@article {1433722,
	title = {Airway dilation in bronchiolitis obliterans after allogeneic hematopoietic stem cell transplantation},
	journal = {Respir Med},
	volume = {107},
	number = {2},
	year = {2013},
	month = {2013 Feb},
	pages = {276-83},
	abstract = {RATIONALE: Bronchiolitis obliterans syndrome (BOS) is a late, non-infectious pulmonary complication following hematopoietic stem cell transplantation (HSCT). There is minimal data published on quantitative radiologic characterization of airway remodeling in these subjects.

OBJECTIVES: To examine quantitative measurements of airway morphology and their correlation with lung function in a cohort of patients who underwent HSCT and developed BOS.

METHODS: All adult patients who underwent allogeneic HSCT at the Dana-Farber Cancer Institute/Brigham and Women{\textquoteright}s Hospital (n~=~1854) between January 1st 2000 and June 30th 2010 were screened for the development of BOS. Clinically acquired high resolution CT (HRCT) scans of the chest were collected. For each subjects discrete measures of airway wall area were performed and the square root of wall area of a 10-mm luminal perimeter (Pi10) was calculated.

MEASUREMENTS AND MAIN RESULTS: We identified 88 cases of BOS, and 37 of these patients had available HRCT. On CT scans obtained after BOS diagnosis, the Pi10 decreased (consistent with airway dilation) as compared with pre-BOS values (p~,
	keywords = {Adult, Aged, Airway Remodeling, Bronchi, Bronchiolitis Obliterans, Bronchography, Case-Control Studies, Dilatation, Pathologic, Female, Forced Expiratory Volume, Hematopoietic Stem Cell Transplantation, Humans, Male, Middle Aged, Tomography, X-Ray Computed, Vital Capacity, Young Adult},
	issn = {1532-3064},
	doi = {10.1016/j.rmed.2012.11.002},
	author = {Gazourian, Lee and Coronata, Anna Maria F and Rogers, Angela J and Weinhouse, Gerald L and Soiffer, Robert J and Antin, Joseph H and Ritz, Jerome and Ho, Vincent T and Baron, Rebecca M and Washko, George R}
}
@article {1433715,
	title = {Application of high-resolution CT imaging data to lung cancer drug development: measuring progress: workshop IX},
	journal = {J Thorac Oncol},
	volume = {8},
	number = {11},
	year = {2013},
	month = {2013 Nov},
	pages = {1352-5},
	abstract = {BACKGROUND: Lung cancer is the leading cause of cancer death and a major public health challenge across the entire world. Computed tomography (CT) imaging of the lung is a rapidly improving medical imaging technique. Spiral CT has been reported to not only improve the early detection of lung cancer in screening high-risk tobacco-exposed populations but also to assist in the clinical assessment of new agents for therapy in lung cancer.

METHODS: The Prevent Cancer Foundation has sponsored a series of workshops to accelerate progress in using quantitative imaging to advance lung cancer research progress, of which this report summarizes the Ninth Workshop. The defining strategy of this forum to support innovation in quantitative research for early lung cancer management was to enable software validations by assembling collections of high-quality images for which long-term clinical follow-up is known. An additional approach was to define a process for high-quality and economical national implementation of lung cancer screening. Representatives from the Quantitative Imaging Biomarker Alliance, the International Association for the Study of Lung Cancer, the Lung Cancer Alliance, and other organizations outlined their efforts in this regard. A major opportunity exists to advance the dialogue on the use of quantitative imaging tools to cross-fertilize and accelerate image-processing research across lung cancer and chronic obstructive pulmonary disease (COPD).

CONCLUSION: The use of high-resolution CT imaging provides a window into a much earlier stage of COPD as well as coronary artery disease, both being tobacco-induced diseases. Progress in this area was reviewed and opportunities for enhanced collaborative progress defined. Key sessions reviewed emerging developments with imaging technology and the infrastructure to support the storage and distribution of these high-content modalities. Cooperation among diverse collaborators is essential to enable the rapid organic evolution of this field, so that improved outcomes with lung cancer, artery disease, and COPD can be obtained.},
	keywords = {Congresses as Topic, Drug Design, Humans, Lung Neoplasms, Pulmonary Disease, Chronic Obstructive, Tomography, X-Ray Computed},
	issn = {1556-1380},
	doi = {10.1097/01.JTO.0000435803.93490.04},
	author = {Mulshine, James L and Avila, Rick and Yankelevitz, David and Baer, Thomas M and Estepar, Raul San Jose and Fenton, Laurie and Aldige, Carolyn R}
}
@article {1433716,
	title = {Characterizing functional lung heterogeneity in COPD using reference equations for CT scan-measured lobar volumes},
	journal = {Chest},
	volume = {143},
	number = {6},
	year = {2013},
	month = {2013 Jun},
	pages = {1607-1617},
	abstract = {BACKGROUND: CT scanning is increasingly used to characterize COPD. Although it is possible to obtain CT scan-measured lung lobe volumes, normal ranges remain unknown. Using COPDGene data, we developed reference equations for lobar volumes at maximal inflation (total lung capacity [TLC]) and relaxed exhalation (approximating functional residual capacity [FRC]).

METHODS: Linear regression was used to develop race-specific (non-Hispanic white [NHW], African American) reference equations for lobar volumes. Covariates included height and sex. Models were developed in a derivation cohort of 469 subjects with normal pulmonary function and validated in 546 similar subjects. These cohorts were combined to produce final prediction equations, which were applied to 2,191 subjects with old GOLD (Global Initiative for Chronic Obstructive Lung Disease) stage II to IV COPD.

RESULTS: In the derivation cohort, women had smaller lobar volumes than men. Height positively correlated with lobar volumes. Adjusting for height, NHWs had larger total lung and lobar volumes at TLC than African Americans; at FRC, NHWs only had larger lower lobes. Age and weight had no effect on lobar volumes at TLC but had small effects at FRC. In subjects with COPD at TLC, upper lobes exceeded 100\% of predicted values in GOLD II disease; lower lobes were only inflated to this degree in subjects with GOLD IV disease. At FRC, gas trapping was severe irrespective of disease severity and appeared uniform across the lobes.

CONCLUSIONS: Reference equations for lobar volumes may be useful in assessing regional lung dysfunction and how it changes in response to pharmacologic therapies and surgical or endoscopic lung volume reduction.},
	keywords = {Aged, Aged, 80 and over, Female, Humans, Linear Models, Lung Volume Measurements, Male, Middle Aged, Pulmonary Disease, Chronic Obstructive, Radiographic Image Interpretation, Computer-Assisted, Reference Values, Respiratory Function Tests, Severity of Illness Index, Tomography, X-Ray Computed},
	issn = {1931-3543},
	doi = {10.1378/chest.12-1616},
	author = {Come, Carolyn E and Diaz, Alejandro A and Curran-Everett, Douglas and Muralidhar, Nivedita and Hersh, Craig P and Zach, Jordan A. and Schroeder, Joyce and Lynch, David A and Celli, Bartolome and Washko, George R}
}
@article {1433724,
	title = {Comparative study of NOTES alone versus NOTES guided by a new image registration system for navigation in the mediastinum: a study in a porcine model},
	journal = {Gastrointest Endosc},
	volume = {77},
	number = {1},
	year = {2013},
	month = {2013 Jan},
	pages = {102-7},
	abstract = {BACKGROUND: Natural orifice transluminal endoscopic surgery (NOTES) mediastinoscopy (MED) through the esophagus has proved to be feasible in the animal model. However, injury of the adjacent pleura and pneumothorax has been reported as a frequent adverse event when using a blind access.

OBJECTIVE: To assess the utility and safety of a CT-based image registration system (IRS) for navigation in the mediastinum.

DESIGN: Prospective, randomized, controlled trial in 30 Yorkshire pigs. Thirty-minute MEDs were performed: 15 MEDs were performed with IRS guidance (MED-IRS), and 15 MEDs were performed with a blind access.

SETTING: Animal research laboratory.

INTERVENTIONS: In both groups, the mediastinum was accessed through a 10-cm submucosal tunnel in the esophageal wall. Timed exploration was performed with identification of 8 mediastinal structures.

MAIN OUTCOME MEASUREMENTS: Technical feasibility, adverse events, and the number of mediastinal structures identified.

RESULTS: Thirty animals weighing 31.5 {\textpm} 3.5 kg were included in this study. MED was not possible in 2 animals in the "MED with blind access" group but was possible in all MEDs performed with IRS. The mean number of identified organs was slightly higher in "with IRS-MED" (6.13 {\textpm} 1.3) than with MED with blind access (4.7 {\textpm} 2.3; P = .066). Moreover, the right atrium and vena cava were identified in more cases with IRS-MED than in MED with blind access (13 vs 3 and 15 vs 11, P = .000 and P = .03, respectively). There were 3 (23\%) adverse events with IRS-MED and 4 (27\%) with "MED with blind access" (P = not significant), with pneumothorax being the most frequent (2 and 3, respectively).

LIMITATIONS: Nonsurvival animal study.

