@article{pmid23744052,

title = {AUTOMATIC AIRWAY ANALYSIS FOR GENOME-WIDE ASSOCIATION STUDIES IN COPD},

author = {Raúl San José Estépar and James C Ross and Gordon L Kindlmann and Alejandro Diaz and Yuka Okajima and Ron Kikinis and Carl-Fredrik Westin and Edwin K Silverman and George G Washko},

doi = {10.1109/ISBI.2012.6235848},

issn = {1945-7928},

year  = {2012},

date = {2012-01-01},

journal = {Proc IEEE Int Symp Biomed Imaging},

pages = {1467--1470},

abstract = {We present an image pipeline for airway phenotype extraction suitable for large-scale genetic and epidemiological studies including genome-wide association studies (GWAS) in Chronic Obstructive Pulmonary Disease (COPD). We use scale-space particles to densely sample intraparenchymal airway locations in a large cohort of high-resolution CT scans. The particle methodology is based on a constrained energy minimization problem that results in a set of candidate airway points situated in both physical space and scale. Those points are further clustered using connected components filtering to increase their specificity. Finally, we use the particle locations to perform airway wall detection using an edge detector based on the zero-crossing of the second order derivative. Given the airway wall locations, we compute three phenotypes for airway disease: wall thickening (Pi10,WA%) and luminal remodeling (P%). We validate the airway extraction technique and present results in 2,500 scans for the association of the extracted phenotypes with clinical outcomes that will be deployed as part of the COPDGene study GWAS analysis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid23743962,

title = {COMPUTATIONAL VASCULAR MORPHOMETRY FOR THE ASSESSMENT OF PULMONARY VASCULAR DISEASE BASED ON SCALE-SPACE PARTICLES},

author = {Raúl San José Estépar and James C Ross and Karl Krissian and Thomas Schultz and George R Washko and Gordon L Kindlmann},

doi = {10.1109/ISBI.2012.6235851},

issn = {1945-7928},

year  = {2012},

date = {2012-01-01},

journal = {Proc IEEE Int Symp Biomed Imaging},

pages = {1479--1482},

abstract = {We present a fully automatic computational vascular morphometry (CVM) approach for the clinical assessment of pulmonary vascular disease (PVD). The approach is based on the automatic extraction of the lung intraparenchymal vasculature using scale-space particles. Based on the detected features, we developed a set of image-based biomarkers for the assessment of the disease using the vessel radii estimation provided by the particle's scale. The biomarkers are based on the interrelation between vessel cross-section area and blood volume. We validate our vascular extraction method using simulated data with different complexity and we present results in 2,500 CT scans with different degrees of chronic obstructive pulmonary disease (COPD) severity. Results indicate that our CVM pipeline may track vascular remodeling present in COPD and it can be used in further clinical studies to assess the involvement of PVD in patient populations.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid21843930,

title = {Lung deflation and oxygen pulse in COPD: results from the NETT randomized trial},

author = {Carolyn E Come and Miguel J Divo and Raúl San José Estépar and Frank C Sciurba and Gerard J Criner and Nathaniel Marchetti and Steven M Scharf and Zab Mosenifar and Barry J Make and Cesar A Keller and Omar A Minai and Fernando J Martinez and MeiLan K Han and John J Reilly and Bartolome R Celli and George R Washko and },

doi = {10.1016/j.rmed.2011.07.012},

issn = {1532-3064},

year  = {2012},

date = {2012-01-01},

journal = {Respir Med},

volume = {106},

number = {1},

pages = {109--119},

abstract = {BACKGROUND: In COPD patients, hyperinflation impairs cardiac function. We examined whether lung deflation improves oxygen pulse, a surrogate marker of stroke volume.nnMETHODS: In 129 NETT patients with cardiopulmonary exercise testing (CPET) and arterial blood gases (ABG substudy), hyperinflation was assessed with residual volume to total lung capacity ratio (RV/TLC), and cardiac function with oxygen pulse (O(2) pulse=VO(2)/HR) at baseline and 6 months. Medical and surgical patients were divided into "deflators" and "non-deflators" based on change in RV/TLC from baseline (∆RV/TLC). We defined deflation as the ∆RV/TLC experienced by 75% of surgical patients. We examined changes in O(2) pulse at peak and similar (iso-work) exercise. Findings were validated in 718 patients who underwent CPET without ABGs.nnRESULTS: In the ABG substudy, surgical and medical deflators improved their RV/TLC and peak O(2) pulse (median ∆RV/TLC -18.0% vs. -9.3%, p=0.0003; median ∆O(2) pulse 13.6% vs. 1.8%, p=0.12). Surgical deflators also improved iso-work O(2) pulse (0.53 mL/beat, p=0.04 at 20 W). In the validation cohort, surgical deflators experienced a greater improvement in peak O(2) pulse than medical deflators (mean 18.9% vs. 1.1%). In surgical deflators improvements in O(2) pulse at rest and during unloaded pedaling (0.32 mL/beat, p<0.0001 and 0.47 mL/beat, p<0.0001, respectively) corresponded with significant reductions in HR and improvements in VO(2). On multivariate analysis, deflators were 88% more likely than non-deflators to have an improvement in O(2) pulse (OR 1.88, 95% CI 1.30-2.72, p=0.0008).nnCONCLUSION: In COPD, decreased hyperinflation through lung volume reduction is associated with improved O(2) pulse.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid21788524,

title = {Chronic obstructive pulmonary disease exacerbations in the COPDGene study: associated radiologic phenotypes},

author = {Meilan K Han and Ella A Kazerooni and David A Lynch and Lyrica X Liu and Susan Murray and Jeffrey L Curtis and Gerard J Criner and Victor Kim and Russell P Bowler and Nicola A Hanania and Antonio R Anzueto and Barry J Make and John E Hokanson and James D Crapo and Edwin K Silverman and Fernando J Martinez and George R Washko and },

doi = {10.1148/radiol.11110173},

issn = {1527-1315},

year  = {2011},

date = {2011-10-01},

journal = {Radiology},

volume = {261},

number = {1},

pages = {274--282},

abstract = {PURPOSE: To test the hypothesis-given the increasing emphasis on quantitative computed tomographic (CT) phenotypes of chronic obstructive pulmonary disease (COPD)-that a relationship exists between COPD exacerbation frequency and quantitative CT measures of emphysema and airway disease.nnMATERIALS AND METHODS: This research protocol was approved by the institutional review board of each participating institution, and all participants provided written informed consent. One thousand two subjects who were enrolled in the COPDGene Study and met the GOLD (Global Initiative for Chronic Obstructive Lung Disease) criteria for COPD with quantitative CT analysis were included. Total lung emphysema percentage was measured by using the attenuation mask technique with a -950-HU threshold. An automated program measured the mean wall thickness and mean wall area percentage in six segmental bronchi. The frequency of COPD exacerbation in the prior year was determined by using a questionnaire. Statistical analysis was performed to examine the relationship of exacerbation frequency with lung function and quantitative CT measurements.nnRESULTS: In a multivariate analysis adjusted for lung function, bronchial wall thickness and total lung emphysema percentage were associated with COPD exacerbation frequency. Each 1-mm increase in bronchial wall thickness was associated with a 1.84-fold increase in annual exacerbation rate (P = .004). For patients with 35% or greater total emphysema, each 5% increase in emphysema was associated with a 1.18-fold increase in this rate (P = .047).nnCONCLUSION: Greater lung emphysema and airway wall thickness were associated with COPD exacerbations, independent of the severity of airflow obstruction. Quantitative CT can help identify subgroups of patients with COPD who experience exacerbations for targeted research and therapy development for individual phenotypes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid21864166,

title = {Azithromycin for prevention of exacerbations of COPD},

author = {Richard K Albert and John Connett and William C Bailey and Richard Casaburi and J Allen D Cooper and Gerard J Criner and Jeffrey L Curtis and Mark T Dransfield and Meilan K Han and Stephen C Lazarus and Barry Make and Nathaniel Marchetti and Fernando J Martinez and Nancy E Madinger and Charlene McEvoy and Dennis E Niewoehner and Janos Porsasz and Connie S Price and John Reilly and Paul D Scanlon and Frank C Sciurba and Steven M Scharf and George R Washko and Prescott G Woodruff and Nicholas R Anthonisen and },

doi = {10.1056/NEJMoa1104623},

issn = {1533-4406},

year  = {2011},

date = {2011-08-01},

journal = {N Engl J Med},

volume = {365},

number = {8},

pages = {689--698},

abstract = {BACKGROUND: Acute exacerbations adversely affect patients with chronic obstructive pulmonary disease (COPD). Macrolide antibiotics benefit patients with a variety of inflammatory airway diseases.nnMETHODS: We performed a randomized trial to determine whether azithromycin decreased the frequency of exacerbations in participants with COPD who had an increased risk of exacerbations but no hearing impairment, resting tachycardia, or apparent risk of prolongation of the corrected QT interval.nnRESULTS: A total of 1577 subjects were screened; 1142 (72%) were randomly assigned to receive azithromycin, at a dose of 250 mg daily (570 participants), or placebo (572 participants) for 1 year in addition to their usual care. The rate of 1-year follow-up was 89% in the azithromycin group and 90% in the placebo group. The median time to the first exacerbation was 266 days (95% confidence interval [CI], 227 to 313) among participants receiving azithromycin, as compared with 174 days (95% CI, 143 to 215) among participants receiving placebo (P<0.001). The frequency of exacerbations was 1.48 exacerbations per patient-year in the azithromycin group, as compared with 1.83 per patient-year in the placebo group (P=0.01), and the hazard ratio for having an acute exacerbation of COPD per patient-year in the azithromycin group was 0.73 (95% CI, 0.63 to 0.84; P<0.001). The scores on the St. George's Respiratory Questionnaire (on a scale of 0 to 100, with lower scores indicating better functioning) improved more in the azithromycin group than in the placebo group (a mean [±SD] decrease of 2.8±12.8 vs. 0.6±11.4, P=0.004); the percentage of participants with more than the minimal clinically important difference of -4 units was 43% in the azithromycin group, as compared with 36% in the placebo group (P=0.03). Hearing decrements were more common in the azithromycin group than in the placebo group (25% vs. 20%, P=0.04).nnCONCLUSIONS: Among selected subjects with COPD, azithromycin taken daily for 1 year, when added to usual treatment, decreased the frequency of exacerbations and improved quality of life but caused hearing decrements in a small percentage of subjects. Although this intervention could change microbial resistance patterns, the effect of this change is not known. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00325897.).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid21396809,

title = {Clinical and radiographic correlates of hypoxemia and oxygen therapy in the COPDGene study},

author = {Deog Kyeom Kim and Francine L Jacobson and George R Washko and Richard Casaburi and Barry J Make and James D Crapo and Edwin K Silverman and Craig P Hersh},

doi = {10.1016/j.rmed.2011.02.015},

issn = {1532-3064},

year  = {2011},

date = {2011-08-01},

journal = {Respir Med},

volume = {105},

number = {8},

pages = {1211--1221},

abstract = {BACKGROUND: Severe hypoxemia is a major complication of chronic obstructive pulmonary disease (COPD). Long-term oxygen therapy is beneficial in hypoxemic COPD patients. However, the clinical and radiographic predictors of hypoxemia and the use of oxygen therapy are not well described. This study aimed to find the correlates of resting hypoxemia and the pattern of oxygen use in moderate to severe COPD patients.nnMETHODS: Subjects with GOLD stage II or higher COPD from the first 2500 COPDGene subjects were included in this analysis. All subjects were current or ex-smokers between ages 45 and 80. Severe resting hypoxemia was defined as room air oxygen saturation (SpO(2)) ≤88%. Use of supplemental oxygen therapy was determined by questionnaire.nnRESULTS: Eighty-two of 1060 COPD subjects (7.7%) had severe resting hypoxemia. Twenty-one of the 82 (25.6%) were not using continuous supplemental oxygen. Female sex, higher BMI, lower FEV(1), and enrollment in Denver were independent risk factors for hypoxemia; emphysema severity on quantitative chest CT scan did not predict hypoxemia. 132 of 971(13.6%) subjects without severe resting hypoxemia were using continuous supplemental oxygen. In non-hypoxemic oxygen users, Denver recruitment, higher BMI, lower FEV(1), and more severe dyspnea were associated with the use of continuous oxygen.nnCONCLUSIONS: A large number of COPD patients without severe hypoxemia were using supplemental oxygen therapy and the pattern of oxygen use was affected by factors other than resting SpO(2) and emphysema severity. Longitudinal data will be required to reveal the effects of oxygen therapy in this subgroup.nnCLINICAL TRIAL REGISTRATION: http://clinicaltrials.gov (NCT00608764).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid21310839,

