@article {1677611,
	title = {DERIVATION OF A TEST STATISTIC FOR EMPHYSEMA QUANTIFICATION},
	journal = {Proc IEEE Int Symp Biomed Imaging},
	volume = {2016},
	year = {2016},
	month = {2016 Apr},
	pages = {1269-1273},
	abstract = {Density masking is the de-facto quantitative imaging phenotype for emphysema that is widely used by the clinical community. Density masking defines the burden of emphysema by a fixed threshold, usually between -910 HU and -950 HU, that has been experimentally validated with histology. In this work, we formalized emphysema quantification by means of statistical inference. We show that a non-central Gamma is a good approximation for the local distribution of image intensities for normal and emphysema tissue. We then propose a test statistic in terms of the sample mean of a truncated non-central Gamma random variable. Our results show that this approach is well-suited for the detection of emphysema and superior to standard density masking. The statistical method was tested in a dataset of 1337 samples obtained from 9 different scanner models in subjects with COPD. Results showed an increase of 17\% when compared to the density masking approach, and an overall accuracy of 94.09\%.},
	issn = {1945-7928},
	doi = {10.1109/ISBI.2016.7493498},
	author = {Vegas-Sanchez-Ferrero, Gonzalo and Washko, George and Rahaghi, Farbod N and Ledesma-Carbayo, Maria J and R San Jos{\'e} Est{\'e}par}
}
@article {1677616,
	title = {Pulmonary vascular morphology as an imaging biomarker in chronic thromboembolic pulmonary hypertension},
	journal = {Pulm Circ},
	volume = {6},
	number = {1},
	year = {2016},
	month = {2016 Mar},
	pages = {70-81},
	abstract = {Patients with chronic thromboembolic pulmonary hypertension (CTEPH) have morphologic changes to the pulmonary vasculature. These include pruning of the distal vessels, dilation of the proximal vessels, and increased vascular tortuosity. Advances in image processing and computer vision enable objective detection and quantification of these processes in clinically acquired computed tomographic (CT) scans. Three-dimensional reconstructions of the pulmonary vasculature were created from the CT angiograms of 18 patients with CTEPH diagnosed using imaging and hemodynamics as well as 15 control patients referred to our Dyspnea Clinic and found to have no evidence of pulmonary vascular disease. Compared to controls, CTEPH patients exhibited greater pruning of the distal vasculature (median density of small-vessel volume: 2.7 [interquartile range (IQR): 2.5-3.0] vs. 3.2 [3.0-3.8]; P = 0.008), greater dilation of proximal arteries (median fraction of blood in large arteries: 0.35 [IQR: 0.30-0.41] vs. 0.23 [0.21-0.31]; P = 0.0005), and increased tortuosity in the pulmonary arterial tree (median: 4.92\% [IQR: 4.85\%-5.21\%] vs. 4.63\% [4.39\%-4.92\%]; P = 0.004). CTEPH was not associated with dilation of proximal veins or increased tortuosity in the venous system. Distal pruning of the vasculature was correlated with the cardiac index (R = 0.51, P = 0.04). Quantitative models derived from CT scans can be used to measure changes in vascular morphology previously described subjectively in CTEPH. These measurements are also correlated with invasive metrics of pulmonary hemodynamics, suggesting that they may be used to assess disease severity. Further work in a larger cohort may enable the use of such measures as a biomarker for diagnostic, phenotyping, and prognostic purposes.},
	issn = {2045-8932},
	doi = {10.1086/685081},
	author = {Rahaghi, F N and Ross, J C and Agarwal, M and Gonz{\'a}lez, G and Come, C E and Diaz, A A and Vegas-S{\'a}nchez-Ferrero, G and Hunsaker, A and San Jos{\'e} Est{\'e}par, R and Waxman, A B and Washko, G R}
}
@article {1433653,
	title = {Association Between Expiratory Central Airway Collapse and Respiratory Outcomes Among Smokers},
	journal = {JAMA},
	volume = {315},
	number = {5},
	year = {2016},
	month = {2016 Feb 02},
	pages = {498-505},
	abstract = {IMPORTANCE: Central airway collapse greater than 50\% of luminal area during exhalation (expiratory central airway collapse [ECAC]) is associated with cigarette smoking and chronic obstructive pulmonary disease (COPD). However, its prevalence and clinical significance are unknown.

OBJECTIVE: To determine whether ECAC is associated with respiratory morbidity in smokers independent of underlying lung disease.

DESIGN, SETTING, AND PARTICIPANTS: Analysis of paired inspiratory-expiratory computed tomography images from a large multicenter study (COPDGene) of current and former smokers from 21 clinical centers across the United States. Participants were enrolled from January 2008 to June 2011 and followed up longitudinally until October 2014. Images were initially screened using a quantitative method to detect at least a 30\% reduction in minor axis tracheal diameter from inspiration to end-expiration. From this sample of screen-positive scans, cross-sectional area of the trachea was measured manually at 3 predetermined levels (aortic arch, carina, and bronchus intermedius) to confirm ECAC (>50\% reduction in cross-sectional area).

EXPOSURES: Expiratory central airway collapse.

MAIN OUTCOMES AND MEASURES: The primary outcome was baseline respiratory quality of life (St George{\textquoteright}s Respiratory Questionnaire [SGRQ] scale 0 to 100; 100 represents worst health status; minimum clinically important difference [MCID], 4 units). Secondary outcomes were baseline measures of dyspnea (modified Medical Research Council [mMRC] scale 0 to 4; 4 represents worse dyspnea; MCID, 0.7 units), baseline 6-minute walk distance (MCID, 30 m), and exacerbation frequency (events per 100 person-years) on longitudinal follow-up.

RESULTS: The study included 8820 participants with and without COPD (mean age, 59.7 [SD, 6.9] years; 4667 [56.7\%] men; 4559 [51.7\%] active smokers). The prevalence of ECAC was 5\% (443 cases). Patients with ECAC compared with those without ECAC had worse SGRQ scores (30.9 vs 26.5 units; P ,
	keywords = {Aged, Aged, 80 and over, Disease Progression, Dyspnea, Exercise Tolerance, Exhalation, Female, Forced Expiratory Volume, Humans, Inhalation, Longitudinal Studies, Male, Middle Aged, Pulmonary Atelectasis, Pulmonary Emphysema, Quality of Life, Respiration, Smoking, Tomography, X-Ray Computed, Tracheal Diseases},
	issn = {1538-3598},
	doi = {10.1001/jama.2015.19431},
	author = {Bhatt, Surya P and Terry, Nina L J and Nath, Hrudaya and Zach, Jordan A. and Tschirren, Juerg and Bolding, Mark S and Stinson, Douglas S and Wilson, Carla G and Curran-Everett, Douglas and Lynch, David A and Putcha, Nirupama and Soler, Xavi and Wise, Robert A and Washko, George R and Hoffman, Eric A and Foreman, Marilyn G and Dransfield, Mark T}
}
@article {1433652,
	title = {Association Between Interstitial Lung Abnormalities and All-Cause Mortality},
	journal = {JAMA},
	volume = {315},
	number = {7},
	year = {2016},
	month = {2016 Feb 16},
	pages = {672-81},
	abstract = {IMPORTANCE: Interstitial lung abnormalities have been associated with lower 6-minute walk distance, diffusion capacity for carbon monoxide, and total lung capacity. However, to our knowledge, an association with mortality has not been previously investigated.

OBJECTIVE: To investigate whether interstitial lung abnormalities are associated with increased mortality.

DESIGN, SETTING, AND POPULATION: Prospective cohort studies of 2633 participants from the FHS (Framingham Heart Study; computed tomographic [CT] scans obtained September 2008-March 2011), 5320 from the AGES-Reykjavik Study (Age Gene/Environment Susceptibility; recruited January 2002-February 2006), 2068 from the COPDGene Study (Chronic Obstructive Pulmonary Disease; recruited November 2007-April 2010), and 1670 from ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints; between December 2005-December 2006).

EXPOSURES: Interstitial lung abnormality status as determined by chest CT evaluation.

MAIN OUTCOMES AND MEASURES: All-cause mortality over an approximate 3- to 9-year median follow-up time. Cause-of-death information was also examined in the AGES-Reykjavik cohort.

