@article {1433551,
	title = {Arterial Vascular Pruning, Right Ventricular Size, and Clinical Outcomes in Chronic Obstructive Pulmonary Disease. A Longitudinal Observational Study},
	journal = {Am J Respir Crit Care Med},
	volume = {200},
	number = {4},
	year = {2019},
	month = {2019 Aug 15},
	pages = {454-461},
	abstract = {Rationale: Cor pulmonale (right ventricular [RV] dilation) and cor pulmonale parvus (RV shrinkage) are both described in chronic obstructive pulmonary disease (COPD). The identification of emphysema as a shared risk factor suggests that additional disease characterization is needed to understand these widely divergent cardiac processes.Objectives: To explore the relationship between computed tomography measures of emphysema and distal pulmonary arterial morphology with RV volume, and their association with exercise capacity and mortality in ever-smokers with COPD enrolled in the COPDGene Study.Methods: Epicardial (myocardium and chamber) RV volume (RVEV), distal pulmonary arterial blood vessel volume (arterial BV5: vessels \<5 mm2 in cross-section), and objective measures of emphysema were extracted from 3,506 COPDGene computed tomography scans. Multivariable linear and Cox regression models and the log-rank test were used to explore the association between emphysema, arterial BV5, and RVEV with exercise capacity (6-min-walk distance) and all-cause mortality.Measurements and Main Results: The RVEV was approximately 10\% smaller in Global Initiative for Chronic Obstructive Lung Disease stage 4 versus stage 1 COPD (P \< 0.0001). In multivariable modeling, a 10-ml decrease in arterial BV5 (pruning) was associated with a 1-ml increase in RVEV. For a given amount of emphysema, relative preservation of the arterial BV5 was associated with a smaller RVEV. An increased RVEV was associated with reduced 6-minute-walk distance and in those with arterial pruning an increased mortality.Conclusions: Pulmonary arterial pruning is associated with clinically significant increases in RV volume in smokers with COPD and is related to exercise capacity and mortality in COPD.Clinical trial registered with www.clinicaltrials.gov (NCT00608764).},
	keywords = {Aged, Exercise Tolerance, Female, Heart Ventricles, Humans, Linear Models, Male, Middle Aged, Mortality, Multivariate Analysis, Organ Size, Proportional Hazards Models, Pulmonary Artery, Pulmonary Disease, Chronic Obstructive, Pulmonary Emphysema, Pulmonary Heart Disease, Severity of Illness Index, Tomography, X-Ray Computed, Vascular Remodeling, Walk Test},
	issn = {1535-4970},
	doi = {10.1164/rccm.201811-2063OC},
	author = {Washko, George R and Nardelli, Pietro and Ash, Samuel Y and Vegas Sanchez-Ferrero, Gonzalo and Rahaghi, Farbod N and Come, Carolyn E and Dransfield, Mark T and Kalhan, Ravi and Han, MeiLan K and Bhatt, Surya P and Wells, J Michael and Aaron, Carrie Pistenmaa and Diaz, Alejandro A and Ross, James C and Cuttica, Michael J and Labaki, Wassim W and Querejeta Roca, Gabriela and Shah, Amil M and Young, Kendra and Kinney, Gregory L and Hokanson, John E and Agust{\'\i}, Alvar and San Jos{\'e} Est{\'e}par, Ra{\'u}l}
}
@article {1433558,
	title = {Association of outdoor temperature with lung function in a temperate climate},
	journal = {Eur Respir J},
	volume = {53},
	number = {1},
	year = {2019},
	month = {2019 Jan},
	abstract = {Acute exposure to cold dry air is a trigger of bronchoconstriction, but little is known about how daily outdoor temperature influences lung function.We investigated associations of temperature from a model using satellite remote sensing data with repeated measures of lung function among 5896 participants of the Framingham Heart Study Offspring and Third Generation cohorts residing in the Northeastern US. We further tested if temperature modified previously reported associations between pollution and lung function. We constructed linear mixed-effects models, and assessed departures from linearity using penalised splines.In fully adjusted linear models, 1-, 2- and 7-day average temperatures were all associated with lower lung function: each 5{\textdegree}C higher previous-week temperature was associated with a 20 mL lower (95\% CI -34---6) forced expiratory volume in 1 s. There was significant effect modification by season: negative associations of temperature and lung function were present in winter and spring only. Negative associations between previous-day fine particulate matter and lung function were present during unseasonably warm but not unseasonably cool days, with a similar pattern for other pollutants.We speculate that temperature-related differences in lung function may be explained by behavioural changes on relatively warm days, which may increase outdoor exposures.},
	issn = {1399-3003},
	doi = {10.1183/13993003.00612-2018},
	author = {Rice, Mary B and Li, Wenyuan and Wilker, Elissa H and Gold, Diane R and Schwartz, Joel and Zanobetti, Antonella and Koutrakis, Petros and Kloog, Itai and Washko, George R and O{\textquoteright}Connor, George T and Mittleman, Murray A}
}
@article {1433554,
	title = {A graph-cut approach for pulmonary artery-vein segmentation in noncontrast CT images},
	journal = {Med Image Anal},
	volume = {52},
	year = {2019},
	month = {2019 Feb},
	pages = {144-159},
	abstract = {Lung vessel segmentation has been widely explored by the biomedical image processing community; however, the differentiation of arterial from venous irrigation is still a challenge. Pulmonary artery-vein (AV) segmentation using computed tomography (CT) is growing in importance owing to its undeniable utility in multiple cardiopulmonary pathological states, especially those implying vascular remodelling, allowing the study of both flow systems separately. We present a new framework to approach the separation of tree-like structures using local information and a specifically designed graph-cut methodology that ensures connectivity as well as the spatial and directional consistency of the derived subtrees. This framework has been applied to the pulmonary AV classification using a random forest (RF) pre-classifier to exploit the local anatomical differences of arteries and veins. The evaluation of the system was performed using 192 bronchopulmonary segment phantoms, 48 anthropomorphic pulmonary CT phantoms, and 26 lungs from noncontrast CT images with precise voxel-based reference standards obtained by manually labelling the vessel trees. The experiments reveal a relevant improvement in the accuracy ( \~{} 20\%) of the vessel particle classification with the proposed framework with respect to using only the pre-classification based on local information applied to the whole area of the lung under study. The results demonstrated the accurate differentiation between arteries and veins in both clinical and synthetic cases, specifically when the image quality can guarantee a good airway segmentation, which opens a huge range of possibilities in the clinical study of cardiopulmonary diseases.},
	keywords = {Humans, Phantoms, Imaging, Pulmonary Artery, Pulmonary Veins, Radiographic Image Interpretation, Computer-Assisted, Tomography, X-Ray Computed},
	issn = {1361-8423},
	doi = {10.1016/j.media.2018.11.011},
	author = {Jimenez-Carretero, Daniel and Bermejo-Pel{\'a}ez, David and Nardelli, Pietro and Fraga, Patricia and Fraile, Eduardo and San Jos{\'e} Est{\'e}par, Ra{\'u}l and Ledesma-Carbayo, Maria J}
}
@article {1433553,
	title = {Imaging Advances in Chronic Obstructive Pulmonary Disease. Insights from the Genetic Epidemiology of Chronic Obstructive Pulmonary Disease (COPDGene) Study},
	journal = {Am J Respir Crit Care Med},
	volume = {199},
	number = {3},
	year = {2019},
	month = {2019 Feb 01},
	pages = {286-301},
	abstract = {The Genetic Epidemiology of Chronic Obstructive Pulmonary Disease (COPDGene) study, which began in 2007, is an ongoing multicenter observational cohort study of more than 10,000 current and former smokers. The study is aimed at understanding the etiology, progression, and heterogeneity of chronic obstructive pulmonary disease (COPD). In addition to genetic analysis, the participants have been extensively characterized by clinical questionnaires, spirometry, volumetric inspiratory and expiratory computed tomography, and longitudinal follow-up, including follow-up computed tomography at 5 years after enrollment. The purpose of this state-of-the-art review is to summarize the major advances in our understanding of COPD resulting from the imaging findings in the COPDGene study. Imaging features that are associated with adverse clinical outcomes include early interstitial lung abnormalities, visual presence and pattern of emphysema, the ratio of pulmonary artery to ascending aortic diameter, quantitative evaluation of emphysema, airway wall thickness, and expiratory gas trapping. COPD is characterized by the early involvement of the small conducting airways, and the addition of expiratory scans has enabled measurement of small airway disease. Computational advances have enabled indirect measurement of nonemphysematous gas trapping. These metrics have provided insights into the pathogenesis and prognosis of COPD and have aided early identification of disease. Important quantifiable extrapulmonary findings include coronary artery calcification, cardiac morphology, intrathoracic and extrathoracic fat, and osteoporosis. Current active research includes identification of novel quantitative measures for emphysema and airway disease, evaluation of dose reduction techniques, and use of deep learning for phenotyping COPD.},
	keywords = {Cohort Studies, Disease Progression, Humans, Lung, Pulmonary Disease, Chronic Obstructive, Severity of Illness Index, Tomography, X-Ray Computed},
	issn = {1535-4970},
	doi = {10.1164/rccm.201807-1351SO},
	author = {Bhatt, Surya P and Washko, George R and Hoffman, Eric A and Newell, John D and Bodduluri, Sandeep and Diaz, Alejandro A and Galban, Craig J and Silverman, Edwin K and San Jos{\'e} Est{\'e}par, Ra{\'u}l and Lynch, David A}
}
@article {1677586,
	title = {Dynamic right ventricular-pulmonary arterial uncoupling during maximum incremental exercise in exercise pulmonary hypertension and pulmonary arterial hypertension},
	journal = {Pulm Circ},
	volume = {9},
	number = {3},
	year = {2019},
	month = {2019 Jul-Sep},
	pages = {2045894019862435},
	abstract = {Despite recent advances, the prognosis of pulmonary hypertension (PH) remains poor. While the initial insult in PH implicates the pulmonary vasculature, the functional state, exercise capacity, and survival of such patients are closely linked to right ventricular (RV) function. In the current study, we sought to investigate the effects of maximum incremental exercise on the matching of RV contractility and afterload (i.e. right ventricular-pulmonary arterial [RV-PA] coupling) in patients with exercise PH (ePH) and pulmonary arterial hypertension (PAH). End-systolic elastance (Ees), pulmonary arterial elastance (Ea), and RV-PA coupling (Ees/Ea) were determined using single-beat pressure-volume loop analysis in 40 patients that underwent maximum invasive cardiopulmonary exercise testing. Eleven patients had ePH, nine had PAH, and 20 were age-matched controls. During exercise, the impaired exertional contractile reserve in PAH was associated with blunted stroke volume index (SVI) augmentation and reduced peak oxygen consumption (peak VO2 \%predicted). Compared to PAH, ePH demonstrated increased RV contractility in response to increasing RV afterload during exercise; however, this was insufficient and resulted in reduced peak RV-PA coupling. The dynamic RV-PA uncoupling in ePH was associated with similarly blunted SVI augmentation and peak VO2 as PAH. In conclusion, dynamic rest-to-peak exercise RV-PA uncoupling during maximum exercise blunts SV increase and reduces exercise capacity in exercise PH and PAH. In ePH, the insufficient increase in RV contractility to compensate for increasing RV afterload during maximum exercise leads to deterioration of RV-PA coupling. These data provide evidence that even in the early stages of PH, RV function is compromised.},
	issn = {2045-8932},
	doi = {10.1177/2045894019862435},
	author = {Singh, Inderjit and Rahaghi, Farbod N and Naeije, Robert and Oliveira, Rudolf K F and Vanderpool, Rebecca R and Waxman, Aaron B and Systrom, David M}
}
@article {1677591,
	title = {Pulmonary Vascular Distensibility and Early Pulmonary Vascular Remodeling in Pulmonary Hypertension},
	journal = {Chest},
	volume = {156},
	number = {4},
	year = {2019},
	month = {2019 Oct},
	pages = {724-732},
	abstract = {BACKGROUND: Exercise stress testing of the pulmonary circulation may uncover decreased pulmonary vascular (PV) distensibility as a cause of impaired aerobic exercise capacity and right ventricular (RV)-pulmonary arterial (PA) uncoupling. As such, it may help in the differential diagnosis of unexplained dyspnea, including pulmonary hypertension (PH) and/or heart failure with preserved ejection fraction (HFpEF). We investigated rest and exercise invasive pulmonary hemodynamics, ventilation, and gas exchange in patients with unexplained dyspnea, including 44 patients with HFpEF (of whom 20 had a normal pulmonary vascular resistance [PVR] during exercise [ie, passive HFpEF] and 24 had a higher than normal exercise PVR), 22 patients with exercise PH, 19 patients with pulmonary arterial hypertension (PAH), and 24 age- and sex-matched normal control subjects.