title = {Family history is a risk factor for COPD},

author = {Craig P Hersh and John E Hokanson and David A Lynch and George R Washko and Barry J Make and James D Crapo and Edwin K Silverman and },

doi = {10.1378/chest.10-2761},

issn = {1931-3543},

year  = {2011},

date = {2011-08-01},

journal = {Chest},

volume = {140},

number = {2},

pages = {343--350},

abstract = {BACKGROUND: Studies have shown that family history is a risk factor for COPD, but have not accounted for family history of smoking. Therefore, we sought to identify the effects of family history of smoking and family history of COPD on COPD susceptibility.nnMETHODS: We compared 821 patients with COPD to 776 control smokers from the Genetic Epidemiology of COPD (COPDGene) Study. Questionnaires captured parental histories of smoking and COPD, as well as childhood environmental tobacco smoke (ETS) exposure. Socioeconomic status was defined by educational achievement.nnRESULTS: Parental history of smoking (85.5% case patients, 82.9% control subjects) was more common than parental history of COPD (43.0% case patients, 30.8% control subjects). In a logistic regression model, parental history of COPD (OR, 1.73; P < .0001) and educational level (OR, 0.48 for some college vs no college; P < .0001) were significant predictors of COPD, but parental history of smoking and childhood ETS exposure were not significant. The population-attributable risk from COPD family history was 18.6%. Patients with COPD with a parental history had more severe disease, with lower lung function, worse quality of life, and more frequent exacerbations. There were nonsignificant trends for more severe emphysema and airway disease on quantitative chest CT scans.nnCONCLUSIONS: Family history of COPD is a strong risk factor for COPD, independent of family history of smoking, personal lifetime smoking, or childhood ETS exposure. Although further studies are required to identify genetic variants that influence COPD susceptibility, clinicians should question all smokers, especially those with known or suspected COPD, regarding COPD family history.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid21756032,

title = {Gender differences of airway dimensions in anatomically matched sites on CT in smokers},

author = {Yu-Il Kim and Joyce Schroeder and David Lynch and John Newell and Barry Make and Adam Friedlander and Raúl San José Estépar and Nicola A Hanania and George Washko and James R Murphy and Carla Wilson and John E Hokanson and Jordan Zach and Kiel Butterfield and Russell P Bowler and Copdgene Investigators},

doi = {10.3109/15412555.2011.586658},

issn = {1541-2563},

year  = {2011},

date = {2011-08-01},

journal = {COPD},

volume = {8},

number = {4},

pages = {285--292},

abstract = {RATIONALE AND OBJECTIVES: There are limited data on, and controversies regarding gender differences in the airway dimensions of smokers. Multi-detector CT (MDCT) images were analyzed to examine whether gender could explain differences in airway dimensions of anatomically matched airways in smokers.nnMATERIALS AND METHODS: We used VIDA imaging software to analyze MDCT scans from 2047 smokers (M:F, 1021:1026) from the COPDGene® cohort. The airway dimensions were analyzed from segmental to subsubsegmental bronchi. We compared the differences of luminal area, inner diameter, wall thickness, wall area percentage (WA%) for each airway between men and women, and multiple linear regression including covariates (age, gender, body sizes, and other relevant confounding factors) was used to determine the predictors of each airway dimensions.nnRESULTS: Lumen area, internal diameter and wall thickness were smaller for women than men in all measured airway (18.4 vs 22.5 mm(2) for segmental bronchial lumen area, 10.4 vs 12.5 mm(2) for subsegmental bronchi, 6.5 vs 7.7 mm(2) for subsubsegmental bronchi, respectively p < 0.001). However, women had greater WA% in subsegmental and subsubsegmental bronchi. In multivariate regression, gender remained one of the most significant predictors of WA%, lumen area, inner diameter and wall thickness.nnCONCLUSION: Women smokers have higher WA%, but lower luminal area, internal diameter and airway thickness in anatomically matched airways as measured by CT scan than do male smokers. This difference may explain, in part, gender differences in the prevalence of COPD and airflow limitation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid21377593,

title = {Assessment of pulmonary hypertension what CT and MRI can provide},

author = {Yuka Okajima and Yoshiharu Ohno and George R Washko and Hiroto Hatabu},

doi = {10.1016/j.acra.2011.01.003},

issn = {1878-4046},

year  = {2011},

date = {2011-04-01},

journal = {Acad Radiol},

volume = {18},

number = {4},

pages = {437--453},

abstract = {RATIONALES AND OBJECTIVES: Pulmonary hypertension (PH) is a life-threatening condition, characterized by elevated pulmonary arterial pressure, which is confirmed based on invasive right heart catheterization (RHC). Noninvasive examinations may support diagnosis of PH before proceeding to RHC and play an important role in management and treatment of the disease. Although echocardiography is considered a standard tool in diagnosis, recent advances have made computed tomography (CT) and magnetic resonance (MR) imaging promising tools, which may provide morphologic and functional information. In this article, we review image-based assessment of PH with a focus on CT and MR imaging.nnCONCLUSIONS: CT may provide useful morphologic information for depicting PH and seeking for underlying diseases. With the accumulated technological advancement, CT and MRI may provide practical tools for not only morphologic but also functional assessment of patients with PH.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid21215660,

title = {Intrathoracic tracheal volume and collapsibility on inspiratory and end-expiratory ct scans correlations with lung volume and pulmonary function in 85 smokers},

author = {Tsuneo Yamashiro and Raúl San José Estépar and Shin Matsuoka and Brian J Bartholmai and James C Ross and Alejandro Diaz and Sadayuki Murayama and Edwin K Silverman and Hiroto Hatabu and George R Washko},

doi = {10.1016/j.acra.2010.11.005},

issn = {1878-4046},

year  = {2011},

date = {2011-03-01},

journal = {Acad Radiol},

volume = {18},

number = {3},

pages = {299--305},

abstract = {RATIONALE AND OBJECTIVES: To evaluate the correlations of tracheal volume and collapsibility on inspiratory and end-expiratory computed tomography (CT) with lung volume and with lung function in smokers.nnMATERIALS AND METHODS: The institutional review board approved this study at each institution. 85 smokers (mean age 68, range 45-87 years; 40 females and 45 males) underwent pulmonary function tests and chest CT at full inspiration and end-expiration. On both scans, intrathoracic tracheal volume and lung volume were measured. Collapsibility of the trachea and the lung was expressed as expiratory/inspiratory (E/I) ratios of these volumes. Correlations of the tracheal measurements with the lung measurements and with lung function were evaluated by the linear regression analysis.nnRESULTS: Tracheal volume showed moderate or strong, positive correlations with lung volume on both inspiratory (r = 0.661, P < .0001) and end-expiratory (r = 0.749, P < .0001) scans. The E/I ratio of tracheal volume showed a strong, positive correlation with the E/I ratio of lung volume (r = 0.711, P < .0001). A weak, negative correlation was found between the E/I ratio of tracheal volume and the ratio of forced expiratory volume in the first second to forced vital capacity (r = -0.436, P < .0001). Also, a weak, positive correlation was observed between the E/I ratio of tracheal volume and the ratio of residual volume to total lung capacity (r = 0.253, P = .02).nnCONCLUSIONS: Tracheal volume and collapsibility, measured by inspiratory and end-expiratory CT scans, is related to lung volume and collapsibility. The highly collapsed trachea on end-expiratory CT does not indicate more severe airflow limitation or air-trapping in smokers.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid21388308,

title = {Lung volumes and emphysema in smokers with interstitial lung abnormalities},

author = {George R Washko and Gary M Hunninghake and Isis E Fernandez and Mizuki Nishino and Yuka Okajima and Tsuneo Yamashiro and James C Ross and Raúl San José Estépar and David A Lynch and John M Brehm and Katherine P Andriole and Alejandro A Diaz and Ramin Khorasani and Katherine D'Aco and Frank C Sciurba and Edwin K Silverman and Hiroto Hatabu and Ivan O Rosas and },

doi = {10.1056/NEJMoa1007285},

issn = {1533-4406},

year  = {2011},

date = {2011-03-01},

journal = {N Engl J Med},

volume = {364},

number = {10},

pages = {897--906},

abstract = {BACKGROUND: Cigarette smoking is associated with emphysema and radiographic interstitial lung abnormalities. The degree to which interstitial lung abnormalities are associated with reduced total lung capacity and the extent of emphysema is not known.nnMETHODS: We looked for interstitial lung abnormalities in 2416 (96%) of 2508 high-resolution computed tomographic (HRCT) scans of the lung obtained from a cohort of smokers. We used linear and logistic regression to evaluate the associations between interstitial lung abnormalities and HRCT measurements of total lung capacity and emphysema.nnRESULTS: Interstitial lung abnormalities were present in 194 (8%) of the 2416 HRCT scans evaluated. In statistical models adjusting for relevant covariates, interstitial lung abnormalities were associated with reduced total lung capacity (-0.444 liters; 95% confidence interval [CI], -0.596 to -0.292; P<0.001) and a lower percentage of emphysema defined by lung-attenuation thresholds of -950 Hounsfield units (-3%; 95% CI, -4 to -2; P<0.001) and -910 Hounsfield units (-10%; 95% CI, -12 to -8; P<0.001). As compared with participants without interstitial lung abnormalities, those with abnormalities were more likely to have a restrictive lung deficit (total lung capacity <80% of the predicted value; odds ratio, 2.3; 95% CI, 1.4 to 3.7; P<0.001) and were less likely to meet the diagnostic criteria for chronic obstructive pulmonary disease (COPD) (odds ratio, 0.53; 95% CI, 0.37 to 0.76; P<0.001). The effect of interstitial lung abnormalities on total lung capacity and emphysema was dependent on COPD status (P<0.02 for the interactions). Interstitial lung abnormalities were positively associated with both greater exposure to tobacco smoke and current smoking.nnCONCLUSIONS: In smokers, interstitial lung abnormalities--which were present on about 1 of every 12 HRCT scans--were associated with reduced total lung capacity and a lesser amount of emphysema. (Funded by the National Institutes of Health and the Parker B. Francis Foundation; ClinicalTrials.gov number, NCT00608764.).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid21111413,

title = {Evaluation of colonoscopy technical skill levels by use of an objective kinematic-based system},

author = {Keith L Obstein and Vaibhav D Patil and Jagadeesan Jayender and Raúl San José Estépar and Inbar S Spofford and Balazs I Lengyel and Kirby G Vosburgh and Christopher C Thompson},