RESULTS: Interstitial lung abnormalities were present in 177 (7\%) of the 2633 participants from FHS, 378 (7\%) of 5320 from AGES-Reykjavik, 156 (8\%) of 2068 from COPDGene, and in 157 (9\%) of 1670 from ECLIPSE. Over median follow-up times of approximately 3 to 9 years, there were more deaths (and a greater absolute rate of mortality) among participants with interstitial lung abnormalities when compared with those who did not have interstitial lung abnormalities in the following cohorts: 7\% vs 1\% in FHS (6\% difference [95\% CI, 2\% to 10\%]), 56\% vs 33\% in AGES-Reykjavik (23\% difference [95\% CI, 18\% to 28\%]), and 11\% vs 5\% in ECLIPSE (6\% difference [95\% CI, 1\% to 11\%]). After adjustment for covariates, interstitial lung abnormalities were associated with a higher risk of death in the FHS (hazard ratio [HR], 2.7 [95\% CI, 1.1 to 6.5]; P = .03), AGES-Reykjavik (HR, 1.3 [95\% CI, 1.2 to 1.4]; P ,
	keywords = {Cause of Death, Cohort Studies, Coronary Artery Disease, Female, Humans, Male, Neoplasms, Prevalence, Proportional Hazards Models, Prospective Studies, Pulmonary Disease, Chronic Obstructive, Pulmonary Emphysema, Radiography, Smoking},
	issn = {1538-3598},
	doi = {10.1001/jama.2016.0518},
	author = {Putman, Rachel K and Hatabu, Hiroto and Araki, Tetsuro and Gudmundsson, Gunnar and Gao, Wei and Nishino, Mizuki and Okajima, Yuka and Dupuis, Jos{\'e}e and Latourelle, Jeanne C and Cho, Michael H and El-Chemaly, Souheil and Coxson, Harvey O and Celli, Bartolome R and Fernandez, Isis E and Zazueta, Oscar E and Ross, James C and Harmouche, Rola and San Jos{\'e} Est{\'e}par, Ra{\'u}l and Diaz, Alejandro A and Sigurdsson, Sigurdur and Gudmundsson, El{\'\i}as F and Eir{\'\i}ksdott{\'\i}r, Gudny and Aspelund, Thor and Budoff, Matthew J and Kinney, Gregory L and Hokanson, John E and Williams, Michelle C and Murchison, John T and MacNee, William and Hoffmann, Udo and O{\textquoteright}Donnell, Christopher J and Launer, Lenore J and Harrris, Tamara B and Gudnason, Vilmundur and Silverman, Edwin K and O{\textquoteright}Connor, George T and Washko, George R and Rosas, Ivan O and Hunninghake, Gary M}
}
@article {1433649,
	title = {AUTOMATED AGATSTON SCORE COMPUTATION IN A LARGE DATASET OF NON ECG-GATED CHEST COMPUTED TOMOGRAPHY},
	journal = {Proc IEEE Int Symp Biomed Imaging},
	volume = {2016},
	year = {2016},
	month = {2016 Apr},
	pages = {53-57},
	abstract = {The Agatston score, computed from ECG-gated computed tomography (CT), is a well established metric of coronary artery disease. It has been recently shown that the Agatston score computed from chest CT (non ECG-gated) studies is highly correlated with the Agatston score computed from cardiac CT scans. In this work we present an automated method to compute the Agatston score from chest CT images. Coronary arteries calcifications (CACs) are defined as voxels contained within the coronary arteries with a value greater or equal to 130 Hounsfield Units (HU). CACs are automatically detected in chest CT studies by locating the heart, generating a region of interest around it, thresholding the image in such region and applying a set of rules to discriminate CACs from calcifications in the main vessels or from metallic implants. We evaluate the methodology in a large cohort of 1500 patients for whom manual reference standard is available. Our results show that the Pearson correlation coefficient between manual and automated Agatston score is ρ = 0.86 ( < 0.0001).},
	issn = {1945-7928},
	doi = {10.1109/ISBI.2016.7493209},
	author = {Gonz{\'a}lez, Germ{\'a}n and Washko, George R and San Jos{\'e} Est{\'e}par, Ra{\'u}l}
}
@article {1433654,
	title = {Automatic Synthesis of Anthropomorphic Pulmonary CT Phantoms},
	journal = {PLoS One},
	volume = {11},
	number = {1},
	year = {2016},
	month = {2016},
	pages = {e0146060},
	abstract = {The great density and structural complexity of pulmonary vessels and airways impose limitations on the generation of accurate reference standards, which are critical in training and in the validation of image processing methods for features such as pulmonary vessel segmentation or artery-vein (AV) separations. The design of synthetic computed tomography (CT) images of the lung could overcome these difficulties by providing a database of pseudorealistic cases in a constrained and controlled scenario where each part of the image is differentiated unequivocally. This work demonstrates a complete framework to generate computational anthropomorphic CT phantoms of the human lung automatically. Starting from biological and image-based knowledge about the topology and relationships between structures, the system is able to generate synthetic pulmonary arteries, veins, and airways using iterative growth methods that can be merged into a final simulated lung with realistic features. A dataset of 24 labeled anthropomorphic pulmonary CT phantoms were synthesized with the proposed system. Visual examination and quantitative measurements of intensity distributions, dispersion of structures and relationships between pulmonary air and blood flow systems show good correspondence between real and synthetic lungs (p > 0.05 with low Cohen{\textquoteright}s d effect size and AUC values), supporting the potentiality of the tool and the usefulness of the generated phantoms in the biomedical image processing field. },
	keywords = {Humans, Lung, Phantoms, Imaging, Pulmonary Artery, Pulmonary Veins, Tomography, X-Ray Computed},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0146060},
	author = {Jimenez-Carretero, Daniel and Estepar, Raul San Jose and Diaz Cacio, Mario and Ledesma-Carbayo, Maria J}
}
@article {1433655,
	title = {Computed Tomographic Airway Morphology in Chronic Obstructive Pulmonary Disease. Remodeling or Innate Anatomy?},
	journal = {Ann Am Thorac Soc},
	volume = {13},
	number = {1},
	year = {2016},
	month = {2016 Jan},
	pages = {4-9},
	abstract = {Computed tomographic measures of central airway morphology have been used in clinical, epidemiologic, and genetic investigation as an inference of the presence and severity of small-airway disease in smokers. Although several association studies have brought us to believe that these computed tomographic measures reflect airway remodeling, a careful review of such data and more recent evidence may reveal underappreciated complexity to these measures and limitations that prompt us to question that belief. This Perspective offers a review of seminal papers and alternative explanations of their data in the light of more recent evidence. The relationships between airway morphology and lung function are observed in subjects who never smoked, implying that native airway structure indeed contributes to lung function; computed tomographic measures of central airways such as wall area, lumen area, and total bronchial area are smaller in smokers with chronic obstructive pulmonary disease versus those without chronic obstructive pulmonary disease; and the airways are smaller as disease severity increases. The observations suggest that (1) native airway morphology likely contributes to the relationships between computed tomographic measures of airways and lung function; and (2) the presence of smaller airways in those with chronic obstructive pulmonary disease versus those without chronic obstructive pulmonary disease as well as their decrease with disease severity suggests that smokers with chronic obstructive pulmonary disease may simply have smaller airways to begin with, which put them at greater risk for the development of smoking-related disease.},
	keywords = {Airway Remodeling, Forced Expiratory Volume, Humans, Lung, Pulmonary Disease, Chronic Obstructive, Severity of Illness Index, Spirometry, Tomography, X-Ray Computed},
	issn = {2325-6621},
	doi = {10.1513/AnnalsATS.201506-371PP},
	author = {Diaz, Alejandro A and San Jos{\'e} Est{\'e}par, Raul and Washko, George R}
}
@article {1433650,
	title = {Imaging Biomarkers in Lymphangioleiomyomatosis Clinical Trials. A Wolf in Sheep{\textquoteright}s Clothing?},
	journal = {Ann Am Thorac Soc},
	volume = {13},
	number = {3},
	year = {2016},
	month = {2016 Mar},
	pages = {307-8},
	keywords = {Animals, Biomarkers, Clothing, Diagnostic Imaging, Humans, Lymphangioleiomyomatosis, Sheep, Wolves},
	issn = {2325-6621},
	doi = {10.1513/AnnalsATS.201512-818ED},
	author = {Washko, George R and Parraga, Grace}
}
@article {1433648,
	title = {Multi-atlas and label fusion approach for patient-specific MRI based skull estimation},
	journal = {Magn Reson Med},
	volume = {75},
	number = {4},
	year = {2016},
	month = {2016 Apr},
	pages = {1797-807},
	abstract = {PURPOSE: MRI-based skull segmentation is a useful procedure for many imaging applications. This study describes a methodology for automatic segmentation of the complete skull from a single T1-weighted volume.