METHODS: A PV distensibility coefficient α (\%/mm~Hg) was determined from multipoint PV pressure-flow plots. RV-PA coupling was quantified from the analysis of RV pressure curves to determine ratios of end-systolic to arterial elastances (Ees/Ea). Aerobic exercise capacity was estimated by peak oxygen consumption.

RESULTS: The α coefficient decreased from 1.35 {\textpm} 0.58\%/mm~Hg in control subjects and 1.1 {\textpm} 0.48\%/mm~Hg in patients with passive HFpEF to 0.62 {\textpm} 0.32\%/mm~Hg in exercise PH, 0.54 {\textpm} 0.27\%/mm~Hg in HFpEF with high exercise PVR, and 0.18 {\textpm} 0.16\%/mm Hg in PAH. On multivariate analysis, PV distensibility was associated with decreased Ees/Ea and maximal volume of oxygen consumed.

CONCLUSIONS: PV distensibility is an early and sensitive hemodynamic marker of PV disease that is associated with RV-PA uncoupling and decreased aerobic exercise capacity.},
	keywords = {Adult, Aged, Aged, 80 and over, Exercise Tolerance, Female, Heart Failure, Humans, Hypertension, Pulmonary, Male, Pulmonary Artery, Retrospective Studies, Stroke Volume, Vascular Remodeling, Ventricular Dysfunction, Right},
	issn = {1931-3543},
	doi = {10.1016/j.chest.2019.04.111},
	author = {Singh, Inderjit and Oliveira, Rudolf K F and Naeije, Robert and Rahaghi, Farbod N and Oldham, William M and Systrom, David M and Waxman, Aaron B}
}
@article {1677596,
	title = {Right Ventricular-Arterial Uncoupling During Exercise in Heart Failure With Preserved Ejection Fraction: Role of Pulmonary Vascular Dysfunction},
	journal = {Chest},
	volume = {156},
	number = {5},
	year = {2019},
	month = {2019 Nov},
	pages = {933-943},
	abstract = {BACKGROUND: Right ventricular (RV) dysfunction is associated with shortened life expectancy in heart failure with preserved ejection fraction (HFpEF). The contribution of pulmonary vascular dysfunction to RV dysfunction in HFpEF is not well understood.

METHODS: We investigated rest and exercise invasive pulmonary hemodynamics, ventilation, and gas exchange in 67 patients with HFpEF (of whom 28 had an abnormal pulmonary vascular response during exercise referred to as HFpEF+PVR group and 39 had a normal pulmonary vascular response during exercise referred to as HFpEF group) and in 21 matched control subjects.

RESULTS: Both groups of patients with HFpEF had a markedly decreased peak oxygen consumption (Vo2), decreased oxygen delivery, and impaired chronotropic response. Single beat analysis of RV pressure waveforms was used to compute the end-systolic elastance (Ees) and pulmonary arterial elastance (Ea). Right ventricular-pulmonary artery (RV-PA) coupling was measured as the ratio of Ees/Ea. Exercise was associated with a preserved Ees response but a decreased Ees/Ea in patients with HFpEF with a normal PVR response, indicating partially preserved RV contractile reserve. In HFpEF+PVR, exercise-induced increase in Ees was markedly reduced, resulting in decreased Ees/Ea and RV-PA uncoupling. Patients with HFpEF+PVR with an exercise-induced decrease in Ees/Ea had lower pulmonary artery compliance, lower peak Vo2, and lower stroke volume than patients with HFpEF.

CONCLUSIONS: We conclude that RV-PA uncoupling is common in HFpEF and is caused by both intrinsic RV contractile impairment and afterload mismatch. Resting and dynamic RV-PA uncoupling in HFpEF is driven by an increase in RV pulsatile rather than resistive afterload. However, with the additive effects of increased RV resistive afterload, RV-PA uncoupling worsens dynamically during exercise.},
	keywords = {Aged, Aged, 80 and over, Exercise, Exercise Test, Exercise Tolerance, Female, Heart Failure, Humans, Male, Middle Aged, Oxygen Consumption, Pulmonary Artery, Pulmonary Circulation, Pulmonary Gas Exchange, Pulmonary Ventilation, Stroke Volume, Vascular Resistance, Vascular Stiffness, Ventricular Dysfunction, Right},
	issn = {1931-3543},
	doi = {10.1016/j.chest.2019.04.109},
	author = {Singh, Inderjit and Rahaghi, Farbod N and Naeije, Robert and Oliveira, Rudolf K F and Systrom, David M and Waxman, Aaron B}
}
@article {1675421,
	title = {Clinical Epidemiology of COPD: Insights From 10 Years of the COPDGene Study},
	journal = {Chest},
	volume = {156},
	number = {2},
	year = {2019},
	month = {2019 Aug},
	pages = {228-238},
	abstract = {The Genetic Epidemiology of COPD (COPDGene) study is a noninterventional, multicenter, longitudinal analysis of \> 10,000 subjects, including smokers with a~>= 10 pack-year history with and without COPD and healthy never smokers. The goal was to characterize disease-related phenotypes and explore associations with susceptibility genes. The subjects were extensively phenotyped with the use of comprehensive symptom and comorbidity questionnaires, spirometry, CT scans of the chest, and genetic and biomarker profiling. The objective of this review was to summarize the major advances in the clinical epidemiology of COPD from the first 10 years of the COPDGene study. We highlight the influence of age, sex, and race on the natural history of COPD, and the impact of comorbid conditions, chronic bronchitis, exacerbations, and asthma/COPD overlap.},
	keywords = {Aged, Case-Control Studies, Female, Humans, Male, Middle Aged, Pulmonary Disease, Chronic Obstructive, Smoking},
	issn = {1931-3543},
	doi = {10.1016/j.chest.2019.04.135},
	author = {Maselli, Diego J and Bhatt, Surya P and Anzueto, Antonio and Bowler, Russell P and DeMeo, Dawn L and Diaz, Alejandro A and Dransfield, Mark T and Fawzy, Ashraf and Foreman, Marilyn G and Hanania, Nicola A and Hersh, Craig P and Kim, Victor and Kinney, Gregory L and Putcha, Nirupama and Wan, Emily S and Wells, J Michael and Westney, Gloria E and Young, Kendra A and Silverman, Edwin K and Han, MeiLan K and Make, Barry J}
}
@article {1675351,
	title = {Ambient air pollution exposure and risk and progression of interstitial lung abnormalities: the Framingham Heart Study},
	journal = {Thorax},
	volume = {74},
	number = {11},
	year = {2019},
	month = {2019 Nov},
	pages = {1063-1069},
	abstract = {BACKGROUND: Ambient air pollution accelerates lung function decline among adults, however, there are limited data about its role in the development and progression of early stages of interstitial lung disease.

AIMS: To evaluate associations of long-term exposure to traffic and ambient pollutants with odds of interstitial lung abnormalities (ILA) and progression of ILA on repeated imaging.

