm were included in bronchiectasis (OR, 0.72; 95% CI: 0.59, 0.87;  < .001). Conclusion In a long-term follow-up, the preservation of cardiorespiratory fitness was associated with lower odds of bronchiectasis at CT. © RSNA, 2021  See also the editorial by Stojanovska in this issue.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33840521,

title = {Relative Predictive Value of Circulating Immune Markers in US Adults Without Cardiovascular Disease: Implications for Risk Reclassification},

author = {Kartik Gupta and Rajat Kalra and Mike Pate and Shivaraj Nagalli and Sameer Ather and Indranee Rajapreyar and Pankaj Arora and Ankur Gupta and Wunan Zhou and Raul San Jose Estepar and Marcelo Di Carli and Sumanth D Prabhu and Navkaranbir S Bajaj},

doi = {10.1016/j.mayocp.2020.11.027},

issn = {1942-5546},

year  = {2021},

date = {2021-07-01},

journal = {Mayo Clin Proc},

volume = {96},

number = {7},

pages = {1812--1821},

abstract = {OBJECTIVE: To investigate the relative predictive value of circulating immune cell markers for cardiovascular mortality in ambulatory adults without cardiovascular disease.nnMETHODS: We analyzed data of participants enrolled in the National Health and Nutrition Examination Survey from January 1, 1999, to December 31, 2010, with the total leukocyte count within a normal range (4000-11,000 cells/μL [to convert to cells ×10/L, multiply by 0.001]) and without cardiovascular disease. The relative predictive value of circulating immune cell markers measured at enrollment-including total leukocyte count, absolute neutrophil count, absolute lymphocyte count, absolute monocyte count, monocyte-lymphocyte ratio (MLR), neutrophil-lymphocyte ratio, and C-reactive protein-for cardiovascular mortality was evaluated. The marker with the best predictive value was added to the 10-year atherosclerotic cardiovascular disease (ASCVD) risk score to estimate net risk reclassification indices for 10-year cardiovascular mortality.nnRESULTS: Among 21,599 participants eligible for this analysis, the median age was 47 years (interquartile range, 34-63 years); 10,651 (49.2%) participants were women, and 10,713 (49.5%) were self-reported non-Hispanic white. During a median follow-up of 9.6 years (interquartile range, 6.8-13.1 years), there were 627 cardiovascular deaths. MLR had the best predictive value for cardiovascular mortality. The addition of elevated MLR (≥0.3) to the 10-year ASCVD risk score improved the classification by 2.7%±1.4% (P=.04). Elevated MLR had better predictive value than C-reactive protein and several components of the 10-year ASCVD risk score.nnCONCLUSION: Among ambulatory US adults without preexisting cardiovascular disease, we found that MLR had the best predictive value for cardiovascular mortality among circulating immune markers. The addition of MLR to the 10-year risk score significantly improved the risk classification of participants.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34422349,

title = {A simple assessment of lung nodule location for reduction in unnecessary invasive procedures},

author = {C Matthew Kinsey and Ehab Billatos and Vitor Mori and Ben Tonelli and Bernard F Cole and Fenghai Duan and Helga Marques and Isaac de la Bruere and Jorge Onieva and Rubén San José Estépar and Alyx Cleveland and Dan Idelkope and Chris Stevenson and Jason H T Bates and Denise Aberle and Avi Spira and George Washko and Raúl San José Estépar},

doi = {10.21037/jtd-20-3093},

issn = {2072-1439},

year  = {2021},

date = {2021-07-01},

journal = {J Thorac Dis},

volume = {13},

number = {7},

pages = {4207--4216},

abstract = {BACKGROUND: CT screening for lung cancer results in a significant mortality reduction but is complicated by invasive procedures performed for evaluation of the many detected benign nodules. The purpose of this study was to evaluate measures of nodule location within the lung as predictors of malignancy.nnMETHODS: We analyzed images and data from 3,483 participants in the National Lung Screening Trial (NLST). All nodules (4-20 mm) were characterized by 3D geospatial location using a Cartesian coordinate system and evaluated in logistic regression analysis. Model development and probability cutpoint selection was performed in the NLST testing set. The Geospatial test was then validated in the NLST testing set, and subsequently replicated in a new cohort of 147 participants from The Detection of Early Lung Cancer Among Military Personnel (DECAMP) Consortium.nnRESULTS: The Geospatial Test, consisting of the superior-inferior distance (Z distance), nodule diameter, and radial distance (carina to nodule) performed well in both the NLST validation set (AUC 0.85) and the DECAMP replication cohort (AUC 0.75). A negative Geospatial Test resulted in a less than 2% risk of cancer across all nodule diameters. The Geospatial Test correctly reclassified 19.7% of indeterminate nodules with a diameter over 6mm as benign, while only incorrectly classifying 1% of cancerous nodules as benign. In contrast, the parsimonious Brock Model applied to the same group of nodules correctly reclassified 64.5% of indeterminate nodules as benign but resulted in misclassification of a cancer as benign in 18.2% of the cases. Applying the Geospatial test would result in reducing invasive procedures performed for benign lesions by 11.3% with a low rate of misclassification (1.3%). In contrast, the Brock model applied to the same group of patients results in decreasing invasive procedures for benign lesion by 39.0% but misclassifying 21.1% of cancers as benign.nnCONCLUSIONS: Utilizing information about geospatial location within the lung improves risk assessment for indeterminate lung nodules and may reduce unnecessary procedures.nnTRIAL REGISTRATION: NCT00047385, NCT01785342.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34226239,

title = {Study protocol for a national cohort of adults focused on respiratory health: the American Lung Association Lung Health Cohort (ALA-LHC) Study},

author = {Paul A Reyfman and Elizabeth Sugar and Heather Hazucha and Jenny Hixon and Curt Reynolds and Sonali Bose and Mark T Dransfield and MeiLan K Han and Raul San Jose Estepar and Mary B Rice and George R Washko and Mercedes Carnethon and Ravi Kalhan and  and },

doi = {10.1136/bmjopen-2021-053342},

issn = {2044-6055},

year  = {2021},

date = {2021-07-01},

journal = {BMJ Open},

volume = {11},

number = {7},

pages = {e053342},

abstract = {INTRODUCTION: The current framework for investigating respiratory diseases is based on defining lung health as the absence of lung disease. In order to develop a comprehensive approach to prevent the development of lung disease, there is a need to evaluate the full spectrum of lung health spanning from ideal to impaired lung health. The American Lung Association (ALA) Lung Health Cohort is a new, population-based, cohort study focused primarily on characterising lung health in members of the millennial generation without diagnosed severe respiratory disease. Participants will be enrolled for the baseline study visit starting in 2021, and funding will be sought to support future study exams as part of a longitudinal cohort study. This study will be crucial for developing a novel paradigm of lung health throughout the adult life course.nnMETHODS AND ANALYSIS: This study will leverage the existing infrastructure of the ALA Airways Clinical Research Centers network to enrol 4000 participants between ages 25 and 35 years old at 39 sites across the USA between April 2021 and December 2024. Study procedures will include physical assessment, spirometry, chest CT scan, accelerometry and collection of nasal epithelial lining fluid, nasal epithelial cells, blood and urine. Participants will complete questionnaires about their sociodemographic characteristics, home address histories and exposures, work history and exposure, medical histories, lung health and health behaviours and activity.nnETHICS AND DISSEMINATION: The study was approved by the Johns Hopkins Medicine Institutional Review Board. Findings will be disseminated to the scientific community through peer-reviewed journals and at professional conferences. The lay public will receive scientific findings directly through the ALA infrastructure including the official public website. Deidentified datasets will be deposited to BioLINCC, and deidentified biospecimens may be made available to qualified investigators along with a limited-use datasets.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33244876,

title = {Association of quantitative CT lung density measurements and lung function decline in World Trade Center workers},

author = {Xiaoyu Liu and Anthony P Reeves and Katherine Antoniak and Raúl San José Estépar and John T Doucette and Yunho Jeon and Jonathan Weber and Dongming Xu and Juan C Celedón and Rafael E de la Hoz},

doi = {10.1111/crj.13313},

issn = {1752-699X},

year  = {2021},

date = {2021-06-01},

journal = {Clin Respir J},

volume = {15},

number = {6},

pages = {613--621},

abstract = {BACKGROUND: Occupational exposures at the WTC site after 11 September 2001 have been associated with presumably inflammatory chronic lower airway diseases.nnAIMS: In this study, we describe the trajectories of expiratory air flow decline, identify subgroups with adverse progression, and investigate the association of those trajectories with quantitative computed tomography (QCT) imaging measurement of increased and decreased lung density.nnMETHODS: We examined the trajectories of expiratory air flow decline in a group of 1,321 former WTC workers and volunteers with at least three periodic spirometries, and using QCT-measured low (LAV%, -950 HU) and high (HAV%, from -600 to -250 HU) attenuation volume percent. We calculated the individual regression line slopes for first-second forced expiratory volume (FEV slope), identified subjects with rapidly declining ("accelerated decliners") and increasing ("improved"), and compared them to subjects with "intermediate" (0 to -66.5 mL/year) FEV slope. We then used multinomial logistic regression to model those three trajectories, and the two lung attenuation metrics.nnRESULTS: The mean longitudinal FEV slopes for the entire study population, and its intermediate, decliner, and improved subgroups were, respectively, -40.4, -34.3, -106.5, and 37.6 mL/year. In unadjusted and adjusted analyses, LAV% and HAV% were both associated with "accelerated decliner" status (OR , 95% CI 2.37, 1.41-3.97, and 1.77, 1.08-2.89, respectively), compared to the intermediate decline.nnCONCLUSIONS: Longitudinal FEV decline in this cohort, known to be associated with QCT proximal airway inflammation metric, is also associated with QCT indicators of increased and decreased lung density. The improved FEV trajectory did not seem to be associated with lung density metrics.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33574123,

title = {Respiratory exacerbations are associated with muscle loss in current and former smokers},

author = {Stefanie Elizabeth Mason and Rafael Moreta-Martinez and Wassim W Labaki and Matthew Strand and David Baraghoshi and Elizabeth A Regan and Jessica Bon and Ruben San Jose Estepar and Richard Casaburi and Merry-Lynn N McDonald and Harry Rossiter and Barry J Make and Mark T Dransfield and MeiLan K Han and Kendra A Young and Greg Kinney and John E Hokanson and Raul San Jose Estepar and George R Washko and  and },