doi = {10.1016/j.gie.2010.09.005},

issn = {1097-6779},

year  = {2011},

date = {2011-02-01},

journal = {Gastrointest Endosc},

volume = {73},

number = {2},

pages = {315--21, 321.e1},

abstract = {BACKGROUND: Colonoscopy requires training and experience to ensure accuracy and safety. Currently, no objective, validated process exists to determine when an endoscopist has attained technical competence. Kinematics data describing movements of laparoscopic instruments have been used in surgical skill assessment to define expert surgical technique. We have developed a novel system to record kinematics data during colonoscopy and quantitatively assess colonoscopist performance.nnOBJECTIVE: To use kinematic analysis of colonoscopy to quantitatively assess endoscopic technical performance.nnDESIGN: Prospective cohort study.nnSETTING: Tertiary-care academic medical center.nnPOPULATION: This study involved physicians who perform colonoscopy.nnINTERVENTION: Application of a kinematics data collection system to colonoscopy evaluation.nnMAIN OUTCOME MEASUREMENTS: Kinematics data, validated task load assessment instrument, and technical difficulty visual analog scale.nnRESULTS: All 13 participants completed the colonoscopy to the terminal ileum on the standard colon model. Attending physicians reached the terminal ileum quicker than fellows (median time, 150.19 seconds vs 299.86 seconds; p<.01) with reduced path lengths for all 4 sensors, decreased flex (1.75 m vs 3.14 m; P=.03), smaller tip angulation, reduced absolute roll, and lower curvature of the endoscope. With performance of attending physicians serving as the expert reference standard, the mean kinematic score increased by 19.89 for each decrease in postgraduate year (P<.01). Overall, fellows experienced greater mental, physical, and temporal demand than did attending physicians.nnLIMITATION: Small cohort size.nnCONCLUSION: Kinematic data and score calculation appear useful in the evaluation of colonoscopy technical skill levels. The kinematic score appears to consistently vary by year of training. Because this assessment is nonsubjective, it may be an improvement over current methods for determination of competence. Ongoing studies are establishing benchmarks and characteristic profiles of skill groups based on kinematics data.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid21299474,

title = {Kurtosis and skewness of density histograms on inspiratory and expiratory CT scans in smokers},

author = {Tsuneo Yamashiro and Shin Matsuoka and Raúl San José Estépar and Brian J Bartholmai and Alejandro Diaz and James C Ross and Sadayuki Murayama and Edwin K Silverman and Hiroto Hatabu and George R Washko},

doi = {10.3109/15412555.2010.541537},

issn = {1541-2563},

year  = {2011},

date = {2011-02-01},

journal = {COPD},

volume = {8},

number = {1},

pages = {13--20},

abstract = {The aim of this study is to evaluate the relationship between lung function and kurtosis or skewness of lung density histograms on computed tomography (CT) in smokers. Forty-six smokers (age range 46?81 years), enrolled in the Lung Tissue Research Consortium, underwent pulmonary function tests (PFT) and chest CT at full inspiration and full expiration. On both inspiratory and expiratory scans, kurtosis and skewness of the density histograms were automatically measured by open-source software. Correlations between CT measurements and lung function were evaluated by the linear regression analysis. Although no significant correlations were found between inspiratory kurtosis or skewness and PFT results, expiratory kurtosis significantly correlated with the following: the percentage of predicted value of forced expiratory volume in the first second (FEV(1)), the ratio of FEV(1) to forced vital capacity (FVC), and the ratio of residual volume (RV) to total lung capacity (TLC) (FEV(1)%predicted, R = -0.581, p < 0.001; FEV(1)/FVC, R = -0.612, p < 0.001; RV/TLC, R = 0.613, p < 0.001, respectively). Similarly, expiratory skewness showed significant correlations with PFT results (FEV(1)%predicted, R = -0.584, p < 0.001; FEV(1)/FVC, R = -0.619, p < 0.001; RV/TLC, R = 0.585, p < 0.001, respectively). Also, the expiratory/inspiratory (E/I) ratios of kurtosis and skewness significantly correlated with FEV(1)%predicted (p < 0.001), FEV(1)/FVC (p < 0.001), RV/TLC (p < 0.001), and the percentage of predicted value of diffusing capacity for carbon monoxide (kurtosis E/I ratio, p = 0.001; skewness E/I ratio, p = 0.03, respectively). We conclude therefore that expiratory values and the E/I ratios of kurtosis and skewness of CT densitometry reflect airflow limitation and air-trapping. Higher kurtosis or skewness on expiratory CT scan indicates more severe conditions in smokers.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid21299475,

title = {Randomized trial of zileuton for treatment of COPD exacerbations requiring hospitalization},

author = {Prescott G Woodruff and Richard K Albert and William C Bailey and Richard Casaburi and John E Connett and John A D Cooper and Gerard J Criner and Jeffrey L Curtis and Mark T Dransfield and Meilan K Han and Sarah M Harnden and Victor Kim and Nathaniel Marchetti and Fernando J Martinez and Charlene E McEvoy and Dennis E Niewoehner and John J Reilly and Kathryn Rice and Paul D Scanlon and Steven M Scharf and Frank C Sciurba and George R Washko and Stephen C Lazarus and },

doi = {10.3109/15412555.2010.540273},

issn = {1541-2563},

year  = {2011},

date = {2011-02-01},

journal = {COPD},

volume = {8},

number = {1},

pages = {21--29},

abstract = {RATIONALE: Leukotrienes have been implicated in the pathogenesis of acute exacerbations of COPD, but leukotriene modifiers have not been studied as a possible therapy for exacerbations.nnOBJECTIVE: We sought to test the safety and efficacy of adding oral zileuton (a 5-lipoxygenase inhibitor) to usual treatment for acute exacerbations of COPD requiring hospitalization.nnMETHODS: Randomized double-blind, placebo-controlled, parallel group study of zileuton 600 mg orally, 4 times daily versus placebo for 14 days starting within 12 hours of hospital admission for COPD exacerbation. Primary outcome measure was hospital length of stay; secondary outcomes included treatment failure and biomarkers of leukotriene production.nnMAIN FINDINGS: Sixty subjects were randomized to zileuton and 59 to placebo (the study was stopped short of enrollment goals because of slow recruitment). There was no difference in hospital length of stay (3.75 +/- 2.19 vs. 3.86 +/- 3.06 days for zileuton vs. placebo, p = 0.39) or treatment failure (23% vs. 27% for zileuton vs. placebo, p = 0.63) despite a decline in urinary LTE(4) levels in the zileuton-treated group as compared to placebo at 24 hours (change in natural log-transformed ng/mg creatinine -1.38 +/- 1.19 vs. 0.14 +/- 1.51, p < 0.0001) and 72 hours (-1.32 +/- 2.08 vs. 0.26 +/- 1.93, p<0.006). Adverse events were similar in both groups.nnPRINCIPAL CONCLUSIONS: While oral zileuton during COPD exacerbations that require hospital admission is safe and reduces urinary LTE(4) levels, we found no evidence suggesting that this intervention shortened hospital stay, with the limitation that our sample size may have been insufficient to detect a modest but potentially meaningful clinical improvement.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid21232152,

title = {Epidemiology, radiology, and genetics of nicotine dependence in COPD},

author = {Deog Kyeom Kim and Craig P Hersh and George R Washko and John E Hokanson and David A Lynch and John D Newell and James R Murphy and James D Crapo and Edwin K Silverman and },

doi = {10.1186/1465-9921-12-9},

issn = {1465-993X},

year  = {2011},

date = {2011-01-01},

journal = {Respir Res},

volume = {12},

number = {1},

pages = {9},

abstract = {BACKGROUND: Cigarette smoking is the principal environmental risk factor for developing COPD, and nicotine dependence strongly influences smoking behavior. This study was performed to elucidate the relationship between nicotine dependence, genetic susceptibility to nicotine dependence, and volumetric CT findings in smokers.nnMETHODS: Current smokers with COPD (GOLD stage ≥ 2) or normal spirometry were analyzed from the COPDGene Study, a prospective observational study. Nicotine dependence was determined by the Fagerstrom test for nicotine dependence (FTND). Volumetric CT acquisitions measuring the percent of emphysema on inspiratory CT (% of lung <-950 HU) and gas trapping on expiratory CT (% of lung <-856 HU) were obtained. Genotypes for two SNPs in the CHRNA3/5 region (rs8034191, rs1051730) previously associated with nicotine dependence and COPD were analyzed for association to COPD and nicotine dependence phenotypes.nnRESULTS: Among 842 currently smoking subjects (335 COPD cases and 507 controls), 329 subjects (39.1%) showed high nicotine dependence. Subjects with high nicotine dependence had greater cumulative and current amounts of smoking. However, emphysema severity was negatively correlated with the FTND score in controls (ρ = -0.19, p < .0001) as well as in COPD cases (ρ = -0.18, p = 0.0008). Lower FTND score, male gender, lower body mass index, and lower FEV1 were independent risk factors for emphysema severity in COPD cases. Both CHRNA3/5 SNPs were associated with FTND in current smokers. An association of genetic variants in CHRNA3/5 with severity of emphysema was only found in former smokers, but not in current smokers.nnCONCLUSIONS: Nicotine dependence was a negative predictor for emphysema on CT in COPD and control smokers. Increased inflammation in more highly addicted current smokers could influence the CT lung density distribution, which may influence genetic association studies of emphysema phenotypes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid21761697,

title = {Probabilistic elastography: estimating lung elasticity},

author = {Petter Risholm and James Ross and George R Washko and William M Wells},

doi = {10.1007/978-3-642-22092-0_57},

issn = {1011-2499},

year  = {2011},

date = {2011-01-01},

journal = {Inf Process Med Imaging},

volume = {22},

pages = {699--710},

abstract = {We formulate registration-based elastography in a probabilistic framework and apply it to study lung elasticity in the presence of emphysematous and fibrotic tissue. The elasticity calculations are based on a Finite Element discretization of a linear elastic biomechanical model. We marginalize over the boundary conditions (deformation) of the biomechanical model to determine the posterior distribution over elasticity parameters. Image similarity is included in the likelihood, an elastic prior is included to constrain the boundary conditions, while a Markov model is used to spatially smooth the inhomogeneous elasticity. We use a Markov Chain Monte Carlo (MCMC) technique to characterize the posterior distribution over elasticity from which we extract the most probable elasticity as well as the uncertainty of this estimate. Even though registration-based lung elastography with inhomogeneous elasticity is challenging due the problem's highly underdetermined nature and the sparse image information available in lung CT, we show promising preliminary results on estimating lung elasticity contrast in the presence of emphysematous and fibrotic tissue.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid20947389,

title = {The relationship between small pulmonary vascular alteration and aortic atherosclerosis in chronic obstructive pulmonary disease: quantitative CT analysis},

author = {Shin Matsuoka and Tsuneo Yamashiro and Alejandro Diaz and Raúl San José Estépar and James C Ross and Edwin K Silverman and Yasuyuki Kobayashi and Mark T Dransfield and Brian J Bartholmai and Hiroto Hatabu and George R Washko},

doi = {10.1016/j.acra.2010.08.013},

issn = {1878-4046},

year  = {2011},

date = {2011-01-01},

journal = {Acad Radiol},

volume = {18},

number = {1},

pages = {40--46},

abstract = {RATIONALE AND OBJECTIVES: The relationship between chronic obstructive pulmonary disease (COPD) and atherosclerosis has been suggested; this association may relate to systemic inflammation and endothelial dysfunction, which can lead to alteration of small pulmonary vessels. The relationship between atherosclerosis and small pulmonary vessel alteration, however, has not been assessed in COPD patients. We tested the hypothesis that the severity of thoracic aortic calcification measured by computed tomography (CT) would be associated with the total cross-sectional area of small pulmonary vessels (CSA) on CT images.nnMATERIALS AND METHODS: The study was approved by the institutional review board and was Health Insurance Portability and Accountability Act-compliant. Informed consent was waived. For 51 COPD patients enrolled in the National Heart, Lung, and Blood Institute Lung Tissue Research Consortium, we calculated the percentage of total CSAs of less than 5 mm² for the total lung area (%CSA<5). Thoracic aortic calcification, quantified by modified Agatston score, was measured. The correlations between thoracic aortic calcification score and %CSA<5, pulmonary function, and extent of emphysema were evaluated. Multiple linear regression analysis using aortic calcification score as the dependent outcome was also performed.nnRESULTS: The %CSA<5 had a significant negative correlation with the thoracic aortic calcification score (r = -0.566, P < .0001). Multiple linear regression analysis showed significant correlation between the aortic calcification score and %CSA<5 (P < .0001) independent of age, pack-years, extent of emphysema, and FEV1%.nnCONCLUSIONS: Atherosclerosis, assessed by aortic calcification, is associated with the small pulmonary vascular alteration in COPD. Systemic inflammation and endothelial dysfunction may cause the close relationship between atherosclerosis and small pulmonary vessel alteration.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid21166628,

