2011
San Jose Estépar R, Ross JC, Kindlmann GL, Diaz AA, Silverman EK, Washko GR, Washko GR.
Airway Extraction In Inspiratory Volumetric CT Using Scale-Space Particles. American journal of respiratory and critical care medicineAmerican journal of respiratory and critical care medicine 2011;183:A4611.
Kim DK, Hersh CP, Washko GR, Hokanson JE, Lynch DA, Newell JD, Murphy JR, Crapo JD, Silverman EK, Silverman EK.
Epidemiology, radiology, and genetics of nicotine dependence in COPD. Respiratory researchRespiratory research 2011;12:9.
AbstractBACKGROUND: Cigarette smoking is the principal environmental risk factor for developing COPD, and nicotine dependence strongly influences smoking behavior. This study was performed to elucidate the relationship between nicotine dependence, genetic susceptibility to nicotine dependence, and volumetric CT findings in smokers. METHODS: Current smokers with COPD (GOLD stage >/= 2) or normal spirometry were analyzed from the COPDGene Study, a prospective observational study. Nicotine dependence was determined by the Fagerstrom test for nicotine dependence (FTND). Volumetric CT acquisitions measuring the percent of emphysema on inspiratory CT (% of lung <-950 HU) and gas trapping on expiratory CT (% of lung <-856 HU) were obtained. Genotypes for two SNPs in the CHRNA3/5 region (rs8034191, rs1051730) previously associated with nicotine dependence and COPD were analyzed for association to COPD and nicotine dependence phenotypes. RESULTS: Among 842 currently smoking subjects (335 COPD cases and 507 controls), 329 subjects (39.1%) showed high nicotine dependence. Subjects with high nicotine dependence had greater cumulative and current amounts of smoking. However, emphysema severity was negatively correlated with the FTND score in controls (rho = -0.19, p < .0001) as well as in COPD cases (rho = -0.18, p = 0.0008). Lower FTND score, male gender, lower body mass index, and lower FEV1 were independent risk factors for emphysema severity in COPD cases. Both CHRNA3/5 SNPs were associated with FTND in current smokers. An association of genetic variants in CHRNA3/5 with severity of emphysema was only found in former smokers, but not in current smokers. CONCLUSIONS: Nicotine dependence was a negative predictor for emphysema on CT in COPD and control smokers. Increased inflammation in more highly addicted current smokers could influence the CT lung density distribution, which may influence genetic association studies of emphysema phenotypes.
respiratory_research_2011_kim.pdf Obstein KL, Patil VD, Jayender J, San Jose Estépar R, Spofford IS, Lengyel BI, Vosburgh KG, Thompson CC.
Evaluation of colonoscopy technical skill levels by use of an objective kinematic-based system. Gastrointestinal endoscopyGastrointestinal endoscopy 2011;73:315-21, 321.e1.
AbstractBACKGROUND:Colonoscopy requires training and experience to ensure accuracy and safety. Currently, no objective, validated process exists to determine when an endoscopist has attained technical competence. Kinematics data describing movements of laparoscopic instruments have been used in surgical skill assessment to define expert surgical technique. We have developed a novel system to record kinematics data during colonoscopy and quantitatively assess colonoscopist performance.OBJECTIVE:To use kinematic analysis of colonoscopy to quantitatively assess endoscopic technical performance.DESIGN:Prospective cohort study.SETTING:Tertiary-care academic medical center.POPULATION:This study involved physicians who perform colonoscopy.INTERVENTION:Application of a kinematics data collection system to colonoscopy evaluation.MAIN OUTCOME MEASUREMENTS:Kinematics data, validated task load assessment instrument, and technical difficulty visual analog scale.RESULTS:All 13 participants completed the colonoscopy to the terminal ileum on the standard colon model. Attending physicians reached the terminal ileum quicker than fellows (median time, 150.19 seconds vs 299.86 seconds; p<.01) with reduced path lengths for all 4 sensors, decreased flex (1.75 m vs 3.14 m; P=.03), smaller tip angulation, reduced absolute roll, and lower curvature of the endoscope. With performance of attending physicians serving as the expert reference standard, the mean kinematic score increased by 19.89 for each decrease in postgraduate year (P<.01). Overall, fellows experienced greater mental, physical, and temporal demand than did attending physicians.LIMITATION:Small cohort size.CONCLUSION:Kinematic data and score calculation appear useful in the evaluation of colonoscopy technical skill levels. The kinematic score appears to consistently vary by year of training. Because this assessment is nonsubjective, it may be an improvement over current methods for determination of competence. Ongoing studies are establishing benchmarks and characteristic profiles of skill groups based on kinematics data.