doi = {10.1136/thoraxjnl-2020-215999},

issn = {1468-3296},

year  = {2021},

date = {2021-06-01},

journal = {Thorax},

volume = {76},

number = {6},

pages = {554--560},

abstract = {OBJECTIVES: Muscle wasting is a recognised extra-pulmonary complication in chronic obstructive pulmonary disease and has been associated with increased risk of death. Acute respiratory exacerbations are associated with reduction of muscle function, but there is a paucity of data on their long-term effect. This study explores the relationship between acute respiratory exacerbations and long-term muscle loss using serial measurements of CT derived pectoralis muscle area (PMA).nnDESIGN AND SETTING: Participants were included from two prospective, longitudinal, observational, multicentre cohorts of ever-smokers with at least 10 pack-year history.nnPARTICIPANTS: The primary analysis included 1332 (of 2501) participants from Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) and 4384 (of 10 198) participants from Genetic Epidemiology of COPD (COPDGene) who had complete data from their baseline and follow-up visits.nnINTERVENTIONS: PMA was measured on chest CT scans at two timepoints. Self-reported exacerbation data were collected from participants in both studies through the use of periodic longitudinal surveys.nnMAIN OUTCOME MEASURES: Age-related and excess muscle loss over time.nnRESULTS: Age, sex, race and body mass index were associated with baseline PMA. Participants experienced age-related decline at the upper end of reported normal ranges. In ECLIPSE, the exacerbation rate over time was associated with an excess muscle area loss of 1.3% (95% CI 0.6 to 1.9, p<0.001) over 3 years and in COPDGene with an excess muscle area loss of 2.1% (95% CI 1.2 to 2.8, p<0.001) over 5 years. Excess muscle area decline was absent in 273 individuals who participated in pulmonary rehabilitation.nnCONCLUSIONS: Exacerbations are associated with accelerated skeletal muscle loss. Each annual exacerbation was associated with the equivalent of 6 months of age-expected decline in muscle mass. Ameliorating exacerbation-associated muscle loss represents an important therapeutic target.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34027328,

title = {COVID-19 vaccination: Helping the latinx community to come forward},

author = {Alejandro A Diaz and Juan C Celedón},

doi = {10.1016/j.eclinm.2021.100860},

issn = {2589-5370},

year  = {2021},

date = {2021-05-01},

journal = {EClinicalMedicine},

volume = {35},

pages = {100860},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33080140,

title = {The Association of Aging Biomarkers, Interstitial Lung Abnormalities, and Mortality},

author = {Jason L Sanders and Rachel K Putman and Josée Dupuis and Hanfei Xu and Joanne M Murabito and Tetsuro Araki and Mizuki Nishino and Emelia J Benjamin and Daniel Levy and Vasan S Ramachandran and George R Washko and Jeffrey L Curtis and Christine M Freeman and Russell P Bowler and Hiroto Hatabu and George T O'Connor and Gary M Hunninghake},

doi = {10.1164/rccm.202007-2993OC},

issn = {1535-4970},

year  = {2021},

date = {2021-05-01},

journal = {Am J Respir Crit Care Med},

volume = {203},

number = {9},

pages = {1149--1157},

abstract = { The association between aging and idiopathic pulmonary fibrosis has been established. The associations between aging-related biomarkers and interstitial lung abnormalities (ILA) have not been comprehensively evaluated. To evaluate the associations among aging biomarkers, ILA, and all-cause mortality. In the FHS (Framingham Heart Study), we evaluated associations among plasma biomarkers (IL-6, CRP [C-reactive protein], TNFR [tumor necrosis factor α receptor II], GDF15 [growth differentiation factor 15], cystatin-C, HGBA1C [Hb A1C], insulin, IGF1 [insulin-like growth factor 1], and IGFBP1 [IGF binding protein 1] and IGFBP3]), ILA, and mortality. Causal inference analysis was used to determine whether biomarkers mediated age. GDF15 results were replicated in the COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease) Study. In the FHS, there were higher odds of ILA per increase in natural log-transformed GDF15 (odds ratio [95% confidence interval], 3.4 [1.8-6.4];  = 0.0002), TNFR (3.1 [1.6-5.8];  = 0.004), IL-6 (1.8 [1.4-2.4];  < 0.0001), and CRP (1.7 [1.3-2.0];  < 0.0001). In the FHS, after adjustment for multiple comparisons, no biomarker was associated with increased mortality, but the associations of GDF15 (hazard ratio, 2.0 [1.1-3.5];  = 0.02), TNFR (1.8 [1.0-3.3];  = 0.05), and IGFBP1 (1.3 [1.1-1.7];  = 0.01) approached significance. In the COPDGene Study, higher natural log-transformed GDF15 was associated with ILA (odds ratio, 8.1 [3.1-21.4];  < 0.0001) and mortality (hazard ratio, 1.6 [1.1-2.2];  = 0.01). Causal inference analysis showed that the association of age with ILA was mediated by IL-6 ( < 0.0001) and TNFR ( = 0.002) and was likely mediated by GDF15 ( = 0.008) in the FHS and was mediated by GDF15 ( = 0.001) in the COPDGene Study. Some aging-related biomarkers are associated with ILA. GDF15, in particular, may explain some of the associations among age, ILA, and mortality.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33290645,

title = {Progression of Emphysema and Small Airways Disease in Cigarette Smokers},

author = {Esther Pompe and Camille M Moore and Firdaus A A Mohamed Hoesein and Pim A de Jong and Jean-Paul Charbonnier and MeiLan K Han and Steven M Humphries and Charles R Hatt and Craig J Galbán and Ed K Silverman and James D Crapo and George R Washko and Elisabeth A Regan and Barry Make and Matthew Strand and Jan-Willem J Lammers and Eva M van Rikxoort and David A Lynch and },

doi = {10.15326/jcopdf.2020.0140},

issn = {2372-952X},

year  = {2021},

date = {2021-04-01},

journal = {Chronic Obstr Pulm Dis},

volume = {8},

number = {2},

pages = {198--212},

abstract = {BACKGROUND: Little is known about factors associated with emphysema progression in cigarette smokers. We evaluated factors associated with change in emphysema and forced expiratory volume in 1 second (FEV) in participants with and without chronic obstructive pulmonary disease (COPD).nnMETHODS: This retrospective study included individuals participating in the COPD Genetic Epidemiology study who completed the 5-year follow-up, including inspiratory and expiratory computed tomography (CT) and spirometry. All paired CT scans were analyzed using micro-mapping, which classifies individual voxels as emphysema or functional small airway disease (fSAD). Presence and progression of emphysema and FEV were determined based on comparison to nonsmoker values. Logistic regression analyses were used to identify clinical parameters associated with disease progression.nnRESULTS: A total of 3088 participants were included with a mean ± SD age of 60.7±8.9 years, including 72 nonsmokers. In all Global initiative for chronic Obstructive Lung Disease (GOLD) stages, the presence of emphysema at baseline was associated with emphysema progression (odds ratio [OR]: GOLD 0: 4.32; preserved ratio-impaired spirometry [PRISm]; 5.73; GOLD 1: 5.16; GOLD 2: 5.69; GOLD 3/4: 5.55; all  ≤0.01). If there was no emphysema at baseline, the amount of fSAD at baseline was associated with emphysema progression (OR for 1% increase: GOLD 0: 1.06; PRISm: 1.20; GOLD 1: 1.7; GOLD 3/4: 1.08; all  ≤ 0.03).In 1735 participants without spirometric COPD, progression in emphysema occurred in 105 (6.1%) participants and only 21 (1.2%) had progression in both emphysema and FEV.nnCONCLUSIONS: The presence of emphysema is an important predictor of emphysema progression. In patients without emphysema, fSAD is associated with the development of emphysema. In participants without spirometric COPD, emphysema progression occurred independently of FEV decline.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33870015,

title = {Ambient air pollution exposure and radiographic pulmonary vascular volumes},

author = {Andrew J Synn and Katerina L Byanova and Wenyuan Li and Diane R Gold and Qian Di and Itai Kloog and Joel Schwartz and Raúl San José Estépar and George R Washko and George T O'Connor and Murray A Mittleman and Mary B Rice},

doi = {10.1097/EE9.0000000000000143},

issn = {2474-7882},

year  = {2021},

date = {2021-04-01},

journal = {Environ Epidemiol},

volume = {5},

number = {2},

pages = {e143},

abstract = {Exposure to higher levels of ambient air pollution is a known risk factor for cardiovascular disease but long-term effects of pollution exposure on the pulmonary vessels are unknown.nnMETHODS: Among 2428 Framingham Heart Study participants who underwent chest computed tomography (CT) between 2008 and 2011, pulmonary vascular volumes were calculated by image analysis, including the total vascular volume and small vessel volume (cross-sectional area <5 mm; BV5 defined as small vessel volume). Using spatiotemporal models and participant home address, we assigned 1-year (2008) and 5-year (2004-2008) average concentrations of fine particulate matter (PM), elemental carbon (EC), and ground-level ozone (O), and distance to major roadway. We examined associations of 1- and 5-year exposures, and distance to road, with CT vascular volumes using multivariable linear regression models.nnRESULTS: There was a consistent negative association of higher O with lower small vessel volumes, which persisted after adjustment for distance to road. Per interquartile range (IQR) of 2008 O, BV5 was 0.34 mL lower (95% confidence intervals [CI], -0.61 to -0.06;  = 0.02), with similar results for 5-year exposure. One-year EC exposure and closer proximity to road were weakly associated with small vessel volumes; BV5 was 0.18 mL higher per IQR of 2008 EC (95% CI, -0.05 to 0.42;  = 0.13) and 0.40 mL higher per IQR closer proximity to road (95% CI: -0.10 to 0.89;  = 0.12). PM was not associated with small vascular volumes; BV5 was 0.26 mL lower per IQR of 2008 PM (95% CI: -0.68 to 0.16;  = 0.22).nnCONCLUSIONS: Among community-dwelling adults living in the northeastern United States, higher exposure to O was associated with lower small pulmonary vessel volumes on CT.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33591891,

title = {Relationship between Emphysema Progression at CT and Mortality in Ever-Smokers: Results from the COPDGene and ECLIPSE Cohorts},

author = {Samuel Y Ash and Raúl San José Estépar and Sean B Fain and Ruth Tal-Singer and Robert A Stockley and Lars H Nordenmark and Stephen Rennard and MeiLan K Han and Debora Merrill and Stephen M Humphries and Alejandro A Diaz and Stefanie E Mason and Farbod N Rahaghi and Carrie L Pistenmaa and Frank C Sciurba and Gonzalo Vegas-Sánchez-Ferrero and David A Lynch and George R Washko and },

doi = {10.1148/radiol.2021203531},

issn = {1527-1315},

year  = {2021},

date = {2021-04-01},

journal = {Radiology},

volume = {299},

number = {1},

pages = {222--231},

abstract = {Background The relationship between emphysema progression and long-term outcomes is unclear. Purpose To determine the relationship between emphysema progression at CT and mortality among participants with emphysema. Materials and Methods In a secondary analysis of two prospective observational studies, COPDGene (, NCT00608764) and Evaluation of Chronic Obstructive Pulmonary Disease Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE; , NCT00292552), emphysema was measured at CT at two points by using the volume-adjusted lung density at the 15th percentile of the lung density histogram (hereafter, lung density perc15) method. The association between emphysema progression rate and all-cause mortality was analyzed by using Cox regression adjusted for ethnicity, sex, baseline age, pack-years, and lung density, baseline and change in smoking status, forced expiratory volume in 1 second, and 6-minute walk distance. In COPDGene, respiratory mortality was analyzed by using the Fine and Gray method. Results A total of 5143 participants (2613 men [51%]; mean age, 60 years ± 9 [standard deviation]) in COPDGene and 1549 participants (973 men [63%]; mean age, 62 years ± 8) in ECLIPSE were evaluated, of which 2097 (40.8%) and 1179 (76.1%) had emphysema, respectively. Baseline imaging was performed between January 2008 and December 2010 for COPDGene and January 2006 and August 2007 for ECLIPSE. Follow-up imaging was performed after 5.5 years ± 0.6 in COPDGene and 3.0 years ± 0.2 in ECLIPSE, and mortality was assessed over the ensuing 5 years in both. For every 1 g/L per year faster rate of decline in lung density perc15, all-cause mortality increased by 8% in COPDGene (hazard ratio [HR], 1.08; 95% CI: 1.01, 1.16;  = .03) and 6% in ECLIPSE (HR, 1.06; 95% CI: 1.00, 1.13;  = .045). In COPDGene, respiratory mortality increased by 22% (HR, 1.22; 95% CI: 1.13, 1.31;  < .001) for the same increase in the rate of change in lung density perc15. Conclusion In ever-smokers with emphysema, emphysema progression at CT was associated with increased all-cause and respiratory mortality. © RSNA, 2021  See also the editorial by Lee and Park in this issue.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33541604,