title = {CT emphysema predicts thoracic aortic calcification in smokers with and without COPD},

author = {Mark T Dransfield and Frank Huang and Hrudaya Nath and Satinder P Singh and William C Bailey and George R Washko},

doi = {10.3109/15412555.2010.528085},

issn = {1541-2563},

year  = {2010},

date = {2010-12-01},

journal = {COPD},

volume = {7},

number = {6},

pages = {404--410},

abstract = {COPD patients are at increased risk for cardiovascular morbidity and mortality independent of smoking habits. Recent studies suggest CT emphysema is an independent predictor of cardiovascular risk as evidenced by its association with arterial stiffness and impaired endothelial function. We examined the relationship between demographics, lung function, CT emphysema and airway wall thickness and thoracic aortic calcification, another marker of cardiovascular risk, in the National Lung Screening Trial. We hypothesized that CT emphysema would be independently associated with thoracic aortic calcification. Two hundred forty current and former smokers were enrolled. After CT examination, we recorded subjects' demographics and they performed spirometry. Subjects were classified into COPD and non-COPD subgroups. CT emphysema was quantified as a percentage of lung volume and measurements of the right upper lobe airway were performed using standard methods and expressed as wall area (%). Total calcification scores for the thoracic aorta were computed using TeraRecon image analysis. Univariate and multivariate analyses were performed to determine the associations between calcium score and subject characteristics. Subjects with COPD were older, more often male, heavier smokers and had more CT emphysema and greater aortic calcification than those without COPD. Calcium score was associated with age, pack-years, CT emphysema, wall area%, and lung function on univariate testing but only with age and CT emphysema on multivariate analysis. We conclude that CT emphysema is independently associated with thoracic calcification and thus may be used to assess cardiovascular risk in smokers with and without COPD.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid20576417,

title = {Predictive accuracy of the pneumonia severity index vs CRB-65 for time to clinical stability: results from the Community-Acquired Pneumonia Organization (CAPO) International Cohort Study},

author = {Forest W Arnold and Guy N Brock and Paula Peyrani and Eduardo L Rodríguez and Alejandro A Díaz and Paolo Rossi and Julio A Ramirez and },

doi = {10.1016/j.rmed.2010.05.022},

issn = {1532-3064},

year  = {2010},

date = {2010-11-01},

journal = {Respir Med},

volume = {104},

number = {11},

pages = {1736--1743},

abstract = {BACKGROUND: The Pneumonia Severity Index (PSI) and CRB-65 are scores used to predict mortality in patients with community-acquired pneumonia (CAP). It is unknown how well either score predicts time to clinical stability in hospitalized patients with CAP. Thus, it is also not known which score predicts time to clinical stability better.nnMETHODS: A secondary analysis of 3087 patients from the Community-Acquired Pneumonia Organization (CAPO) database was performed. Time-dependent receiver-operator characteristic (ROC) curves for time to clinical stability were calculated for the PSI and CRB-65 scores at day seven of hospitalization. Secondary outcomes were to assess the relationship of the PSI and CRB-65 to in-hospital mortality and length of stay (LOS). ROC curves for LOS and mortality were calculated.nnRESULTS: The area under the ROC curve (AUC) for time to clinical stability by day seven was 0.638 (95% CI 0.613, 0.660) when using the PSI, and 0.647 (95% CI 0.619, 0.670) while using the CRB-65. The difference in AUC values was not statistically significant (95% CI for difference of -0.03 to 0.01). However, the difference in the AUC values for discharge within 14 days (0.651 for PSI vs 0.63 for CRB-65, 95% CI for difference 0.001-0.049), and 28-day in-hospital mortality (0.738 for PSI vs 0.69 for CRB-65, 95% CI for difference 0.02-0.082) were both statistically significant.nnCONCLUSIONS: This study demonstrates a moderate ability of both the PSI and CRB-65 scores to predict time to clinical stability, and found that the predictive accuracy of the PSI was equivalent to that of the CRB-65 for this outcome.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid20558554,

title = {Airway count and emphysema assessed by chest CT imaging predicts clinical outcome in smokers},

author = {Alejandro A Diaz and Clarissa Valim and Tsuneo Yamashiro and Raúl San José Estépar and James C Ross and Shin Matsuoka and Brian Bartholmai and Hiroto Hatabu and Edwin K Silverman and George R Washko},

doi = {10.1378/chest.10-0542},

issn = {1931-3543},

year  = {2010},

date = {2010-10-01},

journal = {Chest},

volume = {138},

number = {4},

pages = {880--887},

abstract = {BACKGROUND: Recently, it has been shown that emphysematous destruction of the lung is associated with a decrease in the total number of terminal bronchioles. It is unknown whether a similar decrease is visible in the more proximal airways. We aimed to assess the relationships between proximal airway count, CT imaging measures of emphysema, and clinical prognostic factors in smokers, and to determine whether airway count predicts the BMI, airflow obstruction, dyspnea, and exercise capacity (BODE) index.nnMETHODS: In 50 smokers, emphysema was measured on CT scans and airway branches from the third to eighth generations of the right upper lobe apical bronchus were counted manually. The sum of airway branches from the sixth to eighth generations represented the total airway count (TAC). For each subject, the BODE index was determined. We used logistic regression to assess the ability of TAC to predict a high BODE index (≥ 7 points).nnRESULTS: TAC was inversely associated with emphysema (r = -0.54, P < .0001). TAC correlated with the modified Medical Research Council dyspnea score (r = -0.42, P = .004), FEV(1)% predicted (r = 0.52, P = .0003), 6-min walk distance (r = 0.36, P = .012), and BODE index (r = -0.55, P < .0001). The C-statistics, which correspond to the area under the receiver operating characteristic curve, for the ability of TAC alone and TAC, emphysema, and age to predict a high BODE index were 0.84 and 0.92, respectively.nnCONCLUSIONS: TAC is lower in subjects with greater emphysematous destruction and is a predictor of a high BODE index. These results suggest that CT imaging-based TAC may be a unique COPD-related phenotype in smokers.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid20538961,

title = {Perfusion scintigraphy and patient selection for lung volume reduction surgery},

author = {Divay Chandra and David A Lipson and Eric A Hoffman and John Hansen-Flaschen and Frank C Sciurba and Malcolm M Decamp and John J Reilly and George R Washko and },

doi = {10.1164/rccm.201001-0043OC},

issn = {1535-4970},

year  = {2010},

date = {2010-10-01},

journal = {Am J Respir Crit Care Med},

volume = {182},

number = {7},

pages = {937--946},

abstract = {RATIONALE: It is unclear if lung perfusion can predict response to lung volume reduction surgery (LVRS).nnOBJECTIVES: To study the role of perfusion scintigraphy in patient selection for LVRS.nnMETHODS: We performed an intention-to-treat analysis of 1,045 of 1,218 patients enrolled in the National Emphysema Treatment Trial who were non-high risk for LVRS and had complete perfusion scintigraphy results at baseline. The median follow-up was 6.0 years. Patients were classified as having upper or non-upper lobe-predominant emphysema on visual examination of the chest computed tomography and high or low exercise capacity on cardiopulmonary exercise testing at baseline. Low upper zone perfusion was defined as less than 20% of total lung perfusion distributed to the upper third of both lungs as measured on perfusion scintigraphy.nnMEASUREMENTS AND MAIN RESULTS: Among 284 of 1,045 patients with upper lobe-predominant emphysema and low exercise capacity at baseline, the 202 with low upper zone perfusion had lower mortality with LVRS versus medical management (risk ratio [RR], 0.56; P = 0.008) unlike the remaining 82 with high perfusion where mortality was unchanged (RR, 0.97; P = 0.62). Similarly, among 404 of 1,045 patients with upper lobe-predominant emphysema and high exercise capacity, the 278 with low upper zone perfusion had lower mortality with LVRS (RR, 0.70; P = 0.02) unlike the remaining 126 with high perfusion (RR, 1.05; P = 1.00). Among the 357 patients with non-upper lobe-predominant emphysema (75 with low and 282 with high exercise capacity) there was no improvement in survival with LVRS and measurement of upper zone perfusion did not contribute new prognostic information.nnCONCLUSIONS: Compared with optimal medical management, LVRS reduces mortality in patients with upper lobe-predominant emphysema when there is low rather than high perfusion to the upper lung.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid20522794,

title = {Chronic obstructive pulmonary disease phenotypes: the future of COPD},

author = {MeiLan K Han and Alvar Agusti and Peter M Calverley and Bartolome R Celli and Gerard Criner and Jeffrey L Curtis and Leonardo M Fabbri and Jonathan G Goldin and Paul W Jones and William Macnee and Barry J Make and Klaus F Rabe and Stephen I Rennard and Frank C Sciurba and Edwin K Silverman and Jørgen Vestbo and George R Washko and Emiel F M Wouters and Fernando J Martinez},

doi = {10.1164/rccm.200912-1843CC},

issn = {1535-4970},

year  = {2010},

date = {2010-09-01},

journal = {Am J Respir Crit Care Med},

volume = {182},

number = {5},

pages = {598--604},

abstract = {Significant heterogeneity of clinical presentation and disease progression exists within chronic obstructive pulmonary disease (COPD). Although FEV(1) inadequately describes this heterogeneity, a clear alternative has not emerged. The goal of phenotyping is to identify patient groups with unique prognostic or therapeutic characteristics, but significant variation and confusion surrounds use of the term "phenotype" in COPD. Phenotype classically refers to any observable characteristic of an organism, and up until now, multiple disease characteristics have been termed COPD phenotypes. We, however, propose the following variation on this definition: "a single or combination of disease attributes that describe differences between individuals with COPD as they relate to clinically meaningful outcomes (symptoms, exacerbations, response to therapy, rate of disease progression, or death)." This more focused definition allows for classification of patients into distinct prognostic and therapeutic subgroups for both clinical and research purposes. Ideally, individuals sharing a unique phenotype would also ultimately be determined to have a similar underlying biologic or physiologic mechanism(s) to guide the development of therapy where possible. It follows that any proposed phenotype, whether defined by symptoms, radiography, physiology, or cellular or molecular fingerprint will require an iterative validation process in which "candidate" phenotypes are identified before their relevance to clinical outcome is determined. Although this schema represents an ideal construct, we acknowledge any phenotype may be etiologically heterogeneous and that any one individual may manifest multiple phenotypes. We have much yet to learn, but establishing a common language for future research will facilitate our understanding and management of the complexity implicit to this disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid27278798,

title = {Is the E/V p index useful for evaluating prognosis in chronic heart failure with atrial fibrillation? A pilot study},

author = {Alejandro A Diaz and Edgardo M Rodríguez and Eduardo Escudero},

doi = {10.1007/s12574-010-0036-y},

issn = {1349-0222},

year  = {2010},

date = {2010-09-01},

journal = {J Echocardiogr},

volume = {8},

number = {3},

pages = {80--86},

abstract = {BACKGROUND: The ratio of transmitral peak E wave velocity to color flow propagation velocity (E/V p index) has proved to be a significant predictor of prognosis in cardiac diseases with sinus rhythm. However, its usefulness in patients with atrial fibrillation (AF) and heart failure has not yet been established. The aim of this study was to determine the feasibility of using the E/V p index for the prediction of mortality and heart failure hospitalization in this group.nnMETHODS: We studied 66 ambulatory patients with stable congestive heart failure (CHF) functional class I-III and AF. Patients were divided into group A and B according to an E/V p index <1.5 and ≥1.5, respectively.nnRESULTS: During follow-up (average 430 days) events were more common in group B (75 vs. 17%, log rank test; hazard ratio (HR)  = 6.8). By means of multivariate logistic regression analysis, E/V p proved to be an independent predictor of events (p = 0.0012).nnCONCLUSIONS: In our patients with stable CHF and AF the E/V p index is a significant predictor of clinical outcome.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid20651191,