METHODS: The skull is estimated using a multi-atlas segmentation approach. Using a whole head computed tomography (CT) scan database, the skull in a new MRI volume is detected by nonrigid image registration of the volume to every CT, and combination of the individual segmentations by label-fusion. We have compared Majority Voting, Simultaneous Truth and Performance Level Estimation (STAPLE), Shape Based Averaging (SBA), and the Selective and Iterative Method for Performance Level Estimation (SIMPLE) algorithms.

RESULTS: The pipeline has been evaluated quantitatively using images from the Retrospective Image Registration Evaluation database (reaching an overlap of 72.46 {\textpm} 6.99\%), a clinical CT-MR dataset (maximum overlap of 78.31 {\textpm} 6.97\%), and a whole head CT-MRI pair (maximum overlap 78.68\%). A qualitative evaluation has also been performed on MRI acquisition of volunteers.

CONCLUSION: It is possible to automatically segment the complete skull from MRI data using a multi-atlas and label fusion approach. This will allow the creation of complete MRI-based tissue models that can be used in electromagnetic dosimetry applications and attenuation correction in PET/MR.},
	keywords = {Adult, Algorithms, Brain, Brain Diseases, Brain Mapping, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Middle Aged, Retrospective Studies, Skull, User-Computer Interface, Young Adult},
	issn = {1522-2594},
	doi = {10.1002/mrm.25737},
	author = {Torrado-Carvajal, Angel and Herraiz, Joaquin L and Hernandez-Tamames, Juan A and San Jose-Estepar, Raul and Eryaman, Yigitcan and Rozenholc, Yves and Adalsteinsson, Elfar and Wald, Lawrence L and Malpica, Norberto}
}
@article {1433657,
	title = {Normal thymus in adults: appearance on CT and associations with age, sex, BMI and smoking},
	journal = {Eur Radiol},
	volume = {26},
	number = {1},
	year = {2016},
	month = {2016 Jan},
	pages = {15-24},
	abstract = {OBJECTIVE: To investigate CT appearance and size of the thymus in association with participant characteristics.

MATERIALS AND METHODS: 2540 supposedly healthy participants (mean age 58.9 years, 51 \% female) were evaluated for the CT appearance of thymic glands with four-point scores (according to the ratio of fat and soft tissue), size and morphology. These were correlated with participants{\textquoteright} age, sex, BMI and smoking history.

RESULTS: Of 2540 participants, 1869 (74 \%) showed complete fatty replacement of the thymus (Score 0), 463 (18 \%) predominantly fatty attenuation (Score 1), 172 (7 \%) half fatty and half soft-tissue attenuation (Score 2) and 36 (1 \%) solid thymic gland with predominantly soft-tissue attenuation (Score 3). Female participants showed less fatty degeneration of the thymus with higher thymic scores within age 40-69 years (P < 0.001). Participants with lower thymic scores showed higher BMI (P < 0.001) and were more likely to be former smokers (P < 0.001) with higher pack-years (P = 0.04).

CONCLUSIONS: Visual assessment with four-point thymic scores revealed a sex difference in the fatty degeneration of the thymus with age. Women show significantly higher thymic scores, suggesting less fat content of the thymus, during age 40-69 years. Cigarette smoking and high BMI are associated with advanced fatty replacement of the thymus.

KEY POINTS: 74\% of participants (mean age 58.9 years) demonstrated complete fatty thymus. Women show less fatty thymus compared to men at ages 40-69 years. Smoking and high BMI are associated with advanced fatty degeneration in thymus.},
	keywords = {Adult, Age Factors, Aged, Body Mass Index, Cross-Sectional Studies, Female, Humans, Male, Middle Aged, Sex Characteristics, Smoking, Thymus Gland, Tomography, X-Ray Computed},
	issn = {1432-1084},
	doi = {10.1007/s00330-015-3796-y},
	author = {Araki, Tetsuro and Nishino, Mizuki and Gao, Wei and Dupuis, Jos{\'e}e and Hunninghake, Gary M and Murakami, Takamichi and Washko, George R and O{\textquoteright}Connor, George T and Hatabu, Hiroto}
}
@article {1433656,
	title = {Pulmonary Predictors of Incident Diabetes in Smokers},
	journal = {Chronic Obstr Pulm Dis},
	volume = {3},
	number = {4},
	year = {2016},
	month = {2016},
	pages = {739-747},
	abstract = {BACKGROUND: Diabetes mellitus and its complications are a large and increasing burden for health care worldwide. Reduced pulmonary function has been observed in diabetes (both type 1 and type 2), and this reduction is thought to occur prior to diagnosis. Other measures of pulmonary health are associated with diabetes, including lower exercise tolerance, greater dyspnea, lower quality of life (as measured by the St. George{\textquoteright}s Respiratory Questionaire [SGRQ]) and susceptibility to lung infection and these measures may also predate diabetes diagnosis.

METHODS: We examined 7080 participants in the COPD Genetic Epidemiology (COPDGene) study who did not report diabetes at their baseline visit and who provided health status updates during 4.2 years of longitudinal follow-up (LFU). We used Cox proportional hazards modeling, censoring participants at final LFU contact, reported mortality or report of incident diabetes to model predictors of diabetes. These models were constructed using known risk factors as well as proposed markers related to pulmonary health, forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV/FVC, respiratory exacerbations (RE), 6-minute walk distance (6MWD), pulmonary associated quality of life (as measured by the SGRQ), corticosteroid use, chronic bronchitis and dyspnea.

RESULTS: Over 21,519 person years of follow-up, 392 of 7080 participants reported incident diabetes which was associated with expected predictors; increased body mass index (BMI), high blood pressure, high cholesterol and current smoking status. Age, gender and accumulated smoking exposure were not associated with incident diabetes. Additionally, preserved ratio with impaired spirometry (PRISm) pattern pulmonary function, reduced 6MWD and any report of serious pulmonary events were associated with incident diabetes.

CONCLUSIONS: This cluster of pulmonary indicators may aid clinicians in identifying and treating patients with pre- or undiagnosed diabetes.},
	issn = {2372-952X},
	doi = {10.15326/jcopdf.3.4.2016.0137},
	author = {Kinney, Gregory L and Baker, Emma H and Klein, Oana L and Black-Shinn, Jennifer L and Wan, Emily S and Make, Barry and Regan, Elizabeth and Bowler, Russell P and Lutz, Sharon M and Young, Kendra A and Duca, Lindsey M and Washko, George R and Silverman, Edwin K and Crapo, James D and Hokanson, John E}
}
@article {1433651,
	title = {Robust Spatio-Temporal Registration of 4D Cardiac Ultrasound Sequences},
	journal = {Proc SPIE Int Soc Opt Eng},
	volume = {9790},
	year = {2016},
	month = {2016 Feb 27},
	abstract = {Registration of multiple 3D ultrasound sectors in order to provide an extended field of view is important for the appreciation of larger anatomical structures at high spatial and temporal resolution. In this paper, we present a method for fully automatic spatio-temporal registration between two partially overlapping 3D ultrasound sequences. The temporal alignment is solved by aligning the normalized cross correlation-over-time curves of the sequences. For the spatial alignment, corresponding 3D Scale Invariant Feature Transform (SIFT) features are extracted from all frames of both sequences independently of the temporal alignment. A rigid transform is then calculated by least squares minimization in combination with random sample consensus. The method is applied to 16 echocardiographic sequences of the left and right ventricles and evaluated against manually annotated temporal events and spatial anatomical landmarks. The mean distances between manually identified landmarks in the left and right ventricles after automatic registration were (mean {\textpm} SD) 4.3 {\textpm} 1.2 mm compared to a reference error of 2.8 {\textpm} 0.6 mm with manual registration. For the temporal alignment, the absolute errors in valvular event times were 14.4 {\textpm} 11.6 ms for Aortic Valve (AV) opening, 18.6 {\textpm} 16.0 ms for AV closing, and 34.6 {\textpm} 26.4 ms for mitral valve opening, compared to a mean inter-frame time of 29 ms.},
	issn = {0277-786X},
	doi = {10.1117/12.2217005},
	author = {Bersvendsen, J{\o}rn and Toews, Matthew and Danudibroto, Adriyana and Wells, William M and Urheim, Stig and San Jos{\'e} Est{\'e}par, Ra{\'u}l and Samset, Eigil}
}
@article {1433658,
	title = {β-Blockers are associated with a reduction in COPD exacerbations},
	journal = {Thorax},
	volume = {71},
	number = {1},
	year = {2016},
	month = {2016 Jan},
	pages = {8-14},
	abstract = {BACKGROUND: While some retrospective studies have suggested that β-blocker use in patients with COPD is associated with a reduction in the frequency of acute exacerbations and lower mortality, there is concern that their use in patients with severe COPD on home oxygen may be harmful.