METHODS: We ascertained ILA on chest CT obtained from 2618 Framingham participants from 2008 to 2011. Among 1846 participants who also completed a cardiac CT from 2002 to 2005, we determined interval ILA progression. We assigned distance from home address to major roadway, and the 5-year average of fine particulate matter (PM2.5), elemental carbon (EC, a traffic-related PM2.5 constituent) and ozone using spatio-temporal prediction models. Logistic regression models were adjusted for age, sex, body mass index, smoking status, packyears of smoking, household tobacco exposure, neighbourhood household value, primary occupation, cohort and date.

RESULTS: Among 2618 participants with a chest CT, 176 (6.7\%) had ILA, 1361 (52.0\%) had no ILA, and the remainder were indeterminate. Among 1846 with a preceding cardiac CT, 118 (6.4\%) had ILA with interval progression. In adjusted logistic regression models, an IQR difference in 5-year EC exposure of 0.14 {\textmu}g/m3 was associated with a 1.27 (95\% CI 1.04 to 1.55) times greater odds of ILA, and a 1.33 (95\% CI 1.00 to 1.76) times greater odds of ILA progression. PM2.5 and O3 were not associated with ILA or ILA progression.

CONCLUSIONS: Exposure to EC may increase risk of progressive ILA, however, associations with other measures of ambient pollution were inconclusive.},
	keywords = {Aged, Air Pollution, Carbon, Disease Progression, Environmental Exposure, Female, Health Surveys, Humans, Longitudinal Studies, Lung Diseases, Interstitial, Male, Middle Aged, Ozone, particulate matter, Residence Characteristics, Risk Factors, Time Factors, Tomography, X-Ray Computed, Traffic-Related Pollution},
	issn = {1468-3296},
	doi = {10.1136/thoraxjnl-2018-212877},
	author = {Rice, Mary B and Li, Wenyuan and Schwartz, Joel and Di, Qian and Kloog, Itai and Koutrakis, Petros and Gold, Diane R and Hallowell, Robert W and Zhang, Chunyi and O{\textquoteright}Connor, George and Washko, George R and Hunninghake, Gary M and Mittleman, Murray A}
}
@article {1675361,
	title = {Heart and lungs in a single breath},
	journal = {Respirology},
	volume = {24},
	number = {10},
	year = {2019},
	month = {2019 Oct},
	pages = {937-938},
	issn = {1440-1843},
	doi = {10.1111/resp.13641},
	author = {Washko, George R and Agusti, Alvar}
}
@article {1675356,
	title = {Overlap of Genetic Risk between Interstitial Lung Abnormalities and Idiopathic Pulmonary Fibrosis},
	journal = {Am J Respir Crit Care Med},
	volume = {200},
	number = {11},
	year = {2019},
	month = {2019 Dec 01},
	pages = {1402-1413},
	abstract = {Rationale: Interstitial lung abnormalities (ILAs) are associated with the highest genetic risk locus for idiopathic pulmonary fibrosis (IPF); however, the extent to which there are unique associations among individuals with ILAs or additional overlap with IPF is not known.Objectives: To perform a genome-wide association study (GWAS) of ILAs.Methods: ILAs and a subpleural-predominant subtype were assessed on chest computed tomography (CT) scans in the AGES (Age Gene/Environment Susceptibility), COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease [COPD]), Framingham Heart, ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points), MESA (Multi-Ethnic Study of Atherosclerosis), and SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study) studies. We performed a GWAS of ILAs in each cohort and combined the results using a meta-analysis. We assessed for overlapping associations in independent GWASs of IPF.Measurements and Main Results: Genome-wide genotyping data were available for 1,699 individuals with ILAs and 10,274 control subjects. The MUC5B (mucin 5B) promoter variant rs35705950 was significantly associated with both ILAs (P = 2.6 {\texttimes} 10-27) and subpleural ILAs (P = 1.6 {\texttimes} 10-29). We discovered novel genome-wide associations near IPO11 (rs6886640, P = 3.8 {\texttimes} 10-8) and FCF1P3 (rs73199442, P = 4.8 {\texttimes} 10-8) with ILAs, and near HTRE1 (rs7744971, P = 4.2 {\texttimes} 10-8) with subpleural-predominant ILAs. These novel associations were not associated with IPF. Among 12 previously reported IPF GWAS loci, five (DPP9, DSP, FAM13A, IVD, and MUC5B) were significantly associated (P \< 0.05/12) with ILAs.Conclusions: In a GWAS of ILAs in six studies, we confirmed the association with a MUC5B promoter variant and found strong evidence for an effect of previously described IPF loci; however, novel ILA associations were not associated with IPF. These findings highlight common genetically driven biologic pathways between ILAs and IPF, and also suggest distinct ones.},
	keywords = {Aged, beta Karyopherins, Case-Control Studies, Female, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Idiopathic Pulmonary Fibrosis, Lung Diseases, Interstitial, Male, Middle Aged, Mucin-5B, Polymorphism, Single Nucleotide, Promoter Regions, Genetic, TATA Box Binding Protein-Like Proteins},
	issn = {1535-4970},
	doi = {10.1164/rccm.201903-0511OC},
	author = {Hobbs, Brian D and Putman, Rachel K and Araki, Tetsuro and Nishino, Mizuki and Gudmundsson, Gunnar and Gudnason, Vilmundur and Eiriksdottir, Gudny and Zilhao Nogueira, Nuno Rodrigues and Dupuis, Jos{\'e}e and Xu, Hanfei and O{\textquoteright}Connor, George T and Manichaikul, Ani and Nguyen, Jennifer and Podolanczuk, Anna J and Madahar, Purnema and Rotter, Jerome I and Lederer, David J and Barr, R Graham and Rich, Stephen S and Ampleford, Elizabeth J and Ortega, Victor E and Peters, Stephen P and O{\textquoteright}Neal, Wanda K and Newell, John D and Bleecker, Eugene R and Meyers, Deborah A and Allen, Richard J and Oldham, Justin M and Ma, Shwu-Fan and Noth, Imre and Jenkins, R Gisli and Maher, Toby M and Hubbard, Richard B and Wain, Louise V and Fingerlin, Tasha E and Schwartz, David A and Washko, George R and Rosas, Ivan O and Silverman, Edwin K and Hatabu, Hiroto and Cho, Michael H and Hunninghake, Gary M}
}
@article {1675326,
	title = {A SR-NET 3D-TO-2D ARCHITECTURE FOR PARASEPTAL EMPHYSEMA SEGMENTATION},
	journal = {Proc IEEE Int Symp Biomed Imaging},
	volume = {2019},
	year = {2019},
	month = {2019 Apr},
	pages = {303-306},
	abstract = {Paraseptal emphysema (PSE) is a relatively unexplored emphysema subtype that is usually asymptomatic, but recently associated with interstitial lung abnormalities which are related with clinical outcomes, including mortality. Previous local-based methods for emphysema subtype quantification do not properly characterize PSE. This is in part for their inability to properly capture the global aspect of the disease, as some the PSE lesions can involved large regions along the chest wall. It is our assumption, that path-based approaches are not well-suited to identify this subtype and segmentation is a better paradigm. In this work we propose and introduce the Slice-Recovery network (SR-Net) that leverages 3D contextual information for 2D segmentation of PSE lesions in CT images. For that purpose, a novel convolutional network architecture is presented, which follows an encoding-decoding path that processes a 3D volume to generate a 2D segmentation map. The dataset used for training and testing the method comprised 664 images, coming from 111 CT scans. The results demonstrate the benefit of the proposed approach which incorporate 3D context information to the network and the ability of the proposed method to identify and segment PSE lesions with different sizes even in the presence of other emphysema subtypes in an advanced stage.},
	issn = {1945-7928},
	doi = {10.1109/isbi.2019.8759184},
	author = {Bermejo-Pel{\'a}ez, D and Okajima, Y and Washko, G R and Ledesma-Carbayo, M J and San Jos{\'e} Est{\'e}par, R}
}
@article {1675341,
	title = {Subtypes of COPD Have Unique Distributions and Differential Risk of Mortality},
	journal = {Chronic Obstr Pulm Dis},
	volume = {6},
	number = {5},
	year = {2019},
	month = {2019 Nov},
	pages = {400-413},
	abstract = {BACKGROUND: Previous attempts to explore the heterogeneity of chronic obstructive pulmonary disease (COPD) clustered individual patients using clinical, demographic, and disease features. We developed continuous multidimensional disease axes based on radiographic and spirometric variables that split into an airway-predominant axis and an emphysema-predominant axis.

METHODS: The COPD Genetic Epidemiology study (COPDGene{\textregistered}) is a cohort of current and former smokers, \> 45 years, with at least 10 pack years of smoking history. Spirometry measures, blood pressure and body mass were directly measured. Mortality was assessed through continuing longitudinal follow-up and cause of death was adjudicated. Among 8157 COPDGene{\textregistered} participants with complete spirometry and computed tomography (CT) measures, the top 2 deciles of the airway-predominant and emphysema-predominant axes previously identified were used to categorize individuals into 3 groups having the highest risk for mortality using Cox proportional hazard ratios. These groups were also assessed for causal mortality. Biomarkers of COPD (fibrinogen, soluble receptor for advanced glycation end products [sRAGE], C-reactive protein [CRP], clara cell secretory protein [CC16], surfactant-D [SP-D]) were compared by group.