title = {Quantitative assessment of bronchial wall attenuation with thin-section CT: An indicator of airflow limitation in chronic obstructive pulmonary disease},

author = {Tsuneo Yamashiro and Shin Matsuoka and Raúl San José Estépar and Mark T Dransfield and Alejandro Diaz and John J Reilly and Samuel Patz and Sadayuki Murayama and Edwin K Silverman and Hiroto Hatabu and George R Washko},

doi = {10.2214/AJR.09.3653},

issn = {1546-3141},

year  = {2010},

date = {2010-08-01},

journal = {AJR Am J Roentgenol},

volume = {195},

number = {2},

pages = {363--369},

abstract = {OBJECTIVE: The purpose of this study was to evaluate the relation between bronchial wall attenuation on thin-section CT images and airflow limitation in persons with chronic obstructive pulmonary disease.nnSUBJECTS AND METHODS: One hundred fourteen subjects (65 men, 49 women; age range, 56-74 years) enrolled in the National Lung Screening Trial underwent chest CT and prebronchodilation spirometry at a single institution. At CT, mean peak wall attenuation, wall area percentage, and luminal area were measured in the third, fourth, and fifth generations of the right B(1) and B(10) segmental bronchi. Correlations with forced expiratory volume in the first second of expiration (FEV(1)) expressed as percentage of predicted value were evaluated with Spearman's rank correlation test.nnRESULTS: The peak wall attenuation of each generation of segmental bronchi correlated significantly with FEV(1) as percentage of predicted value (B(1) third, r = -0.323, p = 0.0005; B(1) fourth, r = -0.406, p < 0.0001; B(1) fifth, r = -0.478, p < 0.0001; B(10) third, r = -0.268, p = 0.004; B(10) fourth, r = -0.476, p < 0.0001; B(10) fifth, r = -0.548, p < 0.0001). The correlation coefficients were higher in peripheral airway generations. Wall area percentage and luminal area had similar significant correlations. In multivariate analysis to predict FEV(1) as percentage of predicted value, the coefficient of determination of the model with the combination of percentage of low-attenuation area (< -950 HU) and peak wall attenuation of the fifth generation of the right B(10) was 0.484; the coefficient of determination with percentage of low-attenuation area and wall area percentage was 0.40.nnCONCLUSION: Peak attenuation of the bronchial wall measured at CT correlates significantly with expiratory airflow obstruction in subjects with chronic obstructive pulmonary disease, particularly in the distal airways.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid20385477,

title = {Relationship of emphysema and airway disease assessed by CT to exercise capacity in COPD},

author = {Alejandro A Diaz and Brian Bartholmai and Raúl San José Estépar and James Ross and Shin Matsuoka and Tsuneo Yamashiro and Hiroto Hatabu and John J Reilly and Edwin K Silverman and George R Washko},

doi = {10.1016/j.rmed.2010.02.023},

issn = {1532-3064},

year  = {2010},

date = {2010-08-01},

journal = {Respir Med},

volume = {104},

number = {8},

pages = {1145--1151},

abstract = {OBJECTIVE: To assess the association of emphysema and airway disease assessed by volumetric computed tomography (CT) with exercise capacity in subjects with chronic obstructive pulmonary disease (COPD).nnMETHODS: We studied 93 subjects with COPD (Forced Expiratory Volume in 1 s [FEV(1)] %predicted mean +/- SD 57.1 +/- 24.3%, female gender = 40) enrolled in the Lung Tissue Research Consortium. Emphysema was defined as percentage of low attenuation areas less than a threshold of -950 Hounsfield units (%LAA-950) on CT scan. The wall area percentage (WA%) of the 3rd to 6th generations of the apical bronchus of right upper lobe (RB1) were analyzed. The 6-min walk distance (6MWD) test was used as a measure of exercise capacity.nnRESULTS: The 6MWD was inversely associated with %LAA-950 (r = -0.53, p < 0.0001) and with the WA% of 6th generation of RB1 only (r = -0.28, p = 0.009). In a multivariate regression model including CT indices of emphysema and airway disease that were adjusted for demographic and physiologic variables as well as brand of CT scanner, only the %LAA-950 remained significantly associated with exercise performance. Holding other covariates fixed, this model showed that a 10% increase of CT emphysema reduced the distance walked in 6 min 28.6 m (95% Confidence Interval = -51.2, -6.0, p = 0.01).nnCONCLUSION: These results suggest that the extent of emphysema but not airway disease measured by volumetric CT contributes independently to exercise limitation in subjects with COPD.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid20496297,

title = {Diagnostic imaging in COPD},

author = {George R Washko},

doi = {10.1055/s-0030-1254068},

issn = {1098-9048},

year  = {2010},

date = {2010-06-01},

journal = {Semin Respir Crit Care Med},

volume = {31},

number = {3},

pages = {276--285},

abstract = {Chronic obstructive pulmonary disease (COPD) is a pathological pulmonary condition characterized by expiratory airflow obstruction due to emphysematous destruction of the lung parenchyma and small airways remodeling. Although spirometry is a very useful diagnostic tool for screening large groups of smokers, it cannot readily differentiate the etiologies of COPD and thus has limited utility in characterizing subjects for clinical and investigational purposes. There has been a longstanding interest in thoracic imaging and its role in the in vivo characterization of smoking-related lung disease. Research in this area has spanned readily available modalities such as chest -ray and computed tomography to more advanced imaging techniques such as optical coherence tomography (OCT) and magnetic resonance imaging (MRI). Although the chest x-ray is almost universally available, it lacks sensitivity in detecting both airway disease and mild emphysema and is not generally amenable to objective analysis. Computed tomography has become the standard modality to objectively visualize lung disease. It can provide useful measures of the presence and extent of emphysema, airway disease, and, more recently, pulmonary vascular disease for clinical correlation. It does, however, face limitations in standardization across brands and generations of scanners, and the ionizing radiation associated with image acquisition is of concern to both patients and health care providers. Newer techniques such as OCT and MRI offer exciting in vivo insights into lung structure and function that were previously available only in necropsy specimens and physiology laboratories. Given the more limited availability of these techniques, they will be viewed here as adjuncts to computed tomographic imaging.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid20060751,

title = {Collapsibility of lung volume by paired inspiratory and expiratory CT scans: correlations with lung function and mean lung density},

author = {Tsuneo Yamashiro and Shin Matsuoka and Brian J Bartholmai and Raúl San José Estépar and James C Ross and Alejandro Diaz and Sadayuki Murayama and Edwin K Silverman and Hiroto Hatabu and George R Washko},

doi = {10.1016/j.acra.2009.11.004},

issn = {1878-4046},

year  = {2010},

date = {2010-04-01},

journal = {Acad Radiol},

volume = {17},

number = {4},

pages = {489--495},

abstract = {RATIONALE AND OBJECTIVES: To evaluate the relationship between measurements of lung volume (LV) on inspiratory/expiratory computed tomography (CT) scans, pulmonary function tests (PFT), and CT measurements of emphysema in individuals with chronic obstructive pulmonary disease.nnMATERIALS AND METHODS: Forty-six smokers (20 females and 26 males; age range 46-81 years), enrolled in the Lung Tissue Research Consortium, underwent PFT and chest CT at full inspiration and expiration. Inspiratory and expiratory LV values were automatically measured by open-source software, and the expiratory/inspiratory (E/I) ratio of LV was calculated. Mean lung density (MLD) and low attenuation area percent (<-950 HU) were also measured. Correlations of LV measurements with lung function and other CT indices were evaluated by the Spearman rank correlation test.nnRESULTS: LV E/I ratio significantly correlated with the following: the percentage of predicted value of forced expiratory volume in the first second (FEV(1)), the ratio of FEV(1) to forced vital capacity (FVC), and the ratio of residual volume (RV) to total lung capacity (TLC) (FEV(1)%P, R = -0.56, P < .0001; FEV(1)/FVC, r = -0.59, P < .0001; RV/TLC, r = 0.57, P < .0001, respectively). A higher correlation coefficient was observed between expiratory LV and expiratory MLD (r = -0.73, P < .0001) than between inspiratory LV and inspiratory MLD (r = -0.46, P < .01). LV E/I ratio showed a very strong correlation to MLD E/I ratio (r = 0.95, P < .0001).nnCONCLUSIONS: LV E/I ratio can be considered to be equivalent to MLD E/I ratio and to reflect airflow limitation and air-trapping. Higher collapsibility of lung volume, observed by inspiratory/expiratory CT, indicates less severe conditions in chronic obstructive pulmonary disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid20233420,

title = {Cluster analysis in severe emphysema subjects using phenotype and genotype data: an exploratory investigation},

author = {Michael H Cho and George R Washko and Thomas J Hoffmann and Gerard J Criner and Eric A Hoffman and Fernando J Martinez and Nan Laird and John J Reilly and Edwin K Silverman},

doi = {10.1186/1465-9921-11-30},

issn = {1465-993X},

year  = {2010},

date = {2010-03-01},

journal = {Respir Res},

volume = {11},

number = {1},

pages = {30},

abstract = {BACKGROUND: Numerous studies have demonstrated associations between genetic markers and COPD, but results have been inconsistent. One reason may be heterogeneity in disease definition. Unsupervised learning approaches may assist in understanding disease heterogeneity.nnMETHODS: We selected 31 phenotypic variables and 12 SNPs from five candidate genes in 308 subjects in the National Emphysema Treatment Trial (NETT) Genetics Ancillary Study cohort. We used factor analysis to select a subset of phenotypic variables, and then used cluster analysis to identify subtypes of severe emphysema. We examined the phenotypic and genotypic characteristics of each cluster.nnRESULTS: We identified six factors accounting for 75% of the shared variability among our initial phenotypic variables. We selected four phenotypic variables from these factors for cluster analysis: 1) post-bronchodilator FEV1 percent predicted, 2) percent bronchodilator responsiveness, and quantitative CT measurements of 3) apical emphysema and 4) airway wall thickness. K-means cluster analysis revealed four clusters, though separation between clusters was modest: 1) emphysema predominant, 2) bronchodilator responsive, with higher FEV1; 3) discordant, with a lower FEV1 despite less severe emphysema and lower airway wall thickness, and 4) airway predominant. Of the genotypes examined, membership in cluster 1 (emphysema-predominant) was associated with TGFB1 SNP rs1800470.nnCONCLUSIONS: Cluster analysis may identify meaningful disease subtypes and/or groups of related phenotypic variables even in a highly selected group of severe emphysema subjects, and may be useful for genetic association studies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid20186780,

title = {Pulmonary function and emphysema in Williams-Beuren syndrome},

author = {Emily S Wan and Barbara R Pober and George R Washko and Benjamin A Raby and Edwin K Silverman},