METHODS: Subjects with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 2-4 COPD participating in a prospective follow-up of the COPDGene cohort, a multicentre observational cohort of current and former smokers were recruited. Total and severe exacerbation rates were compared between groups categorised by β-blocker use on longitudinal follow-up using negative binomial regression analyses, after adjustment for demographics, airflow obstruction, \%emphysema on CT, respiratory medications, presence of coronary artery disease, congestive heart failure and coronary artery calcification, and after adjustment for propensity to prescribe β-blockers.

RESULTS: 3464 subjects were included. During a median of 2.1 years of follow-up, β-blocker use was associated with a significantly lower rate of total (incidence risk ratio (IRR) 0.73, 95\% CI 0.60 to 0.90; p=0.003) and severe exacerbations (IRR 0.67, 95\% CI 0.48 to 0.93; p=0.016). In those with GOLD stage 3 and 4 and on home oxygen, use of β-blockers was again associated with a reduction in the rate of total (IRR 0.33, 95\% CI 0.19 to 0.58; p,
	keywords = {Adrenergic beta-Antagonists, Aged, Disease Progression, Female, Follow-Up Studies, Humans, Incidence, Male, Middle Aged, Propensity Score, Prospective Studies, Pulmonary Disease, Chronic Obstructive, Radiography, Risk Factors, Severity of Illness Index},
	issn = {1468-3296},
	doi = {10.1136/thoraxjnl-2015-207251},
	author = {Bhatt, Surya P and Wells, James M and Kinney, Gregory L and Washko, George R and Budoff, Matthew and Kim, Young-Il and Bailey, William C and Nath, Hrudaya and Hokanson, John E and Silverman, Edwin K and Crapo, James and Dransfield, Mark T}
}
@article {1433647,
	title = {Age-Related Differences in Health-Related Quality of Life in COPD: An Analysis of the COPDGene and SPIROMICS Cohorts},
	journal = {Chest},
	volume = {149},
	number = {4},
	year = {2016},
	month = {2016 Apr},
	pages = {927-35},
	abstract = {OBJECTIVE: Younger persons with COPD report worse health-related quality of life (HRQL) than do older individuals. The factors explaining these differences remain unclear. The objective of this article was to explore factors associated with age-related differences in HRQL in COPD.

METHODS: Cross-sectional analysis of participants with COPD, any Global Initiative for Chronic Obstructive Lung Disease grade of airflow limitation, and >= 50 years old in two cohorts: the Genetic Epidemiology of COPD (COPDGene) study and the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS). We compared St. George{\textquoteright}s Respiratory Questionnaire (SGRQ) scores by age group: middle-aged (age, 50-64) vs older (age, 65-80) adults. We used multivariate linear modeling to test associations of age with HRQL, adjusting for demographic and clinical characteristics and comorbidities.

RESULTS: Among 4,097 participants in the COPDGene study (2,170 middle-aged and 1,927 older adults) SGRQ total scores were higher (worse) among middle-aged (mean difference, -4.2 points; 95\% CI, -5.7 to -2.6; P < .001) than older adults. Age had a statistically significant interaction with dyspnea (P < .001). Greater dyspnea severity (modified Medical Research Council >= 2, compared with 0-1) had a stronger association with SGRQ score among middle-aged (β, 24.6; 95\% CI, 23.2-25.9) than older-adult (β, 21.0; 95\% CI, 19.6-22.3) participants. In analyses using SGRQ as outcome in 1,522 participants in SPIROMICS (598 middle-aged and 924 older adults), we found similar associations, confirming that for the same severity of dyspnea there is a stronger association with HRQL among younger individuals.

CONCLUSIONS: Age-related differences in HRQL may be explained by a higher impact of dyspnea among younger subjects with COPD.

TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00608764 and No.: NCT01969344; URL: www.clinicaltrials.gov.},
	keywords = {Age Factors, Aged, Cohort Studies, Cross-Sectional Studies, Dyspnea, Female, Health Status, Humans, Male, Middle Aged, Pulmonary Disease, Chronic Obstructive, Quality of Life},
	issn = {1931-3543},
	doi = {10.1016/j.chest.2015.11.025},
	author = {Martinez, Carlos H and Diaz, Alejandro A and Parulekar, Amit D and Rennard, Stephen I and Kanner, Richard E and Hansel, Nadia N and Couper, David and Holm, Kristen E and Hoth, Karin F and Curtis, Jeffrey L and Martinez, Fernando J and Hanania, Nicola A and Regan, Elizabeth A and Paine, Robert and Cigolle, Christine T and Han, MeiLan K}
}
@article {1433635,
	title = {Arterial and Venous Pulmonary Vascular Morphology and Their Relationship to Findings in Cardiac Magnetic Resonance Imaging in Smokers},
	journal = {J Comput Assist Tomogr},
	volume = {40},
	number = {6},
	year = {2016},
	month = {2016 Nov/Dec},
	pages = {948-952},
	abstract = {OBJECTIVE: Prior work has described the relationship between pulmonary vascular pruning on computed tomography (CT) scans and metrics of right-sided heart dysfunction in smokers. In this analysis, we sought to look at pruning on a lobar level, as well as examine the effect of the arterial and venous circulation on this association.

METHODS: Automated vessel segmentation applied to noncontrast CT scans from the COPDGene Study in 24 subjects with cardiac magnetic resonance imaging scans was used to create a blood volume distribution profile. These vessels were then manually tracked to their origin and characterized as artery or vein.

RESULTS: Assessment of pruning on a lobar level revealed associations between pruning and right ventricular function previously not observed on a global level. The right ventricular mass index, the right ventricular end-systolic volume index, and pulmonary arterial-to-aorta ratio were associated with both arterial and venous pruning, whereas right ventricular ejection fraction was associated with only arterial pruning.

CONCLUSIONS: Lobar assessment and segmentation of the parenchymal vasculature into arterial and venous components provide additional information about the relationship between loss of vasculature on CT scans and right ventricular dysfunction.},
	keywords = {Boston, Female, Humans, Magnetic Resonance Imaging, Cine, Male, Middle Aged, Multimodal Imaging, Prevalence, Pulmonary Artery, Pulmonary Veins, Reproducibility of Results, Risk Factors, Sensitivity and Specificity, Smoking, Ventricular Dysfunction, Right},
	issn = {1532-3145},
	doi = {10.1097/RCT.0000000000000465},
	author = {Rahaghi, Farbod N and Wells, J Michael and Come, Carolyn E and De La Bruere, Isaac A and Bhatt, Surya P and Ross, James C and Vegas-S{\'a}nchez-Ferrero, Gonzalo and Diaz, Alejandro A and Minhas, Jasleen and Dransfield, Mark T and San Jos{\'e} Est{\'e}par, Ra{\'u}l and Washko, George R}
}
@article {1433642,
	title = {Association between Functional Small Airway Disease and FEV1 Decline in Chronic Obstructive Pulmonary Disease},
	journal = {Am J Respir Crit Care Med},
	volume = {194},
	number = {2},
	year = {2016},
	month = {2016 07 15},
	pages = {178-84},
	abstract = {RATIONALE: The small conducting airways are the major site of airflow obstruction in chronic obstructive pulmonary disease and may precede emphysema development.

OBJECTIVES: We hypothesized a novel computed tomography (CT) biomarker of small airway disease predicts FEV1 decline.