CONCLUSIONS: This study demonstrates that the IRS system appears feasible in natural orifice transluminal endoscopic surgery MED and suggests that IRS guidance might be useful for selected procedures.},
	keywords = {Animals, Esophagus, Mediastinoscopy, Natural Orifice Endoscopic Surgery, Prospective Studies, Swine},
	issn = {1097-6779},
	doi = {10.1016/j.gie.2012.09.008},
	author = {C{\'o}rdova, Henry and San Jos{\'e} Est{\'e}par, Ra{\'u}l and Rodr{\'\i}guez-D{\textquoteright}Jes{\'u}s, Antonio and Mart{\'\i}nez-Pall{\'\i}, Graciela and Arguis, Pedro and Rodr{\'\i}guez de Miguel, Cristina and Navarro-Ripoll, Ricard and Perdomo, Juan M and Cuatrecasas, Miriam and Llach, Josep and Kirby G. Vosburgh and Fern{\'a}ndez-Esparrach, Gloria}
}
@article {1433718,
	title = {CT and physiologic determinants of dyspnea and exercise capacity during the six-minute walk test in mild COPD},
	journal = {Respir Med},
	volume = {107},
	number = {4},
	year = {2013},
	month = {2013 Apr},
	pages = {570-9},
	abstract = {OBJECTIVES: We aimed to explore physiological responses to the six-minute walk test (6MWT) and assess computed tomographic (CT) features of the lungs and thigh muscle in order to determine contributors to dyspnea intensity and exercise limitation in dyspneic and non-dyspneic subjects with GOLD-1 COPD and controls.

METHODS: We compared Borg dyspnea ratings, ventilatory responses to 6MWT, and CT-measures of emphysema, airway lumen caliber, and cross-sectional area of the thigh muscle (RTMCT-CSA) in 19 dyspneic, 22 non-dyspneic, and 30 control subjects.

RESULTS: Dyspneic subjects walked less and experienced greater exertional breathlessness than non-dyspneic (105~m less and 2.4 Borg points more, respectively) and control subjects (94~m less and 2.6 Borg points more, respectively (P~,
	keywords = {Aged, Cross-Sectional Studies, Dyspnea, Exercise Test, Exercise Tolerance, Female, Humans, Lung, Male, Middle Aged, Muscle, Skeletal, Oxygen Consumption, Pulmonary Disease, Chronic Obstructive, Pulmonary Emphysema, Respiratory Mechanics, Thigh, Tomography, X-Ray Computed, Walking},
	issn = {1532-3064},
	doi = {10.1016/j.rmed.2012.12.011},
	author = {D{\'\i}az, Alejandro A and Morales, Arturo and D{\'\i}az, Juan C and Ramos, Crist{\'o}bal and Klaassen, Julieta and Sald{\'\i}as, Fernando and Aravena, Carlos and D{\'\i}az, Rodrigo and Lisboa, Carmen and Washko, George R and D{\'\i}az, Orlando}
}
@article {1433719,
	title = {Effect of emphysema on CT scan measures of airway dimensions in smokers},
	journal = {Chest},
	volume = {143},
	number = {3},
	year = {2013},
	month = {2013 Mar},
	pages = {687-693},
	abstract = {BACKGROUND: In CT scans of smokers with COPD, the subsegmental airway wall area percent (WA\%) is greater and more strongly correlated with FEV1 \% predicted than WA\% obtained in the segmental airways. Because emphysema is linked to loss of airway tethering and may limit airway expansion, increases in WA\% may be related to emphysema and not solely to remodeling. We aimed to first determine whether the stronger association of subsegmental vs segmental WA\% with FEV1 \% predicted is mitigated by emphysema and, second, to assess the relationships among emphysema, WA\%, and total bronchial area (TBA).

METHODS: We analyzed CT scan segmental and subsegmental WA\% (WA\% = 100 {\texttimes} wall area/TBA) of six bronchial paths and corresponding lobar emphysema, lung function, and clinical data in 983 smokers with COPD.

RESULTS: Compared with segmental WA\%, the subsegmental WA\% had a greater effect on FEV1\% predicted (-0.8\% to -1.7\% vs -1.9\% to -2.6\% per 1-unit increase in WA\%, respectively; P < .05 for most bronchial paths). After adjusting for emphysema, the association between subsegmental WA\% and FEV1 \% predicted was weakened in two bronchial paths. Increases in WA\% between bronchial segments correlated directly with emphysema in all bronchial paths (P < .05). In multivariate regression models, emphysema was directly related to subsegmental WA\% in most bronchial paths and inversely related to subsegmental TBA in all bronchial paths.

CONCLUSION: The greater effect of subsegmental WA\% on airflow obstruction is mitigated by emphysema. Part of the emphysema effect might be due to loss of airway tethering, leading to a reduction in TBA and an increase in WA\%.},
	keywords = {Adult, Airway Remodeling, Bronchography, Female, Forced Expiratory Volume, Humans, Male, Middle Aged, Multivariate Analysis, Pulmonary Emphysema, Regression Analysis, Smoking, Tomography, X-Ray Computed},
	issn = {1931-3543},
	doi = {10.1378/chest.12-0039},
	author = {Diaz, Alejandro A and Han, MeiLan K and Come, Carolyn E and San Jos{\'e} Est{\'e}par, Ra{\'u}l and Ross, James C and Kim, Victor and Dransfield, Mark T and Curran-Everett, Douglas and Schroeder, Joyce D and Lynch, David A and Tschirren, Juerg and Silverman, Edwin K and Washko, George R}
}
@article {1433725,
	title = {Estimating the burden of pneumococcal pneumonia among adults: a systematic review and meta-analysis of diagnostic techniques},
	journal = {PLoS One},
	volume = {8},
	number = {4},
	year = {2013},
	month = {2013},
	pages = {e60273},
	abstract = {BACKGROUND: Pneumococcal pneumonia causes significant morbidity and mortality among adults. Given limitations of diagnostic tests for non-bacteremic pneumococcal pneumonia, most studies report the incidence of bacteremic or invasive pneumococcal disease (IPD), and thus, grossly underestimate the pneumococcal pneumonia burden. We aimed to develop a conceptual and quantitative strategy to estimate the non-bacteremic disease burden among adults with community-acquired pneumonia (CAP) using systematic study methods and the availability of a urine antigen assay.

METHODS AND FINDINGS: We performed a systematic literature review of studies providing information on the relative yield of various diagnostic assays (BinaxNOW{\textregistered} S. pneumoniae urine antigen test (UAT) with blood and/or sputum culture) in diagnosing pneumococcal pneumonia. We estimated the proportion of pneumococcal pneumonia that is bacteremic, the proportion of CAP attributable to pneumococcus, and the additional contribution of the Binax UAT beyond conventional diagnostic techniques, using random effects meta-analytic methods and bootstrapping. We included 35 studies in the analysis, predominantly from developed countries. The estimated proportion of pneumococcal pneumonia that is bacteremic was 24.8\% (95\% CI: 21.3\%, 28.9\%). The estimated proportion of CAP attributable to pneumococcus was 27.3\% (95\% CI: 23.9\%, 31.1\%). The Binax UAT diagnosed an additional 11.4\% (95\% CI: 9.6, 13.6\%) of CAP beyond conventional techniques. We were limited by the fact that not all patients underwent all diagnostic tests and by the sensitivity and specificity of the diagnostic tests themselves. We address these resulting biases and provide a range of plausible values in order to estimate the burden of pneumococcal pneumonia among adults.

CONCLUSIONS: Estimating the adult burden of pneumococcal disease from bacteremic pneumococcal pneumonia data alone significantly underestimates the true burden of disease in adults. For every case of bacteremic pneumococcal pneumonia, we estimate that there are at least 3 additional cases of non-bacteremic pneumococcal pneumonia.},
	keywords = {Adult, Bacteremia, Community-Acquired Infections, Humans, Pneumonia, Pneumococcal, Sensitivity and Specificity, Streptococcus pneumoniae},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0060273},
	author = {Said, Maria A and Johnson, Hope L and Nonyane, Bareng A S and Deloria-Knoll, Maria and O{\textquoteright}Brien, Katherine L and Andreo, Felipe and Beovic, Bojana and Blanco, Silvia and Boersma, Wim G and Boulware, David R and Butler, Jay C and Carratal{\`a}, Jordi and Chang, Feng-Yee and Charles, Patrick G P and Diaz, Alejandro A and Dom{\'\i}nguez, Jose and Ehara, Naomi and Endeman, Henrik and Falc{\'o}, Vicen{\c c} and Falguera, Miquel and Fukushima, Kiyoyasu and Garcia-Vidal, Carolina and Genne, Daniel and Guchev, Igor A and Gutierrez, Felix and Hernes, Susanne S and Hoepelman, Andy I M and Hohenthal, Ulla and Johansson, Niclas and Kolek, Vitezslav and Kozlov, Roman S and Lauderdale, Tsai-Ling and Marekovi{\'c}, Ivana and Masi{\'a}, Mar and Matta, Matta A and Mir{\'o}, {\`O}scar and Murdoch, David R and Nuermberger, Eric and Paolini, Richard and Perell{\'o}, Rafael and Snijders, Dominic and Ple{\v c}ko, Vanda and Sord{\'e}, Roger and Str{\r a}lin, Kristoffer and van der Eerden, Menno M and Vila-Corcoles, Angel and Watt, James P}
}
@article {1433720,
	title = {GOLD 2011 disease severity classification in COPDGene: a prospective cohort study},
	journal = {Lancet Respir Med},
	volume = {1},
	number = {1},
	year = {2013},
	month = {2013 Mar},
	pages = {43-50},
	abstract = {BACKGROUND: The 2011 GOLD (Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease [COPD]) consensus report uses symptoms, exacerbation history, and forced expiratory volume (FEV1)\% to categorise patients according to disease severity and guide treatment. We aimed to assess both the influence of symptom instrument choice on patient category assignment and prospective exacerbation risk by category.