FINDINGS: High-risk subtype classification was defined for 2638 COPDGene{\textregistered} participants who were in the highest 2 deciles of either the airway-predominant and/or emphysema-predominant axis (32\% of the cohort). These high-risk participants fell into 3 groups: airway-predominant disease only (APD-only), emphysema-predominant disease only (EPD-only) and combined APD-EPD. There was 26\% mortality for the APD-only group, 21\% mortality for the EPD-only group, and 54\% mortality for the combined APD-EPD group. The APD-only group (n=1007) was younger, had a lower forced expiratory volume in 1 second (FEV1) percent (\%) predicted and a strong association with the preserved ratio-impaired spirometry (PRISm) quadrant. The EPD-only group (n=1006) showed a relatively higher FEV1 \% predicted and included largely GOLD stage 0, 1 and 2 partipants. Individuals in each of the 3 high-risk groups were at greater risk for respiratory mortality, while those in the APD-only group were additionally at greater risk for cardiovascular mortality. Biomarker analysis demonstrated a significant association of the APD-only group with CRP, and sRAGE demonstrated greatest significance with both the EPD-only and the combined APD-EPD groups.

INTERPRETATION: Among current and former smokers, individuals in the highest 2 deciles for mortality risk on the airway-predominant axis and the emphysema-predominant axis have unique associations to spirometric patterns, different imaging characteristics, biomarkers and causal mortality.},
	issn = {2372-952X},
	doi = {10.15326/jcopdf.6.5.2019.0150},
	author = {Young, Kendra A and Regan, Elizabeth A and Han, MeiLan K and Lutz, Sharon M and Ragland, Margaret and Castaldi, Peter J and Washko, George R and Cho, Michael H and Strand, Mathew and Curran-Everett, Douglas and Beaty, Terri H and Bowler, Russell P and Wan, Emily S and Lynch, David A and Make, Barry J and Silverman, Edwin K and Crapo, James D and Hokanson, John E and Kinney, Gregory L}
}
@article {1675166,
	title = {Association of Obesity with Quantitative Chest CT Measured Airway Wall Thickness in WTC Workers with Lower Airway Disease},
	journal = {Lung},
	volume = {197},
	number = {4},
	year = {2019},
	month = {2019 Aug},
	pages = {517-522},
	abstract = {BACKGROUND: We previously reported that wall area percent (WAP), a quantitative CT (QCT) indicator of airway wall thickness and, presumably, inflammation, is associated with adverse longitudinal expiratory flow trajectories in WTC workers, but that obesity and weight gain also seemed to be independently predictive of the latter. Previous studies have reported no association between WAP and obesity, so we investigated that association in nonsmoking WTC-exposed individuals and healthy unexposed controls.

METHODS: We assessed WAP using the Chest Imaging Platform QCT system in a segmental bronchus in 118 former WTC workers, and 89 COPDGene{\textregistered} WTC-unexposed and asymptomatic subjects. We used multiple regression to model WAP vs. body mass index (BMI) in the two groups, adjusting for important subject and CT image characteristics.

RESULTS: Unadjusted analyses revealed significant differences between the two groups with regards to WAP, age, gender, scan pixel spacing and slice interval, but not BMI or total lung capacity. In adjusted analysis, there was a significant interaction between BMI and WTC exposure on WAP. BMI was significantly and positively associated with WAP in the WTC group, but not in the COPDGene{\textregistered} group, but stratified analyses revealed that the effect was significant in WTC subjects with clinical evidence of lower airway disease (LAD).

DISCUSSION: Unlike non-diseased subjects, BMI was significantly associated with WAP in WTC workers and, in stratified analyses, the association was significant only among those with LAD. Our findings suggest that this adverse effect of obesity on airway structure and inflammation may be confined to already diseased individuals.},
	keywords = {Body Mass Index, Bronchi, Bronchial Diseases, Case-Control Studies, Humans, Multidetector Computed Tomography, Obesity, Occupational Diseases, Occupational Exposure, Predictive Value of Tests, Risk Factors, September 11 Terrorist Attacks, Smoke Inhalation Injury},
	issn = {1432-1750},
	doi = {10.1007/s00408-019-00246-z},
	author = {de la Hoz, Rafael E and Liu, Xiaoyu and Celed{\'o}n, Juan C and Doucette, John T and Jeon, Yunho and Reeves, Anthony P and San Jos{\'e} Est{\'e}par, Ra{\'u}l}
}
@article {1675151,
	title = {B Cell-Adaptive Immune Profile in Emphysema-Predominant Chronic Obstructive Pulmonary Disease},
	journal = {Am J Respir Crit Care Med},
	volume = {200},
	number = {11},
	year = {2019},
	month = {2019 Dec 01},
	pages = {1434-1439},
	keywords = {Adaptive Immunity, B-Lymphocytes, Female, Humans, Lung, Male, Middle Aged, Pulmonary Disease, Chronic Obstructive, Pulmonary Emphysema},
	issn = {1535-4970},
	doi = {10.1164/rccm.201903-0632LE},
	author = {Sullivan, John-Lawrence and Bagevalu, Bhavani and Glass, Carolyn and Sholl, Lynette and Kraft, Monica and Martinez, Fernando D and Bastarrika, Gorka and de-Torres, Juan P and Estepar, Raul San Jose and Guerra, Stefano and Polverino, Francesca}
}
@article {1675036,
	title = {Bronchial Cartilage Assessment with Model-Based GAN Regressor},
	journal = {Med Image Comput Comput Assist Interv},
	volume = {11769},
	year = {2019},
	month = {2019 Oct},
	pages = {357-365},
	abstract = {In the last two decades, several methods for airway segmentation from chest CT images have been proposed. The following natural step is the development of a tool to accurately assess the morphology of the bronchial system in all its aspects to help physicians better diagnosis and prognosis complex pulmonary diseases such as COPD, chronic bronchitis and bronchiectasis. Traditional methods for the assessment of airway morphology usually focus on lumen and wall thickness and are often limited due to resolution and artifacts of the CT image. Airway wall cartilage is an important characteristic related to airway integrity that has shown to be deteriorated during the airway disease process. In this paper, we propose the development of a Model-Based GAN Regressor (MBGR) that, thanks to a model-based GAN generator, generate synthetic airway samples with the morphological components necessary to resemble the appearance of real airways on CT at will and that simultaneously measures lumen, wall thickness, and amount of cartilage on pulmonary CT images. The method is evaluated by first computing the relative error on generated images to show that simulating the cartilage helps improve the morphological quantification of the airway structure. We then propose a cartilage index that summarizes the degree of cartilage of bronchial trees structures and perform an indirect validation with subjects with COPD. As shown by the results, the proposed approach paves the way for the use of CNNs to precisely and accurately measure small lung airways morphology, with the final goal to improve the diagnosis and prognosis of pulmonary diseases.},
	doi = {10.1007/978-3-030-32226-7_40},
	author = {Nardelli, Pietro and Washko, George R and San Jos{\'e} Est{\'e}par, Ra{\'u}l}
}
@article {1675126,
	title = {COPDGene 2019: Redefining the Diagnosis of Chronic Obstructive Pulmonary Disease},
	journal = {Chronic Obstr Pulm Dis},
	volume = {6},
	number = {5},
	year = {2019},
	month = {2019 Nov},
	pages = {384-399},
	abstract = {BACKGROUND: Chronic obstructive pulmonary disease (COPD) remains a major cause of morbidity and mortality. Present-day diagnostic criteria are largely based solely on spirometric criteria. Accumulating evidence has identified a substantial number of individuals without spirometric evidence of COPD who suffer from respiratory symptoms and/or increased morbidity and mortality. There is a clear need for an expanded definition of COPD that is linked to physiologic, structural (computed tomography [CT]) and clinical evidence of disease. Using data from the COPD Genetic Epidemiology study (COPDGene{\textregistered}), we hypothesized that an integrated approach that includes environmental exposure, clinical symptoms, chest CT imaging and spirometry better defines disease and captures the likelihood of progression of respiratory obstruction and mortality.

METHODS: Four key disease characteristics - environmental exposure (cigarette smoking), clinical symptoms (dyspnea and/or chronic bronchitis), chest CT imaging abnormalities (emphysema, gas trapping and/or airway wall thickening), and abnormal spirometry - were evaluated in a group of 8784 current and former smokers who were participants in COPDGene{\textregistered} Phase 1. Using these 4 disease characteristics, 8 categories of participants were identified and evaluated for odds of spirometric disease progression (FEV1 \> 350 ml loss over 5 years), and the hazard ratio for all-cause mortality was examined.

RESULTS: Using smokers without symptoms, CT imaging abnormalities or airflow obstruction as the reference population, individuals were classified as Possible COPD, Probable COPD and Definite COPD. Current Global initiative for obstructive Lung Disease (GOLD) criteria would diagnose 4062 (46\%) of the 8784 study participants with COPD. The proposed COPDGene{\textregistered} 2019 diagnostic criteria would add an additional 3144 participants. Under the new criteria, 82\% of the 8784 study participants would be diagnosed with Possible, Probable or Definite COPD. These COPD groups showed increased risk of disease progression and mortality. Mortality increased in patients as the number of their COPD characteristics increased, with a maximum hazard ratio for all cause-mortality of 5.18 (95\% confidence interval [CI]: 4.15-6.48) in those with all 4 disease characteristics.