METHODS: We analyzed 1,508 current and former smokers from COPDGene with linear regression to assess predictors of change in FEV1 (ml/yr) over 5 years. Separate models for subjects without and with airflow obstruction were generated using baseline clinical and physiologic predictors in addition to two novel CT metrics created by parametric response mapping (PRM), a technique pairing inspiratory and expiratory CT images to define emphysema (PRM(emph)) and functional small airways disease (PRM(fSAD)), a measure of nonemphysematous air trapping.

MEASUREMENTS AND MAIN RESULTS: Mean (SD) rate of FEV1 decline in ml/yr for GOLD (Global Initiative for Chronic Obstructive Lung Disease) 0-4 was as follows: 41.8 (47.7), 53.8 (57.1), 45.6 (61.1), 31.6 (43.6), and 5.1 (35.8), respectively (trend test for grades 1-4; P ,
	keywords = {Female, Forced Expiratory Volume, Humans, Lung, Male, Middle Aged, Pulmonary Disease, Chronic Obstructive, Respiratory System, Spirometry, Tomography, X-Ray Computed},
	issn = {1535-4970},
	doi = {10.1164/rccm.201511-2219OC},
	author = {Bhatt, Surya P and Soler, Xavier and Wang, Xin and Murray, Susan and Anzueto, Antonio R and Beaty, Terri H and Boriek, Aladin M and Casaburi, Richard and Criner, Gerard J and Diaz, Alejandro A and Dransfield, Mark T and Curran-Everett, Douglas and Galb{\'a}n, Craig J and Hoffman, Eric A and Hogg, James C and Kazerooni, Ella A and Kim, Victor and Kinney, Gregory L and Lagstein, Amir and Lynch, David A and Make, Barry J and Martinez, Fernando J and Ramsdell, Joe W and Reddy, Rishindra and Ross, Brian D and Rossiter, Harry B and Steiner, Robert M and Strand, Matthew J and van Beek, Edwin J R and Wan, Emily S and Washko, George R and Wells, J Michael and Wendt, Chris H and Wise, Robert A and Silverman, Edwin K and Crapo, James D and Bowler, Russell P and Han, MeiLan K}
}
@article {1433633,
	title = {Clinical, physiologic, and radiographic factors contributing to development of hypoxemia in moderate to severe COPD: a cohort study},
	journal = {BMC Pulm Med},
	volume = {16},
	number = {1},
	year = {2016},
	month = {2016 12 01},
	pages = {169},
	abstract = {BACKGROUND: Hypoxemia is a major complication of COPD and is a strong predictor of mortality. We previously identified independent risk factors for the presence of resting hypoxemia in the COPDGene cohort. However, little is known about characteristics that predict onset of resting hypoxemia in patients who are normoxic at baseline. We hypothesized that a combination of clinical, physiologic, and radiographic characteristics would predict development of resting hypoxemia after 5-years of follow-up in participants with moderate to severe COPD METHODS: We analyzed 678 participants with moderate-to-severe COPD recruited into the COPDGene cohort who completed baseline and 5-year follow-up visits and who were normoxic by pulse oximetry at baseline. Development of resting hypoxemia was defined as an oxygen saturation <=88\% on ambient air at rest during follow-up. Demographic and clinical characteristics, lung function, and radiographic indices were analyzed with logistic regression models to identify predictors of the development of hypoxemia.

RESULTS: Forty-six participants (7\%) developed resting hypoxemia at follow-up. Enrollment at Denver (OR 8.30, 95\%CI 3.05-22.6), lower baseline oxygen saturation (OR 0.70, 95\%CI 0.58-0.85), self-reported heart failure (OR 6.92, 95\%CI 1.56-30.6), pulmonary artery (PA) enlargement on computed tomography (OR 2.81, 95\%CI 1.17-6.74), and prior severe COPD exacerbation (OR 3.31, 95\%CI 1.38-7.90) were independently associated with development of resting hypoxemia. Participants who developed hypoxemia had greater decline in 6-min walk distance and greater 5-year decline in quality of life compared to those who remained normoxic at follow-up.

CONCLUSIONS: Development of clinically significant hypoxemia over a 5-year span is associated with comorbid heart failure, PA enlargement and severe COPD exacerbation. Further studies are needed to determine if treatments targeting these factors can prevent new onset hypoxemia.

TRIAL REGISTRATION: COPDGene is registered at ClinicalTrials.gov: NCT00608764 (Registration Date: January 28, 2008).},
	keywords = {Aged, Comorbidity, Cross-Sectional Studies, Disease Progression, Female, Heart Failure, Humans, Hypoxia, Logistic Models, Male, Middle Aged, Multivariate Analysis, Oximetry, Prospective Studies, Pulmonary Disease, Chronic Obstructive, Quality of Life, Rest, Risk Factors, Severity of Illness Index, Tomography, X-Ray Computed, United States, Walk Test},
	issn = {1471-2466},
	doi = {10.1186/s12890-016-0331-0},
	author = {Wells, J Michael and Estepar, Raul San Jose and McDonald, Merry-Lynn N and Bhatt, Surya P and Diaz, Alejandro A and Bailey, William C and Jacobson, Francine L and Dransfield, Mark T and Washko, George R and Make, Barry J and Casaburi, Richard and van Beek, Edwin J R and Hoffman, Eric A and Sciurba, Frank C and Crapo, James D and Silverman, Edwin K and Hersh, Craig P}
}
@article {1433632,
	title = {Development and Progression of Interstitial Lung Abnormalities in the Framingham Heart Study},
	journal = {Am J Respir Crit Care Med},
	volume = {194},
	number = {12},
	year = {2016},
	month = {2016 12 15},
	pages = {1514-1522},
	abstract = {RATIONALE: The relationship between the development and/or progression of interstitial lung abnormalities (ILA) and clinical outcomes has not been previously investigated.

OBJECTIVES: To determine the risk factors for, and the clinical consequences of, having ILA progression in participants from the Framingham Heart Study.

METHODS: ILA were assessed in 1,867 participants who had serial chest computed tomography (CT) scans approximately 6 years apart. Mixed effect regression (and Cox) models were used to assess the association between ILA progression and pulmonary function decline (and mortality).

MEASUREMENTS AND MAIN RESULTS: During the follow-up period 660 (35\%) participants did not have ILA on either CT scan, 37 (2\%) had stable to improving ILA, and 118 (6\%) had ILA with progression (the remaining participants without ILA were noted to be indeterminate on at least one CT scan). Increasing age and increasing copies of the MUC5B promoter polymorphism were associated with ILA progression. After adjustment for covariates, ILA progression was associated with a greater FVC decline when compared with participants without ILA (20 ml; SE, {\textpm}6 ml; P = 0.0005) and with those with ILA without progression (25 ml; SE, {\textpm}11 ml; P = 0.03). Over a median follow-up time of approximately 4 years, after adjustment, ILA progression was associated with an increase in the risk of death (hazard ratio, 3.9; 95\% confidence interval, 1.3-10.9; P = 0.01) when compared with those without ILA.

CONCLUSIONS: These findings demonstrate that ILA progression in the Framingham Heart Study is associated with an increased rate of pulmonary function decline and increased risk of death.},
	keywords = {Age Factors, Aged, Disease Progression, Female, Follow-Up Studies, Humans, Longitudinal Studies, Lung, Male, Middle Aged, Polymorphism, Genetic, Proportional Hazards Models, Respiratory Function Tests, Risk Factors, Tomography, X-Ray Computed},
	issn = {1535-4970},
	doi = {10.1164/rccm.201512-2523OC},
	author = {Araki, Tetsuro and Putman, Rachel K and Hatabu, Hiroto and Gao, Wei and Dupuis, Jos{\'e}e and Latourelle, Jeanne C and Nishino, Mizuki and Zazueta, Oscar E and Kurugol, Sila and Ross, James C and San Jos{\'e} Est{\'e}par, Ra{\'u}l and Schwartz, David A and Rosas, Ivan O and Washko, George R and O{\textquoteright}Connor, George T and Hunninghake, Gary M}
}
@article {1433636,
	title = {Differences in Health-Related Quality of Life Between New Mexican Hispanic and Non-Hispanic White Smokers},
	journal = {Chest},
	volume = {150},
	number = {4},
	year = {2016},
	month = {2016 Oct},
	pages = {869-876},
	abstract = {BACKGROUND: Smoking is associated with impaired health-related quality of life (HRQL) across all populations. Because decline in lung function and risk for COPD are lower in New Mexican Hispanic smokers compared with their non-Hispanic white (NHW) counterparts, the goal of this study was to ascertain whether HRQL differs between these two racial/ethnic groups and determine the factors that contribute to this difference.