doi = {10.1002/ajmg.a.33300},

issn = {1552-4833},

year  = {2010},

date = {2010-03-01},

journal = {Am J Med Genet A},

volume = {152A},

number = {3},

pages = {653--656},

abstract = {Williams-Beuren syndrome (WBS) is caused by a submicroscopic deletion on chromosome 7q11.23 that encompasses the entire elastin (ELN) gene. Elastin, a key component of elastic fibers within the lung, is progressively destroyed in emphysema. Defects in the elastin gene have been associated with increased susceptibility towards developing chronic obstructive pulmonary disease (COPD) and emphysema in both humans and mice. We postulate that hemizygosity at the elastin gene locus may increase susceptibility towards the development of COPD and emphysema in subjects with WBS. We describe an adult subject with WBS who was a lifelong non-smoker and was found to have moderate emphysema. We also examined the pulmonary function of a separate cohort of adolescents and young adults with WBS. Although no significant spirometric abnormalities were identified, a significant proportion of subjects reported respiratory symptoms. Thus, while significant obstructive disease does not appear to be common in relatively young adults with WBS, subclinical emphysema and lung disease may exist which possibly could worsen with advancing age. Further investigation may elucidate the pathogenesis of non-smoking-related emphysema.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid19965810,

title = {Physiological and computed tomographic predictors of outcome from lung volume reduction surgery},

author = {George R Washko and Fernando J Martinez and Eric A Hoffman and Stephen H Loring and Raúl San José Estépar and Alejandro A Diaz and Frank C Sciurba and Edwin K Silverman and MeiLan K Han and Malcolm Decamp and John J Reilly and },

doi = {10.1164/rccm.200906-0911OC},

issn = {1535-4970},

year  = {2010},

date = {2010-03-01},

journal = {Am J Respir Crit Care Med},

volume = {181},

number = {5},

pages = {494--500},

abstract = {RATIONALE: Previous investigations have identified several potential predictors of outcomes from lung volume reduction surgery (LVRS). A concern regarding these studies has been their small sample size, which may limit generalizability. We therefore sought to examine radiographic and physiologic predictors of surgical outcomes in a large, multicenter clinical investigation, the National Emphysema Treatment Trial.nnOBJECTIVES: To identify objective radiographic and physiological indices of lung disease that have prognostic value in subjects with chronic obstructive pulmonary disease being evaluated for LVRS.nnMETHODS: A subset of the subjects undergoing LVRS in the National Emphysema Treatment Trial underwent preoperative high-resolution computed tomographic (CT) scanning of the chest and measures of static lung recoil at total lung capacity (SRtlc) and inspiratory resistance (Ri). The relationship between CT measures of emphysema, the ratio of upper to lower zone emphysema, CT measures of airway disease, SRtlc, Ri, the ratio of residual volume to total lung capacity (RV/TLC), and both 6-month postoperative changes in FEV(1) and maximal exercise capacity were assessed.nnMEASUREMENTS AND MAIN RESULTS: Physiological measures of lung elastic recoil and inspiratory resistance were not correlated with improvement in either the FEV(1) (R = -0.03, P = 0.78 and R = -0.17, P = 0.16, respectively) or maximal exercise capacity (R = -0.02, P = 0.83 and R = 0.08, P = 0.53, respectively). The RV/TLC ratio and CT measures of emphysema and its upper to lower zone ratio were only weakly predictive of postoperative changes in both the FEV(1) (R = 0.11, P = 0.01; R = 0.2, P < 0.0001; and R = 0.23, P < 0.0001, respectively) and maximal exercise capacity (R = 0.17, P = 0.0001; R = 0.15, P = 0.002; and R = 0.15, P = 0.002, respectively). CT assessments of airway disease were not predictive of change in FEV(1) or exercise capacity in this cohort.nnCONCLUSIONS: The RV/TLC ratio and CT measures of emphysema and its distribution are weak but statistically significant predictors of outcome after LVRS.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid19875683,

title = {Pulmonary hypertension and computed tomography measurement of small pulmonary vessels in severe emphysema},

author = {Shin Matsuoka and George R Washko and Tsuneo Yamashiro and Raul San Jose Estepar and Alejandro Diaz and Edwin K Silverman and Eric Hoffman and Henry E Fessler and Gerard J Criner and Nathaniel Marchetti and Steven M Scharf and Fernando J Martinez and John J Reilly and Hiroto Hatabu and },

doi = {10.1164/rccm.200908-1189OC},

issn = {1535-4970},

year  = {2010},

date = {2010-02-01},

journal = {Am J Respir Crit Care Med},

volume = {181},

number = {3},

pages = {218--225},

abstract = {RATIONALE: Vascular alteration of small pulmonary vessels is one of the characteristic features of pulmonary hypertension in chronic obstructive pulmonary disease. The in vivo relationship between pulmonary hypertension and morphological alteration of the small pulmonary vessels has not been assessed in patients with severe emphysema.nnOBJECTIVES: We evaluated the correlation of total cross-sectional area of small pulmonary vessels (CSA) assessed on computed tomography (CT) scans with the degree of pulmonary hypertension estimated by right heart catheterization.nnMETHODS: In 79 patients with severe emphysema enrolled in the National Emphysema Treatment Trial (NETT), we measured CSA less than 5 mm(2) (CSA(<5)) and 5 to 10 mm(2) (CSA(5-10)), and calculated the percentage of total CSA for the lung area (%CSA(<5) and %CSA(5-10), respectively). The correlations of %CSA(<5) and %CSA(5-10) with pulmonary arterial mean pressure (Ppa) obtained by right heart catheterization were evaluated. Multiple linear regression analysis using Ppa as the dependent outcome was also performed.nnMEASUREMENTS AND MAIN RESULTS: The %CSA(<5) had a significant negative correlation with Ppa (r = -0.512, P < 0.0001), whereas the correlation between %CSA(5-10) and Ppa did not reach statistical significance (r = -0.196, P = 0.083). Multiple linear regression analysis showed that %CSA(<5) and diffusing capacity of carbon monoxide (DL(CO)) % predicted were independent predictors of Ppa (r(2) = 0.541): %CSA (<5) (P < 0.0001), and DL(CO) % predicted (P = 0.022).nnCONCLUSIONS: The %CSA(<5) measured on CT images is significantly correlated to Ppa in severe emphysema and can estimate the degree of pulmonary hypertension.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid20378064,

title = {Volumetric expiratory HRCT of the lung: clinical applications},

author = {Mizuki Nishino and George R Washko and Hiroto Hatabu},

doi = {10.1016/j.thorsurg.2009.12.009},

issn = {1547-4127},

year  = {2010},

date = {2010-02-01},

journal = {Thorac Surg Clin},

volume = {20},

number = {1},

pages = {121--7, viii--ix},

abstract = {Expiratory high-resolution CT (HRCT) of the chest offers a powerful adjunct to inspiratory HRCT in the detection of lung diseases involving the small airways. In 2003 a clinical HRCT scan protocol was developed. It has since been used for evaluation of diffuse lung disease with suspected airway abnormalities. It provides volumetric assessment of the entire thorax at end-inspiration and at end-expiration, and allows for detailed analysis of the airway and parenchyma. It offers a powerful adjunct to inspiratory HRCT in the detection of lung diseases involving the small airways. This article explores its clinical applications for chronic obstructive pulmonary disease, bronchiectasis, and sarcoidosis. It concludes that standardization of image acquisition and post-processing in CT examinations will be necessary for the real application of quantitative data derived from volumetric expiratory HRCT to daily clinical medical practice.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid20879396,

title = {Automatic lung lobe segmentation using particles, thin plate splines, and maximum a posteriori estimation},

author = {James C Ross and Rail San José Estépar and Gordon Kindlmann and Alejandro Díaz and Carl-Fredrik Westin and Edwin K Silverman and George R Washko},

doi = {10.1007/978-3-642-15711-0_21},

year  = {2010},

date = {2010-01-01},

journal = {Med Image Comput Comput Assist Interv},

volume = {13},

number = {Pt 3},

pages = {163--171},

abstract = {We present a fully automatic lung lobe segmentation algorithm that is effective in high resolution computed tomography (CT) datasets in the presence of confounding factors such as incomplete fissures (anatomical structures indicating lobe boundaries), advanced disease states, high body mass index (BMI), and low-dose scanning protocols. In contrast to other algorithms that leverage segmentations of auxiliary structures (esp. vessels and airways), we rely only upon image features indicating fissure locations. We employ a particle system that samples the image domain and provides a set of candidate fissure locations. We follow this stage with maximum a posteriori (MAP) estimation to eliminate poor candidates and then perform a post-processing operation to remove remaining noise particles. We then fit a thin plate spline (TPS) interpolating surface to the fissure particles to form the final lung lobe segmentation. Results indicate that our algorithm performs comparably to pulmonologist-generated lung lobe segmentations on a set of challenging cases.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid19781963,

title = {Identification of early interstitial lung disease in smokers from the COPDGene Study},

author = {George R Washko and David A Lynch and Shin Matsuoka and James C Ross and Shigeaki Umeoka and Alejandro Diaz and Frank C Sciurba and Gary M Hunninghake and Raúl San José Estépar and Edwin K Silverman and Ivan O Rosas and Hiroto Hatabu},

doi = {10.1016/j.acra.2009.07.016},

issn = {1878-4046},

year  = {2010},

date = {2010-01-01},

journal = {Acad Radiol},

volume = {17},

number = {1},

pages = {48--53},

abstract = {RATIONALE AND OBJECTIVES: The aim of this study is to compare two subjective methods for the identification of changes suggestive of early interstitial lung disease (ILD) on chest computed tomographic (CT) scans.nnMATERIALS AND METHODS: The CT scans of the first 100 subjects enrolled in the COPDGene Study from a single institution were examined using a sequential reader and a group consensus interpretation scheme. CT scans were evaluated for the presence of parenchymal changes consistent with ILD using the following scoring system: 0 = normal, 1 = equivocal for the presence of ILD, 2 = highly suspicious for ILD, and 3 = classic ILD changes. A statistical comparison of patients with early ILD to normal subjects was performed.nnRESULTS: There was a high degree of agreement between methods (kappa = 0.84; 95% confidence interval, 0.73-0.94; P < .0001 for the sequential and consensus methods). The sequential reading method had both high positive (1.0) and negative (0.97) predictive values for a consensus read despite a 58% reduction in the number of chest CT evaluations. Regardless of interpretation method, the prevalence of chest CT changes consistent with early ILD in this subset of smokers from COPDGene varied between 5% and 10%. Subjects with early ILD tended to have greater tobacco smoke exposure than subjects without early ILD (P = .053).nnCONCLUSIONS: A sequential CT interpretation scheme is an efficient method for the visual interpretation of CT data. Further investigation is required to independently confirm our findings and further characterize early ILD in smokers.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid20083585,

title = {Quantitative CT assessment of chronic obstructive pulmonary disease},

author = {Shin Matsuoka and Tsuneo Yamashiro and George R Washko and Yasuyuki Kurihara and Yasuo Nakajima and Hiroto Hatabu},

doi = {10.1148/rg.301095110},

issn = {1527-1323},

year  = {2010},

date = {2010-01-01},

journal = {Radiographics},

volume = {30},

number = {1},

pages = {55--66},

abstract = {Chronic obstructive pulmonary disease (COPD) is characterized by the presence of airflow limitation that is caused by a combination of small airway remodeling and emphysema-induced loss of elastic recoil. The management of COPD depends on the relative distribution and severity of these two pathologic processes, factors that may vary widely even among patients with a similar degree of airflow limitation. Standard lung function testing with spirometry is unhelpful for distinguishing the specific contribution of each process. Pathologic changes such as emphysema and modification of the small and large airways are better evaluated with quantitative analyses of image data from multidetector computed tomography (CT). CT-based quantitative analyses can help differentiate the COPD phenotype (emphysema-predominant, airway-predominant, or mixed), which is crucial information for determining the appropriate management strategy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid19796970,

title = {Quantitative CT measurement of cross-sectional area of small pulmonary vessel in COPD: correlations with emphysema and airflow limitation},

author = {Shin Matsuoka and George R Washko and Mark T Dransfield and Tsuneo Yamashiro and Raul San Jose Estepar and Alejandro Diaz and Edwin K Silverman and Samuel Patz and Hiroto Hatabu},