title = {Advanced Imaging in Pulmonary Vascular Disease},

author = {Eileen M Harder and Rebecca Vanderpool and Farbod N Rahaghi},

doi = {10.1016/j.ccm.2020.11.004},

issn = {1557-8216},

year  = {2021},

date = {2021-03-01},

journal = {Clin Chest Med},

volume = {42},

number = {1},

pages = {101--112},

abstract = {Although the diagnosis of pulmonary hypertension requires invasive testing, imaging serves an important role in the screening, classification, and monitoring of patients with pulmonary vascular disease (PVD). The development of advanced imaging techniques has led to improvements in the understanding of disease pathophysiology, noninvasive assessment of hemodynamics, and stratification of patient risk. This article discusses the current role of advanced imaging and the emerging novel techniques for visualizing the lung parenchyma, mediastinum, and heart in PVD.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32217055,

title = {Paired CT Measures of Emphysema and Small Airways Disease and Lung Function and Exercise Capacity in Smokers with Radiographic Bronchiectasis},

author = {Carlos H Martinez and Yuka Okajima and Andrew Yen and Diego J Maselli and Pietro Nardelli and Farbord Rahaghi and Kendra Young and Gregory Kinney and Charles Hatt and Craig Galban and George R Washko and MeiLan Han and Raúl San José Estépar and Alejandro A Diaz},

doi = {10.1016/j.acra.2020.02.013},

issn = {1878-4046},

year  = {2021},

date = {2021-03-01},

journal = {Acad Radiol},

volume = {28},

number = {3},

pages = {370--378},

abstract = {RATIONALE AND OBJECTIVES: Bronchiectasis (BE) is associated with chronic obstructive pulmonary disease (COPD), but emphysema and small airways disease, main pathologic features of COPD, have been sparsely studied in BE. We aimed to objectively assess those features in smokers with and without radiographic BE and examine its relationships to airflow obstruction and exercise capacity.nnMATERIAL AND METHODS: We measured emphysema and small airways disease on paired inspiratory-expiratory computed tomography (CT) scans with the parametric response map (PRM and PRM) method in 1184 smokers with and without radiographic BE. PRM and PRM are expressed as the percentage of lung area. Clinical, spirometry, and exercise capacity data were measured with standardized methods. The differences in PRM and PRM between subjects with and without radiographic BE were assessed using multivariable linear regression analysis, and their associations with FEV and six-minute walk test (6MWT) were assessed with generalized linear models.nnRESULTS: Out of 1184 subjects, 383 (32%) had radiographic BE. PRM but not PRM was higher in subjects with radiographic BE than those without radiographic BE in adjusted models. Subjects with radiographic BE and PRM (defined as ≥5% on paired CTs) had lower FEV (least square mean, 1479 mL vs. 2350 mL p < 0.0001) and 6MWT (372 m vs. 426 m p = 0.0007) than those with radiographic BE alone in adjusted models.nnCONCLUSION: Smokers with radiographic BE have an increased burden of emphysema on paired CTs, and those with radiographic BE and emphysema have lower airflow and exercise capacity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32946850,

title = {Distinguishing Smoking-Related Lung Disease Phenotypes Via Imaging and Molecular Features},

author = {Ehab Billatos and Samuel Y Ash and Fenghai Duan and Ke Xu and Justin Romanoff and Helga Marques and Elizabeth Moses and MeiLan K Han and Elizabeth A Regan and Russell P Bowler and Stefanie E Mason and Tracy J Doyle and Rubén San José Estépar and Ivan O Rosas and James C Ross and Xiaohui Xiao and Hanqiao Liu and Gang Liu and Gauthaman Sukumar and Matthew Wilkerson and Clifton Dalgard and Christopher Stevenson and Duncan Whitney and Denise Aberle and Avrum Spira and Raúl San José Estépar and Marc E Lenburg and George R Washko and },

doi = {10.1016/j.chest.2020.08.2115},

issn = {1931-3543},

year  = {2021},

date = {2021-02-01},

journal = {Chest},

volume = {159},

number = {2},

pages = {549--563},

abstract = {BACKGROUND: Chronic tobacco smoke exposure results in a broad range of lung pathologies including emphysema, airway disease and parenchymal fibrosis as well as a multitude of extra-pulmonary comorbidities. Prior work using CT imaging has identified several clinically relevant subgroups of smoking related lung disease, but these investigations have generally lacked organ specific molecular correlates.nnRESEARCH QUESTION: Can CT imaging be used to identify clinical phenotypes of smoking related lung disease that have specific bronchial epithelial gene expression patterns to better understand disease pathogenesis?nnSTUDY DESIGN AND METHODS: Using K-means clustering, we clustered participants from the COPDGene study (n = 5,273) based on CT imaging characteristics and then evaluated their clinical phenotypes. These clusters were replicated in the Detection of Early Lung Cancer Among Military Personnel (DECAMP) cohort (n = 360), and were further characterized using bronchial epithelial gene expression.nnRESULTS: Three clusters (preserved, interstitial predominant and emphysema predominant) were identified. Compared to the preserved cluster, the interstitial and emphysema clusters had worse lung function, exercise capacity and quality of life. In longitudinal follow-up, individuals from the emphysema group had greater declines in exercise capacity and lung function, more emphysema, more exacerbations, and higher mortality. Similarly, genes involved in inflammatory pathways (tumor necrosis factor-α, interferon-β) are more highly expressed in bronchial epithelial cells from individuals in the emphysema cluster, while genes associated with T-cell related biology are decreased in these samples. Samples from individuals in the interstitial cluster generally had intermediate levels of expression of these genes.nnINTERPRETATION: Using quantitative CT imaging, we identified three groups of individuals in older ever-smokers that replicate in two cohorts. Airway gene expression differences between the three groups suggests increased levels of inflammation in the most severe clinical phenotype, possibly mediated by the tumor necrosis factor-α and interferon-β pathways.nnCLINICAL TRIAL REGISTRATION: COPDGene (NCT00608764), DECAMP-1 (NCT01785342), DECAMP-2 (NCT02504697).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32798523,

title = {Vascular Pruning on CT and Interstitial Lung Abnormalities in the Framingham Heart Study},

author = {Andrew J Synn and Wenyuan Li and Gary M Hunninghake and George R Washko and Raúl San José Estépar and George T O'Connor and Cyrus A Kholdani and Robert W Hallowell and Alexander A Bankier and Murray A Mittleman and Mary B Rice},

doi = {10.1016/j.chest.2020.07.082},

issn = {1931-3543},

year  = {2021},

date = {2021-02-01},

journal = {Chest},

volume = {159},

number = {2},

pages = {663--672},

abstract = {BACKGROUND: Pulmonary vascular disease is associated with poor outcomes in individuals affected by interstitial lung disease. The pulmonary vessels can be quantified with noninvasive imaging, but whether radiographic indicators of vasculopathy are associated with early interstitial changes is not known.nnRESEARCH QUESTION: Are pulmonary vascular volumes, quantified from CT scans, associated with interstitial lung abnormalities (ILA) in a community-based sample with a low burden of lung disease?nnSTUDY DESIGN AND METHODS: In 2,386 participants of the Framingham Heart Study, we used CT imaging to calculate pulmonary vascular volumes, including the small vessel fraction (a surrogate of vascular pruning). We constructed multivariable logistic regression models to investigate associations of vascular volumes with ILA, progression of ILA, and restrictive pattern on spirometry. In secondary analyses, we additionally adjusted for diffusing capacity and emphysema, and performed a sensitivity analysis restricted to participants with normal FVC and diffusing capacity.nnRESULTS: In adjusted models, we found that lower pulmonary vascular volumes on CT were associated with greater odds of ILA, antecedent ILA progression, and restrictive pattern on spirometry. For example, each SD lower small vessel fraction was associated with 1.81-fold greater odds of ILA (95% CI, 1.41-2.31; P < .0001), and 1.63-fold greater odds of restriction on spirometry (95% CI, 1.18-2.24; P = .003). Similar patterns were seen after adjustment for diffusing capacity for carbon monoxide, emphysema, and among participants with normal lung function.nnINTERPRETATION: In this cohort of community-dwelling adults not selected on the basis of lung disease, more severe vascular pruning on CT was associated with greater odds of ILA, ILA progression, and restrictive pattern on spirometry. Pruning on CT may be an indicator of early pulmonary vasculopathy associated with interstitial lung disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34471517,

title = {What's new in pulmonary hypertension clinical research: lessons from the best abstracts at the 2020 American Thoracic Society International Conference},

author = {Andrew J Sweatt and Raju Reddy and Farbod N Rahaghi and Nadine Al-Naamani and },

doi = {10.1177/20458940211040713},

issn = {2045-8932},

year  = {2021},

date = {2021-01-01},

journal = {Pulm Circ},

volume = {11},

number = {3},

pages = {20458940211040713},

abstract = {In this conference paper, we review the 2020 American Thoracic Society International Conference session titled, "What's New in Pulmonary Hypertension Clinical Research: Lessons from the Best Abstracts". This virtual mini-symposium took place on 21 October 2020, in lieu of the annual in-person ATS International Conference which was cancelled due to the COVID-19 pandemic. Seven clinical research abstracts were selected for presentation in the session, which encompassed five major themes: (1) standardizing diagnosis and management of pulmonary hypertension, (2) improving risk assessment in pulmonary arterial hypertension, (3) evaluating biomarkers of disease activity, (4) understanding metabolic dysregulation across the spectrum of pulmonary hypertension, and (5) advancing knowledge in chronic thromboembolic pulmonary hypertension. Focusing on these five thematic contexts, we review the current state of knowledge, summarize presented research abstracts, appraise their significance and limitations, and then discuss relevant future directions in pulmonary hypertension clinical research.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33748259,

title = {The presence of emphysema on chest imaging and mid-life cognition},

author = {Benjamin E Henkle and Laura A Colangelo and Mark T Dransfield and Lifang Hou and David R Jacobs and Brian T Joyce and Carrie L Pistenmaa and Rachel K Putman and Steve Sidney and Bharat Thyagarajan and George R Washko and Kristine Yaffe and Ravi Kalhan and Ken M Kunisaki},