METHODS: We compared the score results of the Medical Outcomes Short-Form 36 Health Survey (SF-36) and St. George{\textquoteright}s Respiratory Questionnaire (SGRQ) in 378 Hispanic subjects and 1,597 NHW subjects enrolled in the Lovelace Smokers{\textquoteright} Cohort (LSC) from New Mexico. The associations of race/ethnicity with SGRQ and SF-36 were assessed by using multivariable regression.

RESULTS: Physical functioning (difference, -4.5; P~= .0008) but not mental health or role emotional domains of the SF-36 was worse in Hispanic smokers than in their NWH counterparts in multivariable analysis. SGRQ total score and its activity and impact subscores were worse in Hispanic (vs NHW) smokers after adjustment for education level, current smoking, pack-years smoked, BMI, number of comorbidities, and FEV \%~predicted (difference~range, 2.9-5.0; all comparisons, P~<= .001). Although the difference in the SGRQ activity domain was above the clinically important difference of four units, the total score was~not.

CONCLUSIONS: New Mexican Hispanic smokers have clinically relevant, lower HRQL than their NHW counterparts. A perception of diminished physical functioning and impairment in daily life activities contribute to the poorer HRQL among Hispanic subjects.},
	keywords = {Activities of Daily Living, Adult, Aged, Asthma, Bronchitis, Chronic, European Continental Ancestry Group, Female, Forced Expiratory Volume, Health Status, Health Status Disparities, Hispanic Americans, Humans, Male, Middle Aged, New Mexico, Pulmonary Disease, Chronic Obstructive, Quality of Life, Smoking, Surveys and Questionnaires, Vital Capacity},
	issn = {1931-3543},
	doi = {10.1016/j.chest.2016.06.011},
	author = {Diaz, Alejandro A and Petersen, Hans and Meek, Paula and Sood, Akshay and Celli, Bartolome and Tesfaigzi, Yohannes}
}
@article {1433641,
	title = {Distinct emphysema subtypes defined by quantitative CT analysis are associated with specific pulmonary matrix metalloproteinases},
	journal = {Respir Res},
	volume = {17},
	number = {1},
	year = {2016},
	month = {2016 07 26},
	pages = {92},
	abstract = {BACKGROUND: Emphysema is characterised by distinct pathological sub-types, but little is known about the divergent underlying aetiology. Matrix-metalloproteinases (MMPs) are proteolytic enzymes that can degrade the extracellular matrix and have been identified as potentially important in the development of emphysema. However, the relationship between MMPs and emphysema sub-type is unknown. We investigated the role of MMPs and their inhibitors in the development of emphysema sub-types by quantifying levels and determining relationships with these sub-types in mild-moderate COPD patients and ex/current smokers with preserved lung function.

METHODS: Twenty-four mild-moderate COPD and 8 ex/current smokers with preserved lung function underwent high resolution CT and distinct emphysema sub-types were quantified using novel local histogram-based assessment of lung density. We analysed levels of MMPs and tissue inhibitors of MMPs (TIMPs) in bronchoalveolar lavage (BAL) and assessed their relationship with these emphysema sub-types.

RESULTS: The most prevalent emphysema subtypes in COPD subjects were mild and moderate centrilobular (CLE) emphysema, while only small amounts of severe centrilobular emphysema, paraseptal emphysema (PSE) and panlobular emphysema (PLE) were present. MMP-3, and -10 associated with all emphysema sub-types other than mild CLE, while MMP-7 and -8 had associations with moderate and severe CLE and PSE. MMP-9 also had associations with moderate CLE and paraseptal emphysema. Mild CLE occurred in substantial quantities irrespective of whether airflow obstruction was present and did not show any associations with MMPs.

CONCLUSION: Multiple MMPs are directly associated with emphysema sub-types identified by CT imaging, apart from mild CLE. This suggests that MMPs play a significant role in the tissue destruction seen in the more severe sub-types of emphysema, whereas early emphysematous change may be driven by a different mechanism.

TRIAL REGISTRATION: Trial registration number NCT01701869 .},
	keywords = {Aged, Airway Obstruction, Bronchoalveolar Lavage Fluid, Bronchoscopy, Female, Humans, Lung, Male, Matrix Metalloproteinase Inhibitors, Matrix Metalloproteinases, Middle Aged, Pulmonary Disease, Chronic Obstructive, Pulmonary Emphysema, Respiratory Function Tests, Smoking, Tissue Inhibitor of Metalloproteinase-1, Tomography, X-Ray Computed},
	issn = {1465-993X},
	doi = {10.1186/s12931-016-0402-z},
	author = {Ostridge, Kristoffer and Williams, Nicholas and Kim, Viktoriya and Harden, Stephen and Bourne, Simon and Coombs, Ngaire A and Elkington, Paul T and Estepar, Raul San Jose and Washko, George and Staples, Karl J and Wilkinson, Tom M A}
}
@article {1433643,
	title = {Galectin-3 Is Associated with Restrictive Lung Disease and Interstitial Lung Abnormalities},
	journal = {Am J Respir Crit Care Med},
	volume = {194},
	number = {1},
	year = {2016},
	month = {2016 07 01},
	pages = {77-83},
	abstract = {RATIONALE: Galectin-3 (Gal-3) has been implicated in the development of pulmonary fibrosis in experimental studies, and Gal-3 levels have been found to be elevated in small studies of human pulmonary fibrosis.

OBJECTIVES: We sought to study whether circulating Gal-3 concentrations are elevated early in the course of pulmonary fibrosis.

METHODS: We examined 2,596 Framingham Heart Study participants (mean age, 57 yr; 54\% women; 14\% current smokers) who underwent Gal-3 assessment using plasma samples and pulmonary function testing between 1995 and 1998. Of this sample, 1,148 underwent subsequent volumetric chest computed tomography.

MEASUREMENTS AND MAIN RESULTS: Higher Gal-3 concentrations were associated with lower lung volumes (1.4\% decrease in percentage of predicted FEV1 per 1 SD increase in log Gal-3; 95\% confidence interval [CI], 0.8-2.0\%; P ,
	keywords = {Female, Galectin 3, Humans, Lung, Male, Middle Aged, Odds Ratio, Pulmonary Fibrosis, Respiratory Function Tests, Tomography, X-Ray Computed},
	issn = {1535-4970},
	doi = {10.1164/rccm.201509-1753OC},
	author = {Ho, Jennifer E and Gao, Wei and Levy, Daniel and Santhanakrishnan, Rajalakshmi and Araki, Tetsuro and Rosas, Ivan O and Hatabu, Hiroto and Latourelle, Jeanne C and Nishino, Mizuki and Dupuis, Jos{\'e}e and Washko, George R and O{\textquoteright}Connor, George T and Hunninghake, Gary M}
}
@article {1433639,
	title = {Imaging Phenotype of Occupational Endotoxin-Related Lung Function Decline},
	journal = {Environ Health Perspect},
	volume = {124},
	number = {9},
	year = {2016},
	month = {2016 09},
	pages = {1436-42},
	abstract = {BACKGROUND: Although occupational exposures contribute to a significant proportion of obstructive lung disease, the phenotype of obstructive lung disease associated with work-related organic dust exposure independent of smoking remains poorly defined.

OBJECTIVE: We identified the relative contributions of smoking and occupational endotoxin exposure to parenchymal and airway remodeling as defined by quantitative computed tomography (CT).

METHODS: The Shanghai Textile Worker Study is a longitudinal study of endotoxin-exposed cotton workers and endotoxin-unexposed silk workers that was initiated in 1981. Spirometry, occupational endotoxin exposure, and smoking habits were assessed at 5-year intervals. High-resolution computed tomography (CT) was performed in 464 retired workers in 2011, along with quantitative lung densitometric and airway analysis.

RESULTS: Significant differences in all CT measures were noted across exposure groups. Occupational endotoxin exposure was associated with a decrease (-1.3\%) in percent emphysema (LAAI-950), a 3.3-Hounsfield unit increase in 15th percentile density, an 18.1-g increase in lung mass, and a 2.3\% increase in wall area percent. Current but not former smoking was associated with a similar CT phenotype. Changes in LAAI-950 were highly correlated with 15th percentile density (correlation -1.0). Lung mass was the only measure associated with forced expiratory volume in 1 sec (FEV1) decline, with each 10-g increase in lung mass associated with an additional loss (-6.1 mL) of FEV1 (p = 0.001) between 1981 and 2011.