METHODS: Patients were recruited from 21 centres in the USA, as part of the COPDGene study. Eligible patients were aged 45-80 years, had smoked for 10 pack-years or more, and had an FEV1/forced vital capacity (FVC) ,
	keywords = {Aged, Female, Forced Expiratory Volume, Health Status, Humans, Male, Middle Aged, Prospective Studies, Pulmonary Disease, Chronic Obstructive, Severity of Illness Index, Surveys and Questionnaires, Vital Capacity},
	issn = {2213-2619},
	doi = {10.1016/S2213-2600(12)70044-9},
	author = {Han, MeiLan K and Muellerova, Hana and Curran-Everett, Douglas and Dransfield, Mark T and Washko, George R and Regan, Elizabeth A and Bowler, Russell P and Beaty, Terri H and Hokanson, John E and Lynch, David A and Jones, Paul W and Anzueto, Antonio and Martinez, Fernando J and Crapo, James D and Silverman, Edwin K and Make, Barry J}
}
@article {1433714,
	title = {Histone deacetylase 6-mediated selective autophagy regulates COPD-associated cilia dysfunction},
	journal = {J Clin Invest},
	volume = {123},
	number = {12},
	year = {2013},
	month = {2013 Dec},
	pages = {5212-30},
	abstract = {Chronic obstructive pulmonary disease (COPD) involves aberrant airway inflammatory responses to cigarette smoke (CS) that are associated with epithelial cell dysfunction, cilia shortening, and mucociliary clearance disruption. Exposure to CS reduced cilia length and induced autophagy in vivo and in differentiated mouse tracheal epithelial cells (MTECs). Autophagy-impaired (Becn1+/- or Map1lc3B-/-) mice and MTECs resisted CS-induced cilia shortening. Furthermore, CS increased the autophagic turnover of ciliary proteins, indicating that autophagy may regulate cilia homeostasis. We identified cytosolic deacetylase HDAC6 as a critical regulator of autophagy-mediated cilia shortening during CS exposure. Mice bearing an X chromosome deletion of Hdac6 (Hdac6-/Y) and MTECs from these mice had reduced autophagy and were protected from CS-induced cilia shortening. Autophagy-impaired Becn1-/-, Map1lc3B-/-, and Hdac6-/Y mice or mice injected with an HDAC6 inhibitor were protected from CS-induced mucociliary clearance (MCC) disruption. MCC was preserved in mice given the chemical chaperone 4-phenylbutyric acid, but was disrupted in mice lacking the transcription factor NRF2, suggesting that oxidative stress and altered proteostasis contribute to the disruption of MCC. Analysis of human COPD specimens revealed epigenetic deregulation of HDAC6 by hypomethylation and increased protein expression in the airways. We conclude that an autophagy-dependent pathway regulates cilia length during CS exposure and has potential as a therapeutic target for COPD. },
	keywords = {Animals, Apoptosis Regulatory Proteins, Autophagy, Beclin-1, Cells, Cultured, Cilia, Cytosol, Epithelial Cells, Female, Histone Deacetylase 6, Histone Deacetylase Inhibitors, Histone Deacetylases, Humans, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Microscopy, Electron, Scanning, Microtubule-Associated Proteins, Mucus, NF-E2-Related Factor 2, Phenotype, Phenylbutyrates, Proteasome Endopeptidase Complex, Protein Processing, Post-Translational, Pulmonary Disease, Chronic Obstructive, Sirtuin 1, Tobacco Products, Tobacco Smoke Pollution, Trachea, Ubiquitination},
	issn = {1558-8238},
	doi = {10.1172/JCI69636},
	author = {Lam, Hilaire C and Cloonan, Suzanne M and Bhashyam, Abhiram R and Haspel, Jeffery A and Singh, Anju and Sathirapongsasuti, J Fah and Cervo, Morgan and Hongwei Yao and Chung, Anna L and Mizumura, Kenji and An, Chang Hyeok and Shan, Bin and Franks, Jonathan M and Haley, Kathleen J and Owen, Caroline A and Tesfaigzi, Yohannes and Washko, George R and Quackenbush, John and Silverman, Edwin K and Irfan Rahman and Kim, Hong Pyo and Mahmood, Ashfaq and Biswal, Shyam S and Ryter, Stefan W and Choi, Augustine M K}
}
@article {1433723,
	title = {Lung CD8+ T cells in COPD have increased expression of bacterial TLRs},
	journal = {Respir Res},
	volume = {14},
	year = {2013},
	month = {2013 Feb 01},
	pages = {13},
	abstract = {BACKGROUND: Toll-like receptors (TLRs) on T cells can modulate their responses, however, the extent and significance of TLR expression by lung T cells, NK cells, or NKT cells in chronic obstructive pulmonary disease (COPD) is unknown.

METHODS: Lung tissue collected from clinically-indicated resections (n = 34) was used either: (a) to compare the expression of TLR1, TLR2, TLR2/1, TLR3, TLR4, TLR5, TLR6 and TLR9 on lung CD8+ T cells, CD4+ T cells, NK cells and NKT cells from smokers with or without COPD; or (b) to isolate CD8+ T cells for culture with anti-CD3ε without or with various TLR ligands. We measured protein expression of IFN-γ, TNF-α, IL-13, perforin, granzyme A, granzyme B, soluble FasL, CCL2, CCL3, CCL4, CCL5, CCL11, and CXCL9 in supernatants.

RESULTS: All the lung subsets analyzed demonstrated low levels of specific TLR expression, but the percentage of CD8+ T cells expressing TLR1, TLR2, TLR4, TLR6 and TLR2/1 was significantly increased in COPD subjects relative to those without COPD. In contrast, from the same subjects, only TLR2/1 and TLR2 on lung CD4+ T cells and CD8+ NKT cells, respectively, showed a significant increase in COPD and there was no difference in TLR expression on lung CD56+ NK cells. Production of the Tc1 cytokines IFN-γ and TNF-α by lung CD8+ T cells were significantly increased via co-stimulation by Pam3CSK4, a specific TLR2/1 ligand, but not by other agonists. Furthermore, this increase in cytokine production was specific to lung CD8+ T cells from patients with COPD as compared to lung CD8+ T cells from smokers without COPD.

CONCLUSIONS: These data suggest that as lung function worsens in COPD, the auto-aggressive behavior of lung CD8+ T cells could increase in response to microbial TLR ligands, specifically ligands against TLR2/1.},
	keywords = {Aged, CD8-Positive T-Lymphocytes, Cells, Cultured, Female, Gene Expression Regulation, Bacterial, Humans, Lung, Male, Middle Aged, Prospective Studies, Pulmonary Disease, Chronic Obstructive, Toll-Like Receptors},
	issn = {1465-993X},
	doi = {10.1186/1465-9921-14-13},
	author = {Freeman, Christine M and Martinez, Fernando J and Han, MeiLan K and Washko, George R and McCubbrey, Alexandra L and Chensue, Stephen W and Arenberg, Douglas A and Meldrum, Catherine A and McCloskey, Lisa and Curtis, Jeffrey L}
}
@article {1433717,
	title = {Paired inspiratory-expiratory chest CT scans to assess for small airways disease in COPD},
	journal = {Respir Res},
	volume = {14},
	year = {2013},
	month = {2013 Apr 08},
	pages = {42},
	abstract = {BACKGROUND: Gas trapping quantified on chest CT scans has been proposed as a surrogate for small airway disease in COPD. We sought to determine if measurements using paired inspiratory and expiratory CT scans may be better able to separate gas trapping due to emphysema from gas trapping due to small airway disease.