doi = {10.1183/23120541.00048-2021},

issn = {2312-0541},

year  = {2021},

date = {2021-01-01},

journal = {ERJ Open Res},

volume = {7},

number = {1},

abstract = {BACKGROUND: Airflow obstruction is associated with cognitive dysfunction but studies have not assessed how emphysema, a structural phenotype of lung disease, might be associated with cognitive function independent from pulmonary function measured by spirometry. We aimed to determine the relationship between the presence of visually detectable emphysema on chest computed tomography (CT) imaging and cognitive function.nnMETHODS: We examined 2491 participants, mean age of 50 years, from the Coronary Artery Risk Development in Young Adults study who were assessed for the presence of emphysema on chest CT imaging and had cognitive function measured 5 years later with a battery of six cognitive tests.nnRESULTS: Of those assessed, 172 (7%) had emphysema. After adjusting for age, sex, height, study centre, race, body mass index, education and smoking, visual emphysema was significantly associated with worse performance on most cognitive tests. Compared to those without emphysema, participants with emphysema performed worse on cognitive testing: 0.39 sd units lower (95% CI -0.53- -0.25) on the Montreal Cognitive Assessment, 0.27 sd units lower (95% CI -0.42- -0.12) on the Rey Auditory Verbal Learning Test, 0.29 sd units lower (95% CI -0.43- -0.14) on the Digit Symbol Substitution Test and 0.25 sd units lower (95% CI -0.42- -0.09) on letter fluency. Further adjustment for forced expiratory volume in 1 s (FEV), peak FEV and annualised FEV decline did not attenuate these associations.nnCONCLUSIONS: The presence of emphysema on chest CT is associated with worse cognitive function, independent of airflow obstruction. These data suggest that emphysema may be a novel risk factor for cognitive impairment.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33253972,

title = {Qualitative emphysema and risk of COPD hospitalization in a multicenter CT lung cancer screening cohort study},

author = {Lee Gazourian and William B Thedinger and Shawn M Regis and Elizabeth J Pagura and Lori Lyn Price and Melissa Gawlik and Cristina F Stefanescu and Carla Lamb and Kimberly M Rieger-Christ and Harpreet Singh and Marcel Casasola and Alexander R Walker and Arashdeep Rupal and Avignat S Patel and Carolyn E Come and Ava M Sanayei and William P Long and Giulia S Rizzo and Andrea B McKee and George R Washko and Raul San Jose Estepar and Christoph Wald and Brady J McKee and Carey C Thomson and Timothy N Liesching},

doi = {10.1016/j.rmed.2020.106245},

issn = {1532-3064},

year  = {2021},

date = {2021-01-01},

journal = {Respir Med},

volume = {176},

pages = {106245},

abstract = {BACKGROUND: In the United States, 9 to 10 million Americans are estimated to be eligible for computed tomographic lung cancer screening (CTLS). Those meeting criteria for CTLS are at high-risk for numerous cardio-pulmonary co-morbidities. The objective of this study was to determine the association between qualitative emphysema identified on screening CTs and risk for hospital admission.nnSTUDY DESIGN AND METHODS: We conducted a retrospective multicenter study from two CTLS cohorts: Lahey Hospital and Medical Center (LHMC) CTLS program, Burlington, MA and Mount Auburn Hospital (MAH) CTLS program, Cambridge, MA. CTLS exams were qualitatively scored by radiologists at time of screening for presence of emphysema. Multivariable Cox regression models were used to evaluate the association between CT qualitative emphysema and all-cause, COPD-related, and pneumonia-related hospital admission.nnRESULTS: We included 4673 participants from the LHMC cohort and 915 from the MAH cohort. 57% and 51.9% of the LHMC and MAH cohorts had presence of CT emphysema, respectively. In the LHMC cohort, the presence of emphysema was associated with all-cause hospital admission (HR 1.15, CI 1.07-1.23; p < 0.001) and COPD-related admission (HR 1.64; 95% CI 1.14-2.36; p = 0.007), but not with pneumonia-related admission (HR 1.52; 95% CI 1.27-1.83; p < 0.001). In the MAH cohort, the presence of emphysema was only associated with COPD-related admission (HR 2.05; 95% CI 1.07-3.95; p = 0.031).nnCONCLUSION: Qualitative CT assessment of emphysema is associated with COPD-related hospital admission in a CTLS population. Identification of emphysema on CLTS exams may provide an opportunity for prevention and early intervention to reduce admission risk.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33748349,

title = {Progression of traction bronchiectasis/bronchiolectasis in interstitial lung abnormalities is associated with increased all-cause mortality: Age Gene/Environment Susceptibility-Reykjavik Study},

author = {Takuya Hino and Tomoyuki Hida and Mizuki Nishino and Junwei Lu and Rachel K Putman and Elias F Gudmundsson and Akinori Hata and Tetsuro Araki and Vladimir I Valtchinov and Osamu Honda and Masahiro Yanagawa and Yoshitake Yamada and Takeshi Kamitani and Masahiro Jinzaki and Noriyuki Tomiyama and Kousei Ishigami and Hiroshi Honda and Raul San Jose Estepar and George R Washko and Takeshi Johkoh and David C Christiani and David A Lynch and Vilmundur Gudnason and Gunnar Gudmundsson and Gary M Hunninghake and Hiroto Hatabu},

doi = {10.1016/j.ejro.2021.100334},

issn = {2352-0477},

year  = {2021},

date = {2021-01-01},

journal = {Eur J Radiol Open},

volume = {8},

pages = {100334},

abstract = {PURPOSE: The aim of this study is to assess the role of traction bronchiectasis/bronchiolectasis and its progression as a predictor for early fibrosis in interstitial lung abnormalities (ILA).nnMETHODS: Three hundred twenty-seven ILA participants out of 5764 in the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study who had undergone chest CT twice with an interval of approximately five-years were enrolled in this study. Traction bronchiectasis/bronchiolectasis index (TBI) was classified on a four-point scale: 0, ILA without traction bronchiectasis/bronchiolectasis; 1, ILA with bronchiolectasis but without bronchiectasis or architectural distortion; 2, ILA with mild to moderate traction bronchiectasis; 3, ILA and severe traction bronchiectasis and/or honeycombing. Traction bronchiectasis (TB) progression was classified on a five-point scale: 1, Improved; 2, Probably improved; 3, No change; 4, Probably progressed; 5, Progressed. Overall survival (OS) among participants with different TB Progression Score and between the TB progression group and No TB progression group was also investigated. Hazard radio (HR) was estimated with Cox proportional hazards model.nnRESULTS: The higher the TBI at baseline, the higher TB Progression Score (P < 0.001). All five participants with TBI = 3 at baseline progressed; 46 (90 %) of 51 participants with TBI = 2 progressed. TB progression was also associated with shorter OS with statistically significant difference (adjusted HR = 1.68, P < 0.001).nnCONCLUSION: TB progression was visualized on chest CT frequently and clearly. It has the potential to be the predictor for poorer prognosis of ILA.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34881020,

title = {Vascular remodeling of the small pulmonary arteries and measures of vascular pruning on computed tomography},

author = {Andrew J Synn and Constance De Margerie-Mellon and Sun Young Jeong and Farbod N Rahaghi and Iny Jhun and George R Washko and Raúl San José Estépar and Alexander A Bankier and Murray A Mittleman and Paul A VanderLaan and Mary B Rice},

doi = {10.1177/20458940211061284},

issn = {2045-8932},

year  = {2021},

date = {2021-01-01},

journal = {Pulm Circ},

volume = {11},

number = {4},

pages = {20458940211061284},

abstract = {Pulmonary hypertension is characterized histologically by intimal and medial thickening in the small pulmonary arteries, eventually resulting in vascular "pruning." Computed tomography (CT)-based quantification of pruning is associated with clinical measures of pulmonary hypertension, but it is not established whether CT-based pruning correlates with histologic arterial remodeling. Our sample consisted of 138 patients who underwent resection for early-stage lung adenocarcinoma. From histologic sections, we identified small pulmonary arteries and measured the relative area comprising the intima and media (VWA%), with higher VWA% representing greater histologic remodeling. From pre-operative CTs, we used image analysis algorithms to calculate the small vessel volume fraction (BV5/TBV) as a CT-based indicator of pruning (lower BV5/TBV represents greater pruning). We investigated relationships of CT pruning and histologic remodeling using Pearson correlation, simple linear regression, and multivariable regression with adjustment for age, sex, height, weight, smoking status, and total pack-years. We also tested for effect modification by sex and smoking status. In primary models, more severe CT pruning was associated with greater histologic remodeling. The Pearson correlation coefficient between BV5/TBV and VWA% was -0.41, and in linear regression models, VWA% was 3.13% higher (95% CI: 1.95-4.31%, p < 0.0001) per standard deviation lower BV5/TBV. This association persisted after multivariable adjustment. We found no evidence that these relationships differed by sex or smoking status. Among individuals who underwent resection for lung adenocarcinoma, more severe CT-based vascular pruning was associated with greater histologic arterial remodeling. These findings suggest CT imaging may be a non-invasive indicator of pulmonary vascular pathology.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33870318,

title = {Creating Multilingual COVID-19-related Material. Expanding Health Literacy in Vulnerable Populations},

author = {Priya P Shah and Alejandro A Diaz},

doi = {10.34197/ats-scholar.2020-0131CM},

issn = {2690-7097},

year  = {2020},

date = {2020-12-01},

journal = {ATS Sch},

volume = {2},

number = {1},

pages = {9--12},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32890777,

title = {Position paper on COVID-19 imaging and AI: From the clinical needs and technological challenges to initial AI solutions at the lab and national level towards a new era for AI in healthcare},

author = {Hayit Greenspan and Raúl San José Estépar and Wiro J Niessen and Eliot Siegel and Mads Nielsen},

doi = {10.1016/j.media.2020.101800},

issn = {1361-8423},

year  = {2020},

date = {2020-12-01},

journal = {Med Image Anal},

volume = {66},

pages = {101800},

abstract = {In this position paper, we provide a collection of views on the role of AI in the COVID-19 pandemic, from clinical requirements to the design of AI-based systems, to the translation of the developed tools to the clinic. We highlight key factors in designing system solutions - per specific task; as well as design issues in managing the disease at the national level. We focus on three specific use-cases for which AI systems can be built: early disease detection, management in a hospital setting, and building patient-specific predictive models that require the combination of imaging with additional clinical data. Infrastructure considerations and population modeling in two European countries will be described. This pandemic has made the practical and scientific challenges of making AI solutions very explicit. A discussion concludes this paper, with a list of challenges facing the community in the AI road ahead.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid31446829,

title = {Equipoise in Appropriate Initial Volume Resuscitation for Patients in Septic Shock With Heart Failure: Results of a Multicenter Clinician Survey},

author = {Gabriel Wardi and Ian Joel and Julian Villar and Michael Lava and Eric Gross and Vaishal Tolia and Raghu R Seethala and Robert L Owens and Rebecca E Sell and Sydney B Montesi and Farbod N Rahaghi and Somnath Bose and Ashish Rai and Elizabeth K Stevenson and Jakob McSparron and Vaishal Tolia and Jeremy R Beitler},