doi = {10.1016/j.acra.2009.07.022},

issn = {1878-4046},

year  = {2010},

date = {2010-01-01},

journal = {Acad Radiol},

volume = {17},

number = {1},

pages = {93--99},

abstract = {RATIONALE AND OBJECTIVES: Pulmonary vascular alteration is one of the characteristic features of chronic obstructive pulmonary disease (COPD). Recent studies suggest that vascular alteration is closely related to endothelial dysfunction and may be further influenced by emphysema. However, the relationship between morphological alteration of small pulmonary vessels and the extent of emphysema has not been assessed in vivo. The objectives of this study are: to evaluate the correlation of total cross-sectional area (CSA) of small pulmonary vessels with the extent of emphysema and airflow obstruction using CT scans and to assess the difference of total CSA between COPD phenotypes.nnMATERIALS AND METHODS: We measured CSA less than 5 mm(2) and 5-10 mm(2), and calculated the percentage of the total CSA for the lung area (%CSA < 5, and %CSA5-10, respectively) using CT scans in 191 subjects. The extent of emphysema (%LAA-950) was calculated, and the correlations of %CSA < 5 and %CSA5-10 with %LAA-950 and results of pulmonary function tests (PFTs) were evaluated. The differences in %CSA between COPD phenotypes were also assessed.nnRESULTS: The %CSA < 5 had significant negative correlations with %LAA-950 (r = -0.83, P < .0001). There was a weak but statistically significant correlation of %CSA < 5 with forced expiratory volume in 1 second (FEV1)% predicted (r = 0.29, P < .0001) and FEV1/forced vital capacity (r = 0.45, P < .0001). A %CSA 5-10 had weak correlations with %LAA-950 and results of PFTs. %CSA < 5 was significantly higher in bronchitis phenotype than in the emphysema phenotype (P < .0001).nnCONCLUSIONS: Total CSA of small pulmonary vessels at sub-subsegmental levels strongly correlates with the extent of emphysema (%LAA-950) and reflects differences between COPD phenotypes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid19995635,

title = {Volumetric expiratory HRCT of the lung: clinical applications},

author = {Mizuki Nishino and George R Washko and Hiroto Hatabu},

doi = {10.1016/j.rcl.2009.09.003},

issn = {1557-8275},

year  = {2010},

date = {2010-01-01},

journal = {Radiol Clin North Am},

volume = {48},

number = {1},

pages = {177--183},

abstract = {Expiratory high-resolution CT (HRCT) of the chest offers a powerful adjunct to inspiratory HRCT in the detection of lung diseases involving the small airways. In 2003 a clinical HRCT scan protocol was developed. It has since been used for evaluation of diffuse lung disease with suspected airway abnormalities. It provides volumetric assessment of the entire thorax at end-inspiration and at end-expiration, and allows for detailed analysis of the airway and parenchyma. It offers a powerful adjunct to inspiratory HRCT in the detection of lung diseases involving the small airways. This article explores its clinical applications for chronic obstructive pulmonary disease, bronchiectasis, and sarcoidosis. It concludes that standardization of image acquisition and post-processing in CT examinations will be necessary for the real application of quantitative data derived from volumetric expiratory HRCT to daily clinical medical practice.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid19938971,

title = {Quantitative airway assessment on computed tomography in patients with alpha1-antitrypsin deficiency},

author = {Tsuneo Yamashiro and Shin Matsuoka and Raúl San José Estépar and Alejandro Diaz and John D Newell and Robert A Sandhaus and Patricia J Mergo and Mark L Brantly and Sadayuki Murayama and John J Reilly and Hiroto Hatabu and Edwin K Silverman and George R Washko},

doi = {10.3109/15412550903341521},

issn = {1541-2563},

year  = {2009},

date = {2009-12-01},

journal = {COPD},

volume = {6},

number = {6},

pages = {468--477},

abstract = {The relationship between quantitative airway measurements on computed tomography (CT) and airflow limitation in individuals with severe alpha (1)-antitrypsin deficiency (AATD) is undefined. Thus, we planned to clarify the relationship between CT-based airway indices and airflow limitation in AATD. 52 patients with AATD underwent chest CT and pre-bronchodilator spirometry at three institutions. In the right upper (RUL) and lower (RLL) lobes, wall area percent (WA%) and luminal area (Ai) were measured in the third, fourth, and fifth generations of the bronchi. The severity of emphysema was also calculated in each lobe and expressed as low attenuation area percent (LAA%). Correlations between obtained measurements and FEV(1)% predicted (FEV(1)%P) were evaluated by the Spearman rank correlation test. In RUL, WA% of all generations was significantly correlated with FEV(1)%P (3rd, R = -0.33, p = 0.02; 4th, R = -0.39, p = 0.004; 5th, R = -0.57, p < 0.001; respectively). Ai also showed significant correlations (3rd, R = 0.32, p = 0.02; 4th, R = 0.34, p = 0.01; 5th, R = 0.56, p < 0.001; respectively). Measured correlation coefficients improved when the airway progressed distally from the third to fifth generations. LAA% also correlated with FEV(1)%P (R = -0.51, p < 0.001). In RLL, WA% showed weak correlations with FEV(1)%P in all generations (3rd, R = -0.34, p = 0.01; 4th, R = -0.30, p = 0.03; 5th, R = -0.31, p = 0.03; respectively). Only Ai from the fifth generation significantly correlated with FEV(1)%P in this lobe (R = 0.34, p = 0.01). LAA% strongly correlated with FEV(1)%P (R = -0.71, p < 0.001). We conclude therefore that quantitative airway measurements are significantly correlated with airflow limitation in AATD, particularly in the distal airways of RUL. Emphysema of the lower lung is the predominant component; however, airway disease also has a significant impact on airflow limitation in AATD.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid20033331,

title = {Towards real time 2D to 3D registration for ultrasound-guided endoscopic and laparoscopic procedures},

author = {Raúl San José Estépar and Carl-Fredrik Westin and Kirby G Vosburgh},

doi = {10.1007/s11548-009-0369-z},

issn = {1861-6429},

year  = {2009},

date = {2009-11-01},

journal = {Int J Comput Assist Radiol Surg},

volume = {4},

number = {6},

pages = {549--560},

abstract = {PURPOSE: A method to register endoscopic and laparoscopic ultrasound (US) images in real time with pre-operative computed tomography (CT) data sets has been developed with the goal of improving diagnosis, biopsy guidance, and surgical interventions in the abdomen.nnMETHODS: The technique, which has the potential to operate in real time, is based on a new phase correlation technique: LEPART, which specifies the location of a plane in the CT data which best corresponds to the US image. Validation of the method was carried out using an US phantom with cyst regions and with retrospective analysis of data sets from animal model experiments.nnRESULTS: The phantom validation study shows that local translation displacements can be recovered for each US frame with a root mean squared error of 1.56 +/- 0.78 mm in less than 5 sec, using non-optimized algorithm implementations.nnCONCLUSION: A new method for multimodality (preoperative CT and intraoperative US endoscopic images) registration to guide endoscopic interventions was developed and found to be efficient using clinically realistic datasets. The algorithm is inherently capable of being implemented in a parallel computing system so that full real time operation appears likely.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid19556517,

title = {Superior immune response to protein-conjugate versus free pneumococcal polysaccharide vaccine in chronic obstructive pulmonary disease},

author = {Mark T Dransfield and Moon H Nahm and Meilan K Han and Sarah Harnden and Gerard J Criner and Fernando J Martinez and Paul D Scanlon and Prescott G Woodruff and George R Washko and John E Connett and Nicholas R Anthonisen and William C Bailey and },

doi = {10.1164/rccm.200903-0488OC},

issn = {1535-4970},

year  = {2009},

date = {2009-09-01},

journal = {Am J Respir Crit Care Med},

volume = {180},

number = {6},

pages = {499--505},

abstract = {RATIONALE: Debate exists about the immunogenicity and protective efficacy of antibodies produced by the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in chronic obstructive pulmonary disease (COPD). The 7-valent diphtheria-conjugated pneumococcal polysaccharide vaccine (PCV7) induces a more robust immune response than PPSV23 in healthy elderly adults.nnOBJECTIVES: We hypothesized that serotype-specific IgG antibody concentration and functional antibody activity would be superior after PCV7 vaccination compared with PPSV23 in moderate to severe COPD. We also posited that older age and prior PPSV23 vaccination would be associated with reduced vaccine responsiveness.nnMETHODS: One hundred twenty patients with COPD were randomized to PPSV23 (63 subjects) or PCV7 (57 subjects). IgG concentrations were determined by ELISA; functional antibody activity was assayed with a standardized opsonophagocytosis assay and reported as an opsonization killing index (OPK). Increases in serotype-specific IgG and OPK at 1 month post vaccination were compared within and between vaccine groups.nnMEASUREMENTS AND MAIN RESULTS: Both vaccines were well tolerated. Within each study group, postvaccination IgG and OPK were higher than baseline (P < 0.01) for all serotypes. Adjusted for baseline levels, postvaccination IgG was higher in the PCV7 group than the PPSV23 group for all seven serotypes, reaching statistical significance for five (P < 0.05). PCV7 resulted in a higher OPK for six of seven serotypes (statistically greater for four) compared with PPSV23. In multivariate analyses, younger age, vaccine naivety, and receipt of PCV7 were associated with increased OPK responses.nnCONCLUSIONS: PCV7 induces a superior immune response at 1 month post vaccination compared with PPSV23 in COPD. Older age and prior PPSV23 reduce vaccine responsiveness. Clinical trial registered with www.clinicaltrials.gov (NCT00457977).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid19411295,

title = {CT metrics of airway disease and emphysema in severe COPD},

author = {Woo Jin Kim and Edwin K Silverman and Eric Hoffman and Gerard J Criner and Zab Mosenifar and Frank C Sciurba and Barry J Make and Vincent Carey and Raúl San José Estépar and Alejandro Diaz and John J Reilly and Fernando J Martinez and George R Washko and },

doi = {10.1378/chest.08-2858},

issn = {1931-3543},

year  = {2009},

date = {2009-08-01},

journal = {Chest},

volume = {136},

number = {2},

pages = {396--404},

abstract = {BACKGROUND: CT scan measures of emphysema and airway disease have been correlated with lung function in cohorts of subjects with a range of COPD severity. The contribution of CT scan-assessed airway disease to objective measures of lung function and respiratory symptoms such as dyspnea in severe emphysema is less clear.nnMETHODS: Using data from 338 subjects in the National Emphysema Treatment Trial (NETT) Genetics Ancillary Study, densitometric measures of emphysema using a threshold of -950 Hounsfield units (%LAA-950) and airway wall phenotypes of the wall thickness (WT) and the square root of wall area (SRWA) of a 10-mm luminal perimeter airway were calculated for each subject. Linear regression analysis was performed for outcome variables FEV(1) and percent predicted value of FEV(1) with CT scan measures of emphysema and airway disease.nnRESULTS: In univariate analysis, there were significant negative correlations between %LAA-950 and both the WT (r = -0.28, p = 0.0001) and SRWA (r = -0.19, p = 0.0008). Airway wall thickness was weakly but significantly correlated with postbronchodilator FEV(1)% predicted (R = -0.12, p = 0.02). Multivariate analysis showed significant associations between either WT or SRWA (beta = -5.2, p = 0.009; beta = -2.6, p = 0.008, respectively) and %LAA-950 (beta = -10.6, p = 0.03) with the postbronchodilator FEV(1)% predicted. Male subjects exhibited significantly thicker airway wall phenotypes (p = 0.007 for WT and p = 0.0006 for SRWA).nnCONCLUSIONS: Airway disease and emphysema detected by CT scanning are inversely related in patients with severe COPD. Airway wall phenotypes were influenced by gender and associated with lung function in subjects with severe emphysema.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid19407254,

title = {Airway wall attenuation: a biomarker of airway disease in subjects with COPD},