METHODS: Smokers with and without COPD from the COPDGene Study underwent inspiratory and expiratory chest CT scans. Emphysema was quantified by the percent of lung with attenuation ,
	keywords = {Comorbidity, Female, Humans, Male, Middle Aged, Prevalence, Pulmonary Alveoli, Pulmonary Disease, Chronic Obstructive, Pulmonary Emphysema, Radiographic Image Enhancement, Radiography, Thoracic, Reproducibility of Results, Respiratory Mechanics, Sensitivity and Specificity, Smoking, Tomography, X-Ray Computed, United States},
	issn = {1465-993X},
	doi = {10.1186/1465-9921-14-42},
	author = {Hersh, Craig P and Washko, George R and San Jos{\'e} Est{\'e}par, Ra{\'u}l and Lutz, Sharon and Friedman, Paul J and Han, MeiLan K and Hokanson, John E and Judy, Philip F and Lynch, David A and Make, Barry J and Marchetti, Nathaniel and Newell, John D and Sciurba, Frank C and Crapo, James D and Silverman, Edwin K}
}
@article {1433721,
	title = {Racial differences in CT phenotypes in COPD},
	journal = {COPD},
	volume = {10},
	number = {1},
	year = {2013},
	month = {2013 Feb},
	pages = {20-7},
	abstract = {BACKGROUND: Whether African Americans (AA) are more susceptible to COPD than non-Hispanic Whites (NHW) and whether racial differences in disease phenotype exist is controversial. The objective is to determine racial differences in the extent of emphysema and airway remodeling in COPD.

METHODS: First, 2,500 subjects enrolled in the COPDGene study were used to evaluate racial differences in quantitative CT (QCT) parameters of\% emphysema, air trapping and airway wall thickness. Independent variables studied included race, age, gender, education, BMI, pack-years, smoking status, age at smoking initiation, asthma, previous work in dusty job, CT scanner and center of recruitment.

RESULTS: Of the 1,063 subjects with GOLD Stage II-IV COPD, 200 self-reported as AA. AAs had a lower mean\% emphysema (13.1\% vs. 16.1\%, p = 0.005) than NHW and proportionately less emphysema in the lower lung zones. After adjustment for covariates, there was no statistical difference by race in air trapping or airway wall thickness. Measured QCT parameters were more predictive of poor functional status in NHWs compared to AAs.

CONCLUSIONS: AAs have less emphysema than NHWs but the same degree of airway disease. Additional factors not easily assessed by current QCT techniques may account for the poor functional status in AAs.},
	keywords = {African Americans, Aged, Airway Remodeling, European Continental Ancestry Group, Female, Forced Expiratory Volume, Humans, Male, Middle Aged, Multivariate Analysis, Phenotype, Pulmonary Disease, Chronic Obstructive, Pulmonary Emphysema, Severity of Illness Index, Tomography, X-Ray Computed},
	issn = {1541-2563},
	doi = {10.3109/15412555.2012.727921},
	author = {Hansel, Nadia N and Washko, George R and Foreman, Marilyn G and Han, MeiLan K and Hoffman, Eric A and DeMeo, Dawn L and Barr, R Graham and van Beek, Edwin J R and Kazerooni, Ella A and Wise, Robert A and Brown, Robert H and Black-Shinn, Jennifer and Hokanson, John E and Hanania, Nicola A and Make, Barry and Silverman, Edwin K and Crapo, James D and Dransfield, Mark T}
}
@article {1433713,
	title = {Short-term exposure to air pollution and lung function in the Framingham Heart Study},
	journal = {Am J Respir Crit Care Med},
	volume = {188},
	number = {11},
	year = {2013},
	month = {2013 Dec 01},
	pages = {1351-7},
	abstract = {RATIONALE: Short-term exposure to ambient air pollution has been associated with lower lung function. Few studies have examined whether these associations are detectable at relatively low levels of pollution within current U.S. Environmental Protection Agency (EPA) standards.

OBJECTIVES: To examine exposure to ambient air pollutants within EPA standards and lung function in a large cohort study.

METHODS: We included 3,262 participants of the Framingham Offspring and Third Generation cohorts living within 40 km of the Harvard Supersite monitor in Boston, Massachusetts (5,358 examinations, 1995-2011) who were not current smokers, with previous-day pollutant levels in compliance with EPA standards. We compared lung function (FEV1 and FVC) after previous-day exposure to particulate matter less than 2.5 μm in diameter (PM2.5), nitrogen dioxide (NO2), and ozone (O3) in the "moderate" range of the EPA Air Quality Index to exposure in the "good" range. We also examined linear relationships between moving averages of pollutant concentrations 1, 2, 3, 5, and 7 days before spirometry and lung function.

MEASUREMENTS AND MAIN RESULTS: Exposure to pollutant concentrations in the "moderate" range of the EPA Air Quality Index was associated with a 20.1-ml lower FEV1 for PM2.5 (95\% confidence interval [CI], -33.4, -6.9), a 30.6-ml lower FEV1 for NO2 (95\% CI, -60.9, -0.2), and a 55.7-ml lower FEV1 for O3 (95\% CI, -100.7, -10.8) compared with the "good" range. The 1- and 2-day moving averages of PM2.5, NO2, and O3 before testing were negatively associated with FEV1 and FVC.