CONCLUSIONS: A substantial portion of smokers with respiratory symptoms and imaging abnormalities do not manifest spirometric obstruction as defined by population normals. These individuals are at significant risk of death and spirometric disease progression. We propose to redefine the diagnosis of COPD through an integrated approach using environmental exposure, clinical symptoms, CT imaging and spirometric criteria. These expanded criteria offer the potential to stimulate both current and future interventions that could slow or halt disease progression in patients before disability or irreversible lung structural changes develop.},
	issn = {2372-952X},
	doi = {10.15326/jcopdf.6.5.2019.0149},
	author = {Lowe, Katherine E and Regan, Elizabeth A and Anzueto, Antonio and Austin, Erin and Austin, John H M and Beaty, Terri H and Benos, Panayiotis V and Benway, Christopher J and Bhatt, Surya P and Bleecker, Eugene R and Bodduluri, Sandeep and Bon, Jessica and Boriek, Aladin M and Boueiz, Adel Re and Bowler, Russell P and Budoff, Matthew and Casaburi, Richard and Castaldi, Peter J and Charbonnier, Jean-Paul and Cho, Michael H and Comellas, Alejandro and Conrad, Douglas and Costa Davis, Corinne and Criner, Gerard J and Curran-Everett, Douglas and Curtis, Jeffrey L and DeMeo, Dawn L and Diaz, Alejandro A and Dransfield, Mark T and Dy, Jennifer G and Fawzy, Ashraf and Fleming, Margaret and Flenaugh, Eric L and Foreman, Marilyn G and Fortis, Spyridon and Gebrekristos, Hirut and Grant, Sarah and Grenier, Philippe A and Gu, Tian and Gupta, Abhya and Han, MeiLan K and Hanania, Nicola A and Hansel, Nadia N and Hayden, Lystra P and Hersh, Craig P and Hobbs, Brian D and Hoffman, Eric A and Hogg, James C and Hokanson, John E and Hoth, Karin F and Hsiao, Albert and Humphries, Stephen and Jacobs, Kathleen and Jacobson, Francine L and Kazerooni, Ella A and Kim, Victor and Kim, Woo Jin and Kinney, Gregory L and Koegler, Harald and Lutz, Sharon M and Lynch, David A and MacIntye, Neil R and Make, Barry J and Marchetti, Nathaniel and Martinez, Fernando J and Maselli, Diego J and Mathews, Anne M and McCormack, Meredith C and McDonald, Merry-Lynn N and McEvoy, Charlene E and Moll, Matthew and Molye, Sarah S and Murray, Susan and Nath, Hrudaya and Newell, John D and Occhipinti, Mariaelena and Paoletti, Matteo and Parekh, Trisha and Pistolesi, Massimo and Pratte, Katherine A and Putcha, Nirupama and Ragland, Margaret and Reinhardt, Joseph M and Rennard, Stephen I and Rosiello, Richard A and Ross, James C and Rossiter, Harry B and Ruczinski, Ingo and Estepar, Raul San Jose and Sciurba, Frank C and Sieren, Jessica C and Singh, Harjinder and Soler, Xavier and Steiner, Robert M and Strand, Matthew J and Stringer, William W and Tal-Singer, Ruth and Thomashow, Byron and Vegas S{\'a}nchez-Ferrero, Gonzalo and Walsh, John W and Wan, Emily S and Washko, George R and Michael Wells, J and Wendt, Chris H and Westney, Gloria and Wilson, Ava and Wise, Robert A and Yen, Andrew and Young, Kendra and Yun, Jeong and Silverman, Edwin K and Crapo, James D}
}
@article {1675161,
	title = {Identification of an emphysema-associated genetic variant near  with regulatory effects in lung fibroblasts},
	journal = {Elife},
	volume = {8},
	year = {2019},
	month = {2019 Jul 25},
	abstract = {Murine studies have linked TGF-β signaling to emphysema, and human genome-wide association studies (GWAS) studies of lung function and COPD have identified associated regions near genes in the TGF-β superfamily. However, the functional regulatory mechanisms at these loci have not been identified. We performed the largest GWAS of emphysema patterns to date, identifying 10 GWAS loci including an association peak spanning a 200 kb region downstream from TGFB2. Integrative analysis of publicly available eQTL, DNaseI, and chromatin conformation data identified a putative functional variant, rs1690789, that may regulate TGFB2 expression in human fibroblasts. Using chromatin conformation capture, we confirmed that the region containing rs1690789 contacts the TGFB2 promoter in fibroblasts, and CRISPR/Cas-9 targeted deletion of a ~ 100 bp region containing rs1690789 resulted in decreased TGFB2 expression in primary human lung fibroblasts. These data provide novel mechanistic evidence linking genetic variation affecting the TGF-β pathway to emphysema in humans.},
	keywords = {Aged, Aged, 80 and over, Emphysema, Fibroblasts, Gene Expression Regulation, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Lung, Middle Aged, Transforming Growth Factor beta2, United States},
	issn = {2050-084X},
	doi = {10.7554/eLife.42720},
	author = {Parker, Margaret M and Hao, Yuan and Guo, Feng and Pham, Betty and Chase, Robert and Platig, John and Cho, Michael H and Hersh, Craig P and Thannickal, Victor J and Crapo, James and Washko, George and Randell, Scott H and Silverman, Edwin K and San Jos{\'e} Est{\'e}par, Ra{\'u}l and Zhou, Xiaobo and Castaldi, Peter J}
}
@article {1675156,
	title = {Increased pulmonary artery diameter is associated with reduced FEV in former World Trade Center workers},
	journal = {Clin Respir J},
	volume = {13},
	number = {10},
	year = {2019},
	month = {2019 Oct},
	pages = {614-623},
	abstract = {RATIONALE: Occupational exposures at the WTC site after September 11, 2001 have been associated with several presumably inflammatory lower airway diseases. Pulmonary arterial enlargement, as suggested by an increased ratio of the diameter of the pulmonary artery to the diameter of the aorta (PAAr) has been reported as a computed tomographic (CT) scan marker of adverse respiratory health outcomes, including WTC-related disease. In this study, we sought to utilize a novel quantitative CT (QCT) measurement of PAAr to test the hypothesis that an increased ratio is associated with FEV1 below each subject{\textquoteright}s statistically determined lower limit of normal (FEV1 ~\<~LLN).

METHODS: In a group of 1,180 WTC workers and volunteers, we examined whether FEV1 ~\<~LLN was associated with an increased QCT-measured PAAr, adjusting for previously identified important covariates.

RESULTS: Unadjusted analyses showed a statistically significant association of FEV1 ~\<~LLN with PAAr (35.3\% vs 24.7\%, P~=~0.0001), as well as with height, body mass index, early arrival at the WTC disaster site, shorter WTC exposure duration, post-traumatic stress disorder checklist (PCL) score, wall area percent and evidence of bronchodilator response. The multivariate logistic regression model confirmed the association of FEV1 ~\<~LLN with PAAr (OR 1.63, 95\% CI 1.21, 2.20, P~=~0.0015) and all the unadjusted associations, except for PCL score.

CONCLUSIONS: In WTC workers, FEV1 ~\<~LLN is associated with elevated PAAr which, although likely multifactorial, may be related to distal vasculopathy, as has been hypothesized for chronic obstructive pulmonary disease.},
	keywords = {Adult, Bronchodilator Agents, Female, Forced Expiratory Volume, Humans, Male, Middle Aged, New York, Occupational Exposure, Pulmonary Artery, Pulmonary Disease, Chronic Obstructive, Respiratory Function Tests, September 11 Terrorist Attacks, Smoke Inhalation Injury, Stress Disorders, Post-Traumatic, Tomography, X-Ray Computed},
	issn = {1752-699X},
	doi = {10.1111/crj.13067},
	author = {de la Hoz, Rafael E and Jeon, Yunho and Reeves, Anthony P and San Jos{\'e} Est{\'e}par, Ra{\'u}l and Liu, Xiaoyu and Doucette, John T and Celed{\'o}n, Juan C and Nolan, Anna}
}
@article {1675051,
	title = {LOCALIZING IMAGE-BASED BIOMARKER REGRESSION WITHOUT TRAINING MASKS: A NEW APPROACH TO BIOMARKER DISCOVERY},
	journal = {Proc IEEE Int Symp Biomed Imaging},
	volume = {2019},
	year = {2019},
	month = {2019 Apr},
	pages = {679-682},
	abstract = {Biomarker inference from biomedical images is one of the main tasks of medical image analysis. Standard techniques follow a segmentation-and-measure strategy, where the structure is first segmented and then the measurement is performed. Recent work has shown that such strategy could be replaced by a direct regression of the biomarker value in using regression networks. While achieving high correlation coefficients, such techniques operate as a {\textquoteright}black-box{\textquoteright}, not offering quality-control images. We present a methodology to regress the biomarker from the image while simultaneously computing the quality control image. Our proposed methodology does not require segmentation masks for training, but infers the segmentations directly from the pixels that used to compute the biomarker value. The network proposed consists of two steps: a segmentation method to an unknown reference and a summation method for the biomarker estimation. The network is optimized using a dual loss function, L2 for the biomarkers and an L1 to enforce sparsity. We showcase our methodology in the problem of pectoralis muscle area (PMA) and subcutaneous fat area (SFA) inference in a single slice from chest-CT images. We use a database of 7000 cases to which only the value of the biomarker is known for training and a test set of 3000 cases with both, biomarkers and segmentations. We achieve a correlation coefficient of 0.97 for PMA and 0.98 for SFA with respect to the reference standard. The average DICE coefficient is of 0.88 (PMA) and 0.89 (SFA). Comparing with standard segment-and-measure techniques, we achieve the same correlation for the biomarkers but smaller DICE coefficients in segmentation. Such is of little surprise, since segmentation networks are the upper limit of performance achievable, and we are not using segmentation masks for training. We can conclude that it is possible to infer segmentation masks from biomarker regression networks.},
	issn = {1945-7928},
	doi = {10.1109/isbi.2019.8759474},
	author = {Cano-Espinosa, Carlos and Gonz{\'a}lez, Germ{\'a}n and Washko, George R and Cazorla, Miguel and San Jos{\'e} Est{\'e}par, Ra{\'u}l}
}
@article {1675176,
	title = {Objectively Measured Chronic Lung Injury~on Chest CT},
	journal = {Chest},
	volume = {156},
	number = {6},
	year = {2019},
	month = {2019 Dec},
	pages = {1149-1159},
	abstract = {BACKGROUND: Tobacco smoke exposure is associated with emphysema and pulmonary fibrosis, both of which are irreversible. We have developed a new objective CT analysis tool that combines densitometry with machine learning to detect high attenuation changes in visually normal appearing lung (NormHA) that may precede these diseases.