Obstein L K, San Jose Estépar R, Jayender J, Patil D V, Spofford S I, Ryan B M, Lengyel I B, Shams R, Vosburgh G K, Thompson CC.
Image Registered Gastroscopic Ultrasound (IRGUS) in human subjects: a pilot study to assess feasibility. EndoscopyEndoscopy 2011;43:394-399.
AbstractBACKGROUND AND STUDY AIMS: Endoscopic ultrasound (EUS) is a complex procedure due to the subtleties of ultrasound interpretation, the small field of observation, and the uncertainty of probe position and orientation. Animal studies demonstrated that Image Registered Gastroscopic Ultrasound (IRGUS) is feasible and may be superior to conventional EUS in efficiency and image interpretation. This study explores whether these attributes of IRGUS will be evident in human subjects, with the aim of assessing the feasibility, effectiveness, and efficiency of IRGUS in patients with suspected pancreatic lesions. PATIENTS AND METHODS: This was a prospective feasibility study at a tertiary care academic medical center in human patients with pancreatic lesions on computed tomography (CT) scan. Patients who were scheduled to undergo conventional EUS were randomly chosen to undergo their procedure with IRGUS. Main outcome measures included feasibility, ease of use, system function, validated task load (TLX) assessment instrument, and IRGUS experience questionnaire. RESULTS: Five patients underwent IRGUS without complication. Localization of pancreatic lesions was accomplished efficiently and accurately (TLX temporal demand 3.7 %; TLX effort 8.6 %). Image synchronization and registration was accomplished in real time without procedure delay. The mean assessment score for endoscopist experience with IRGUS was positive (66.6 ± 29.4). Real-time display of CT images in the EUS plane and echoendoscope orientation were the most beneficial characteristics. CONCLUSIONS: IRGUS appears feasible and safe in human subjects, and efficient and accurate at identification of probe position and image interpretation. IRGUS has the potential to broaden the adoption of EUS techniques and shorten EUS learning curves. Clinical studies comparing IRGUS with conventional EUS are ongoing.
Yamashiro T, San Jose Estépar R, Matsuoka S, Bartholmai BJ, Ross JC, Diaz A, Murayama S, Silverman EK, Hatabu H, Washko GR.
Intrathoracic tracheal volume and collapsibility on inspiratory and end-expiratory ct scans correlations with lung volume and pulmonary function in 85 smokers. Academic RadiologyAcademic Radiology 2011;18:299-305.
AbstractRATIONALE AND OBJECTIVES:To evaluate the correlations of tracheal volume and collapsibility on inspiratory and end-expiratory computed tomography (CT) with lung volume and with lung function in smokers.MATERIALS AND METHODS:The institutional review board approved this study at each institution. 85 smokers (mean age 68, range 45-87 years; 40 females and 45 males) underwent pulmonary function tests and chest CT at full inspiration and end-expiration. On both scans, intrathoracic tracheal volume and lung volume were measured. Collapsibility of the trachea and the lung was expressed as expiratory/inspiratory (E/I) ratios of these volumes. Correlations of the tracheal measurements with the lung measurements and with lung function were evaluated by the linear regression analysis.RESULTS:Tracheal volume showed moderate or strong, positive correlations with lung volume on both inspiratory (r = 0.661, P < .0001) and end-expiratory (r = 0.749, P < .0001) scans. The E/I ratio of tracheal volume showed a strong, positive correlation with the E/I ratio of lung volume (r = 0.711, P < .0001). A weak, negative correlation was found between the E/I ratio of tracheal volume and the ratio of forced expiratory volume in the first second to forced vital capacity (r = -0.436, P < .0001). Also, a weak, positive correlation was observed between the E/I ratio of tracheal volume and the ratio of residual volume to total lung capacity (r = 0.253, P = .02).CONCLUSIONS:Tracheal volume and collapsibility, measured by inspiratory and end-expiratory CT scans, is related to lung volume and collapsibility. The highly collapsed trachea on end-expiratory CT does not indicate more severe airflow limitation or air-trapping in smokers.