doi = {10.1177/0885066619871247},

issn = {1525-1489},

year  = {2020},

date = {2020-11-01},

journal = {J Intensive Care Med},

volume = {35},

number = {11},

pages = {1338--1345},

abstract = {PURPOSE: International clinical practice guidelines call for initial volume resuscitation of at least 30 mL/kg body weight for patients with sepsis-induced hypotension or shock. Although not considered in the guidelines, preexisting cardiac dysfunction may be an important factor clinicians weigh in deciding the quantity of volume resuscitation for patients with septic shock.nnMETHODS: We conducted a multicenter survey of clinicians who routinely treat patients with sepsis to evaluate their beliefs, behaviors, knowledge, and perceived structural barriers regarding initial volume resuscitation for patients with sepsis and concomitant heart failure with reduced ejection fraction (HFrEF) <40%. Initial volume resuscitation preferences were captured as ordinal values, and additional testing for volume resuscitation preferences was performed using McNemar and Wilcoxon signed rank tests as indicated. Univariable logistic regression models were used to identify significant predictors of ≥30 mL/kg fluid administration.nnRESULTS: A total of 317 clinicians at 9 US hospitals completed the survey (response rate 47.3%). Most respondents were specialists in either internal medicine or emergency medicine. Substantial heterogeneity was found regarding sepsis resuscitation preferences for patients with concomitant HFrEF. The belief that patients with septic shock and HFrEF should be exempt from current sepsis bundle initiatives was shared by 39.4% of respondents. A minimum fluid challenge of ∼30 mL/kg or more was deemed appropriate in septic shock by only 56.4% of respondents for patients with concomitant HFrEF, compared to 89.1% of respondents for patients without HFrEF ( < .01). Emergency medicine physicians were most likely to feel that <30 mL/kg was most appropriate in patients with septic shock and HFrEF.nnCONCLUSIONS: Clinical equipoise exists regarding initial volume resuscitation for patients with sepsis-induced hypotension or shock and concomitant HFrEF. Future studies and clinical practice guidelines should explicitly address resuscitation in this subpopulation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33136096,

title = {Histone deacetylase 6-mediated selective autophagy regulates COPD-associated cilia dysfunction},

author = {Hilaire C Lam and Suzanne M Cloonan and Abhiram R Bhashyam and Jeffery A Haspel and Anju Singh and J Fah Sathirapongsasuti and Morgan Cervo and Hongwei Yao and Anna L Chung and Kenji Mizumura and Chang Hyeok An and Bin Shan and Jonathan M Franks and Kathleen J Haley and Caroline A Owen and Yohannes Tesfaigzi and George R Washko and John Quackenbush and Edwin K Silverman and Irfan Rahman and Hong Pyo Kim and Ashfaq Mahmood and Shyam S Biswal and Stefan W Ryter and Augustine Mk Choi},

doi = {10.1172/JCI143863},

issn = {1558-8238},

year  = {2020},

date = {2020-11-01},

journal = {J Clin Invest},

volume = {130},

number = {11},

pages = {6189},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32599066,

title = {Evidence for Expanding Invasive Mediastinal Staging for Peripheral T1 Lung Tumors},

author = {Emily A DuComb and Benjamin A Tonelli and Ya Tuo and Bernard F Cole and Vitor Mori and Jason H T Bates and George R Washko and Raúl San José Estépar and C Matthew Kinsey},

doi = {10.1016/j.chest.2020.05.607},

issn = {1931-3543},

year  = {2020},

date = {2020-11-01},

journal = {Chest},

volume = {158},

number = {5},

pages = {2192--2199},

abstract = {BACKGROUND: Guidelines recommend invasive mediastinal staging for patients with non-small cell lung cancer and a "central" tumor. However, there is no consensus definition for central location. As such, the decision to perform invasive staging largely remains on an empirical foundation.nnRESEARCH QUESTION: Should patients with peripheral T1 lung tumors undergo invasive mediastinal staging?nnSTUDY DESIGN AND METHODS: All participants with a screen-detected cancer with a solid component between 8 and 30 mm were identified from the National Lung Screening Trial. After translation of CT data, cancer location was identified and the X, Y, Z coordinates were determined as well as distance from the main carina. A multivariable logistic regression model was constructed to evaluate for predictors associated with lymph node metastasis.nnRESULTS: Three hundred thirty-two participants were identified, of which 69 had lymph node involvement (20.8%). Of those with lymph node metastasis, 39.1% were N2. There was no difference in rate of lymph node metastasis based on tumor size (OR, 1.03; P = .248). There was also no statistical difference in rate of lymph node metastasis based on location, either by distance from the carina (OR, 0.99; P = .156) or tumor coordinates (X: P = .180; Y: P = .311; Z: P = .292). When adjusted for age, sex, histology, and smoking history, there was no change in the magnitude of the risk, and tests of significance were not altered.nnINTERPRETATION: Our data indicate a high rate of N2 metastasis among T1 tumors and no significant relationship between tumor diameter or location. This suggests that patients with small, peripheral lung cancers may benefit from invasive mediastinal staging.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32654155,

title = {Statistical characterization of the linear attenuation coefficient in polychromatic CT scans},

author = {Gonzalo Vegas and Raúl San José Estépar},

doi = {10.1002/mp.14384},

issn = {2473-4209},

year  = {2020},

date = {2020-11-01},

journal = {Med Phys},

volume = {47},

number = {11},

pages = {5568--5581},

abstract = {PURPOSE: To provide a unifying statistical model that characterizes the integrated x-ray intensity at the detector after logarithmic transformation and can be extended to the characterization of computed tomography (CT) numbers in the reconstructed image.nnMETHODS: We study the statistical characteristics of polyenergetic x-ray beams in the detector. Firstly, we consider the characterization of the integrated x-ray intensity at the detector through a probabilistic model (compound Poisson) that describes its statistics. We analyze its properties and derive the probabilistic distribution after the logarithmic transformation analytically. Finally, we propose a more tractable probabilistic distribution with the same features observed in the characterization, the noncentral Gamma (nc-Gamma). This distribution exhibits desirable properties for the statistical characterization across the reconstruction process. We assess the assumptions adopted in the derivation of the statistical models throughout Monte Carlo simulations and validate them with a water phantom and a lung phantom acquired in a Siemens clinical CT scan. We evaluate the statistical similarities between the theoretical distribution and the nc-Gamma using a power analysis with a Kolmogorov-Smirnov test for a 95% confidence level.nnRESULTS: The Kolmogorov-Smirnov goodness-of-fit test obtained for the Monte Carlo simulation shows an extremely high agreement between the empirical distribution of the post-logarithmic-integrated x-ray intensity and the nc-Gamma. The experimental validation performed with both phantoms confirmed the excellent match between the theoretical distribution, the proposed nc-Gamma, and sample distributions in all situations.nnCONCLUSION: We derive an analytical model describing the post-log distribution of the linear attenuation coefficient in the sensor for polychromatic CT scans. We also demonstrate that the nc-Gamma distribution approximates well the theoretical distribution. This distribution also approximates well the CT numbers after reconstruction since it naturally extends across linear operations involved in filtered back projection reconstructions. This probabilistic model may provide the analytical foundation to define new likelihood-based reconstruction methodologies for polychromatic scans.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32711368,

title = {Automatic estimation of aortic and mitral valve displacements in dynamic CTA with 4D graph-cuts},

author = {Juan E Ortuño and Gonzalo Vegas-Sánchez-Ferrero and Juan J Gómez-Valverde and Marcus Y Chen and Andrés Santos and Elliot R McVeigh and María J Ledesma-Carbayo},

doi = {10.1016/j.media.2020.101748},

issn = {1361-8423},

year  = {2020},

date = {2020-10-01},

journal = {Med Image Anal},

volume = {65},

pages = {101748},

abstract = {The location of the mitral and aortic valves in dynamic cardiac imaging is useful for extracting functional derived parameters such as ejection fraction, valve excursions, and global longitudinal strain, and when performing anatomical structures tracking using slice following or valve intervention's planning. Completely automatic segmentation methods are still challenging tasks because of their fast movements and the different positions that prevent good visibility of the leaflets along the full cardiac cycle. In this article, we propose a processing pipeline to track the displacement of the aortic and mitral valve annuli from high-resolution cardiac four-dimensional computed tomographic angiography (4D-CTA). The proposed method is based on the dynamic separation of left ventricle, left atrium and aorta using statistical shape modeling and an energy minimization algorithm based on graph-cuts and has been evaluated on a set of 15 electrocardiography-gated 4D-CTAs. We report a mean agreement distance between manual annotations and our proposed method of 2.52±1.06 mm for the mitral annulus and 2.00±0.69 mm for the aortic valve annulus based on valve locations detected from manual anatomical landmarks. In addition, we show the effect of detecting the valvular planes on derived functional parameters (ejection fraction, global longitudinal strain, and excursions of the mitral and aortic valves).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32877963,

title = {A Risk Prediction Model for Mortality Among Smokers in the COPDGene® Study},

author = {Matthew Strand and Erin Austin and Matthew Moll and Katherine A Pratte and Elizabeth A Regan and Lystra P Hayden and Surya P Bhatt and Aladin M Boriek and Richard Casaburi and Edwin K Silverman and Spyridon Fortis and Ingo Ruczinski and Harald Koegler and Harry B Rossiter and Mariaelena Occhipinti and Nicola A Hanania and Hirut T Gebrekristos and David A Lynch and Ken M Kunisaki and Kendra A Young and Jessica C Sieren and Margaret Ragland and John E Hokanson and Sharon M Lutz and Barry J Make and Gregory L Kinney and Michael H Cho and Massimo Pistolesi and Dawn L DeMeo and Frank C Sciurba and Alejandro P Comellas and Alejandro A Diaz and Igor Barjaktarevic and Russell P Bowler and Richard E Kanner and Stephen P Peters and Victor E Ortega and Mark T Dransfield and James D Crapo},

doi = {10.15326/jcopdf.7.4.2020.0146},

issn = {2372-952X},

year  = {2020},

date = {2020-10-01},

journal = {Chronic Obstr Pulm Dis},

volume = {7},

number = {4},

pages = {346--361},

abstract = {BACKGROUND: Risk factor identification is a proven strategy in advancing treatments and preventive therapy for many chronic conditions. Quantifying the impact of those risk factors on health outcomes can consolidate and focus efforts on individuals with specific high-risk profiles. Using multiple risk factors and longitudinal outcomes in 2 independent cohorts, we developed and validated a risk score model to predict mortality in current and former cigarette smokers.nnMETHODS: We obtained extensive data on current and former smokers from the COPD Genetic Epidemiology (COPDGene) study at enrollment. Based on physician input and model goodness-of-fit measures, a subset of variables was selected to fit final Weibull survival models separately for men and women. Coefficients and predictors were translated into a point system, allowing for easy computation of mortality risk scores and probabilities. We then used the SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS) cohort for external validation of our model.nnRESULTS: Of 9867 COPDGene participants with standard baseline data, 17.6% died over 10 years of follow-up, and 9074 of these participants had the full set of baseline predictors (standard plus 6-minute walk distance and computed tomography variables) available for full model fits. The average age of participants in the cohort was 60 for both men and women, and the average predicted 10-year mortality risk was 18% for women and 25% for men. Model time-integrated area under the receiver operating characteristic curve statistics demonstrated good predictive model accuracy (0.797 average), validated in the external cohort (0.756 average). Risk of mortality was impacted most by 6-minute walk distance, forced expiratory volume in 1 second and age, for both men and women.nnCONCLUSIONS: Current and former smokers exhibited a wide range of mortality risk over a 10- year period. Our models can identify higher risk individuals who can be targeted for interventions to reduce risk of mortality, for participants with or without chronic obstructive pulmonary disease (COPD) using current Global initiative for obstructive Lung Disease (GOLD) criteria.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33043045,