CONCLUSIONS: Short-term exposure to PM2.5, NO2, and O3 within current EPA standards was associated with lower lung function in this cohort of adults.},
	keywords = {Air Pollutants, Boston, Cohort Studies, Female, Forced Expiratory Volume, Humans, Inhalation Exposure, Linear Models, Male, Middle Aged, Nitric Oxide, Ozone, particulate matter, Spirometry, Total Lung Capacity, United States, United States Environmental Protection Agency},
	issn = {1535-4970},
	doi = {10.1164/rccm.201308-1414OC},
	author = {Rice, Mary B and Ljungman, Petter L and Wilker, Elissa H and Gold, Diane R and Schwartz, Joel D and Koutrakis, Petros and Washko, George R and O{\textquoteright}Connor, George T and Mittleman, Murray A}
}
@article {473151,
	title = {Diffeomorphic point set registration using non-stationary mixture models},
	journal = {Biomedical Imaging (ISBI), 2013 IEEE 10th International Symposium onBiomedical Imaging (ISBI), 2013 IEEE 10th International Symposium on},
	year = {2013},
	pages = {1042-1045},
	abstract = {This paper investigates a diffeomorphic point-set registration based on non-stationary mixture models. The goal is to improve the non-linear registration of anatomical structures by representing each point as a general non-stationary kernel that provides information about the shape of that point. Our framework generalizes work done by others that use stationary models. We achieve this by integrating the shape at each point when calculating the point-set similarity and transforming it according to the calculated deformation. We also restrict the non-rigid transform to the space of symmetric diffeomorphisms. Our algorithm is validated in synthetic and human datasets in two different applications: fiber bundle and lung airways registration. Our results shows that nonstationary mixture models are superior to Gaussian mixture models and methods that do not take into account the shape of each point. View full abstract},
	author = {Wassermann, D and Ross, J and Washko, G and CF Westin and San Jose Est{\'e}par, Ra{\'u}l}
}
@inbook {473136,
	title = {Distinct Quantitative CT Emphysema Patterns Are Associated With Physiology And Function In Smokers},
	booktitle = {American Thoracic Society International Conference Abstracts},
	year = {2013},
	note = {doi:10.1164/ajrccm-conference.2013.187.1_MeetingAbstracts.A3728},
	month = {Feb 27},
	pages = {A3728-A3728},
	publisher = {American Thoracic Society},
	organization = {American Thoracic Society},
	author = {Castaldi, Peter and San Jose Est{\'e}par, Ra{\'u}l and Mendoza, Carlos S and Hersh, Craig P and Laird, Nan and Crapo, James and Lynch, David A and Silverman, Edwin K and Washko, George R}
}
@inbook {473131,
	title = {MUC5B Promoter Polymorphism (rs35705950) Is Predictive Of Interstitial Lung Abnormalities In The General Population},
	booktitle = {American Thoracic Society International Conference Abstracts},
	year = {2013},
	note = {doi:10.1164/ajrccm-conference.2013.187.1_MeetingAbstracts.A5980},
	month = {Feb 27},
	pages = {A5980-A5980},
	publisher = {American Thoracic Society},
	organization = {American Thoracic Society},
	author = {Hunninghake, Gary M and Hatabu, Hiroto and Okajima, Yuka and Gao, Wei and Dupuis, Jos{\'e}e and Latourelle, Jeanne and Nishino, Mizuki and Kurugol, Sila and Ross, James and San Jose Est{\'e}par, Ra{\'u}l and Murphy, Elissa and Steele, Mark P and Loyd, James E and Schwarz, Marvin I and Fingerlin, Tasha and Rosas, Ivan O and Washko, George R and O\&apos;Connor, George and Schwartz, David A}
}
@article {473161,
	title = {Semi-automated airway segmentation of lung CT using 3D slicer},
	journal = {International journal of computer assisted radiology and surgeryInternational journal of computer assisted radiology and surgery},
	volume = {8},
	year = {2013},
	pages = {46-47},
	publisher = {Springer-Verlag},
	author = {Nardelli, Pietro and San Jose Est{\'e}par, Ra{\'u}l and Cantillon-Murphy, Padraig}
}
@inbook {473121,
	title = {Adenocarcinoma Occurs Predominantly In The Upper Regions Of The Lung And Is Associated With Improved Survival Compared To Occurrence In Other Regions},
	booktitle = {American Thoracic Society International Conference Abstracts},
	year = {2013},
	note = {doi:10.1164/ajrccm-conference.2013.187.1_MeetingAbstracts.A3604},
	month = {Feb 27},
	pages = {A3604-A3604},
	publisher = {American Thoracic Society},
	organization = {American Thoracic Society},
	author = {Kinsey, Charles M and San Jose Est{\'e}par, Ra{\'u}l and Zhao, Yang and Yu, Xiaojin and Heist, Rebecca S and Wain, John and Washko, George R and Christiani, David C}
}
@inbook {473116,
	title = {Automated Quantification Of Aorta Morphology And Mural Calcifications In Inspiratory Volumetric CTs Of COPD Patients},
	booktitle = {American Thoracic Society International Conference Abstracts},
	year = {2013},
	note = {doi:10.1164/ajrccm-conference.2013.187.1_MeetingAbstracts.A5453},
	month = {Feb 27},
	pages = {A5453-A5453},
	publisher = {American Thoracic Society},
	organization = {American Thoracic Society},
	author = {Kurugol, Sila and San Jose Est{\'e}par, Ra{\'u}l and Ross, James C and Kinney, Gregory L and Black-Shinn, Jennifer L and Budoff, Matthew and Hokanson, John E}
}
@inbook {473126,
	title = {CT Measures Of Pulmonary Vascular Morphology Are Associated With 6 Minute Walk Distance And BODE Score},
	booktitle = {American Thoracic Society International Conference Abstracts},
	year = {2013},
	note = {doi:10.1164/ajrccm-conference.2013.187.1_MeetingAbstracts.A2874},
	month = {Feb 27},
	pages = {A2874-A2874},
	publisher = {American Thoracic Society},
	organization = {American Thoracic Society},
	author = {Kinney, Gregory L and San Jose Est{\'e}par, Ra{\'u}l and Black-Shinn, Jennifer L and Bowler, Russell P and Han, MeiLan K and Come, Carolyn E and Cho, Michael H and Hersh, Craig P and Reilly, John P and Lynch, David A and Dransfield, Mark T and Hokanson, John and Washko, George R}
}
@inbook {473106,
	title = {Differences In Blood Volume Distribution In COPD: A Pilot Study},
	booktitle = {American Thoracic Society International Conference Abstracts},
	year = {2013},
	note = {doi:10.1164/ajrccm-conference.2013.187.1_MeetingAbstracts.A2374},
	month = {Feb 27},
	pages = {A2374-A2374},
	publisher = {American Thoracic Society},
	organization = {American Thoracic Society},
	author = {San Jose Est{\'e}par, Ra{\'u}l and Kinney, Gregory L and Hokanson, John and Washko, George R}
}
@inbook {473111,
	title = {Pectoralis Muscle Area Is More Highly Associated Than BMI With COPD Severity},
	booktitle = {American Thoracic Society International Conference Abstracts},
	year = {2013},
	note = {doi:10.1164/ajrccm-conference.2013.187.1_MeetingAbstracts.A5454},
	month = {Feb 27},
	pages = {A5454-A5454},
	publisher = {American Thoracic Society},
	organization = {American Thoracic Society},
	author = {McDonald, Merry-Lynn N and Diaz, Alejandro A and Ross, James C and San Jose Est{\'e}par, Ra{\'u}l and Regan, Elizabeth A and Eckbo, Eric and Muralidhar, N and Come, Carolyn E and Cho, Michael H and Hersh, Craig P and Lange, Christoph and Celli, Bartolome R and Kinney, Gregory L and Hokanson, John and Silverman, Edwin K and Washko, George R}
}
@inbook {473101,
	title = {Upper Airway Dynamics In Patients With COPD And Concomitant Obstructive Sleep Apnea (OSA): A Pilot Study},
	booktitle = {American Thoracic Society International Conference Abstracts},
	year = {2013},
	note = {doi:10.1164/ajrccm-conference.2013.187.1_MeetingAbstracts.A5705},
	month = {Feb 27},
	pages = {A5705-A5705},
	publisher = {American Thoracic Society},
	organization = {American Thoracic Society},
	author = {Soler, Xavier and Yen, Andrew and Black-Shinn, Jennifer L and San Jose Est{\'e}par, Ra{\'u}l and Hokanson, John E and Ramsdell, Joe W and Ries, Andrew and Malhotra, Atul}
}
@article {473076,
	title = {Application of High-Resolution CT Imaging Data to Lung Cancer Drug Development: Measuring Progress: Workshop IX},
	journal = {Journal of Thoracic OncologyJournal of Thoracic Oncology},
	volume = {8},
	year = {2013},
	month = {Nov},
	pages = {1352-1355},
	abstract = {Background:Lung cancer is the leading cause of cancer death and a major public health challenge across the entire world. Computed tomography (CT) imaging of the lung is a rapidly improving medical imaging technique. Spiral CT has been reported to not only improve the early detection of lung cancer in screening high-risk tobacco-exposed populations but also to assist in the clinical assessment of new agents for therapy in lung cancer. Methods:The Prevent Cancer Foundation has sponsored a series of workshops to accelerate progress in using quantitative imaging to advance lung cancer research progress, of which this report summarizes the Ninth Workshop. The defining strategy of this forum to support innovation in quantitative research for early lung cancer management was to enable software validations by assembling collections of high-quality images for which long-term clinical follow-up is known. An additional approach was to define a process for high-quality and economical national implementation of lung cancer screening. Representatives from the Quantitative Imaging Biomarker Alliance, the International Association for the Study of Lung Cancer, the Lung Cancer Alliance, and other organizations outlined their efforts in this regard. A major opportunity exists to advance the dialogue on the use of quantitative imaging tools to cross-fertilize and accelerate image-processing research across lung cancer and chronic obstructive pulmonary disease (COPD). Conclusion:The use of high-resolution CT imaging provides a window into a much earlier stage of COPD as well as coronary artery disease, both being tobacco-induced diseases. Progress in this area was reviewed and opportunities for enhanced collaborative progress defined. Key sessions reviewed emerging developments with imaging technology and the infrastructure to support the storage and distribution of these high-content modalities. Cooperation among diverse collaborators is essential to enable the rapid organic evolution of this field, so that improved outcomes with lung cancer, artery disease, and COPD can be obtained.},
	author = {Mulshine, James L and Avila, Rick and Yankelevitz, David and Baer, Thomas M and San Jose Est{\'e}par, Ra{\'u}l and Fenton, Laurie and Aldige, Carolyn R}
}
@inbook {473156,
	title = {Advances in Texture Analysis for Emphysema Classification},
	booktitle = {Lecture Notes in Computer Science},
	volume = {8259},
	year = {2013},
	pages = {214-221-221},
	publisher = {Springer Berlin Heidelberg},
	organization = {Springer Berlin Heidelberg},
	address = {Berlin, Heidelberg},
	abstract = {Abstract. In recent years, with the advent of High-resolution Com- puted Tomography (HRCT), there has been an increased interest for diagnosing Chronic Obstructive Pulmonary Disease (COPD), which is commonly presented as emphysema . Since low-attenuation ...},
	isbn = {978-3-642-41827-3},
	author = {Nava, Rodrigo and Marcos, J Victor and Escalante-Ram{\'\i}rez, Boris and Cristobal, Gabriel and Perrinet, LaurentU and San Jos{\'e} Est{\'e}par, Ra{\'u}l},
	editor = {Ruiz-Shulcloper, Jos{\'e} and Sanniti di Baja, Gabriella}
}
@article {473141,
	title = {Comparative study of NOTES alone versus NOTES guided by a new image registration system for navigation in the mediastinum: a study in a porcine model.},
	journal = {Gastrointestinal endoscopyGastrointestinal endoscopy},
	volume = {77},
	year = {2013},
	month = {Feb},
	pages = {102-107},
	abstract = {BACKGROUND:Natural orifice transluminal endoscopic surgery (NOTES) mediastinoscopy (MED) through the esophagus has proved to be feasible in the animal model. However, injury of the adjacent pleura and pneumothorax has been reported as a frequent adverse event when using a blind access.OBJECTIVE:To assess the utility and safety of a CT-based image registration system (IRS) for navigation in the mediastinum.DESIGN:Prospective, randomized, controlled trial in 30 Yorkshire pigs. Thirty-minute MEDs were performed: 15 MEDs were performed with IRS guidance (MED-IRS), and 15 MEDs were performed with a blind access.SETTING:Animal research laboratory.INTERVENTIONS:In both groups, the mediastinum was accessed through a 10-cm submucosal tunnel in the esophageal wall. Timed exploration was performed with identification of 8 mediastinal structures.MAIN OUTCOME MEASUREMENTS:Technical feasibility, adverse events, and the number of mediastinal structures identified.RESULTS:Thirty animals weighing 31.5 {\textpm} 3.5 kg were included in this study. MED was not possible in 2 animals in the "MED with blind access" group but was possible in all MEDs performed with IRS. The mean number of identified organs was slightly higher in "with IRS-MED" (6.13 {\textpm} 1.3) than with MED with blind access (4.7 {\textpm} 2.3; P = .066). Moreover, the right atrium and vena cava were identified in more cases with IRS-MED than in MED with blind access (13 vs 3 and 15 vs 11, P = .000 and P = .03, respectively). There were 3 (23\%) adverse events with IRS-MED and 4 (27\%) with "MED with blind access" (P = not significant), with pneumothorax being the most frequent (2 and 3, respectively).LIMITATIONS:Nonsurvival animal study.CONCLUSIONS:This study demonstrates that the IRS system appears feasible in natural orifice transluminal endoscopic surgery MED and suggests that IRS guidance might be useful for selected procedures.},