Yamashiro T, Matsuoka S, San Jose Estépar R, Bartholmai BJ, Diaz A, Ross JC, Murayama S, Silverman EK, Hatabu H, Washko GR.
Kurtosis and skewness of density histograms on inspiratory and expiratory CT scans in smokers. COPDCOPD 2011;8:13-20.
AbstractThe aim of this study is to evaluate the relationship between lung function and kurtosis or skewness of lung density histograms on computed tomography (CT) in smokers. Forty-six smokers (age range 46?81 years), enrolled in the Lung Tissue Research Consortium, underwent pulmonary function tests (PFT) and chest CT at full inspiration and full expiration. On both inspiratory and expiratory scans, kurtosis and skewness of the density histograms were automatically measured by open-source software. Correlations between CT measurements and lung function were evaluated by the linear regression analysis. Although no significant correlations were found between inspiratory kurtosis or skewness and PFT results, expiratory kurtosis significantly correlated with the following: the percentage of predicted value of forced expiratory volume in the first second (FEV(1)), the ratio of FEV(1) to forced vital capacity (FVC), and the ratio of residual volume (RV) to total lung capacity (TLC) (FEV(1)%predicted, R = -0.581, p < 0.001; FEV(1)/FVC, R = -0.612, p < 0.001; RV/TLC, R = 0.613, p < 0.001, respectively). Similarly, expiratory skewness showed significant correlations with PFT results (FEV(1)%predicted, R = -0.584, p < 0.001; FEV(1)/FVC, R = -0.619, p < 0.001; RV/TLC, R = 0.585, p < 0.001, respectively). Also, the expiratory/inspiratory (E/I) ratios of kurtosis and skewness significantly correlated with FEV(1)%predicted (p < 0.001), FEV(1)/FVC (p < 0.001), RV/TLC (p < 0.001), and the percentage of predicted value of diffusing capacity for carbon monoxide (kurtosis E/I ratio, p = 0.001; skewness E/I ratio, p = 0.03, respectively). We conclude therefore that expiratory values and the E/I ratios of kurtosis and skewness of CT densitometry reflect airflow limitation and air-trapping. Higher kurtosis or skewness on expiratory CT scan indicates more severe conditions in smokers.
Washko GR, Hunninghake GM, Fernandez IE, Nishino M, Okajima Y, Yamashiro T, Ross JC, San Jose Estépar R, Lynch DA, Brehm JM, Andriole KP, Diaz AA, Khorasani R, D'Aco K, Sciurba FC, Silverman EK, Hatabu H, Rosas IO, Rosas IO.
Lung volumes and emphysema in smokers with interstitial lung abnormalities. The New England journal of medicineThe New England journal of medicine 2011;364:897-906.
AbstractBACKGROUND: Cigarette smoking is associated with emphysema and radiographic interstitial lung abnormalities. The degree to which interstitial lung abnormalities are associated with reduced total lung capacity and the extent of emphysema is not known. METHODS: We looked for interstitial lung abnormalities in 2416 (96%) of 2508 high-resolution computed tomographic (HRCT) scans of the lung obtained from a cohort of smokers. We used linear and logistic regression to evaluate the associations between interstitial lung abnormalities and HRCT measurements of total lung capacity and emphysema. RESULTS: Interstitial lung abnormalities were present in 194 (8%) of the 2416 HRCT scans evaluated. In statistical models adjusting for relevant covariates, interstitial lung abnormalities were associated with reduced total lung capacity (-0.444 liters; 95% confidence interval [CI], -0.596 to -0.292; P<0.001) and a lower percentage of emphysema defined by lung-attenuation thresholds of -950 Hounsfield units (-3%; 95% CI, -4 to -2; P<0.001) and -910 Hounsfield units (-10%; 95% CI, -12 to -8; P<0.001). As compared with participants without interstitial lung abnormalities, those with abnormalities were more likely to have a restrictive lung deficit (total lung capacity <80% of the predicted value; odds ratio, 2.3; 95% CI, 1.4 to 3.7; P<0.001) and were less likely to meet the diagnostic criteria for chronic obstructive pulmonary disease (COPD) (odds ratio, 0.53; 95% CI, 0.37 to 0.76; P<0.001). The effect of interstitial lung abnormalities on total lung capacity and emphysema was dependent on COPD status (P<0.02 for the interactions). Interstitial lung abnormalities were positively associated with both greater exposure to tobacco smoke and current smoking. CONCLUSIONS: In smokers, interstitial lung abnormalities--which were present on about 1 of every 12 HRCT scans--were associated with reduced total lung capacity and a lesser amount of emphysema. (Funded by the National Institutes of Health and the Parker B. Francis Foundation; ClinicalTrials.gov number, NCT00608764.).