title = {Phenotypic characterisation of early COPD: a prospective case-control study},

author = {Borja G Cosío and Sergi Pascual-Guardia and Alicia Borras-Santos and Germán Peces-Barba and Salud Santos and Laura Vigil and Juan José Soler-Cataluña and Cristina Martínez-González and Ciro Casanova and Pedro J Marcos and Carlos J Alvarez and José Luis López-Campos and Joaquim Gea and Judith Garcia-Aymerich and Jesús Molina and Miguel Román and Jorge Moises and Viktoria Szabo and Elizabeth A Reagan and Raúl San José Estépar and George Washko and Alvar Agustí and Rosa Faner},

doi = {10.1183/23120541.00047-2020},

issn = {2312-0541},

year  = {2020},

date = {2020-10-01},

journal = {ERJ Open Res},

volume = {6},

number = {4},

abstract = {The phenotypic characteristics of chronic obstructive pulmonary disease (COPD) in individuals younger than 50 years of age (early COPD) are not well defined. This prospective, multicentre, case-control study sought to describe these characteristics and compare them with those of smokers (≥10 pack-years) of similar age with normal spirometry (controls). We studied 92 cases (post-bronchodilator forced expiratory volume in 1 s (FEV)/forced vital capacity (FVC) <0.7) and 197 controls. Results were contrasted with participants with similar inclusion criteria recruited into the ECLIPSE and COPDGene cohorts. Cases had moderate airflow limitation (FEV 71.3±20.8%) but were often symptomatic, used healthcare resources frequently, had air trapping (residual volume 150.6±55.5% ref.), had reduced diffusing capacity (84.2±20.7% ref.) and had frequent evidence of computed tomography (CT) emphysema (61%). Of note, less than half of cases (46%) had been previously diagnosed with COPD. Interestingly, they also often reported a family history of respiratory diseases and had been hospitalised because of respiratory problems before the age of 5 years more frequently than controls (12%  3%, p=0.009). By and large, these observations were reproduced when available in the ECLIPSE and COPDGene cohorts. These results show that early COPD is associated with substantial health impact and significant structural and functional abnormalities, albeit it is often not diagnosed (hence, treated). The fact that a sizeable proportion of patients with early COPD report a family history of respiratory diseases and/or early-life events (including hospitalisations before the age of 5 years) renders further support to the possibility of early-life origin of COPD.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32889594,

title = {Quantitative Pectoralis Muscle Area is Associated with the Development of Lung Cancer in a Large Lung Cancer Screening Cohort},

author = {Lee Gazourian and Chantal S Durgana and Devon Huntley and Giulia S Rizzo and William B Thedinger and Shawn M Regis and Lori Lyn Price and Elizabeth J Pagura and Carla Lamb and Kimberly Rieger-Christ and Carey C Thomson and Cristina F Stefanescu and Ava Sanayei and William P Long and Andrea B McKee and George R Washko and Raul San José Estépar and Christoph Wald and Timothy N Liesching and Brady J McKee},

doi = {10.1007/s00408-020-00388-5},

issn = {1432-1750},

year  = {2020},

date = {2020-10-01},

journal = {Lung},

volume = {198},

number = {5},

pages = {847--853},

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

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32800192,

title = {Computerized Chest Imaging in the Diagnosis and Assessment of the Patient with Chronic Obstructive Pulmonary Disease},

author = {Carrie L Pistenmaa and George R Washko},

doi = {10.1016/j.ccm.2020.06.012},

issn = {1557-8216},

year  = {2020},

date = {2020-09-01},

journal = {Clin Chest Med},

volume = {41},

number = {3},

pages = {375--381},

abstract = {Computerized tomography in chronic obstructive pulmonary disease (COPD) has been the subject of intense interest in the research and clinical community. Methods have been developed to objectively detect and quantify processes affecting the lung parenchyma, airways and vasculature, as well as extrapulmonary manifestations of the noxious effects of chronic inhalational exposures, such as tobacco smoke. This article provides a brief overview of image-based advances in COPD research and then discusses how these advances have translated to clinical care, finishing with a brief description of a path forward for the convergence of research and care at the bedside.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32353417,

title = {Machine Learning and Prediction of All-Cause Mortality in COPD},

author = {Matthew Moll and Dandi Qiao and Elizabeth A Regan and Gary M Hunninghake and Barry J Make and Ruth Tal-Singer and Michael J McGeachie and Peter J Castaldi and Raul San Jose Estepar and George R Washko and James M Wells and David LaFon and Matthew Strand and Russell P Bowler and MeiLan K Han and Jorgen Vestbo and Bartolome Celli and Peter Calverley and James Crapo and Edwin K Silverman and Brian D Hobbs and Michael H Cho},

doi = {10.1016/j.chest.2020.02.079},

issn = {1931-3543},

year  = {2020},

date = {2020-09-01},

journal = {Chest},

volume = {158},

number = {3},

pages = {952--964},

abstract = {BACKGROUND: COPD is a leading cause of mortality.nnRESEARCH QUESTION: We hypothesized that applying machine learning to clinical and quantitative CT imaging features would improve mortality prediction in COPD.nnSTUDY DESIGN AND METHODS: We selected 30 clinical, spirometric, and imaging features as inputs for a random survival forest. We used top features in a Cox regression to create a machine learning mortality prediction (MLMP) in COPD model and also assessed the performance of other statistical and machine learning models. We trained the models in subjects with moderate to severe COPD from a subset of subjects in Genetic Epidemiology of COPD (COPDGene) and tested prediction performance in the remainder of individuals with moderate to severe COPD in COPDGene and Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE). We compared our model with the BMI, airflow obstruction, dyspnea, exercise capacity (BODE) index; BODE modifications; and the age, dyspnea, and airflow obstruction index.nnRESULTS: We included 2,632 participants from COPDGene and 1,268 participants from ECLIPSE. The top predictors of mortality were 6-min walk distance, FEV % predicted, and age. The top imaging predictor was pulmonary artery-to-aorta ratio. The MLMP-COPD model resulted in a C index ≥ 0.7 in both COPDGene and ECLIPSE (6.4- and 7.2-year median follow-ups, respectively), significantly better than all tested mortality indexes (P < .05). The MLMP-COPD model had fewer predictors but similar performance to that of other models. The group with the highest BODE scores (7-10) had 64% mortality, whereas the highest mortality group defined by the MLMP-COPD model had 77% mortality (P = .012).nnINTERPRETATION: An MLMP-COPD model outperformed four existing models for predicting all-cause mortality across two COPD cohorts. Performance of machine learning was similar to that of traditional statistical methods. The model is available online at: https://cdnm.shinyapps.io/cgmortalityapp/.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33145055,

title = {Tumor density is associated with response to endobronchial ultrasound-guided transbronchial needle injection of cisplatin},

author = {C Matthew Kinsey and Raúl San José Estépar and Jason H T Bates and Bernard F Cole and George Washko and Michael Jantz and Hiren Mehta},

doi = {10.21037/jtd-20-674},

issn = {2072-1439},

year  = {2020},

date = {2020-09-01},

journal = {J Thorac Dis},

volume = {12},

number = {9},

pages = {4825--4832},

abstract = {BACKGROUND: Endobronchial ultrasound-guided transbronchial needle injection of cisplatin (EBUS-TBNI cisplatin) is a therapeutic option for patients with recurrent lung cancer. However, the tumor characteristics that influence the distribution of the agent following intratumoral delivery remain largely unknown.nnMETHODS: We performed a retrospective evaluation of EBUS-TBNI cisplatin cases performed at two centers. Semi-automated tumor segmentation from CT scans was performed while blinded to the outcome of response. Twenty-four algorithmic radiomics features from two categories, Morphology (i.e., shape, volume) and Intensity (i.e., density), were extracted, and feature selection performed via least absolute shrinkage and selection operator (LASSO) regression. Models were constructed from clinicoepidemiologic variables and selected radiomics features and evaluated using the likelihood ratio chi-square assessment and Akaike's information criterion (AIC).nnRESULTS: Thirty-eight patients with available imaging data were analyzed. Based on RECIST criteria, 27 of 38 treated sites demonstrated complete or partial remission (71%). The top three features identified by LASSO regression were variance, energy, and kurtosis. All three are measures of intensity, a surrogate for tumor density. Two logistic regression models with the outcome of response were created, each with the top 3 categorical features: (I) an Intensity model including variance, energy, and kurtosis, and (II) a Morphology model including surface-to-volume ratio, spherical disproportion, and maximum 3-dimensional (3D) diameter. Only the Intensity model met criteria for significance (P=0.024), and it resulted in a lower AIC and higher pseudo R square value vs. the Morphology model.nnCONCLUSIONS: Measures of tumor density are more highly associated with response to EBUS-TBNI cisplatin than measures of morphology.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32480316,

title = {Traction Bronchiectasis/Bronchiolectasis is Associated with Interstitial Lung Abnormality Mortality},

author = {Tomoyuki Hida and Mizuki Nishino and Takuya Hino and Junwei Lu and Rachel K Putman and Elias F Gudmundsson and Tetsuro Araki and Vladimir I Valtchinov and Osamu Honda and Masahiro Yanagawa and Yoshitake Yamada and Akinori Hata and Masahiro Jinzaki and Noriyuki Tomiyama and Hiroshi Honda and Raul San Jose Estepar and George R Washko and Takeshi Johkoh and David C Christiani and David A Lynch and Vilmundur Gudnason and Gunnar Gudmundsson and Gary M Hunninghake and Hiroto Hatabu},

doi = {10.1016/j.ejrad.2020.109073},

issn = {1872-7727},

year  = {2020},

date = {2020-08-01},

journal = {Eur J Radiol},

volume = {129},

pages = {109073},

abstract = {PURPOSE: To investigate if the presence and severity of traction bronchiectasis/bronchiolectasis are associated with poorer survival in subjects with ILA.nnMETHOD: The study included 3,594 subjects (378 subjects with ILA and 3,216 subjects without ILA) in AGES-Reykjavik Study. Chest CT scans of 378 subjects with ILA were evaluated for traction bronchiectasis/bronchiolectasis, defined as dilatation of bronchi/bronchioles within areas demonstrating ILA. Traction bronchiectasis/bronchiolectasis Index (TBI) was assigned as: TBI = 0, ILA without traction bronchiectasis/bronchiolectasis: TBI = 1, ILA with bronchiolectasis but without bronchiectasis or architectural distortion: TBI = 2, ILA with mild to moderate traction bronchiectasis: TBI = 3, ILA and severe traction bronchiectasis and/or honeycombing. Overall survival (OS) was compared among the subjects in different TBI groups and those without ILA.nnRESULTS: The median OS was 12.93 years (95%CI; 12.67 - 13.43) in the subjects without ILA; 11.95 years (10.03 - not reached) in TBI-0 group; 8.52 years (7.57 - 9.30) in TBI-1 group; 7.63 years (6.09 - 9.10) in TBI-2 group; 5.40 years (1.85 - 5.98) in TBI-3 group. The multivariable Cox models demonstrated significantly shorter OS of TBI-1, TBI-2, and TBI-3 groups compared to subjects without ILA (P < 0.0001), whereas TBI-0 group had no significant OS difference compared to subjects without ILA, after adjusting for age, sex, and smoking status.nnCONCLUSIONS: The presence and severity of traction bronchiectasis/bronchiolectasis are associated with shorter survival. The traction bronchiectasis/bronchiolectasis is an important contributor to increased mortality among subjects with ILA.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32963991,