	author = {C{\'o}rdova, Henry and San Jose Est{\'e}par, Ra{\'u}l and Rodr{\'\i}guez-D\&apos;Jes{\'u}s, Antonio and Mart{\'\i}nez-Pall{\'\i}, Graciela and Arguis, Pedro and Rodr{\'\i}guez de Miguel, Cristina and Navarro-Ripoll, Ricard and Perdomo, Juan M and Cuatrecasas, Miriam and Llach, Josep and Kirby G. Vosburgh and Fernandez-Esparrach, Gloria}
}
@article {473081,
	title = {Computed Tomographic Measures of Pulmonary Vascular Morphology in Smokers and Their Clinical Implications.},
	journal = {American journal of respiratory and critical care medicineAmerican journal of respiratory and critical care medicine},
	volume = {188},
	year = {2013},
	month = {Jul 15},
	pages = {231-239},
	abstract = {Rationale: Angiographic investigation suggests that pulmonary vascular remodeling in smokers is characterized by distal pruning of the blood vessels. Objectives: Using volumetric computed tomography scans of the chest we sought to quantitatively evaluate this process and assess its clinical associations. Methods: Pulmonary vessels were automatically identified, segmented, and measured. Total blood vessel volume (TBV) and the aggregate vessel volume for vessels less than 5 mm(2) (BV5) were calculated for all lobes. The lobe-specific BV5 measures were normalized to the TBV of that lobe and the nonvascular tissue volume (BV5/T(issue)V) to calculate lobe-specific BV5/TBV and BV5/T(issue)V ratios. Densitometric measures of emphysema were obtained using a Hounsfield unit threshold of -950 (\%LAA-950). Measures of chronic obstructive pulmonary disease severity included single breath measures of diffusing capacity of carbon monoxide, oxygen saturation, the 6-minute-walk distance, St George{\textquoteright}s Respiratory Questionnaire total score (SGRQ), and the body mass index, airflow obstruction, dyspnea, and exercise capacity (BODE) index. Measurements and Main Results: The \%LAA-950 was inversely related to all calculated vascular ratios. In multivariate models including age, sex, and \%LAA-950, lobe-specific measurements of BV5/TBV were directly related to resting oxygen saturation and inversely associated with both the SGRQ and BODE scores. In similar multivariate adjustment lobe-specific BV5/T(issue)V ratios were inversely related to resting oxygen saturation, diffusing capacity of carbon monoxide, 6-minute-walk distance, and directly related to the SGRQ and BODE. Conclusions: Smoking-related chronic obstructive pulmonary disease is characterized by distal pruning of the small blood vessels (\&lt;5 mm(2)) and loss of tissue in excess of the vasculature. The magnitude of these changes predicts the clinical severity of disease.},
	author = {San Jose Est{\'e}par, Ra{\'u}l and Kinney, Gregory L and Black-Shinn, Jennifer L and Bowler, Russell P and Kindlmann, Gordon L and Ross, James C and Kikinis, Ron and Han, MeiLan K and Come, Carolyn E and Diaz, Alejandro A and Cho, Michael H and Hersh, Craig P and Schroeder, Joyce D and Reilly, John J and Lynch, David A and Crapo, James D and Wells, J Michael and Dransfield, Mark T and Hokanson, John E and Washko, George R and COPDGene Study}
}
@article {473071,
	title = {Distinct Quantitative Computed Tomography Emphysema Patterns Are Associated with Physiology and Function in Smokers},
	journal = {American journal of respiratory and critical care medicineAmerican journal of respiratory and critical care medicine},
	volume = {188},
	year = {2013},
	month = {Nov 14},
	pages = {1083-1090},
	publisher = {American Thoracic Society - AJRCCM},
	abstract = {Rationale: Emphysema occurs in distinct pathologic patterns, but little is known about the epidemiologic associations of these patterns. Standard quantitative measures of emphysema from computed tomography (CT) do not distinguish between distinct patterns of parenchymal destruction. Objectives: To study the epidemiologic associations of distinct emphysema patterns with measures of lung-related physiology, function, and health care use in smokers. Methods: Using a local histogram-based assessment of lung density, we quantified distinct patterns of low attenuation in 9,313 smokers in the COPDGene Study. To determine if such patterns provide novel insights into chronic obstructive pulmonary disease epidemiology, we tested for their association with measures of physiology, function, and health care use. Measurements and Main Results: Compared with percentage of low-attenuation area less than -950 Hounsfield units (\%LAA-950), local histogram-based measures of distinct CT low-attenuation patterns are more predictive of measures of lung function, dyspnea, quality of life, and health care use. These patterns are strongly associated with a wide array of measures of respiratory physiology and function, and most of these associations remain highly significant (P \&lt; 0.005) after adjusting for \%LAA-950. In smokers without evidence of chronic obstructive pulmonary disease, the mild centrilobular disease pattern is associated with lower FEV1 and worse functional status (P \&lt; 0.005). Conclusions: Measures of distinct CT emphysema patterns provide novel information about the relationship between emphysema and key measures of physiology, physical function, and health care use. Measures of mild emphysema in smokers with preserved lung function can be extracted from CT scans and are significantly associated with functional measures.},
	author = {Castaldi, Peter J and San Jose Est{\'e}par, Ra{\'u}l and Mendoza, Carlos S and Hersh, Craig P and Laird, Nan and Crapo, James D and Lynch, David A and Silverman, Edwin K and Washko, George R}
}
@article {473096,
	title = {The Effect of Emphysema on Computed Tomographic Measures of Airway Dimensions in Smokers.},
	journal = {Chest },
	volume = {143},
	year = {2013},
	month = {Mar 08},
	pages = {1-7},
	abstract = {ABSTRACT BACKGROUND: In CT scans of smokers with COPD, the subsegmental airway wall area percent (WA\%) is greater and more strongly correlated with FEV1\% predicted than WA\% obtained in the segmental airways. Since emphysema is linked to loss of airway tethering and may limit airway expansion, increases in WA\% may be related to emphysema and not solely due to remodeling. We aimed to first determine if the stronger association of subsegmental vs. segmental WA\% with FEV1\% predicted is mitigated by emphysema; and second, to assess the relationships between emphysema, WA\%, and total bronchial area (TBA). METHODS: We analyzed CT segmental and subsegmental WA\% (WA\%=100*wall area/TBA) of six bronchial paths and corresponding lobar emphysema, lung function, and clinical data in 983 smokers with COPD. RESULTS: Compared to segmental, the subsegmental WA\% had a greater effect on FEV1\% predicted (-0.8 to -1.7\% vs. -1.9 to -2.6\% per 1-unit increase in WA\%, respectively; P\&amp;lt;0.05 for most bronchial paths). After adjusting for emphysema, the association between subsegmental WA\% and FEV1\% predicted was weakened in two bronchial paths. Increases in WA\% between bronchial segments correlated directly with emphysema in all bronchial paths (P\&amp;lt;0.05). In multivariate regression models, emphysema was directly related to subsegmental WA\% in most bronchial paths and inversely related to subsegmental TBA in all bronchial paths. CONCLUSION: The greater effect of subsegmental WA\% on airflow obstruction is mitigated by emphysema. Part of the emphysema effect might be due to loss of airway tethering leading to reduction in TBA and increase in WA\%.},
	author = {Diaz, A A and Han, M K and Come, C E and San Jose Est{\'e}par, Ra{\'u}l and Ross, J C and Kim, V and Dransfield, M T and Curran-Everett, D and Schroeder, J D and Lynch, D A and Tschirren, J and Silverman, E K and Washko, G R}
}
@article {473091,
	title = {Modeling Airway Probability},
	journal = {Biomedical Imaging (ISBI), 2013 IEEE 10th International Symposium onBiomedical Imaging (ISBI), 2013 IEEE 10th International Symposium on},
	year = {2013},
	month = {May},
	pages = {378-381},
	abstract = {We present a probability model for lung airways in computed tomography (CT) images. Lung airways are tubular structures that display specific features, such as low intensity and proximity to vessels and bronchial walls. From these features, the posterior probability for the airway feature space was computed using a Bayesian model based on 20 CT images from subjects with different degrees of Chronic Obstructive Pulmonary Disease (COPD). The likelihood probability was modeled using both a Gaussian distribution and a nonparametric kernel density estimation method. After exhaustive feature selection, good specificity and sensitivity were achieved in a cross-validation study for both the Gaussian (0.83, 0.87) and the nonparametric method (0.79, 0.89). The model generalizes well when trained using images from a late stage COPD group. This probability model may facilitate airway extraction and quantitative assessment of lung diseases, which is useful in many clinical and research settings. View full abstract},
	author = {Rudyanto, R D and Munoz-Barrutia, A and Diaz, A A and Ross, J and Washko, G R and Ortiz-de-Solorzano, C and San Jose Est{\'e}par, Ra{\'u}l}
}
@article {473166,
	title = {Paired inspiratory-expiratory chest CT scans to assess for small airways disease in COPD.},
	journal = {Respiratory researchRespiratory research},
	volume = {14},
	year = {2013},
	pages = {42},
	abstract = {BACKGROUND: Gas trapping quantified on chest CT scans has been proposed as a surrogate for small airway disease in COPD. We sought to determine if measurements using paired inspiratory and expiratory CT scans may be better able to separate gas trapping due to emphysema from gas trapping due to small airway disease. METHODS: Smokers with and without COPD from the COPDGene Study underwent inspiratory and expiratory chest CT scans. Emphysema was quantified by the percent of lung with attenuation \&lt; -950HU on inspiratory CT. Four gas trapping measures were defined: (1) Exp(-856), the percent of lung \&lt; -856HU on expiratory imaging; (2) E/I MLA, the ratio of expiratory to inspiratory mean lung attenuation; (3) RVC(856-950), the difference between expiratory and inspiratory lung volumes with attenuation between -856 and -950 HU; and (4) Residuals from the regression of Exp(-856) on percent emphysema. RESULTS: In 8517 subjects with complete data, Exp(-856) was highly correlated with emphysema. The measures based on paired inspiratory and expiratory CT scans were less strongly correlated with emphysema. Exp(-856), E/I MLA and RVC(856-950) were predictive of spirometry, exercise capacity and quality of life in all subjects and in subjects without emphysema. In subjects with severe emphysema, E/I MLA and RVC(856-950) showed the highest correlations with clinical variables. CONCLUSIONS: Quantitative measures based on paired inspiratory and expiratory chest CT scans can be used as markers of small airway disease in smokers with and without COPD, but this will require that future studies acquire both inspiratory and expiratory CT scans.},
	author = {Hersh, Craig P and Washko, George R and San Jose Est{\'e}par, Ra{\'u}l and Lutz, Sharon and Friedman, Paul J and Han, MeiLan K and Hokanson, John E and Judy, Philip F and Lynch, David A and Make, Barry J and Marchetti, Nathaniel and Newell, John D and Sciurba, Frank C and Crapo, James D and Silverman, Edwin K and COPDGene investigators}
}
@article {469826,
	title = {MUC5B promoter polymorphism and interstitial lung abnormalities},
	journal = {N Engl J Med},
	volume = {368},
	number = {23},
	year = {2013},
	month = {2013 Jun 06},
	pages = {2192-200},
	abstract = {BACKGROUND: A common promoter polymorphism (rs35705950) in MUC5B, the gene encoding mucin 5B, is associated with idiopathic pulmonary fibrosis. It is not known whether this polymorphism is associated with interstitial lung disease in the general population.

