2014
Kinsey MC, San Jose Estépar R, Zhao Y, Yu X, Diao N, Heist RS, Wain JC, Mark EJ, Washko G, Christiani DC.
Invasive adenocarcinoma of the lung is associated with the upper lung regions. Lung cancerLung cancer 2014;84:145-150.
AbstractOBJECTIVES:We postulated that ventilation-perfusion (V/Q) relationships within the lung might influence where lung cancer occurs. To address this hypothesis we evaluated the location of lung adenocarcinoma, by both tumor lobe and superior-inferior regional distribution, and associated variables such as emphysema.MATERIALS AND METHODS:One hundred fifty-nine cases of invasive adenocarcinoma and adenocarcinoma with lepidic features were visually evaluated to identify lobar or regional tumor location. Regions were determined by automated division of the lungs into three equal volumes: (upper region, middle region, or lower region). Automated densitometry was used to measure radiographic emphysema.RESULTS:The majority of invasive adenocarcinomas occurred in the upper lobes (69%), with 94% of upper lobe adenocarcinomas occurring in the upper region of the lung. The distribution of adenocarcinoma, when classified as upper or lower lobe, was not different between invasive adenocarcinoma and adenocarcinoma with lepidic features (formerly bronchioloalveolar cell carcinoma, P=0.08). Regional distribution of tumor was significantly different between invasive adenocarcinoma and adenocarcinoma with lepidic features (P=0.001). Logistic regression analysis with the outcome of invasive adenocarcinoma histology was used to adjust for confounders. Tumor region continued to be a significant predictor (OR 8.5, P=0.008, compared to lower region), whereas lobar location of tumor was not (P=0.09). In stratified analysis, smoking was not associated with region of invasive adenocarcinoma occurrence (P=0.089). There was no difference in total emphysema scores between invasive adenocarcinoma cases occurring in each of the three regions (P=0.155). There was also no difference in the distribution of region of adenocarcinoma occurrence between quartiles of emphysema (P=0.217).CONCLUSION:Invasive adenocarcinoma of the lung is highly associated with the upper lung regions. This association is not related to smoking, history of COPD, or total emphysema. The regional distribution of invasive adenocarcinoma may be due to V/Q relationships or other local factors.
Paper Rahaghi FN, Lazea D, Dihya S, San Jose Estépar R, Bueno R, Sugarbaker D, Frendl G, Washko GR.
Preoperative Pulmonary Vascular Morphology and Its Relationship to Postpneumonectomy Hemodynamics. Academic RadiologyAcademic Radiology 2014;21:704-710.
AbstractPulmonary edema and pulmonary hypertension are postsurgical complications of pneumonectomy that may represent the remaining pulmonary vasculature's inability to accommodate the entirety of the cardiac output. Quantification of the aggregate pulmonary vascular cross-sectional area (CSA) has been used to study the development of pulmonary vascular disease in smokers. In this study, we applied this technique to demonstrate the potential utility of pulmonary vascular quantification in surgical risk assessment. Our hypothesis was that those subjects with the lowest aggregate vascular CSA in the nonoperative lung would be most likely to have elevated pulmonary vascular pressures in the postoperative period.A total of 61 subjects with postoperative hemodynamics and adequate imaging were identified from 159 patients undergoing pneumonectomies for mesothelioma. The total CSA of blood vessels perpendicular to the plane of computed tomographic (CT) scan slices was computed for blood vessels <5 mm(2) (CSA 5 mm). This measurement expressed as a percentage of lung parenchyma area (CSA 5%) was compared to postoperative hemodynamic measurements obtained by right heart catheterization.In patients where a contrasted CT scan was used (n = 26), CSA 5% was correlated with postoperative day 0 minimum cardiac index (R = 0.37, P = .03) but not with the maximum pulmonary arterial pressures. In patients with noncontrast CT scans (n = 35), CSA 5% was inversely correlated with postoperative day 0 maximum pulmonary arterial pressures (R = 0.43, P = .03) but not with the minimum cardiac index. The preoperative perfusion fraction of the nonsurgical lung did not correlate with postoperative hemodynamics.CSA of pulmonary vasculature with an area ≤5 mm(2) has potential in estimating the ability of pulmonary vascular bed to accommodate postsurgical changes in pneumonectomy.Copyright © 2014 AUR. Published by Elsevier Inc. All rights reserved.