title = {Somatotypes trajectories during adulthood and their association with COPD phenotypes},

author = {Miguel J Divo and Marta Marin Oto and Ciro Casanova Macario and Carlos Cabrera Lopez and Juan P de-Torres and Jose Maria Marin Trigo and Craig P Hersh and Ana Ezponda Casajús and Cherie Maguire and Victor M Pinto-Plata and Francesca Polverino and James C Ross and Dawn DeMeo and Gorka Bastarrika and Edwin K Silverman and Bartolome R Celli},

doi = {10.1183/23120541.00122-2020},

issn = {2312-0541},

year  = {2020},

date = {2020-07-01},

journal = {ERJ Open Res},

volume = {6},

number = {3},

abstract = {RATIONALE: Chronic obstructive pulmonary disease (COPD) comprises distinct phenotypes, all characterised by airflow limitation.nnOBJECTIVES: We hypothesised that somatotype changes - as a surrogate of adiposity - from early adulthood follow different trajectories to reach distinct phenotypes.nnMETHODS: Using the validated Stunkard's Pictogram, 356 COPD patients chose the somatotype that best reflects their current body build and those at ages 18, 30, 40 and 50 years. An unbiased group-based trajectory modelling was used to determine somatotype trajectories. We then compared the current COPD-related clinical and phenotypic characteristics of subjects belonging to each trajectory.nnMEASUREMENTS AND MAIN RESULTS: At 18 years of age, 88% of the participants described having a lean or medium somatotype (estimated body mass index (BMI) between 19 and 23 kg·m) while the other 12% a heavier somatotype (estimated BMI between 25 and 27 kg·m). From age 18 onwards, five distinct trajectories were observed. Four of them demonstrating a continuous increase in adiposity throughout adulthood with the exception of one, where the initial increase was followed by loss of adiposity after age 40. Patients with this trajectory were primarily females with low BMI and   (diffusing capacity of the lung for carbon monoxide). A persistently lean trajectory was seen in 14% of the cohort. This group had significantly lower forced expiratory volume in 1 s (FEV),  , more emphysema and a worse BODE (BMI, airflow obstruction, dyspnoea and exercise capacity) score thus resembling the multiple organ loss of tissue (MOLT) phenotype.nnCONCLUSIONS: COPD patients have distinct somatotype trajectories throughout adulthood. Those with the MOLT phenotype maintain a lean trajectory throughout life. Smoking subjects with this lean phenotype in early adulthood deserve particular attention as they seem to develop more severe COPD.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32649918,

title = {Chronic obstructive pulmonary disease and related phenotypes: polygenic risk scores in population-based and case-control cohorts},

author = {Matthew Moll and Phuwanat Sakornsakolpat and Nick Shrine and Brian D Hobbs and Dawn L DeMeo and Catherine John and Anna L Guyatt and Michael J McGeachie and Sina A Gharib and Ma'en Obeidat and Lies Lahousse and Sara R A Wijnant and Guy Brusselle and Deborah A Meyers and Eugene R Bleecker and Xingnan Li and Ruth Tal-Singer and Ani Manichaikul and Stephen S Rich and Sungho Won and Woo Jin Kim and Ah Ra Do and George R Washko and R Graham Barr and Bruce M Psaty and Traci M Bartz and Nadia N Hansel and Kathleen Barnes and John E Hokanson and James D Crapo and David Lynch and Per Bakke and Amund Gulsvik and Ian P Hall and Louise Wain and  and  and Scott T Weiss and Edwin K Silverman and Frank Dudbridge and Martin D Tobin and Michael H Cho},

doi = {10.1016/S2213-2600(20)30101-6},

issn = {2213-2619},

year  = {2020},

date = {2020-07-01},

journal = {Lancet Respir Med},

volume = {8},

number = {7},

pages = {696--708},

abstract = {BACKGROUND: Genetic factors influence chronic obstructive pulmonary disease (COPD) risk, but the individual variants that have been identified have small effects. We hypothesised that a polygenic risk score using additional variants would predict COPD and associated phenotypes.nnMETHODS: We constructed a polygenic risk score using a genome-wide association study of lung function (FEV and FEV/forced vital capacity [FVC]) from the UK Biobank and SpiroMeta. We tested this polygenic risk score in nine cohorts of multiple ethnicities for an association with moderate-to-severe COPD (defined as FEV/FVC <0·7 and FEV <80% of predicted). Associations were tested using logistic regression models, adjusting for age, sex, height, smoking pack-years, and principal components of genetic ancestry. We assessed predictive performance of models by area under the curve. In a subset of studies, we also studied quantitative and qualitative CT imaging phenotypes that reflect parenchymal and airway pathology, and patterns of reduced lung growth.nnFINDINGS: The polygenic risk score was associated with COPD in European (odds ratio [OR] per SD 1·81 [95% CI 1·74-1·88] and non-European (1·42 [1·34-1·51]) populations. Compared with the first decile, the tenth decile of the polygenic risk score was associated with COPD, with an OR of 7·99 (6·56-9·72) in European ancestry and 4·83 (3·45-6·77) in non-European ancestry cohorts. The polygenic risk score was superior to previously described genetic risk scores and, when combined with clinical risk factors (ie, age, sex, and smoking pack-years), showed improved prediction for COPD compared with a model comprising clinical risk factors alone (AUC 0·80 [0·79-0·81] vs 0·76 [0·75-0·76]). The polygenic risk score was associated with CT imaging phenotypes, including wall area percent, quantitative and qualitative measures of emphysema, local histogram emphysema patterns, and destructive emphysema subtypes. The polygenic risk score was associated with a reduced lung growth pattern.nnINTERPRETATION: A risk score comprised of genetic variants can identify a small subset of individuals at markedly increased risk for moderate-to-severe COPD, emphysema subtypes associated with cigarette smoking, and patterns of reduced lung growth.nnFUNDING: US National Institutes of Health, Wellcome Trust.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32832599,

title = {Single-cell RNA-seq reveals ectopic and aberrant lung-resident cell populations in idiopathic pulmonary fibrosis},

author = {Taylor S Adams and Jonas C Schupp and Sergio Poli and Ehab A Ayaub and Nir Neumark and Farida Ahangari and Sarah G Chu and Benjamin A Raby and Giuseppe DeIuliis and Michael Januszyk and Qiaonan Duan and Heather A Arnett and Asim Siddiqui and George R Washko and Robert Homer and Xiting Yan and Ivan O Rosas and Naftali Kaminski},

doi = {10.1126/sciadv.aba1983},

issn = {2375-2548},

year  = {2020},

date = {2020-07-01},

journal = {Sci Adv},

volume = {6},

number = {28},

pages = {eaba1983},

abstract = {We provide a single-cell atlas of idiopathic pulmonary fibrosis (IPF), a fatal interstitial lung disease, by profiling 312,928 cells from 32 IPF, 28 smoker and nonsmoker controls, and 18 chronic obstructive pulmonary disease (COPD) lungs. Among epithelial cells enriched in IPF, we identify a previously unidentified population of aberrant basaloid cells that coexpress basal epithelial, mesenchymal, senescence, and developmental markers and are located at the edge of myofibroblast foci in the IPF lung. Among vascular endothelial cells, we identify an ectopically expanded cell population transcriptomically identical to bronchial restricted vascular endothelial cells in IPF. We confirm the presence of both populations by immunohistochemistry and independent datasets. Among stromal cells, we identify IPF myofibroblasts and invasive fibroblasts with partially overlapping cells in control and COPD lungs. Last, we confirm previous findings of profibrotic macrophage populations in the IPF lung. Our comprehensive catalog reveals the complexity and diversity of aberrant cellular populations in IPF.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32294604,

title = {Generative-based airway and vessel morphology quantification on chest CT images},

author = {Pietro Nardelli and James C Ross and Raúl San José Estépar},

doi = {10.1016/j.media.2020.101691},

issn = {1361-8423},

year  = {2020},

date = {2020-07-01},

journal = {Med Image Anal},

volume = {63},

pages = {101691},

abstract = {Accurately and precisely characterizing the morphology of small pulmonary structures from Computed Tomography (CT) images, such as airways and vessels, is becoming of great importance for diagnosis of pulmonary diseases. The smaller conducting airways are the major site of increased airflow resistance in chronic obstructive pulmonary disease (COPD), while accurately sizing vessels can help identify arterial and venous changes in lung regions that may determine future disorders. However, traditional methods are often limited due to image resolution and artifacts. We propose a Convolutional Neural Regressor (CNR) that provides cross-sectional measurement of airway lumen, airway wall thickness, and vessel radius. CNR is trained with data created by a generative model of synthetic structures which is used in combination with Simulated and Unsupervised Generative Adversarial Network (SimGAN) to create simulated and refined airways and vessels with known ground-truth. For validation, we first use synthetically generated airways and vessels produced by the proposed generative model to compute the relative error and directly evaluate the accuracy of CNR in comparison with traditional methods. Then, in-vivo validation is performed by analyzing the association between the percentage of the predicted forced expiratory volume in one second (FEV1%) and the value of the Pi10 parameter, two well-known measures of lung function and airway disease, for airways. For vessels, we assess the correlation between our estimate of the small-vessel blood volume and the lungs' diffusing capacity for carbon monoxide (DLCO). The results demonstrate that Convolutional Neural Networks (CNNs) provide a promising direction for accurately measuring vessels and airways on chest CT images with physiological correlates.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32619491,

title = {A Highly Phenotyped Open Access Repository of Alpha-1 Antitrypsin Deficiency Pluripotent Stem Cells},

author = {Joseph E Kaserman and Killian Hurley and Mark Dodge and Carlos Villacorta-Martin and Marall Vedaie and Jyh-Chang Jean and Derek C Liberti and Marianne F James and Michelle I Higgins and Nora J Lee and George R Washko and Raul San Jose Estepar and Jeffrey Teckman and Darrell N Kotton and Andrew A Wilson},

doi = {10.1016/j.stemcr.2020.06.006},

issn = {2213-6711},

year  = {2020},

date = {2020-07-01},

journal = {Stem Cell Reports},

volume = {15},

number = {1},

pages = {242--255},

abstract = {Individuals with the genetic disorder alpha-1 antitrypsin deficiency (AATD) are at risk of developing lung and liver disease. Patient induced pluripotent stem cells (iPSCs) have been found to model features of AATD pathogenesis but only a handful of AATD patient iPSC lines have been published. To capture the significant phenotypic diversity of the patient population, we describe here the establishment and characterization of a curated repository of AATD iPSCs with associated disease-relevant clinical data. To highlight the utility of the repository, we selected a subset of iPSC lines for functional characterization. Selected lines were differentiated to generate both hepatic and lung cell lineages and analyzed by RNA sequencing. In addition, two iPSC lines were targeted using CRISPR/Cas9 editing to accomplish scarless repair. Repository iPSCs are available to investigators for studies of disease pathogenesis and therapeutic discovery.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32649920,