METHODS: We performed a blinded assessment of interstitial lung abnormalities detected in 2633 participants in the Framingham Heart Study by means of volumetric chest computed tomography (CT). We evaluated the relationship between the abnormalities and the genotype at the rs35705950 locus.

RESULTS: Of the 2633 chest CT scans that were evaluated, interstitial lung abnormalities were present in 177 (7\%). Participants with such abnormalities were more likely to have shortness of breath and chronic cough and reduced measures of total lung and diffusion capacity, as compared with participants without such abnormalities. After adjustment for covariates, for each copy of the minor rs35705950 allele, the odds of interstitial lung abnormalities were 2.8 times greater (95\% confidence interval [CI], 2.0 to 3.9; P,
	keywords = {Aged, Female, Genotype, Humans, Longitudinal Studies, Lung, Lung Diseases, Interstitial, Male, Middle Aged, Mucin-5B, Polymorphism, Genetic, Respiratory Function Tests, Smoking, Tomography, X-Ray Computed, Total Lung Capacity},
	issn = {1533-4406},
	doi = {10.1056/NEJMoa1216076},
	author = {Hunninghake, Gary M and Hatabu, Hiroto and Okajima, Yuka and Gao, Wei and Dupuis, Jos{\'e}e and Latourelle, Jeanne C and Nishino, Mizuki and Araki, Tetsuro and Zazueta, Oscar E and Kurugol, Sila and Ross, James C and San Jos{\'e} Est{\'e}par, Ra{\'u}l and Murphy, Elissa and Steele, Mark P and Loyd, James E and Schwarz, Marvin I and Fingerlin, Tasha E and Rosas, Ivan O and Washko, George R and O{\textquoteright}Connor, George T and Schwartz, David A}
}
@article {450421,
	title = {Computed tomographic measures of pulmonary vascular morphology in smokers and their clinical implications},
	journal = {Am J Respir Crit Care Med},
	volume = {188},
	number = {2},
	year = {2013},
	month = {2013 Jul 15},
	pages = {231-9},
	abstract = {RATIONALE: Angiographic investigation suggests that pulmonary vascular remodeling in smokers is characterized by distal pruning of the blood vessels.

OBJECTIVES: Using volumetric computed tomography scans of the chest we sought to quantitatively evaluate this process and assess its clinical associations.

METHODS: Pulmonary vessels were automatically identified, segmented, and measured. Total blood vessel volume (TBV) and the aggregate vessel volume for vessels less than 5 mm(2) (BV5) were calculated for all lobes. The lobe-specific BV5 measures were normalized to the TBV of that lobe and the nonvascular tissue volume (BV5/T(issue)V) to calculate lobe-specific BV5/TBV and BV5/T(issue)V ratios. Densitometric measures of emphysema were obtained using a Hounsfield unit threshold of -950 (\%LAA-950). Measures of chronic obstructive pulmonary disease severity included single breath measures of diffusing capacity of carbon monoxide, oxygen saturation, the 6-minute-walk distance, St George{\textquoteright}s Respiratory Questionnaire total score (SGRQ), and the body mass index, airflow obstruction, dyspnea, and exercise capacity (BODE) index.

MEASUREMENTS AND MAIN RESULTS: The \%LAA-950 was inversely related to all calculated vascular ratios. In multivariate models including age, sex, and \%LAA-950, lobe-specific measurements of BV5/TBV were directly related to resting oxygen saturation and inversely associated with both the SGRQ and BODE scores. In similar multivariate adjustment lobe-specific BV5/T(issue)V ratios were inversely related to resting oxygen saturation, diffusing capacity of carbon monoxide, 6-minute-walk distance, and directly related to the SGRQ and BODE.