METHODS: We trained the classification tool by placing 34,528 training points in chest CT scans from 297 COPDGene participants. The tool was then used to classify lung tissue in 9,038 participants as normal, emphysema, fibrotic/interstitial, or NormHA. Associations between the quartile of NormHA and plasma-based biomarkers, clinical severity, and mortality were evaluated using Jonckheere-Terpstra, pairwise Wilcoxon rank-sum tests, and multivariable linear and Cox regression.

RESULTS: A higher percentage of lung occupied by NormHA was associated with higher C-reactive protein and intercellular adhesion molecule 1 (P for trend for both~\< .001). In analyses adjusted for multiple covariates, including high and low attenuation area, compared with those in the lowest quartile of NormHA, those in the highest quartile had a 6.50 absolute percent lower percent predicted lower FEV1 (P~\< .001), an 8.48 absolute percent lower percent predicted forced expiratory volume, a 10.78-meter shorter 6-min walk distance (P~= .011), and a 56\%~higher risk of death (P~= .003). These findings were present even in those individuals without visually defined interstitial lung abnormalities.

CONCLUSIONS: A new class of NormHA on CT may represent a unique tissue class associated with adverse outcomes, independent of emphysema and fibrosis.},
	keywords = {Aged, Female, Humans, Lung Diseases, Interstitial, Lung Injury, Male, Middle Aged, Pulmonary Emphysema, Pulmonary Fibrosis, Tomography, X-Ray Computed},
	issn = {1931-3543},
	doi = {10.1016/j.chest.2019.05.020},
	author = {Harmouche, Rola and Ash, Samuel Y and Putman, Rachel K and Hunninghake, Gary M and San Jose Estepar, Ruben and Martinez, Fernando J and Choi, Augustine M and Lynch, David A and Hatabu, Hiroto and Han, MeiLan K and Bowler, Russell P and Kalhan, Ravi and Rosas, Ivan O and Washko, George R and Estepar, Raul San Jose}
}
@article {1675181,
	title = {Pulmonary vascular density: comparison of findings on computed tomography imaging with histology},
	journal = {Eur Respir J},
	volume = {54},
	number = {2},
	year = {2019},
	month = {2019 Aug},
	abstract = {BACKGROUND: Exposure to cigarette smoke has been shown to lead to vascular remodelling. Computed tomography (CT) imaging measures of vascular pruning have been associated with pulmonary vascular disease, an important morbidity associated with smoking. In this study we compare CT-based measures of distal vessel loss to histological vascular and parenchymal changes.

METHODS: A retrospective review of 80 patients who had undergone lung resection identified patients with imaging appropriate for three-dimensional (3D) vascular reconstruction (n=18) and a second group for two-dimensional (2D) analysis (n=19). Measurements of the volume of the small vessels (3D) and the cross-sectional area of the small vessels (\<5 mm2 cross-section) were computed. Histological measures of cross-sectional area of the vasculature and loss of alveoli septa were obtained for all subjects.

RESULTS: The 2D cross-sectional area of the vasculature on CT imaging was associated with the histological vascular cross-sectional area (r=0.69; p=0.001). The arterial small vessel volume assessed by CT correlated with the histological vascular cross-sectional area (r=0.50; p=0.04), a relationship that persisted even when adjusted for CT-derived measures of emphysema in a regression model.

CONCLUSIONS: Loss of small vessel volume in CT imaging of smokers is associated with histological loss of vascular cross-sectional area. Imaging-based quantification of pulmonary vasculature provides a noninvasive method to study the multiscale effects of smoking on the pulmonary circulation.},
	keywords = {Aged, Artifacts, Female, Humans, Image Processing, Computer-Assisted, Imaging, Three-Dimensional, Lung, Male, Microcirculation, Middle Aged, Pulmonary Emphysema, Pulmonary Veins, Regression Analysis, Respiratory Function Tests, Retrospective Studies, Smoking, Tomography, X-Ray Computed, Vascular Remodeling},
	issn = {1399-3003},
	doi = {10.1183/13993003.00370-2019},
	author = {Rahaghi, Farbod N and Argem{\'\i}, Gemma and Nardelli, Pietro and Dom{\'\i}nguez-Fandos, David and Arguis, Pedro and Peinado, V{\'\i}ctor I and Ross, James C and Ash, Samuel Y and De La Bruere, Isaac and Come, Carolyn E and Diaz, Alejandro A and S{\'a}nchez, Marcelo and Washko, George R and Barber{\`a}, Joan Albert and San Jos{\'e} Est{\'e}par, Ra{\'u}l}
}
@article {1675111,
	title = {Quantification and Significance of Pulmonary Vascular Volume in Predicting Response to Ultrasound-Facilitated, Catheter-Directed Fibrinolysis in Acute Pulmonary Embolism (SEATTLE-3D)},
	journal = {Circ Cardiovasc Imaging},
	volume = {12},
	number = {12},
	year = {2019},
	month = {2019 Dec},
	pages = {e009903},
	keywords = {Acute Disease, Angiography, Cardiac Catheterization, Fibrinolytic Agents, Humans, Pulmonary Artery, Pulmonary Embolism, Therapy, Computer-Assisted, Thrombolytic Therapy, Tomography, X-Ray Computed, Ultrasonography},
	issn = {1942-0080},
	doi = {10.1161/CIRCIMAGING.119.009903},
	author = {Rahaghi, Farbod N and San Jos{\'e} Est{\'e}par, Ra{\'u}l and Goldhaber, Samuel Z and Minhas, Jasleen K and Nardelli, Pietro and Vegas Sanchez-Ferrero, Gonzalo and De La Bruere, Isaac and Hassan, Syed M and Mason, Stefanie and Ash, Samuel Y and Come, Carolyn E and Washko, George R and Piazza, Gregory}
}
@article {1675171,
	title = {Radiographic pulmonary vessel volume, lung function and airways disease in the Framingham Heart Study},
	journal = {Eur Respir J},
	volume = {54},
	number = {3},
	year = {2019},
	month = {2019 Sep},
	abstract = {Radiographic abnormalities of the pulmonary vessels, such as vascular pruning, are common in advanced airways disease, but it is unknown if pulmonary vascular volumes are related to measures of lung health and airways disease in healthier populations.In 2388 participants of the Framingham Heart Study computed tomography (CT) sub-study, we calculated total vessel volumes and the small vessel fraction using automated CT image analysis. We evaluated associations with measures of lung function, airflow obstruction on spirometry and emphysema on CT. We further tested if associations of vascular volumes with lung function were present among those with normal forced expiratory volume in 1 s and forced vital capacity.In fully adjusted linear and logistic models, we found that lower total and small vessel volumes were consistently associated with worse measures of lung health, including lower spirometric volumes, lower diffusing capacity and/or higher odds of airflow obstruction. For example, each standard deviation lower small vessel fraction (indicating more severe pruning) was associated with a 37\% greater odds of obstruction (OR 1.37, 95\% CI 1.11-1.71, p=0.004). A similar pattern was observed in the subset of participants with normal spirometry.Lower total and small vessel pulmonary vascular volumes were associated with poorer measures of lung health and/or greater odds of airflow obstruction in this cohort of generally healthy adults without high burdens of smoking or airways disease. Our findings suggest that quantitative CT assessment may detect subtle pulmonary vasculopathy that occurs in the setting of subclinical and early pulmonary and airways pathology.},
	keywords = {Aged, Algorithms, Female, Forced Expiratory Volume, Humans, Image Processing, Computer-Assisted, Linear Models, Longitudinal Studies, Lung, Male, Middle Aged, Pulmonary Disease, Chronic Obstructive, Pulmonary Emphysema, Respiratory Function Tests, Smoking, Spirometry, Tomography, X-Ray Computed, Vital Capacity},
	issn = {1399-3003},
	doi = {10.1183/13993003.00408-2019},
	author = {Synn, Andrew J and Li, Wenyuan and San Jos{\'e} Est{\'e}par, Ra{\'u}l and Zhang, Chunyi and Washko, George R and O{\textquoteright}Connor, George T and Araki, Tetsuro and Hatabu, Hiroto and Bankier, Alexander A and Mittleman, Murray A and Rice, Mary B}
}
@article {1675131,
	title = {Semi-quantitative visual assessment of chest radiography is associated with clinical outcomes in critically ill patients},
	journal = {Respir Res},
	volume = {20},
	number = {1},
	year = {2019},
	month = {2019 Oct 12},
	pages = {218},
	abstract = {BACKGROUND: Respiratory pathology is a major driver of mortality in the intensive care unit (ICU), even in the absence of a primary respiratory diagnosis. Prior work has demonstrated that a visual scoring system applied to chest radiographs (CXR) is associated with adverse outcomes in ICU patients with Acute Respiratory Distress Syndrome (ARDS). We hypothesized that a simple, semi-quantitative CXR score would be associated with clinical outcomes for the general ICU population, regardless of underlying diagnosis.

METHODS: All individuals enrolled in the Registry of Critical Illness at Brigham and Women{\textquoteright}s Hospital between June 2008 and August 2018 who had a CXR within 24 h of admission were included. Each patient{\textquoteright}s CXR was assigned an opacification score of 0-4 in each of four quadrants with the total score being the sum of all four quadrants. Multivariable negative binomial, logistic, and Cox regression, adjusted for age, sex, race, immunosuppression, a history of chronic obstructive pulmonary disease, a history of congestive heart failure, and APACHE II scores, were used to assess the total score{\textquoteright}s association with ICU length of stay (LOS), duration of mechanical ventilation, in-hospital mortality, 60-day mortality, and overall mortality, respectively.

RESULTS: A total of 560 patients were included. Higher CXR scores were associated with increased mortality; for every one-point increase in score, in-hospital mortality increased 10\% (OR 1.10, CI 1.05-1.16, p \< 0.001) and 60-day mortality increased by 12\% (OR 1.12, CI 1.07-1.17, p \< 0.001). CXR scores were also independently associated with both ICU length of stay (rate ratio 1.06, CI 1.04-1.07, p \< 0.001) and duration of mechanical ventilation (rate ratio 1.05, CI 1.02-1.07, p \< 0.001).