CONCLUSIONS: There are many similarities between the effects of occupational endotoxin exposure and those of tobacco smoke exposure on lung parenchyma and airway remodeling. The effects of occupational endotoxin exposure appear to persist even after the cessation of exposure. LAAI-950 may not be a reliable indicator of emphysema in subjects without spirometric impairment. Lung mass is a CT-based biomarker of accelerated lung function decline.

CITATION: Lai PS, Hang J, Zhang F, Sun J, Zheng BY, Su L, Washko GR, Christiani DC. 2016. Imaging phenotype of occupational endotoxin-related lung function decline. Environ Health Perspect 124:1436-1442; http://dx.doi.org/10.1289/EHP195.},
	keywords = {Aged, Air Pollutants, Occupational, Airway Remodeling, China, Endotoxins, Female, Humans, Longitudinal Studies, Lung, Lung Diseases, Male, Middle Aged, Occupational Diseases, Occupational Exposure, Parenchymal Tissue, Respiratory Function Tests, Smoking, Tomography, X-Ray Computed},
	issn = {1552-9924},
	doi = {10.1289/EHP195},
	author = {Lai, Peggy S and Hang, Jing-Qing and Zhang, Feng-Ying and J Sun and Zheng, Bu-Yong and Su, Li and Washko, George R and Christiani, David C}
}
@article {1433645,
	title = {Implementation and Performance of Automated Software for Computing Right-to-Left Ventricular Diameter Ratio From Computed Tomography Pulmonary Angiography Images},
	journal = {J Comput Assist Tomogr},
	volume = {40},
	number = {3},
	year = {2016},
	month = {2016 May-Jun},
	pages = {387-92},
	abstract = {OBJECTIVE: The aim of this study was to prospectively test the performance and potential for clinical integration of software that automatically calculates the right-to-left ventricular (RV/LV) diameter ratio from computed tomography pulmonary angiography images.

METHODS: Using 115 computed tomography pulmonary angiography images that were positive for acute pulmonary embolism, we prospectively evaluated RV/LV ratio measurements that were obtained as follows: (1) completely manual measurement (reference standard), (2) completely automated measurement using the software, and (3 and 4) using a customized software interface that allowed 2 independent radiologists to manually adjust the automatically positioned calipers.

RESULTS: Automated measurements underestimated (P < 0.001) the reference standard (1.09 [0.25] vs1.03 [0.35]). With manual correction of the automatically positioned calipers, the mean ratio became closer to the reference standard (1.06 [0.29] by read 1 and 1.07 [0.30] by read 2), and the correlation improved (r = 0.675 to 0.872 and 0.887). The mean time required for manual adjustment (37 [20] seconds) was significantly less than the time required to perform measurements entirely manually (100 [23] seconds).

CONCLUSIONS: Automated CT RV/LV diameter ratio software shows promise for integration into the clinical workflow for patients with acute pulmonary embolism.},
	keywords = {Algorithms, Computed Tomography Angiography, Heart Ventricles, Humans, machine learning, Middle Aged, Observer Variation, Organ Size, Pattern Recognition, Automated, Pulmonary Artery, Pulmonary Embolism, Radiographic Image Enhancement, Radiographic Image Interpretation, Computer-Assisted, Reproducibility of Results, Sensitivity and Specificity, Software},
	issn = {1532-3145},
	doi = {10.1097/RCT.0000000000000375},
	author = {Kumamaru, Kanako K and George, Elizabeth and Aghayev, Ayaz and Saboo, Sachin S and Khandelwal, Ashish and Rodr{\'\i}guez-L{\'o}pez, Sara and Cai, Tianrun and Jim{\'e}nez-Carretero, Daniel and San Jos{\'e} Est{\'e}par, Ra{\'u}l and Ledesma-Carbayo, Maria J and Gonz{\'a}lez, Germ{\'a}n and Rybicki, Frank J.}
}
@article {1433638,
	title = {Increasing the impact of medical image computing using community-based open-access hackathons: The NA-MIC and 3D Slicer experience},
	journal = {Med Image Anal},
	volume = {33},
	year = {2016},
	month = {2016 10},
	pages = {176-180},
	abstract = {The National Alliance for Medical Image Computing (NA-MIC) was launched in 2004 with the goal of investigating and developing an open source software infrastructure for the extraction of information and knowledge from medical images using computational methods. Several leading research and engineering groups participated in this effort that was funded by the US National Institutes of Health through a variety of infrastructure grants. This effort transformed 3D Slicer from an internal, Boston-based, academic research software application into a professionally maintained, robust, open source platform with an international leadership and developer and user communities. Critical improvements to the widely used underlying open source libraries and tools-VTK, ITK, CMake, CDash, DCMTK-were an additional consequence of this effort. This project has contributed to close to a thousand peer-reviewed publications and a growing portfolio of US and international funded efforts expanding the use of these tools in new medical computing applications every year. In this editorial, we discuss what we believe are gaps in the way medical image computing is pursued today; how a well-executed research platform can enable discovery, innovation and reproducible science ("Open Science"); and how our quest to build such a software platform has evolved into a productive and rewarding social engineering exercise in building an open-access community with a shared vision.},
	keywords = {Algorithms, Diagnostic Imaging, Humans, Image Processing, Computer-Assisted, Open Access Publishing, Reproducibility of Results, Software},
	issn = {1361-8423},
	doi = {10.1016/j.media.2016.06.035},
	author = {Kapur, Tina and Pieper, Steve and Fedorov, Andriy and Fillion-Robin, J-C and Halle, Michael and O{\textquoteright}Donnell, Lauren and Lasso, Andras and Ungi, Tamas and Pinter, Csaba and Finet, Julien and Pujol, Sonia and Jagadeesan, Jayender and Tokuda, Junichi and Norton, Isaiah and Estepar, Raul San Jose and Gering, David and Aerts, Hugo J W L and Jakab, Marianna and Hata, Nobuhiko and Ibanez, Luiz and Blezek, Daniel and Miller, Jim and Aylward, Stephen and Grimson, W Eric L and Fichtinger, Gabor and Wells, William M and Lorensen, William E and Schroeder, Will and Kikinis, Ron}
}
@article {1433640,
	title = {Magnetic resonance imaging provides sensitive in vivo assessment of experimental ventilator-induced lung injury},
	journal = {Am J Physiol Lung Cell Mol Physiol},
	volume = {311},
	number = {2},
	year = {2016},
	month = {2016 08 01},
	pages = {L208-18},
	abstract = {Animal models play a critical role in the study of acute respiratory distress syndrome (ARDS) and ventilator-induced lung injury (VILI). One limitation has been the lack of a suitable method for serial assessment of acute lung injury (ALI) in vivo. In this study, we demonstrate the sensitivity of magnetic resonance imaging (MRI) to assess ALI in real time in rat models of VILI. Sprague-Dawley rats were untreated or treated with intratracheal lipopolysaccharide or PBS. After 48 h, animals were mechanically ventilated for up to 15 h to induce VILI. Free induction decay (FID)-projection images were made hourly. Image data were collected continuously for 30 min and divided into 13 phases of the ventilatory cycle to make cinematic images. Interleaved measurements of respiratory mechanics were performed using a flexiVent ventilator. The degree of lung infiltration was quantified in serial images throughout the progression or resolution of VILI. MRI detected VILI significantly earlier (3.8 {\textpm} 1.6 h) than it was detected by altered lung mechanics (9.5 {\textpm} 3.9 h, P = 0.0156). Animals with VILI had a significant increase in the Index of Infiltration (P = 0.0027), and early regional lung infiltrates detected by MRI correlated with edema and inflammatory lung injury on histopathology. We were also able to visualize and quantify regression of VILI in real time upon institution of protective mechanical ventilation. Magnetic resonance lung imaging can be utilized to investigate mechanisms underlying the development and propagation of ALI, and to test the therapeutic effects of new treatments and ventilator strategies on the resolution of ALI.},
	keywords = {Airway Resistance, Animals, Lipopolysaccharides, Lung, Magnetic Resonance Imaging, Male, Neutrophil Infiltration, Rats, Sprague-Dawley, Respiration, Artificial, Ventilator-Induced Lung Injury},
	issn = {1522-1504},
	doi = {10.1152/ajplung.00459.2015},
	author = {Kuethe, Dean O and Filipczak, Piotr T and Hix, Jeremy M and Gigliotti, Andrew P and San Jos{\'e} Est{\'e}par, Ra{\'u}l and Washko, George R and Baron, Rebecca M and Fredenburgh, Laura E}
}
@article {1433634,
	title = {A Novel Spirometric Measure Identifies Mild COPD Unidentified by Standard Criteria},
	journal = {Chest},
	volume = {150},
	number = {5},
	year = {2016},
	month = {2016 Nov},
	pages = {1080-1090},
	abstract = {BACKGROUND: In chronic obstructive pulmonary disease, both smaller and larger airways are affected. FEV mainly reflects large airways obstruction, while the later fraction of forced exhalation reflects reduction in terminal expiratory flow. In this study, the objective was to evaluate the relationship between spirometric ratios, including the ratio of forced expiratory volume in 3 and 6~seconds (FEV/FEV), and small airways measures and gas trapping at quantitative chest CT scanning, and clinical outcomes in the Genetic Epidemiology of COPD (COPDGene) cohort.