McDonald M-LN, Diaz AA, Ross JC, San Jose Estépar R, Zhou L, Regan EA, Eckbo E, Muralidhar N, Come CE, Cho MH, Hersh CP, Lange C, Wouters E, Casaburi RH, Coxson HO, MacNee W, Rennard SI, Lomas DA, Agusti A, Celli BR, Black-Shinn JL, Kinney GL, Lutz SM, Hokanson JE, Silverman EK, Washko GR.
Quantitative Computed Tomography Measures of Pectoralis Muscle Area and Disease Severity in Chronic Obstructive Pulmonary Disease. A Cross-Sectional Study. Annals ATSAnnals ATS 2014;11:326-334.
AbstractRationale: Muscle wasting in chronic obstructive pulmonary disease (COPD) is associated with a poor prognosis and is not readily assessed by measures of body mass index (BMI). BMI does not discriminate between relative proportions of adipose tissue and lean muscle and may be insensitive to early pathologic changes in body composition. Computed tomography (CT)-based assessments of the pectoralis muscles may provide insight into the clinical significance of skeletal muscles in smokers. Objectives: We hypothesized that objective assessment of the pectoralis muscle area on chest CT scans provides information that is clinically relevant and independent of BMI. Methods: Data from the ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) Study (n = 73) were used to assess the relationship between pectoralis muscle area and fat-free mass. We then used data in a subset (n = 966) of a larger cohort, the COPDGene (COPD Genetic Epidemiology) Study, to explore the relationship between pectoralis muscle area and COPD-related traits. Measurements and Main Results: We first investigated the correlation between pectoralis muscle area and fat-free mass, using data from a subset of participants in the ECLIPSE Study. We then further investigated pectoralis muscle area in COPDGene Study participants and found that higher pectoralis muscle area values were associated with greater height, male sex, and younger age. On subsequent clinical correlation, compared with BMI, pectoralis muscle area was more significantly associated with COPD-related traits, including spirometric measures, dyspnea, and 6-minute-walk distance (6MWD). For example, on average, each 10-cm(2) increase in pectoralis muscle area was associated with a 0.8-unit decrease in the BODE (Body mass index, Obstruction, Dyspnea, Exercise) index (95% confidence interval, -1.0 to -0.6; P < 0.001). Furthermore, statistically significant associations between pectoralis muscle area and COPD-related traits remained even after adjustment for BMI. Conclusions: CT-derived pectoralis muscle area provides relevant indices of COPD morbidity that may be more predictive of important COPD-related traits than BMI. However, the relationship with clinically relevant outcomes such as hospitalization and death requires additional investigation. Pectoralis muscle area is a convenient measure that can be collected in the clinical setting in addition to BMI.
San Jose Estépar R, Reeves AP, Yankelevitz D, Henschke CI, Mendelson DS, de la Hoz RE.
A Quantitative Method for Mosaic Gas Trapping based on Residual Mass. International journal of computer assisted radiology and surgeryInternational journal of computer assisted radiology and surgery 2014;9 Suppl 1:9-10.
Abstract
Purpose
Air trapping is a pathophysiologic condition indicating the retention of excess gas in all or part of the lung at any stage of expiration. Expiratory CT has been used to reveal air trapping in patients with airway diseases such as pulmonary emphysema, chronic bronchitis, asthma, and small-airway disease. Air trapping can be classified as extensive and mosaic. Extensive gas trapping is characterized by well-defined low attenuation areas in expiratory scans. Mosaic air trapping is characterized by the appearance of inhomogeneous air emptying on expiratory compared to normal inspiratory chest CT scans. A number of quantitative chest CT methods have been pro- posed to assess extensive gas trapping [1, 2], however those methods fail to detect the diffuse nature of mosaic gas trapping. We have developed an approach to tackle this problem and we have validated the technique in a population of World Trade Center workers with abnormal lung emptying reported by a radiologist.
Perez F, Vera S, Fernandez-Esparrach G, Córdova H, San Jose Estépar R, Jover JH, González Ballester MÁ.
Surgical Workflow Analysis, Design and Development of an Image-Based Navigation System for Endoscopic Interventions. In:
Erdt M, Linguraru MG, Oyarzun Laura C, Shekhar R, Wesarg S, González Ballester MÁ, Drechsler K Lecture Notes in Computer Science. Cham: Springer International Publishing; 2014 p. 91-98-98.