CONCLUSIONS: Higher values on a simple visual score of a patient{\textquoteright}s CXR on admission to the medical ICU are associated with increased in-hospital mortality, 60-day mortality, overall mortality, length of ICU stay, and duration of mechanical ventilation.},
	keywords = {Adult, Aged, APACHE, Biomarkers, Critical Illness, Female, Hospital Mortality, Humans, Length of Stay, Lung, Male, Middle Aged, Organ Size, Respiration, Artificial, Respiratory Distress Syndrome, Retrospective Studies, Thorax, Treatment Outcome},
	issn = {1465-993X},
	doi = {10.1186/s12931-019-1201-0},
	author = {Mason, Stefanie E and Dieffenbach, Paul B and Englert, Joshua A and Rogers, Angela A and Massaro, Anthony F and Fredenburgh, Laura E and Higuera, Angelica and Pinilla-Vera, Mayra and Vilas, Marta and Estepar, Raul San Jose and Washko, George R and Baron, Rebecca M and Ash, Samuel Y}
}
@article {1675046,
	title = {Targeting Precision with Data Augmented Samples in Deep Learning},
	journal = {Med Image Comput Comput Assist Interv},
	volume = {11769},
	year = {2019},
	month = {2019 Oct},
	pages = {284-292},
	abstract = {In the last five years, deep learning (DL) has become the state-of-the-art tool for solving various tasks in medical image analysis. Among the different methods that have been proposed to improve the performance of Convolutional Neural Networks (CNNs), one typical approach is the augmentation of the training data set through various transformations of the input image. Data augmentation is typically used in cases where a small amount of data is available, such as the majority of medical imaging problems, to present a more substantial amount of data to the network and improve the overall accuracy. However, the ability of the network to improve the accuracy of the results when a slightly modified version of the same input is presented is often overestimated. This overestimation is the result of the strong correlation between data samples when they are considered independently in the training phase. In this paper, we emphasize the importance of optimizing for accuracy as well as precision among multiple replicates of the same training data in the context of data augmentation. To this end, we propose a new approach that leverages the augmented data to help the network focus on the precision through a specifically-designed loss function, with the ultimate goal to improve both the overall performance and the network{\textquoteright}s precision at the same time. We present two different applications of DL (regression and segmentation) to demonstrate the strength of the proposed strategy. We think that this work will pave the way to a explicit use of data augmentation within the loss function that helps the network to be invariant to small variations of the same input samples, a characteristic that is always required to every application in the medical imaging field.},
	doi = {10.1007/978-3-030-32226-7_32},
	author = {Nardelli, Pietro and San Jos{\'e} Est{\'e}par, Ra{\'u}l}
}
@article {1675121,
	title = {Using a spatial point process framework to characterize lung computed tomography scans},
	journal = {Spat Stat},
	volume = {29},
	year = {2019},
	month = {2019 Mar},
	pages = {243-267},
	abstract = {Pulmonary emphysema is a destructive disease of the lungs that is currently diagnosed via visual assessment of lung Computed Tomography (CT) scans by a radiologist. Visual assessment can have poor inter-rater reliability, is time consuming, and requires access to trained assessors. Quantitative methods that reliably summarize the biologically relevant characteristics of an image are needed to improve the way lung diseases are characterized. The goal of this work was to show how spatial point process models can be used to create a set of radiologically derived quantitative lung biomarkers of emphysema. We formalized a general framework for applying spatial point processes to lung CT scans, and developed a Shot Noise Cox Process to quantify how radiologically based emphysematous tissue clusters into larger structures. Bayesian estimation of model parameters was done using spatial Birth-Death MCMC (BD-MCMC). In simulations, we showed the BD-MCMC estimation algorithm is able to accurately recover model parameters. In an application to real lung CT scans from the COPDGene cohort, we showed variability in the clustering characteristics of emphysematous tissue across disease subtypes that were based on visual assessments of the CT scans.},
	issn = {2211-6753},
	doi = {10.1016/j.spasta.2018.12.003},
	author = {Vestal, Brian E and Carlson, Nichole E and San Jos{\'e} Est{\'e}par, Ra{\'u}l and Fingerlin, Tasha and Ghosh, Debashis and Kechris, Katerina and Lynch, David}
}
@article {1436282,
	title = {Harmonization of chest CT scans for different doses and reconstruction methods},
	journal = {Med Phys},
	volume = {46},
	number = {7},
	year = {2019},
	month = {2019 Jul},
	pages = {3117-3132},
	abstract = {PURPOSE: To develop and validate a computed tomography (CT) harmonization technique by combining noise-stabilization and autocalibration methodologies to provide reliable densitometry measurements in heterogeneous acquisition protocols.

METHODS: We propose to reduce the effects of spatially variant noise such as nonuniform patterns of noise and biases. The method combines the statistical characterization of the signal-to-noise relationship in the CT image intensities, which allows us to estimate both the signal and spatially variant variance of noise, with an autocalibration technique that reduces the nonuniform biases caused by noise and reconstruction techniques. The method is firstly validated with anthropomorphic synthetic images that simulate CT acquisitions with variable scanning parameters: different dosage, nonhomogeneous variance of noise, and various reconstruction methods. We finally evaluate these effects and the ability of our method to provide consistent densitometric measurements in a cohort of clinical chest CT scans from two vendors (Siemens, n~=~54 subjects; and GE, n~=~50 subjects) acquired with several reconstruction algorithms (filtered back-projection and iterative reconstructions) with high-dose and low-dose protocols.

RESULTS: The harmonization reduces the effect of nonhomogeneous noise without compromising the resolution of the images (25\% RMSE reduction in both clinical datasets). An analysis through hierarchical linear models showed that the average biases induced by differences in dosage and reconstruction methods are also reduced up to 74.20\%, enabling comparable results between high-dose and low-dose reconstructions. We also assessed the statistical similarity between acquisitions obtaining increases of up to 30\% points and showing that the low-dose vs high-dose comparisons of harmonized data obtain similar and even higher similarity than the observed for high-dose vs high-dose comparisons of nonharmonized data.

CONCLUSION: The proposed harmonization technique allows to compare measures of low-dose with high-dose acquisitions without using a specific reconstruction as a reference. Since the harmonization does not require a precalibration with a phantom, it can be applied to retrospective studies. This approach might be suitable for multicenter trials for which a reference reconstruction is not feasible or hard to define due to differences in vendors, models, and reconstruction techniques.},
	keywords = {Computer Simulation, Humans, Image Processing, Computer-Assisted, Radiation Dosage, Reference Standards, Signal-To-Noise Ratio, Thorax, Tomography, X-Ray Computed},
	issn = {2473-4209},
	doi = {10.1002/mp.13578},
	author = {Vegas-S{\'a}nchez-Ferrero, Gonzalo and Ledesma-Carbayo, Maria Jesus and Washko, George R and San Jos{\'e} Est{\'e}par, Ra{\'u}l}
}
@article {1433552,
	title = {Cigarette Smoke Exposure and Radiographic Pulmonary Vascular Morphology in the Framingham Heart Study},
	journal = {Ann Am Thorac Soc},
	volume = {16},
	number = {6},
	year = {2019},
	month = {2019 Jun},
	pages = {698-706},
	abstract = {Rationale: Cigarette smoke exposure is a risk factor for many lung diseases, and histologic studies suggest that tobacco-related vasoconstriction and vessel loss plays a role in the development of emphysema. However, it remains unclear how tobacco affects the pulmonary vasculature in general populations with a typical range of tobacco exposure, and whether these changes are detectable by radiographic methods. Objectives: To determine whether tobacco exposure in a generally healthy population manifests as lower pulmonary blood vessel volumes and vascular pruning on imaging. Methods: A total of 2,410 Framingham Heart Study participants with demographic data and smoking history underwent volumetric whole-lung computed tomography from 2008 to 2011. Automated algorithms calculated the total blood volume of all intrapulmonary vessels (TBV), smaller peripheral vessels (defined as cross-sectional area \<5 mm2 [BV5]), and the relative fraction of small vessels (BV5/TBV). Tobacco exposure was assessed as smoking status, cumulative pack-years, and second-hand exposure. We constructed multivariable linear regression models to evaluate associations of cigarette exposure and pulmonary blood vessel volume measures, adjusting for demographic covariates, including age, sex, height, weight, education, occupation, and median neighborhood income. Results: All metrics of tobacco exposure (including smoking status, pack-years, and second-hand exposure) were consistently associated with higher absolute pulmonary blood vessel volume, higher small vessel volume, and/or higher small vessel fraction. For example, ever-smokers had a 4.6 ml higher TBV (95\% confidence interval [CI] = 2.9-6.3, P \< 0.001), 2.1 ml higher BV5 (95\% CI = 1.3-2.9, P \< 0.001), and 0.28 percentage-point-higher BV5/TBV (95\% CI = 0.03-0.52, P = 0.03) compared with never-smokers. These associations remained significant after adjustment for percent predicted forced expiratory volume in 1 second, cardiovascular comorbidities, and did not differ based on presence or absence of airflow obstruction. Conclusions: Using computed tomographic imaging, we found that cigarette exposure was associated with higher pulmonary blood vessel volumes, especially in the smaller peripheral vessels. Although, histologically, tobacco-related vasculopathy is characterized by vessel narrowing and loss, our results suggest that radiographic vascular pruning may not be a surrogate of these pathologic changes.},
	keywords = {Aged, Cigarette Smoking, Ex-Smokers, Female, Forced Expiratory Volume, Humans, Linear Models, Longitudinal Studies, Lung, Male, Middle Aged, Multidetector Computed Tomography, Multivariate Analysis, Non-Smokers, Organ Size, Pulmonary Artery, Pulmonary Emphysema, Pulmonary Veins, Smokers, Spirometry, Tobacco Smoke Pollution, Vital Capacity},
	issn = {2325-6621},
	doi = {10.1513/AnnalsATS.201811-795OC},
	author = {Synn, Andrew J and Zhang, Chunyi and Washko, George R and San Jos{\'e} Est{\'e}par, Ra{\'u}l and O{\textquoteright}Connor, George T and Li, Wenyuan and Mittleman, Murray A and Rice, Mary B}
}
@article {1433555,
	title = {Imaging Patterns Are Associated with Interstitial Lung Abnormality Progression and Mortality},
	journal = {Am J Respir Crit Care Med},
	volume = {200},
	number = {2},
	year = {2019},
	month = {2019 Jul 15},
	pages = {175-183},
	abstract = {Rationale: Interstitial lung abnormalities (ILA) are radiologic abnormalities on chest computed tomography scans that have been associated with an early or mild form of pulmonary fibrosis. Although ILA have been associated with radiologic progression, it is not known if specific imaging patterns are associated with progression or risk of mortality. Objectives: To determine the role of imaging patterns on the risk of death and ILA progression. Methods: ILA (and imaging pattern) were assessed in 5,320 participants from the AGES-Reykjavik Study, and ILA progression was assessed in 3,167 participants. Multivariable logistic regression was used to assess factors associated with ILA progression, and Cox proportional hazards models were used to assess time to mortality. Measurements and Main Results: Over 5 years, 327 (10\%) had ILA on at least one computed tomography, and 1,435 (45\%) did not have ILA on either computed tomography. Of those with ILA, 238 (73\%) had imaging progression, whereas 89 (27\%) had stable to improved imaging; increasing age and copies of MUC5B genotype were associated with imaging progression. The definite fibrosis pattern was associated with the highest risk of progression (odds ratio, 8.4; 95\% confidence interval, 2.7-25; P = 0.0003). Specific imaging patterns were also associated with an increased risk of death. After adjustment, both a probable usual interstitial pneumonia and usual interstitial pneumonia pattern were associated with an increased risk of death when compared with those indeterminate for usual interstitial pneumonia (hazard ratio, 1.7; 95\% confidence interval, 1.2-2.4; P = 0.001; hazard ratio, 3.9; 95\% confidence interval, 2.3-6.8;P \< 0.0001), respectively. Conclusions: In those with ILA, imaging patterns can be used to help predict who is at the greatest risk of progression and early death.},
	keywords = {Age Factors, Aged, Aged, 80 and over, Disease Progression, Female, Humans, Iceland, Idiopathic Pulmonary Fibrosis, Logistic Models, Lung Diseases, Interstitial, Male, Mucin-5B, Multivariate Analysis, Prognosis, Proportional Hazards Models, Survival Rate, Tomography, X-Ray Computed},
	issn = {1535-4970},
	doi = {10.1164/rccm.201809-1652OC},
	author = {Putman, Rachel K and Gudmundsson, Gunnar and Axelsson, Gisli Thor and Hida, Tomoyuki and Honda, Osamu and Araki, Tetsuro and Yanagawa, Masahiro and Nishino, Mizuki and Miller, Ezra R and Eiriksdottir, Gudny and Gudmundsson, El{\'\i}as F and Tomiyama, Noriyuki and Honda, Hiroshi and Rosas, Ivan O and Washko, George R and Cho, Michael H and Schwartz, David A and Gudnason, Vilmundur and Hatabu, Hiroto and Hunninghake, Gary M}
}
@article {1433549,
	title = {Increased Airway Wall Thickness in Interstitial Lung Abnormalities and Idiopathic Pulmonary Fibrosis},
	journal = {Ann Am Thorac Soc},
	volume = {16},
	number = {4},
	year = {2019},
	month = {2019 Apr},
	pages = {447-454},
	abstract = {RATIONALE: There is increasing evidence that aberrant processes occurring in the airways may precede the development of idiopathic pulmonary fibrosis (IPF); however, there has been no prior confirmatory data derived from imaging studies.