title = {Interstitial lung abnormalities detected incidentally on CT: a Position Paper from the Fleischner Society},

author = {Hiroto Hatabu and Gary M Hunninghake and Luca Richeldi and Kevin K Brown and Athol U Wells and Martine Remy-Jardin and Johny Verschakelen and Andrew G Nicholson and Mary B Beasley and David C Christiani and Raúl San José Estépar and Joon Beom Seo and Takeshi Johkoh and Nicola Sverzellati and Christopher J Ryerson and R Graham Barr and Jin Mo Goo and John H M Austin and Charles A Powell and Kyung Soo Lee and Yoshikazu Inoue and David A Lynch},

doi = {10.1016/S2213-2600(20)30168-5},

issn = {2213-2619},

year  = {2020},

date = {2020-07-01},

journal = {Lancet Respir Med},

volume = {8},

number = {7},

pages = {726--737},

abstract = {The term interstitial lung abnormalities refers to specific CT findings that are potentially compatible with interstitial lung disease in patients without clinical suspicion of the disease. Interstitial lung abnormalities are increasingly recognised as a common feature on CT of the lung in older individuals, occurring in 4-9% of smokers and 2-7% of non-smokers. Identification of interstitial lung abnormalities will increase with implementation of lung cancer screening, along with increased use of CT for other diagnostic purposes. These abnormalities are associated with radiological progression, increased mortality, and the risk of complications from medical interventions, such as chemotherapy and surgery. Management requires distinguishing interstitial lung abnormalities that represent clinically significant interstitial lung disease from those that are subclinical. In particular, it is important to identify the subpleural fibrotic subtype, which is more likely to progress and to be associated with mortality. This multidisciplinary Position Paper by the Fleischner Society addresses important issues regarding interstitial lung abnormalities, including standardisation of the definition and terminology; predisposing risk factors; clinical outcomes; options for initial evaluation, monitoring, and management; the role of quantitative evaluation; and future research needs.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32017932,

title = {Luminal Plugging on Chest CT Scan: Association With Lung Function, Quality of Life, and COPD Clinical Phenotypes},

author = {Yuka Okajima and Carolyn E Come and Pietro Nardelli and Sushil K Sonavane and Andrew Yen and Hrudaya P Nath and Nina Terry and Scott A Grumley and Asmaa Ahmed and Seth Kligerman and Kathleen Jacobs and David A Lynch and Barry J Make and Edwin K Silverman and George R Washko and Raúl San José Estépar and Alejandro A Diaz},

doi = {10.1016/j.chest.2019.12.046},

issn = {1931-3543},

year  = {2020},

date = {2020-07-01},

journal = {Chest},

volume = {158},

number = {1},

pages = {121--130},

abstract = {BACKGROUND: Mucous exudates occluding the lumen of small airways are associated with reduced lung function and mortality in subjects with COPD; however, luminal plugs in large airways have not been widely studied. We aimed to examine the associations of chest CT scan-identified luminal plugging with lung function, health-related quality of life, and COPD phenotypes.nnMETHODS: We randomly selected 100 smokers without COPD and 400 smokers with COPD from the COPDGene Study. Luminal plugging was visually identified on inspiratory CT scans at baseline and 5-year follow-up. The relationships of luminal plugging to FEV, St. George's Respiratory Questionnaire (SGRQ) score, emphysema on CT scan (defined as the percentage of low attenuation area < 950 Hounsfield units [%LAA-950]), and chronic bronchitis were assessed using linear and logistic multivariable analyses.nnRESULTS: Overall, 111 subjects (22%) had luminal plugging. The prevalence of luminal plugging was higher in subjects with COPD than those without COPD (25% vs 10%, respectively; P = .001). In subjects with COPD, luminal plugging was significantly associated with FEV % predicted (estimate, -6.1; SE, 2.1; P = .004) and SGRQ score (estimate, 4.9; SE, 2.4; P = .04) in adjusted models. Although luminal plugging was associated with log %LAA-950 (estimate, 0.43; SE, 0.16; P = .007), its relationship with chronic bronchitis did not reach statistical significance (P = .07). Seventy-three percent of subjects with COPD with luminal plugging at baseline had it 5 years later.nnCONCLUSIONS: In subjects with COPD, CT-identified luminal plugging is associated with airflow obstruction, worse health-related quality of life, and emphysema phenotype. This imaging feature may supplement the current clinical assessment of chronic mucus hypersecretion in COPD.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32115275,

title = {An open-source framework for pulmonary fissure completeness assessment},

author = {James C Ross and Pietro Nardelli and Jorge Onieva and Sarah E Gerard and Rola Harmouche and Yuka Okajima and Alejandro A Diaz and George Washko and Raúl San José Estépar},

doi = {10.1016/j.compmedimag.2020.101712},

issn = {1879-0771},

year  = {2020},

date = {2020-07-01},

journal = {Comput Med Imaging Graph},

volume = {83},

pages = {101712},

abstract = {We present an open-source framework for pulmonary fissure completeness assessment. Fissure incompleteness has been shown to associate with emphysema treatment outcomes, motivating the development of tools that facilitate completeness estimation. Generally, the task of fissure completeness assessment requires accurate detection of fissures and definition of the boundary surfaces separating the lung lobes. The framework we describe acknowledges a) the modular nature of fissure detection and lung lobe segmentation (lobe boundary detection), and b) that methods to address these challenges are varied and continually developing. It is designed to be readily deployable on existing lung lobe segmentation and fissure detection data sets. The framework consists of multiple components: a flexible quality control module that enables rapid assessment of lung lobe segmentations, an interactive lobe segmentation tool exposed through 3D Slicer for handling challenging cases, a flexible fissure representation using particles-based sampling that can handle fissure feature-strength or binary fissure detection images, and a module that performs fissure completeness estimation using voxel counting and a novel surface area estimation approach. We demonstrate the usage of the proposed framework by deploying on 100 cases exhibiting various levels of fissure completeness. We compare the two completeness level approaches and also compare to visual reads. The code is available to the community via github as part of the Chest Imaging Platform and a 3D Slicer extension module.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32368963,

title = {Smaller Left Ventricle Size at Noncontrast CT Is Associated with Lower Mortality in COPDGene Participants},

author = {George R Washko and Pietro Nardelli and Samuel Y Ash and Farbod N Rahaghi and Gonzalo Vegas Sanchez-Ferrero and Carolyn E Come and Mark T Dransfield and Ravi Kalhan and MeiLan K Han and Surya P Bhatt and J Michael Wells and Carrie L Pistenmaa and Alejandro A Diaz and James C Ross and Stephen Rennard and Gabriela Querejeta Roca and Amil M Shah and Kendra Young and Gregory L Kinney and John E Hokanson and Alvar Agustí and Raúl San José Estépar and },

doi = {10.1148/radiol.2020191793},

issn = {1527-1315},

year  = {2020},

date = {2020-07-01},

journal = {Radiology},

volume = {296},

number = {1},

pages = {208--215},

abstract = {Background Smokers with chronic obstructive pulmonary disease (COPD) have smaller left ventricles (LVs) due to reduced preload. Skeletal muscle wasting is also common in COPD, but less is known about its contribution to LV size. Purpose To explore the relationships between CT metrics of emphysema, venous vascular volume, and sarcopenia with the LV epicardial volume (LV) (myocardium and chamber) estimated from chest CT images in participants with COPD and then to determine the clinical relevance of the LV in multivariable models, including sex and anthropomorphic metrics. Materials and Methods The COPDGene study (ClinicalTrials.gov identifier: NCT00608764) is an ongoing prospective longitudinal observational investigation that began in 2006. LV, distal pulmonary venous blood volume for vessels smaller than 5 mm in cross section (BV5), CT emphysema, and pectoralis muscle area were retrospectively extracted from 3318 nongated, unenhanced COPDGene CT scans. Multivariable linear and Cox regression models were used to explore the association between emphysema, venous BV5, pectoralis muscle area, and LV as well as the association of LV with health status using the St George's Respiratory Questionnaire, 6-minute walk distance, and all-cause mortality. Results The median age of the cohort was 64 years (interquartile range, 57-70 years). Of the 2423 participants, 1806 were men and 617 were African American. The median LV between Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1 and GOLD 4 COPD was reduced by 13.9% in women and 17.7% in men ( < .001 for both). In fully adjusted models, higher emphysema percentage (β = -4.2; 95% confidence interval [CI]: -5.0, -3.4;  < .001), venous BV5 (β = 7.0; 95% CI: 5.7, 8.2;  < .001), and pectoralis muscle area (β = 2.7; 95% CI: 1.2, 4.1;  < .001) were independently associated with reduced LV. Reductions in LV were associated with improved health status (β = 0.3; 95% CI: 0.1, 0.4) and 6-minute walk distance (β = -12.2; 95% CI: -15.2, -9.3). These effects were greater in women than in men. The effect of reduced LV on mortality (hazard ratio: 1.07; 95% CI: 1.05, 1.09) did not vary by sex. Conclusion In women more than men with chronic obstructive pulmonary disease, a reduction in the estimated left ventricle epicardial volume correlated with a loss of pulmonary venous vasculature, greater pectoralis muscle sarcopenia, and lower all-cause mortality. © RSNA, 2020 },

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32518239,

title = {Lung Function and Gene Expression of Pathogen Recognition Pathway Receptors: the Cardia Lung Study},

author = {Ramya Ramasubramanian and Ravi Kalhan and David R Jacobs and George R Washko and Lifang Hou and Myron D Gross and Weihua Guan and Bharat Thyagarajan},

doi = {10.1038/s41598-020-65923-z},

issn = {2045-2322},

year  = {2020},

date = {2020-06-01},

journal = {Sci Rep},

volume = {10},

number = {1},

pages = {9360},

abstract = {Activation of toll-like receptors (TLR1, TLR5, TLR6) and downstream markers (CCR1, MAPK14, ICAM1) leads to increased systemic inflammation. Our objective was to study the association between the gene expression levels of these six genes and lung function (Forced Expiratory Volume in one second (FEV), Forced Vital Capacity (FVC) and FEV/FVC). We studied gene expression levels and lung function in the Coronary Artery Risk Development in Young Adults study. Spirometry testing was used to measure lung function and gene expression levels were measured using the Nanostring platform. Multivariate linear regression models were used to study the association between lung function measured at year 30, 10-year decline from year 20 to year 30, and gene expression levels (highest quartile divided into two levels - 75th to 95th and>95th to 100th percentile) adjusting for center, smoking and BMI, measured at year 25. Year 30 FEV and FVC were lower in the highest level of TLR5 compared to the lowest quartile with difference of 4.00% (p for trend: 0.04) and 3.90% (p for trend: 0.05), respectively. The 10-year decline of FEV was faster in the highest level of CCR1 as compared to the lowest quartile with a difference of 1.69% (p for trend: 0.01). There was no association between gene expression and FEV/FVC. Higher gene expression levels in TLR5 and CCR1 are associated with lower lung function and faster decline in FEV over 10 years, in a threshold manner, providing new insights into the role of inflammation in lung function.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}