Matsuoka S, Yamashiro T, Diaz A, San Jose Estépar R, Ross JC, Silverman EK, Kobayashi Y, Dransfield MT, Bartholmai BJ, Hatabu H, Washko GR.
The relationship between small pulmonary vascular alteration and aortic atherosclerosis in chronic obstructive pulmonary disease: quantitative CT analysis. Academic RadiologyAcademic Radiology 2011;18:40-46.
AbstractRATIONALE AND OBJECTIVES: The relationship between chronic obstructive pulmonary disease (COPD) and atherosclerosis has been suggested; this association may relate to systemic inflammation and endothelial dysfunction, which can lead to alteration of small pulmonary vessels. The relationship between atherosclerosis and small pulmonary vessel alteration, however, has not been assessed in COPD patients. We tested the hypothesis that the severity of thoracic aortic calcification measured by computed tomography (CT) would be associated with the total cross-sectional area of small pulmonary vessels (CSA) on CT images. MATERIALS AND METHODS: The study was approved by the institutional review board and was Health Insurance Portability and Accountability Act-compliant. Informed consent was waived. For 51 COPD patients enrolled in the National Heart, Lung, and Blood Institute Lung Tissue Research Consortium, we calculated the percentage of total CSAs of less than 5 mm(2) for the total lung area (%CSA<5). Thoracic aortic calcification, quantified by modified Agatston score, was measured. The correlations between thoracic aortic calcification score and %CSA<5, pulmonary function, and extent of emphysema were evaluated. Multiple linear regression analysis using aortic calcification score as the dependent outcome was also performed. RESULTS: The %CSA<5 had a significant negative correlation with the thoracic aortic calcification score (r = -0.566, P < .0001). Multiple linear regression analysis showed significant correlation between the aortic calcification score and %CSA<5 (P < .0001) independent of age, pack-years, extent of emphysema, and FEV1%. CONCLUSIONS: Atherosclerosis, assessed by aortic calcification, is associated with the small pulmonary vascular alteration in COPD. Systemic inflammation and endothelial dysfunction may cause the close relationship between atherosclerosis and small pulmonary vessel alteration.
Kim Y-I, Schroeder J, Lynch D, Newell J, Make B, Friedlander A, San José Estépar R, Hanania NA, Washko G, Murphy JR, Wilson C, Hokanson JE, Zach J, Butterfield K, Bowler RP, Bowler RP.
Gender differences of airway dimensions in anatomically matched sites on CT in smokers. COPD 2011;8(4):285-92.
AbstractRATIONALE AND OBJECTIVES: There are limited data on, and controversies regarding gender differences in the airway dimensions of smokers. Multi-detector CT (MDCT) images were analyzed to examine whether gender could explain differences in airway dimensions of anatomically matched airways in smokers.
MATERIALS AND METHODS: We used VIDA imaging software to analyze MDCT scans from 2047 smokers (M:F, 1021:1026) from the COPDGene® cohort. The airway dimensions were analyzed from segmental to subsubsegmental bronchi. We compared the differences of luminal area, inner diameter, wall thickness, wall area percentage (WA%) for each airway between men and women, and multiple linear regression including covariates (age, gender, body sizes, and other relevant confounding factors) was used to determine the predictors of each airway dimensions.