author = {George R Washko and Mark T Dransfield and Raúl San José Estépar and Alejandro Diaz and Shin Matsuoka and Tsuneo Yamashiro and Hiroto Hatabu and Edwin K Silverman and William C Bailey and John J Reilly},

doi = {10.1152/japplphysiol.00216.2009},

issn = {8750-7587},

year  = {2009},

date = {2009-07-01},

journal = {J Appl Physiol (1985)},

volume = {107},

number = {1},

pages = {185--191},

abstract = {The computed tomographic (CT) densities of imaged structures are a function of the CT scanning protocol, the structure size, and the structure density. For objects that are of a dimension similar to the scanner point spread function, CT will underestimate true structure density. Prior investigation suggests that this process, termed contrast reduction, could be used to estimate the strength of thin structures, such as cortical bone. In this investigation, we endeavored to exploit this process to provide a CT-based measure of airway disease that can assess changes in airway wall thickening and density that may be associated with the mural remodeling process in subjects with chronic obstructive pulmonary disease (COPD). An initial computer-based study using a range of simulated airway wall sizes and densities suggested that CT measures of airway wall attenuation could detect changes in both wall thickness and structure density. A second phantom-based study was performed using a series of polycarbonate tubes of known density. The results of this again demonstrated the process of contrast reduction and further validated the computer-based simulation. Finally, measures of airway wall attenuation, wall thickness, and wall area (WA) divided by total cross-sectional area, WA percent (WA%), were performed in a cohort of 224 subjects with COPD and correlated with spirometric measures of lung function. The results of this analysis demonstrated that wall attenuation is comparable to WA% in predicting lung function on univariate correlation and remain as a statistically significant correlate to the percent forced expiratory volume in 1 s predicted when adjusted for measures of both emphysema and WA%. These latter findings suggest that the quantitative assessment of airway wall attenuation may offer complementary information to WA% in characterizing airway disease in subjects with COPD.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid20426172,

title = {Lung extraction, lobe segmentation and hierarchical region assessment for quantitative analysis on high resolution computed tomography images},

author = {James C Ross and Raúl San José Estépar and Alejandro Díaz and Carl-Fredrik Westin and Ron Kikinis and Edwin K Silverman and George R Washko},

doi = {10.1007/978-3-642-04271-3_84},

year  = {2009},

date = {2009-01-01},

journal = {Med Image Comput Comput Assist Interv},

volume = {12},

number = {Pt 2},

pages = {690--698},

abstract = {Regional assessment of lung disease (such as chronic obstructive pulmonary disease) is a critical component to accurate patient diagnosis. Software tools than enable such analysis are also important for clinical research studies. In this work, we present an image segmentation and data representation framework that enables quantitative analysis specific to different lung regions on high resolution computed tomography (HRCT) datasets. We present an offline, fully automatic image processing chain that generates airway, vessel, and lung mask segmentations in which the left and right lung are delineated. We describe a novel lung lobe segmentation tool that produces reproducible results with minimal user interaction. A usability study performed across twenty datasets (inspiratory and expiratory exams including a range of disease states) demonstrates the tool's ability to generate results within five to seven minutes on average. We also describe a data representation scheme that involves compact encoding of label maps such that both "regions" (such as lung lobes) and "types" (such as emphysematous parenchyma) can be simultaneously represented at a given location in the HRCT.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid19834216,

title = {Sampling and visualizing creases with scale-space particles},

author = {Gordon L Kindlmann and Raúl San José Estépar and Stephen M Smith and Carl-Fredrik Westin},

doi = {10.1109/TVCG.2009.177},

issn = {1077-2626},

year  = {2009},

date = {2009-01-01},

journal = {IEEE Trans Vis Comput Graph},

volume = {15},

number = {6},

pages = {1415--1424},

abstract = {Particle systems have gained importance as a methodology for sampling implicit surfaces and segmented objects to improve mesh generation and shape analysis. We propose that particle systems have a significantly more general role in sampling structure from unsegmented data. We describe a particle system that computes samplings of crease features (i.e. ridges and valleys, as lines or surfaces) that effectively represent many anatomical structures in scanned medical data. Because structure naturally exists at a range of sizes relative to the image resolution, computer vision has developed the theory of scale-space, which considers an n-D image as an (n+1)-D stack of images at different blurring levels. Our scale-space particles move through continuous four-dimensional scale-space according to spatial constraints imposed by the crease features, a particle-image energy that draws particles towards scales of maximal feature strength, and an inter-particle energy that controls sampling density in space and scale. To make scale-space practical for large three-dimensional data, we present a spline-based interpolation across scale from a small number of pre-computed blurrings at optimally selected scales. The configuration of the particle system is visualized with tensor glyphs that display information about the local Hessian of the image, and the scale of the particle. We use scale-space particles to sample the complex three-dimensional branching structure of airways in lung CT, and the major white matter structures in brain DTI.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid19056714,

title = {Three-dimensional airway measurements and algorithms},

author = {Raúl San José Estépar and John J Reilly and Edwin K Silverman and George R Washko},

doi = {10.1513/pats.200809-104QC},

issn = {1546-3222},

year  = {2008},

date = {2008-12-01},

journal = {Proc Am Thorac Soc},

volume = {5},

number = {9},

pages = {905--909},

abstract = {Advances in high-resolution computed tomography (CT) imaging are making a full three-dimensional analysis of the lungs feasible. In particular, airway morphology can be studied in vivo and quantitative metrics of airway size and shape can be extracted. The thickening process associated with the inflammatory response in the diseased lung can be quantified by means of image processing techniques that extract the airway lumen and airway wall. In this article, we give an overview of these imaging techniques and their diverse nature. We also offer a comprehensive view of the analysis pipeline for three-dimensional airway trees and a validation framework that is needed to compare different techniques.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid18568842,

title = {Computed tomographic-based quantification of emphysema and correlation to pulmonary function and mechanics},

author = {George R Washko and Gerald J Criner and Zab Mohsenifar and Frank C Sciurba and Amir Sharafkhaneh and Barry J Make and Eric A Hoffman and John J Reilly},

doi = {10.1080/15412550802093025},

issn = {1541-2563},

year  = {2008},

date = {2008-06-01},

journal = {COPD},

volume = {5},

number = {3},

pages = {177--186},

abstract = {Computed tomographic based indices of emphysematous lung destruction may highlight differences in disease pathogenesis and further enable the classification of subjects with Chronic Obstructive Pulmonary Disease. While there are multiple techniques that can be utilized for such radiographic analysis, there is very little published information comparing the performance of these methods in a clinical case series. Our objective was to examine several quantitative and semi-quantitative methods for the assessment of the burden of emphysema apparent on computed tomographic scans and compare their ability to predict lung mechanics and function. Automated densitometric analysis was performed on 1094 computed tomographic scans collected upon enrollment into the National Emphysema Treatment Trial. Trained radiologists performed an additional visual grading of emphysema on high resolution CT scans. Full pulmonary function test results were available for correlation, with a subset of subjects having additional measurements of lung static recoil. There was a wide range of emphysematous lung destruction apparent on the CT scans and univariate correlations to measures of lung function were of modest strength. No single method of CT scan analysis clearly outperformed the rest of the group. Quantification of the burden of emphysematous lung destruction apparent on CT scan is a weak predictor of lung function and mechanics in severe COPD with no uniformly superior method found to perform this analysis. The CT based quantification of emphysema may augment pulmonary function testing in the characterization of COPD by providing complementary phenotypic information.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid18453349,

title = {Radiographic evaluation of the potential lung volume reduction surgery candidate},

author = {George R Washko and Eric Hoffman and John J Reilly},

doi = {10.1513/pats.200802-017ET},

issn = {1546-3222},

year  = {2008},

date = {2008-05-01},

journal = {Proc Am Thorac Soc},

volume = {5},

number = {4},

pages = {421--426},

abstract = {Delineating the extent and distribution of emphysema is an essential component of the evaluation of candidates for lung volume reduction surgery (LVRS). Imaging also may identify contraindications to LVRS, including bronchiectasis and pleural scarring. The chest X-ray is of limited utility in LVRS evaluation. Chest computed tomography (CT) scanning is an essential component of the evaluation, demonstrating the presence of emphysema and its amount and distribution. Clinical experience has shown that a substantial minority of chest CT scans will also demonstrate pulmonary nodules, some of which represent lung cancers. Published series, including the National Emphysema Treatment Trial, consistently demonstrate that patients with upper lobe predominant or heterogeneous emphysema are most likely to benefit from LVRS. Heterogeneity and distribution can also be assessed by radionuclide ventilation perfusion scanning, but this modality adds little additional information to CT scanning.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid17962632,

title = {The effect of lung volume reduction surgery on chronic obstructive pulmonary disease exacerbations},

author = {George R Washko and Vincent S Fan and Scott D Ramsey and Zab Mohsenifar and Fernando Martinez and Barry J Make and Frank C Sciurba and Gerald J Criner and Omar Minai and Malcolm M Decamp and John J Reilly and },

doi = {10.1164/rccm.200708-1194OC},

issn = {1535-4970},

year  = {2008},

date = {2008-01-01},

journal = {Am J Respir Crit Care Med},

volume = {177},

number = {2},

pages = {164--169},

abstract = {RATIONALE: Lung volume reduction surgery (LVRS) has been demonstrated to provide a functional and mortality benefit to a select group of subjects with chronic obstructive pulmonary disease (COPD). The effect of LVRS on COPD exacerbations has not been as extensively studied, and whether improvement in postoperative lung function alters the risk of disease exacerbations is not known.nnOBJECTIVES: To examine the effect, and mechanism of potential benefit, of LVRS on COPD exacerbations by comparing the medical and surgical cohorts of the National Emphysema Treatment Trial (NETT).nnMETHODS: A COPD exacerbation was defined using Centers for Medicare and Medicaid Services data and International Classification of Diseases, Ninth Revision, discharge diagnosis.nnMEASUREMENTS AND MAIN RESULTS: There was no difference in exacerbation rate or time to first exacerbation between the medical and surgical cohorts during the year before study randomization (P = 0.58 and 0.85, respectively). Postrandomization, the surgical cohort experienced an approximate 30% reduction in exacerbation frequency (P = 0.0005). This effect was greatest in those subjects with the largest postoperative improvement in FEV(1) (P = 0.04) when controlling for changes in other spirometric measures of lung function, lung capacities, and room air arterial blood gas tensions. Finally, LVRS increased the time to first exacerbation in both those subjects with and those without a prior history of exacerbations (P = 0.0002 and P < 0.0001, respectively).nnCONCLUSIONS: LVRS reduces the frequency of COPD exacerbations and increases the time to first exacerbation. One explanation for this benefit may be the postoperative improvement in lung function.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid18391363,

title = {Image registration assists novice operators in ultrasound assessment of abdominal trauma},

author = {Kirby G Vosburgh and Jeffrey Stoll and Vicki Noble and Kilian Pohl and Raul San José Estepar and Barnabas Takacs},

issn = {0926-9630},

year  = {2008},

date = {2008-01-01},

journal = {Stud Health Technol Inform},

volume = {132},

pages = {532--537},

abstract = {Transcutaneous ultrasound imaging may be used to detect abdominal hemorrhage in the field setting. The Focused Assessment with Sonography for Trauma (FAST) examination was developed to characterize blunt abdominal trauma and has been shown to be effective for assessing penetrating trauma as well. However, it is unlikely that a minimally trained operator could perform a diagnostic examination. In our system, the operator is be supported by real-time 3D volume displays. The operator will be directed through the examination by prompts from a computer system or outside expert, potentially with knowledge of the anatomy of the injured patient. The key elements of the tele-operated FAST exam capability have been demonstrated; the exam is performed with real-time guidance from anatomic images registered to the body. It appears likely that Image Registration will assist hemorrhage detection at the point of injury or in the initial evaluation by a trauma response team.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}