AbstractAbstract Endoscopic interventions in the abdominal and thoracic cavity are often hampered by the difficulty to orient in the endoscopic view. This is due to the small field of view and the inhomogeneous illumination, but also because abdominal organs are highly deformable ...
Gazourian L, Rogers AJ, Ibanga R, Weinhouse GL, Pinto-Plata V, Ritz J, Soiffer RJ, Antin JH, Washko GR, Baron RM, Ho VT.
Factors associated with bronchiolitis obliterans syndrome and chronic graft-versus-host disease after allogeneic hematopoietic cell transplantation. Am J Hematol 2014;89(4):404-9.
AbstractBronchiolitis obliterans syndrome (BOS) is a form of chronic graft vs. host disease (cGVHD) and a highly morbid pulmonary complication after allogeneic hematopoietic stem cell transplantation (HSCT). We assessed the prevalence and risk factors for BOS and cGVHD in a cohort of HSCT recipients, including those who received reduced intensity conditioning (RIC) HSCT. Between January 1, 2000 and June 30, 2010, all patients who underwent allogeneic HSCT at our institution (n = 1854) were retrospectively screened for the development of BOS by PFT criteria. We matched the BOS cases with two groups of control patients: (1) patients who had concurrent cGVHD without BOS and (2) those who developed neither cGVHD nor BOS. Comparisons between BOS patients and controls were conducted using t-test or Fisher's exact tests. Multivariate regression analysis was performed to examine factors associated with BOS diagnosis. All statistical analyses were performed using SAS 9.2. We identified 89 patients (4.8%) meeting diagnostic criteria for BOS at a median time of 491 days (range: 48-2067) after HSCT. Eighty-six (97%) of our BOS cohort had extra-pulmonary cGVHD. In multivariate analysis compared to patients without cGVHD, patients who received busulfan-based conditioning, had unrelated donors, and had female donors were significantly more likely to develop BOS, while ATG administration was associated with a lower risk of BOS. Our novel results suggest that busulfan conditioning, even in RIC transplantation, could be an important risk factor for BOS and cGVHD.
Ross JC, Díaz AA, Okajima Y, Wassermann D, Washko GR, Dy J, San José Estépar R.
AIRWAY LABELING USING A HIDDEN MARKOV TREE MODEL. Proc IEEE Int Symp Biomed Imaging 2014;2014:554-558.
AbstractWe present a novel airway labeling algorithm based on a Hidden Markov Tree Model (HMTM). We obtain a collection of discrete points along the segmented airway tree using particles sampling [1] and establish topology using Kruskal's minimum spanning tree algorithm. Following this, our HMTM algorithm probabilistically assigns labels to each point. While alternative methods label airway branches out to the segmental level, we describe a general method and demonstrate its performance out to the subsubsegmental level (two generations further than previously published approaches). We present results on a collection of 25 computed tomography (CT) datasets taken from a Chronic Obstructive Pulmonary Disease (COPD) study.
biomedical_imaging_isbi_2014_ieee_11th_international_symposium_on_2014_ross.pdf Diaz AA, Zhou L, Young TP, McDonald M-L, Harmouche R, Ross JC, Estepar RSJ, Wouters EFM, Coxson HO, MacNee W, Rennard S, Maltais F, Kinney GL, Hokanson JE, Washko GR.
Chest CT measures of muscle and adipose tissue in COPD: gender-based differences in content and in relationships with blood biomarkers. Acad Radiol 2014;21(10):1255-61.
AbstractRATIONALE AND OBJECTIVES: Computed tomography (CT) of the chest can be used to assess pectoralis muscle area (PMA) and subcutaneous adipose tissue (SAT) area. Adipose tissue content is associated with inflammatory mediators in chronic obstructive pulmonary disease (COPD) subjects. Based on gender differences in body composition, we aimed to assess the hypothesis that in subjects with COPD, the relationships between PMA, SAT, and blood biomarkers of inflammation differ by gender.
MATERIALS AND METHODS: We compared chest CT measures of PMA and SAT on a single slice at aortic arch and supraesternal notch levels from 73 subjects (28 women) with COPD between genders. The relationships of PMA and SAT area to biomarkers were assessed using within-gender regression models.