METHODS: Seven thousand eight hundred fifty-three current and ex-smokers were evaluated for airflow obstruction by using recently defined linear iteratively derived equations of Hansen et al to determine lower limit of normal (LLN) equations for prebronchodilator FEV/FVC, FEV/FEV, FEV/FEV, and FEV/FVC. General linear and ordinal regression models were applied to the relationship between prebronchodilator spirometric and radiologic and clinical data.

RESULTS: Of the 10,311 participants included in the COPDGene phase I study, participants with incomplete quantitative CT scanning or relevant spirometric data were excluded, resulting in 7,853 participants in the present study. Of 4,386 participants with FEV/FVC greater than or equal to the LLN, 15.4\%~had abnormal FEV/FEV. Compared with normal FEV/FEV and FEV/FVC, abnormal FEV/FEV was associated with significantly greater gas trapping; St. George{\textquoteright}s Respiratory Questionnaire score; modified Medical Research Council dyspnea score; and BMI, airflow obstruction, dyspnea, and exercise index and with shorter 6-min walking distance (all P~< .0001) but not with CT scanning evidence of emphysema.

CONCLUSIONS: Current and ex-smokers with prebronchodilator FEV/FEV less than the LLN as the sole abnormality identifies a distinct population with evidence of small airways disease in quantitative CT scanning, impaired indexes of physical function and quality of life otherwise deemed normal by using the current spirometric definition.},
	keywords = {Aged, Aged, 80 and over, Disability Evaluation, Female, Humans, Male, Middle Aged, Pulmonary Disease, Chronic Obstructive, Quality of Life, Risk Assessment, Risk Factors, Spirometry, Tomography, X-Ray Computed},
	issn = {1931-3543},
	doi = {10.1016/j.chest.2016.06.047},
	author = {Dilektasli, Asli Gorek and Porszasz, Janos and Casaburi, Richard and Stringer, William W and Bhatt, Surya P and Pak, Youngju and Rossiter, Harry B and Washko, George and Castaldi, Peter J and Estepar, Raul San Jose and Hansen, James E}
}
@article {1433646,
	title = {A Robust Emphysema Severity Measure Based on Disease Subtypes},
	journal = {Acad Radiol},
	volume = {23},
	number = {4},
	year = {2016},
	month = {2016 Apr},
	pages = {421-8},
	abstract = {RATIONALE AND OBJECTIVES: We propose a novel single index for the quantification of emphysema severity based on an aggregation of multiple computed tomographic features evident in the lung parenchyma of smokers. Our goal was to demonstrate that this single index provides complementary information to the current standard measure of emphysema, percent emphysema (percent low attenuation areas [LAA\%]), and may be superior in its association with clinically relevant outcomes.

MATERIALS AND METHODS: The inputs to our algorithm were objective assessments of multiple emphysema subtypes (normal tissue; panlobular; paraseptal; and mild, moderate, and severe centrilobular emphysema). We applied dimensionality reduction techniques to the emphysema quantities to find a space that maximizes the variance of these subtypes. A single emphysema severity index was then derived from a parametrization of the reduced space, and the clinical utility of the measure was explored in a large cross-sectional cohort of 8914 subjects from the COPDGene Study.

RESULTS: There was a statistically significant association between the severity index and the LAA\%. Subjects with more severe chronic obstructive pulmonary disease (higher Global initiative for Obstructive Lung Disease stage) tended to have a higher computed tomography severity index. Finally, the severity index was associated with clinical outcomes such as lung function and provided a stronger association to these measures than the LAA\%.

CONCLUSIONS: The method provides a single clinically relevant index that can assess the severity of emphysema and that provides information that is complimentary to the more commonly used LAA\%.},
	keywords = {Emphysema, Female, Humans, Lung, Male, Middle Aged, Reproducibility of Results, Severity of Illness Index, Tomography, X-Ray Computed},
	issn = {1878-4046},
	doi = {10.1016/j.acra.2015.12.021},
	author = {Harmouche, Rola and Ross, James C and Diaz, Alejandro A and Washko, George R and Estepar, Raul San Jose}
}
@article {1433644,
	title = {Three-dimensional Printing and 3D Slicer: Powerful Tools in Understanding and Treating Structural Lung Disease},
	journal = {Chest},
	volume = {149},
	number = {5},
	year = {2016},
	month = {2016 May},
	pages = {1136-42},
	abstract = {Recent advances in the three-dimensional (3D) printing industry have enabled clinicians to explore the use of 3D printing in preprocedural planning, biomedical tissue modeling, and direct implantable device manufacturing. Despite the increased adoption of rapid prototyping and additive manufacturing techniques in the health-care field, many physicians lack the technical skill set to use this exciting and useful technology. Additionally, the growth in the 3D printing sector brings an ever-increasing number of 3D printers and printable materials. Therefore, it is important for clinicians to keep abreast of this rapidly developing field in order to benefit. In this Ahead of the Curve, we review the history of 3D printing from its inception to the most recent biomedical applications. Additionally, we will address some of the major barriers to wider adoption of the technology in the medical field. Finally, we will provide an initial guide to 3D modeling and printing by demonstrating how to design a personalized airway prosthesis via 3D Slicer. We hope this information will reduce the barriers to use and increase clinician participation in the 3D printing health-care sector. },
	keywords = {Computer-Aided Design, Humans, Imaging, Three-Dimensional, Lung, Lung Diseases, Printing, Three-Dimensional, Prosthesis Design, Prosthesis Implantation, Stents},
	issn = {1931-3543},
	doi = {10.1016/j.chest.2016.03.001},
	author = {Cheng, George Z and Estepar, Raul San Jose and Folch, Erik and Onieva, Jorge and Gangadharan, Sidhu and Majid, Adnan}
}
@article {1433637,
	title = {Unsupervised Discovery of Emphysema Subtypes in a Large Clinical Cohort},
	journal = {Mach Learn Med Imaging},
	volume = {10019},
	year = {2016},
	month = {2016 Oct},
	pages = {180-187},
	abstract = {Emphysema is one of the hallmarks of Chronic Obstructive Pulmonary Disorder (COPD), a devastating lung disease often caused by smoking. Emphysema appears on Computed Tomography (CT) scans as a variety of textures that correlate with disease subtypes. It has been shown that the disease subtypes and textures are linked to physiological indicators and prognosis, although neither is well characterized clinically. Most previous computational approaches to modeling emphysema imaging data have focused on supervised classification of lung textures in patches of CT scans. In this work, we describe a generative model that jointly captures heterogeneity of disease subtypes and of the patient population. We also describe a corresponding inference algorithm that simultaneously discovers disease subtypes and population structure in an unsupervised manner. This approach enables us to create image-based descriptors of emphysema beyond those that can be identified through manual labeling of currently defined phenotypes. By applying the resulting algorithm to a large data set, we identify groups of patients and disease subtypes that correlate with distinct physiological indicators.},
	doi = {10.1007/978-3-319-47157-0_22},
	author = {Binder, Polina and Batmanghelich, Nematollah K and Estepar, Raul San Jose and Golland, Polina}
}