CONCLUSIONS: Smoking-related chronic obstructive pulmonary disease is characterized by distal pruning of the small blood vessels (,
	keywords = {Aged, Angiography, Blood Vessels, Body Mass Index, Female, Humans, Lung, Male, Middle Aged, Multivariate Analysis, Pulmonary Diffusing Capacity, Severity of Illness Index, Smoking, Tomography, X-Ray Computed},
	issn = {1535-4970},
	doi = {10.1164/rccm.201301-0162OC},
	author = {San Jos{\'e} Est{\'e}par, Ra{\'u}l and Kinney, Gregory L and Black-Shinn, Jennifer L and Bowler, Russell P and Kindlmann, Gordon L and Ross, James C and Kikinis, Ron and Han, MeiLan K and Come, Carolyn E and Diaz, Alejandro A and Cho, Michael H and Hersh, Craig P and Schroeder, Joyce D and Reilly, John J and Lynch, David A and Crapo, James D and Wells, J Michael and Dransfield, Mark T and Hokanson, John E and Washko, George R}
}
@article {450431,
	title = {DIFFEOMORPHIC POINT SET REGISTRATION USING NON-STATIONARY MIXTURE MODELS.},
	journal = {Proc IEEE Int Symp Biomed Imaging},
	year = {2013},
	month = {2013},
	abstract = {This paper investigates a diffeomorphic point-set registration based on non-stationary mixture models. The goal is to improve the non-linear registration of anatomical structures by representing each point as a general non-stationary kernel that provides information about the shape of that point. Our framework generalizes work done by others that use stationary models. We achieve this by integrating the shape at each point when calculating the point-set similarity and transforming it according to the calculated deformation. We also restrict the non-rigid transform to the space of symmetric diffeomorphisms. Our algorithm is validated in synthetic and human datasets in two different applications: fiber bundle and lung airways registration. Our results shows that non-stationary mixture models are superior to Gaussian mixture models and methods that do not take into account the shape of each point.},
	issn = {1945-7928},
	doi = {10.1109/ISBI.2013.6556656},
	author = {Wassermann, D and Ross, J and Washko, G and Westin, C-F and R San Jos{\'e} Est{\'e}par}
}
@article {450436,
	title = {Emphysema classification based on embedded probabilistic PCA},
	journal = {Conf Proc IEEE Eng Med Biol Soc},
	volume = {2013},
	year = {2013},
	month = {2013},
	pages = {3969-72},
	abstract = {In this article we investigate the suitability of a manifold learning technique to classify different types of emphysema based on embedded Probabilistic PCA (PPCA). Our approach finds the most discriminant linear space for each emphysema pattern against the remaining patterns where lung CT image patches can be embedded. In this embedded space, we train a PPCA model for each pattern. The main novelty of our technique is that it is possible to compute the class membership posterior probability for each emphysema pattern rather than a hard assignment as it is typically done by other approaches. We tested our algorithm with six emphysema patterns using a data set of 1337 CT training patches. Using a 10-fold cross validation experiment, an average recall rate of 69\% is achieved when the posterior probability is greater than 75\%. A quantitative comparison with a texture-based approach based on Local Binary Patterns and with an approach based on local intensity distributions shows that our method is competitive. The analysis of full lungs using our approach shows a good visual agreement with the underlying emphysema types and a smooth spatial relation. },
	keywords = {Algorithms, Discriminant Analysis, Humans, Lung, Principal Component Analysis, Pulmonary Emphysema, Radiographic Image Interpretation, Computer-Assisted, Tomography, X-Ray Computed},
	issn = {1557-170X},
	doi = {10.1109/EMBC.2013.6610414},
	author = {Zulueta-Coarasa, Teresa and Kurugol, Sila and Ross, James C and Washko, George G and San Jos{\'e} Est{\'e}par, Ra{\'u}l}
}
@article {450446,
	title = {MODELING AIRWAY PROBABILITY},
	journal = {Proc IEEE Int Symp Biomed Imaging},
	year = {2013},
	month = {2013},
	abstract = {We present a probability model for lung airways in computed tomography (CT) images. Lung airways are tubular structures that display specific features, such as low intensity and proximity to vessels and bronchial walls. From these features, the posterior probability for the airway feature space was computed using a Bayesian model based on 20 CT images from subjects with different degrees of Chronic Obstructive Pulmonary Disease (COPD). The likelihood probability was modeled using both a Gaussian distribution and a nonparametric kernel density estimation method. After exhaustive feature selection, good specificity and sensitivity were achieved in a cross-validation study for both the Gaussian (0.83, 0.87) and the nonparametric method (0.79, 0.89). The model generalizes well when trained using images from a late stage COPD group. This probability model may facilitate airway extraction and quantitative assessment of lung diseases, which is useful in many clinical and research settings.},
	issn = {1945-7928},
	doi = {10.1109/ISBI.2013.6556491},
	author = {Rudyanto, Rina D and Mu{\~n}oz-Barrutia, Arrate and Diaz, Alejandro A and Ross, James and Washko, George R and Ortiz-de-Solorzano, Carlos and Estepar, Raul San Jose}
}
@article {450456,
	title = {Pulmonary lobe segmentation based on ridge surface sampling and shape model fitting},
	journal = {Med Phys},
	volume = {40},
	number = {12},
	year = {2013},
	month = {2013 Dec},
	pages = {121903},
	abstract = {PURPOSE: Performing lobe-based quantitative analysis of the lung in computed tomography (CT) scans can assist in efforts to better characterize complex diseases such as chronic obstructive pulmonary disease (COPD). While airways and vessels can help to indicate the location of lobe boundaries, segmentations of these structures are not always available, so methods to define the lobes in the absence of these structures are desirable.

METHODS: The authors present a fully automatic lung lobe segmentation algorithm that is effective in volumetric inspiratory and expiratory computed tomography (CT) datasets. The authors rely on ridge surface image features indicating fissure locations and a novel approach to modeling shape variation in the surfaces defining the lobe boundaries. The authors employ a particle system that efficiently samples ridge surfaces in the image domain and provides a set of candidate fissure locations based on the Hessian matrix. Following this, lobe boundary shape models generated from principal component analysis (PCA) are fit to the particles data to discriminate between fissure and nonfissure candidates. The resulting set of particle points are used to fit thin plate spline (TPS) interpolating surfaces to form the final boundaries between the lung lobes.

RESULTS: The authors tested algorithm performance on 50 inspiratory and 50 expiratory CT scans taken from the COPDGene study. Results indicate that the authors{\textquoteright} algorithm performs comparably to pulmonologist-generated lung lobe segmentations and can produce good results in cases with accessory fissures, incomplete fissures, advanced emphysema, and low dose acquisition protocols. Dice scores indicate that only 29 out of 500 (5.85\%) lobes showed Dice scores lower than 0.9. Two different approaches for evaluating lobe boundary surface discrepancies were applied and indicate that algorithm boundary identification is most accurate in the vicinity of fissures detectable on CT.

CONCLUSIONS: The proposed algorithm is effective for lung lobe segmentation in absence of auxiliary structures such as vessels and airways. The most challenging cases are those with mostly incomplete, absent, or near-absent fissures and in cases with poorly revealed fissures due to high image noise. However, the authors observe good performance even in the majority of these cases.},
	keywords = {Algorithms, Exhalation, Humans, Image Processing, Computer-Assisted, Inhalation, Lung, Models, Statistical, Principal Component Analysis, Tomography, X-Ray Computed},
	issn = {2473-4209},
	doi = {10.1118/1.4828782},
	author = {Ross, James C and Kindlmann, Gordon L and Okajima, Yuka and Hatabu, Hiroto and D{\'\i}az, Alejandro A and Silverman, Edwin K and Washko, George R and Dy, Jennifer and San Jos{\'e} Est{\'e}par, Ra{\'u}l}
}
@article {449201,
	title = {Nonparametric Mixture of Gaussian Processes with Constraints},
	journal = {JMLR Workshop and Conference Proceedings},
	volume = {28},
	year = {2013},
	pages = {1346-1354},
	abstract = {Motivated by the need to identify new and clinically relevant categories of lung disease, we propose a novel clustering with constraints method using a Dirichlet process mixture of Gaussian processes in a variational Bayesian nonparametric framework. We claim that individuals should be grouped according to biological and/or genetic similarity regardless of their level of disease severity; therefore, we introduce a new way of looking at subtyping/clustering by recasting it in terms of discovering associations of individuals to disease trajectories (i.e., grouping individuals based on their similarity in response to environmental and/or disease causing variables). The nonparametric nature of our algorithm allows for learning the unknown number of meaningful trajectories. Additionally, we acknowledge the usefulness of expert guidance by providing for their input using must-link and cannot- link constraints. These constraints are encoded with Markov random fields. We also provide an efficient variational approach for performing inference on our model.},
	author = {Ross, James and Dy, Jennifer}
}
@article {444361,
	title = {Distinct quantitative computed tomography emphysema patterns are associated with physiology and function in smokers},
	journal = {Am J Respir Crit Care Med},
	volume = {188},
	number = {9},
	year = {2013},
	month = {2013 Nov 01},
	pages = {1083-90},
	abstract = {RATIONALE: Emphysema occurs in distinct pathologic patterns, but little is known about the epidemiologic associations of these patterns. Standard quantitative measures of emphysema from computed tomography (CT) do not distinguish between distinct patterns of parenchymal destruction.

OBJECTIVES: To study the epidemiologic associations of distinct emphysema patterns with measures of lung-related physiology, function, and health care use in smokers.

METHODS: Using a local histogram-based assessment of lung density, we quantified distinct patterns of low attenuation in 9,313 smokers in the COPDGene Study. To determine if such patterns provide novel insights into chronic obstructive pulmonary disease epidemiology, we tested for their association with measures of physiology, function, and health care use.

MEASUREMENTS AND MAIN RESULTS: Compared with percentage of low-attenuation area less than -950 Hounsfield units (\%LAA-950), local histogram-based measures of distinct CT low-attenuation patterns are more predictive of measures of lung function, dyspnea, quality of life, and health care use. These patterns are strongly associated with a wide array of measures of respiratory physiology and function, and most of these associations remain highly significant (P < 0.005) after adjusting for \%LAA-950. In smokers without evidence of chronic obstructive pulmonary disease, the mild centrilobular disease pattern is associated with lower FEV1 and worse functional status (P < 0.005).

CONCLUSIONS: Measures of distinct CT emphysema patterns provide novel information about the relationship between emphysema and key measures of physiology, physical function, and health care use. Measures of mild emphysema in smokers with preserved lung function can be extracted from CT scans and are significantly associated with functional measures.},
	keywords = {Aged, Cohort Studies, Dyspnea, Female, Health Services, Humans, Lung, Male, Middle Aged, Pulmonary Emphysema, Quality of Life, Severity of Illness Index, Smoking, Spirometry, Tomography, Spiral Computed},
	issn = {1535-4970},
	doi = {10.1164/rccm.201305-0873OC},
	author = {Castaldi, Peter J and San Jos{\'e} Est{\'e}par, Ra{\'u}l and Mendoza, Carlos S and Hersh, Craig P and Laird, Nan and Crapo, James D and Lynch, David A and Silverman, Edwin K and Washko, George R}
}