RESULTS: Lumen area, internal diameter and wall thickness were smaller for women than men in all measured airway (18.4 vs 22.5 mm(2) for segmental bronchial lumen area, 10.4 vs 12.5 mm(2) for subsegmental bronchi, 6.5 vs 7.7 mm(2) for subsubsegmental bronchi, respectively p < 0.001). However, women had greater WA% in subsegmental and subsubsegmental bronchi. In multivariate regression, gender remained one of the most significant predictors of WA%, lumen area, inner diameter and wall thickness.
CONCLUSION: Women smokers have higher WA%, but lower luminal area, internal diameter and airway thickness in anatomically matched airways as measured by CT scan than do male smokers. This difference may explain, in part, gender differences in the prevalence of COPD and airflow limitation.
copd_2011_kim.pdf 2010
Diaz AA, Valim C, Yamashiro T, San José Estépar R, Ross JC, Matsuoka S, Bartholmai B, Hatabu H, Silverman EK, Washko GR.
Airway count and emphysema assessed by chest CT imaging predicts clinical outcome in smokers. Chest 2010;138(4):880-7.
AbstractBACKGROUND: Recently, it has been shown that emphysematous destruction of the lung is associated with a decrease in the total number of terminal bronchioles. It is unknown whether a similar decrease is visible in the more proximal airways. We aimed to assess the relationships between proximal airway count, CT imaging measures of emphysema, and clinical prognostic factors in smokers, and to determine whether airway count predicts the BMI, airflow obstruction, dyspnea, and exercise capacity (BODE) index.
METHODS: In 50 smokers, emphysema was measured on CT scans and airway branches from the third to eighth generations of the right upper lobe apical bronchus were counted manually. The sum of airway branches from the sixth to eighth generations represented the total airway count (TAC). For each subject, the BODE index was determined. We used logistic regression to assess the ability of TAC to predict a high BODE index (≥ 7 points).
RESULTS: TAC was inversely associated with emphysema (r = -0.54, P < .0001). TAC correlated with the modified Medical Research Council dyspnea score (r = -0.42, P = .004), FEV(1)% predicted (r = 0.52, P = .0003), 6-min walk distance (r = 0.36, P = .012), and BODE index (r = -0.55, P < .0001). The C-statistics, which correspond to the area under the receiver operating characteristic curve, for the ability of TAC alone and TAC, emphysema, and age to predict a high BODE index were 0.84 and 0.92, respectively.
CONCLUSIONS: TAC is lower in subjects with greater emphysematous destruction and is a predictor of a high BODE index. These results suggest that CT imaging-based TAC may be a unique COPD-related phenotype in smokers.
Ross JC, San José Estépar R, Kindlmann G, Díaz A, Westin C-F, Silverman EK, Washko GR.
Automatic lung lobe segmentation using particles, thin plate splines, and maximum a posteriori estimation. Med Image Comput Comput Assist Interv 2010;13(Pt 3):163-71.
AbstractWe present a fully automatic lung lobe segmentation algorithm that is effective in high resolution computed tomography (CT) datasets in the presence of confounding factors such as incomplete fissures (anatomical structures indicating lobe boundaries), advanced disease states, high body mass index (BMI), and low-dose scanning protocols. In contrast to other algorithms that leverage segmentations of auxiliary structures (esp. vessels and airways), we rely only upon image features indicating fissure locations. We employ a particle system that samples the image domain and provides a set of candidate fissure locations. We follow this stage with maximum a posteriori (MAP) estimation to eliminate poor candidates and then perform a post-processing operation to remove remaining noise particles. We then fit a thin plate spline (TPS) interpolating surface to the fissure particles to form the final lung lobe segmentation. Results indicate that our algorithm performs comparably to pulmonologist-generated lung lobe segmentations on a set of challenging cases.
Han MLK, Agusti A, Calverley PM, Celli BR, Criner G, Curtis JL, Fabbri LM, Goldin JG, Jones PW, MacNee W, Make BJ, Rabe KF, Rennard SI, Sciurba FC, Silverman EK, Vestbo J, Washko GR, Wouters EFM, Martinez FJ.
Chronic obstructive pulmonary disease phenotypes: the future of COPD. Am J Respir Crit Care Med 2010;182(5):598-604.