RESULTS: Women had a lesser PMA and a greater SAT area than men (difference range for PMA, 13.3-22.8 cm²; for SAT, 11.8-12.4 cm²; P < .05 for all comparisons) at both anatomic levels. These differences in PMA and SAT remained significant after adjustment for age and body mass index. Within-gender regression models adjusted for age showed that SAT was directly associated with C-reactive protein (for aortic arch level, P = .04) and fibrinogen (for both anatomic locations, P = .003) only in women, whereas PMA was not associated with any biomarkers in either gender.
CONCLUSIONS: It appears that in subjects with COPD, there are gender-based differences in the relationships between subcutaneous adipose tissue and inflammatory biomarkers.
Wassermann D, Ross J, Washko G, Wells WM, San Jose-Estepar R.
Deformable Registration of Feature-Endowed Point Sets Based on Tensor Fields. Proc IEEE Comput Soc Conf Comput Vis Pattern Recognit 2014;2014:2729-2735.
AbstractThe main contribution of this work is a framework to register anatomical structures characterized as a point set where each point has an associated symmetric matrix. These matrices can represent problem-dependent characteristics of the registered structure. For example, in airways, matrices can represent the orientation and thickness of the structure. Our framework relies on a dense tensor field representation which we implement sparsely as a kernel mixture of tensor fields. We equip the space of tensor fields with a norm that serves as a similarity measure. To calculate the optimal transformation between two structures we minimize this measure using an analytical gradient for the similarity measure and the deformation field, which we restrict to be a diffeomorphism. We illustrate the value of our tensor field model by comparing our results with scalar and vector field based models. Finally, we evaluate our registration algorithm on synthetic data sets and validate our approach on manually annotated airway trees.
computer_vision_and_pattern_recognition_cvpr_2014_ieee_conference_on_2014_wasserman.pdf Ross JC, Castaldi PJ, Cho MH, Dy JG.
Dual Beta Process Priors for Latent Cluster Discovery in Chronic Obstructive Pulmonary Disease [Internet]. In: Proceedings of the 20th ACM SIGKDD International Conference on Knowledge Discovery and Data Mining. New York, NY, USA: ACM; 2014 p. 155–162.
Publisher's VersionAbstract
Chronic obstructive pulmonary disease (COPD) is a lung disease characterized by airflow limitation usually associated with an inflammatory response to noxious particles, such as cigarette smoke. COPD is currently the third leading cause of death in the United States and is the only leading cause of death that is increasing in prevalence. It also represents an enormous financial burden to society, costing tens of billions of dollars annually in the U.S. It is widely accepted by the medical community that COPD is a heterogeneous disease, with substantial evidence indicating that genetic variation contributes to varying levels of disease susceptibility. This heterogeneity makes it difficult to predict health decline and develop targeted treatments for better patient care. Although researchers have made several attempts to discover disease subtypes, results have been inconclusive, in part because standard clustering methods have not properly dealt with disease manifestations that may worsen with increased exposure. In this paper we introduce a transformative way of looking at the COPD subtyping task. Specifically, we model the relationship between risk factors (such as age and smoke exposure) and manifestations of disease severity using Gaussian Processes, which allow us to represent so-called "disease trajectories". We also posit that individuals can be associated with multiple disease types (latent clusters), which we assume are influenced by genetics. Furthermore, we predict that only subsets of the numerous disease-related quantitative features are useful for describing each latent subtype. We model these associations using two separate beta process priors, and we describe a variational inference approach to discover the most probable latent cluster assignments. Results are validated with associations to genetic markers.
Nava R, Escalante-Ramírez B, Cristóbal G, San José Estépar R.
Extended Gabor approach applied to classification of emphysematous patterns in computed tomography. Med Biol Eng Comput 2014;52(4):393-403.
AbstractChronic obstructive pulmonary disease (COPD) is a progressive and irreversible lung condition typically related to emphysema. It hinders air from passing through airpaths and causes that alveolar sacs lose their elastic quality. Findings of COPD may be manifested in a variety of computed tomography (CT) studies. Nevertheless, visual assessment of CT images is time-consuming and depends on trained observers. Hence, a reliable computer-aided diagnosis system would be useful to reduce time and inter-evaluator variability. In this paper, we propose a new emphysema classification framework based on complex Gabor filters and local binary patterns. This approach simultaneously encodes global characteristics and local information to describe emphysema morphology in CT images. Kernel Fisher analysis was used to reduce dimensionality and to find the most discriminant nonlinear boundaries among classes. Finally, classification was performed using the k-nearest neighbor classifier. The results have shown the effectiveness of our approach for quantifying lesions due to emphysema and that the combination of descriptors yields to a better classification performance.
medical_biological_engineering_computing_2014_nava.pdf Kurugol S, Washko GR, Estepar RSJ.