OBJECTIVES: To assess quantitative measures of airway wall thickness (AWT) in populations characterized for interstitial lung abnormalities (ILA) and for IPF.

METHODS: Computed tomographic imaging of the chest and measures of AWT were available for 6,073, 615, 1,167, and 38 participants from COPDGene (Genetic Epidemiology of COPD study), ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints study), and the Framingham Heart Study (FHS) and in patients with IPF from the Brigham and Women{\textquoteright}s Hospital Herlihy Registry, respectively. To evaluate these associations, we used multivariable linear regression to compare a standardized measure of AWT (the square root of AWT for airways with an internal perimeter of 10 mm [Pi10]) and characterizations of ILA and IPF by computed tomographic imaging of the chest.

RESULTS: In COPDGene, ECLIPSE, and FHS, research participants with ILA had increased measures of Pi10 compared with those without ILA. Patients with IPF had mean measures of Pi10 that were even greater than those noted in research participants with ILA. After adjustment for important covariates (e.g., age, sex, race, body mass index, smoking behavior, and chronic obstructive pulmonary disease severity when appropriate), research participants with ILA had increased measures of Pi10 compared with those without ILA (0.03 mm in COPDGene, 95\% confidence interval [CI], 0.02-0.03; P \< 0.001; 0.02 mm in ECLIPSE, 95\% CI, 0.005-0.04; P = 0.01; 0.07 mm in FHS, 95\% CI, 0.01-0.1; P = 0.01). Compared with COPDGene participants without ILA older than 60 years of age, patients with IPF were also noted to have increased measures of Pi10 (2.0 mm, 95\% CI, 2.0-2.1; P \< 0.001). Among research participants with ILA, increases in Pi10 were correlated with reductions in lung volumes in some but not all populations.

CONCLUSIONS: These results demonstrate that measurable increases in AWT are consistently noted in research participants with ILA and in patients with IPF. These findings suggest that abnormalities of the airways may play a role in, or be correlated with, early pathogenesis of pulmonary fibrosis.},
	keywords = {Adult, Aged, Cohort Studies, Female, Humans, Idiopathic Pulmonary Fibrosis, Linear Models, Logistic Models, Lung, Lung Diseases, Interstitial, Male, Middle Aged, Multivariate Analysis, Pulmonary Emphysema, Registries, Spirometry, Tomography, X-Ray Computed},
	issn = {2325-6621},
	doi = {10.1513/AnnalsATS.201806-424OC},
	author = {Miller, Ezra R and Putman, Rachel K and Diaz, Alejandro A and Xu, Hanfei and San Jos{\'e} Est{\'e}par, Ra{\'u}l and Araki, Tetsuro and Nishino, Mizuki and Poli de Fr{\'\i}as, Sergio and Hida, Tomoyuki and Ross, James and Coxson, Harvey and Dupuis, Jos{\'e}e and O{\textquoteright}Connor, George T and Silverman, Edwin K and Rosas, Ivan O and Hatabu, Hiroto and Washko, George and Hunninghake, Gary M}
}
@article {1433556,
	title = {Inflammation and endothelial activation in early adulthood are associated with future emphysema: the CARDIA Lung Study},
	journal = {Eur Respir J},
	volume = {53},
	number = {1},
	year = {2019},
	month = {2019 Jan},
	issn = {1399-3003},
	doi = {10.1183/13993003.01532-2018},
	author = {Wells, J Michael and Colangelo, Laura A and Sivarajan, Lakshmi and Thyagarajan, Bharat and Dransfield, Mark T and Iribarren, Carlos and Reyfman, Paul A and Jacobs, David R and Washko, George R and Kalhan, Ravi}
}
@article {1433557,
	title = {Life-Course Smoking Trajectories and Risk for Emphysema in Middle Age: The CARDIA Lung Study},
	journal = {Am J Respir Crit Care Med},
	volume = {199},
	number = {2},
	year = {2019},
	month = {2019 Jan 15},
	pages = {237-240},
	issn = {1535-4970},
	doi = {10.1164/rccm.201808-1568LE},
	author = {Mathew, Amanda R and Bhatt, Surya P and Colangelo, Laura A and Allen, Norrina B and Jacobs, David R and Auer, Reto and Dransfield, Mark T and Hitsman, Brian and Washko, George R and Kalhan, Ravi}
}
@article {1433548,
	title = {Quantification of the Pulmonary Vascular Response to Inhaled Nitric Oxide Using Noncontrast Computed Tomography Imaging},
	journal = {Circ Cardiovasc Imaging},
	volume = {12},
	number = {1},
	year = {2019},
	month = {2019 Dec},
	pages = {e008338},
	keywords = {Administration, Inhalation, Computed Tomography Angiography, Deep Learning, Healthy Volunteers, Humans, Nitric Oxide, Phlebography, Predictive Value of Tests, Pulmonary Artery, Pulmonary Veins, Radiographic Image Interpretation, Computer-Assisted, Reproducibility of Results, Vasodilation, Vasodilator Agents},
	issn = {1942-0080},
	doi = {10.1161/CIRCIMAGING.118.008338},
	author = {Rahaghi, Farbod Nicholas and Winkler, Tilo and Kohli, Puja and Nardelli, Pietro and Mart{\'\i}-Fuster, Berta and Ross, James C and Radhakrishnan, Ramya and Blackwater, Tyler and Ash, Samuel Y and De La Bruere, Isaac and Diaz, Alejandro A and Channick, Richard N and Harris, R Scott and Washko, George R and San Jos{\'e} Est{\'e}par, Ra{\'u}l}
}
@article {1433550,
	title = {Validation of Imaging Measures in Chronic Obstructive Pulmonary Disease},
	journal = {Am J Respir Crit Care Med},
	volume = {200},
	number = {5},
	year = {2019},
	month = {2019 Sep 01},
	pages = {524-525},
	keywords = {Biomarkers, Humans, Pulmonary Disease, Chronic Obstructive, Respiratory System},
	issn = {1535-4970},
	doi = {10.1164/rccm.201902-0395ED},
	author = {Aaron, Carrie Pistenmaa and Washko, George R}
}