AbstractSignificant heterogeneity of clinical presentation and disease progression exists within chronic obstructive pulmonary disease (COPD). Although FEV(1) inadequately describes this heterogeneity, a clear alternative has not emerged. The goal of phenotyping is to identify patient groups with unique prognostic or therapeutic characteristics, but significant variation and confusion surrounds use of the term "phenotype" in COPD. Phenotype classically refers to any observable characteristic of an organism, and up until now, multiple disease characteristics have been termed COPD phenotypes. We, however, propose the following variation on this definition: "a single or combination of disease attributes that describe differences between individuals with COPD as they relate to clinically meaningful outcomes (symptoms, exacerbations, response to therapy, rate of disease progression, or death)." This more focused definition allows for classification of patients into distinct prognostic and therapeutic subgroups for both clinical and research purposes. Ideally, individuals sharing a unique phenotype would also ultimately be determined to have a similar underlying biologic or physiologic mechanism(s) to guide the development of therapy where possible. It follows that any proposed phenotype, whether defined by symptoms, radiography, physiology, or cellular or molecular fingerprint will require an iterative validation process in which "candidate" phenotypes are identified before their relevance to clinical outcome is determined. Although this schema represents an ideal construct, we acknowledge any phenotype may be etiologically heterogeneous and that any one individual may manifest multiple phenotypes. We have much yet to learn, but establishing a common language for future research will facilitate our understanding and management of the complexity implicit to this disease.
Cho MH, Washko GR, Hoffmann TJ, Criner GJ, Hoffman EA, Martinez FJ, Laird N, Reilly JJ, Silverman EK.
Cluster analysis in severe emphysema subjects using phenotype and genotype data: an exploratory investigation. Respir Res 2010;11:30.
AbstractBACKGROUND: Numerous studies have demonstrated associations between genetic markers and COPD, but results have been inconsistent. One reason may be heterogeneity in disease definition. Unsupervised learning approaches may assist in understanding disease heterogeneity.
METHODS: We selected 31 phenotypic variables and 12 SNPs from five candidate genes in 308 subjects in the National Emphysema Treatment Trial (NETT) Genetics Ancillary Study cohort. We used factor analysis to select a subset of phenotypic variables, and then used cluster analysis to identify subtypes of severe emphysema. We examined the phenotypic and genotypic characteristics of each cluster.
RESULTS: We identified six factors accounting for 75% of the shared variability among our initial phenotypic variables. We selected four phenotypic variables from these factors for cluster analysis: 1) post-bronchodilator FEV1 percent predicted, 2) percent bronchodilator responsiveness, and quantitative CT measurements of 3) apical emphysema and 4) airway wall thickness. K-means cluster analysis revealed four clusters, though separation between clusters was modest: 1) emphysema predominant, 2) bronchodilator responsive, with higher FEV1; 3) discordant, with a lower FEV1 despite less severe emphysema and lower airway wall thickness, and 4) airway predominant. Of the genotypes examined, membership in cluster 1 (emphysema-predominant) was associated with TGFB1 SNP rs1800470.
CONCLUSIONS: Cluster analysis may identify meaningful disease subtypes and/or groups of related phenotypic variables even in a highly selected group of severe emphysema subjects, and may be useful for genetic association studies.
Yamashiro T, Matsuoka S, Bartholmai BJ, San José Estépar R, Ross JC, Diaz A, Murayama S, Silverman EK, Hatabu H, Washko GR.
Collapsibility of lung volume by paired inspiratory and expiratory CT scans: correlations with lung function and mean lung density. Acad Radiol 2010;17(4):489-95.
AbstractRATIONALE AND OBJECTIVES: To evaluate the relationship between measurements of lung volume (LV) on inspiratory/expiratory computed tomography (CT) scans, pulmonary function tests (PFT), and CT measurements of emphysema in individuals with chronic obstructive pulmonary disease.
MATERIALS AND METHODS: Forty-six smokers (20 females and 26 males; age range 46-81 years), enrolled in the Lung Tissue Research Consortium, underwent PFT and chest CT at full inspiration and expiration. Inspiratory and expiratory LV values were automatically measured by open-source software, and the expiratory/inspiratory (E/I) ratio of LV was calculated. Mean lung density (MLD) and low attenuation area percent (<-950 HU) were also measured. Correlations of LV measurements with lung function and other CT indices were evaluated by the Spearman rank correlation test.