RANKING AND CLASSIFICATION OF MONOTONIC EMPHYSEMA PATTERNS WITH A MULTI-CLASS HIERARCHICAL APPROACH. Proc IEEE Int Symp Biomed Imaging 2014;2014:1031-1034.
AbstractEmphysema has distinct and well-defined visually apparent CT patterns called centrilobular and panlobular emphysema. Existing studies concentrated on the classification of these patterns but they have not looked at the complete evolution of this disease as the destruction of lung parenchyma progresses from normal lung tissue to mild, moderate, and severe disease with complete effacement of the lung architecture. In this paper, we discretize this continuous process into five classes of increasing disease severity and construct a training set of 1161 CT patches. We exploit three solutions to this monotonic multi-class classification problem: a global rankSVM for ranking, hierarchical SVM for classification and a combination of these two, which we call a hierarchical rankSVM. Results showed that both hierarchical approaches were computationally efficient. The classification accuracies were slightly better for hierarchical SVM. However, in addition to classification, ranking approaches also provided a ranking of patterns, which can be utilized as a continuous disease progression score. In terms of the classification accuracy and ratio of pair-wise constraints satisfied, hierarchical rankSVM outperformed the global rankSVM.
biomedical_imaging_isbi_2014_ieee_11th_international_symposium_on_2014_kurugol-1.pdf Castaldi PJ, Cho MH, San José Estépar R, McDonald M-LN, Laird N, Beaty TH, Washko G, Crapo JD, Silverman EK.
Genome-wide association identifies regulatory Loci associated with distinct local histogram emphysema patterns. Am J Respir Crit Care Med 2014;190(4):399-409.
AbstractRATIONALE: Emphysema is a heritable trait that occurs in smokers with and without chronic obstructive pulmonary disease. Emphysema occurs in distinct pathologic patterns, but the genetic determinants of these patterns are unknown.
OBJECTIVES: To identify genetic loci associated with distinct patterns of emphysema in smokers and investigate the regulatory function of these loci.
METHODS: Quantitative measures of distinct emphysema patterns were generated from computed tomography scans from smokers in the COPDGene Study using the local histogram emphysema quantification method. Genome-wide association studies (GWAS) were performed in 9,614 subjects for five emphysema patterns, and the results were referenced against enhancer and DNase I hypersensitive regions from ENCODE and Roadmap Epigenomics cell lines.
MEASUREMENTS AND MAIN RESULTS: Genome-wide significant associations were identified for seven loci. Two are novel associations (top single-nucleotide polymorphism rs379123 in MYO1D and rs9590614 in VMA8) located within genes that function in cell-cell signaling and cell migration, and five are in loci previously associated with chronic obstructive pulmonary disease susceptibility (HHIP, IREB2/CHRNA3, CYP2A6/ADCK, TGFB2, and MMP12). Five of these seven loci lay within enhancer or DNase I hypersensitivity regions in lung fibroblasts or small airway epithelial cells, respectively. Enhancer enrichment analysis for top GWAS associations (single-nucleotide polymorphisms associated at P < 5 × 10(-6)) identified multiple cell lines with significant enhancer enrichment among top GWAS loci, including lung fibroblasts.
CONCLUSIONS: This study demonstrates for the first time genetic associations with distinct patterns of pulmonary emphysema quantified by computed tomography scan. Enhancer regions are significantly enriched among these GWAS results, with pulmonary fibroblasts among the cell types showing the strongest enrichment.
2013
Gazourian L, Coronata AMF, Rogers AJ, Weinhouse GL, Soiffer RJ, Antin JH, Ritz J, Ho VT, Baron RM, Washko GR.
Airway dilation in bronchiolitis obliterans after allogeneic hematopoietic stem cell transplantation. Respir Med 2013;107(2):276-83.
AbstractRATIONALE: 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'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 < 0.001). After HSCT the Pi10 correlated with FEV(1)% predicted (r = 0.636, p < 0.0001), and RV/TLC% predicted (r = -0.736, p < 0.0001), even after adjusting for age, sex and total lung capacity (p < 0.0001 for both).