RESULTS: LV E/I ratio significantly correlated with the following: the percentage of predicted value of forced expiratory volume in the first second (FEV(1)), the ratio of FEV(1) to forced vital capacity (FVC), and the ratio of residual volume (RV) to total lung capacity (TLC) (FEV(1)%P, R = -0.56, P < .0001; FEV(1)/FVC, r = -0.59, P < .0001; RV/TLC, r = 0.57, P < .0001, respectively). A higher correlation coefficient was observed between expiratory LV and expiratory MLD (r = -0.73, P < .0001) than between inspiratory LV and inspiratory MLD (r = -0.46, P < .01). LV E/I ratio showed a very strong correlation to MLD E/I ratio (r = 0.95, P < .0001).
CONCLUSIONS: LV E/I ratio can be considered to be equivalent to MLD E/I ratio and to reflect airflow limitation and air-trapping. Higher collapsibility of lung volume, observed by inspiratory/expiratory CT, indicates less severe conditions in chronic obstructive pulmonary disease.
Dransfield MT, Huang F, Nath H, Singh SP, Bailey WC, Washko GR.
CT emphysema predicts thoracic aortic calcification in smokers with and without COPD. COPD 2010;7(6):404-10.
AbstractCOPD patients are at increased risk for cardiovascular morbidity and mortality independent of smoking habits. Recent studies suggest CT emphysema is an independent predictor of cardiovascular risk as evidenced by its association with arterial stiffness and impaired endothelial function. We examined the relationship between demographics, lung function, CT emphysema and airway wall thickness and thoracic aortic calcification, another marker of cardiovascular risk, in the National Lung Screening Trial. We hypothesized that CT emphysema would be independently associated with thoracic aortic calcification. Two hundred forty current and former smokers were enrolled. After CT examination, we recorded subjects' demographics and they performed spirometry. Subjects were classified into COPD and non-COPD subgroups. CT emphysema was quantified as a percentage of lung volume and measurements of the right upper lobe airway were performed using standard methods and expressed as wall area (%). Total calcification scores for the thoracic aorta were computed using TeraRecon image analysis. Univariate and multivariate analyses were performed to determine the associations between calcium score and subject characteristics. Subjects with COPD were older, more often male, heavier smokers and had more CT emphysema and greater aortic calcification than those without COPD. Calcium score was associated with age, pack-years, CT emphysema, wall area%, and lung function on univariate testing but only with age and CT emphysema on multivariate analysis. We conclude that CT emphysema is independently associated with thoracic calcification and thus may be used to assess cardiovascular risk in smokers with and without COPD.
Washko GR.
Diagnostic imaging in COPD. Semin Respir Crit Care Med 2010;31(3):276-85.
AbstractChronic obstructive pulmonary disease (COPD) is a pathological pulmonary condition characterized by expiratory airflow obstruction due to emphysematous destruction of the lung parenchyma and small airways remodeling. Although spirometry is a very useful diagnostic tool for screening large groups of smokers, it cannot readily differentiate the etiologies of COPD and thus has limited utility in characterizing subjects for clinical and investigational purposes. There has been a longstanding interest in thoracic imaging and its role in the in vivo characterization of smoking-related lung disease. Research in this area has spanned readily available modalities such as chest -ray and computed tomography to more advanced imaging techniques such as optical coherence tomography (OCT) and magnetic resonance imaging (MRI). Although the chest x-ray is almost universally available, it lacks sensitivity in detecting both airway disease and mild emphysema and is not generally amenable to objective analysis. Computed tomography has become the standard modality to objectively visualize lung disease. It can provide useful measures of the presence and extent of emphysema, airway disease, and, more recently, pulmonary vascular disease for clinical correlation. It does, however, face limitations in standardization across brands and generations of scanners, and the ionizing radiation associated with image acquisition is of concern to both patients and health care providers. Newer techniques such as OCT and MRI offer exciting in vivo insights into lung structure and function that were previously available only in necropsy specimens and physiology laboratories. Given the more limited availability of these techniques, they will be viewed here as adjuncts to computed tomographic imaging.
Diaz AA, Rodríguez EM, Escudero E.