CONCLUSIONS: On HRCT scan BOS is characterized by central airway dilation, the degree of which is correlated to decrements in lung function. This is opposite of what has been previously demonstrated in COPD and asthma that quantitative measure of proximal airway wall thickening directly correlate with pulmonary function. Our data suggests that the pathologic process affecting the central airways is different from the pathology observed in the distal airways. Further work is needed to determine if such change can be used as a sensitive and specific tool for the future diagnosis and staging of BOS.
Mulshine JL, Avila R, Yankelevitz D, Baer TM, Estepar RSJ, Fenton L, Aldige CR.
Application of high-resolution CT imaging data to lung cancer drug development: measuring progress: workshop IX. J Thorac Oncol 2013;8(11):1352-5.
AbstractBACKGROUND: 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.
Come CE, Diaz AA, Curran-Everett D, Muralidhar N, Hersh CP, Zach JA, Schroeder J, Lynch DA, Celli B, Washko GR.
Characterizing functional lung heterogeneity in COPD using reference equations for CT scan-measured lobar volumes. Chest 2013;143(6):1607-1617.
AbstractBACKGROUND: 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.
Córdova H, San José Estépar R, Rodríguez-D'Jesús A, Martínez-Pallí G, Arguis P, Rodríguez de Miguel C, Navarro-Ripoll R, Perdomo JM, Cuatrecasas M, Llach J, Vosburgh KG, Fernández-Esparrach G.
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. Gastrointest Endosc 2013;77(1):102-7.
AbstractBACKGROUND: 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 ± 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 ± 1.3) than with MED with blind access (4.7 ± 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.
Díaz AA, Morales A, Díaz JC, Ramos C, Klaassen J, Saldías F, Aravena C, Díaz R, Lisboa C, Washko GR, Díaz O.
CT and physiologic determinants of dyspnea and exercise capacity during the six-minute walk test in mild COPD. Respir Med 2013;107(4):570-9.
AbstractOBJECTIVES: 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 < 005 for all comparisons). At rest, dyspneic subjects had significant greater expiratory airflow obstruction, air trapping, ventilation/perfusion mismatch, burden of emphysema, narrower airway lumen, and lower RTMCT-CSA than comparison subjects. During walking dyspneic subjects had a decreased inspiratory capacity (IC) along with high ventilatory demand. Dyspneic subjects exhibited higher end-exercise tidal expiratory flow limitation and oxygen saturation drop than comparison subjects. In regression analysis, dyspnea intensity was best explained by ΔIC and forced expiratory volume in 1 s %predicted. RTMCT-CSA and ΔIC were independent determinants of distance walked.
CONCLUSIONS: Among subjects with mild COPD, those with daily-life dyspnea have worse exercise outcomes; distinct lung and thigh muscle morphologic features; and different pulmonary physiologic characteristics at rest and exercise. ΔIC was the main contributor to dyspnea intensity and ΔIC and thigh muscle wasting were determinants of exercise capacity.
Diaz AA, Han MLK, Come CE, San José Estépar R, Ross JC, Kim V, Dransfield MT, Curran-Everett D, Schroeder JD, Lynch DA, Tschirren J, Silverman EK, Washko GR.
Effect of emphysema on CT scan measures of airway dimensions in smokers. Chest 2013;143(3):687-693.
AbstractBACKGROUND: 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 × 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%.
Said MA, Johnson HL, Nonyane BAS, Deloria-Knoll M, O'Brien KL, Andreo F, Beovic B, Blanco S, Boersma WG, Boulware DR, Butler JC, Carratalà J, Chang F-Y, Charles PGP, Diaz AA, Domínguez J, Ehara N, Endeman H, Falcó V, Falguera M, Fukushima K, Garcia-Vidal C, Genne D, Guchev IA, Gutierrez F, Hernes SS, Hoepelman AIM, Hohenthal U, Johansson N, Kolek V, Kozlov RS, Lauderdale T-L, Mareković I, Masiá M, Matta MA, Miró Ò, Murdoch DR, Nuermberger E, Paolini R, Perelló R, Snijders D, Plečko V, Sordé R, Strålin K, van der Eerden MM, Vila-Corcoles A, Watt JP.
Estimating the burden of pneumococcal pneumonia among adults: a systematic review and meta-analysis of diagnostic techniques. PLoS One 2013;8(4):e60273.
AbstractBACKGROUND: 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® 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.