Is the E/V p index useful for evaluating prognosis in chronic heart failure with atrial fibrillation? A pilot study. J Echocardiogr 2010;8(3):80-6.
AbstractBACKGROUND: The ratio of transmitral peak E wave velocity to color flow propagation velocity (E/V p index) has proved to be a significant predictor of prognosis in cardiac diseases with sinus rhythm. However, its usefulness in patients with atrial fibrillation (AF) and heart failure has not yet been established. The aim of this study was to determine the feasibility of using the E/V p index for the prediction of mortality and heart failure hospitalization in this group.
METHODS: We studied 66 ambulatory patients with stable congestive heart failure (CHF) functional class I-III and AF. Patients were divided into group A and B according to an E/V p index <1.5 and ≥1.5, respectively.
RESULTS: During follow-up (average 430 days) events were more common in group B (75 vs. 17%, log rank test; hazard ratio (HR) = 6.8). By means of multivariate logistic regression analysis, E/V p proved to be an independent predictor of events (p = 0.0012).
CONCLUSIONS: In our patients with stable CHF and AF the E/V p index is a significant predictor of clinical outcome.
Washko GR, Lynch DA, Matsuoka S, Ross JC, Umeoka S, Diaz A, Sciurba FC, Hunninghake GM, San José Estépar R, Silverman EK, Rosas IO, Hatabu H.
Identification of early interstitial lung disease in smokers from the COPDGene Study. Acad Radiol 2010;17(1):48-53.
AbstractRATIONALE AND OBJECTIVES: The aim of this study is to compare two subjective methods for the identification of changes suggestive of early interstitial lung disease (ILD) on chest computed tomographic (CT) scans.
MATERIALS AND METHODS: The CT scans of the first 100 subjects enrolled in the COPDGene Study from a single institution were examined using a sequential reader and a group consensus interpretation scheme. CT scans were evaluated for the presence of parenchymal changes consistent with ILD using the following scoring system: 0 = normal, 1 = equivocal for the presence of ILD, 2 = highly suspicious for ILD, and 3 = classic ILD changes. A statistical comparison of patients with early ILD to normal subjects was performed.
RESULTS: There was a high degree of agreement between methods (kappa = 0.84; 95% confidence interval, 0.73-0.94; P < .0001 for the sequential and consensus methods). The sequential reading method had both high positive (1.0) and negative (0.97) predictive values for a consensus read despite a 58% reduction in the number of chest CT evaluations. Regardless of interpretation method, the prevalence of chest CT changes consistent with early ILD in this subset of smokers from COPDGene varied between 5% and 10%. Subjects with early ILD tended to have greater tobacco smoke exposure than subjects without early ILD (P = .053).
CONCLUSIONS: A sequential CT interpretation scheme is an efficient method for the visual interpretation of CT data. Further investigation is required to independently confirm our findings and further characterize early ILD in smokers.
Chandra D, Lipson DA, Hoffman EA, Hansen-Flaschen J, Sciurba FC, Decamp MM, Reilly JJ, Washko GR.
Perfusion scintigraphy and patient selection for lung volume reduction surgery. Am J Respir Crit Care Med 2010;182(7):937-46.
AbstractRATIONALE: It is unclear if lung perfusion can predict response to lung volume reduction surgery (LVRS).
OBJECTIVES: To study the role of perfusion scintigraphy in patient selection for LVRS.
METHODS: We performed an intention-to-treat analysis of 1,045 of 1,218 patients enrolled in the National Emphysema Treatment Trial who were non-high risk for LVRS and had complete perfusion scintigraphy results at baseline. The median follow-up was 6.0 years. Patients were classified as having upper or non-upper lobe-predominant emphysema on visual examination of the chest computed tomography and high or low exercise capacity on cardiopulmonary exercise testing at baseline. Low upper zone perfusion was defined as less than 20% of total lung perfusion distributed to the upper third of both lungs as measured on perfusion scintigraphy.
MEASUREMENTS AND MAIN RESULTS: Among 284 of 1,045 patients with upper lobe-predominant emphysema and low exercise capacity at baseline, the 202 with low upper zone perfusion had lower mortality with LVRS versus medical management (risk ratio [RR], 0.56; P = 0.008) unlike the remaining 82 with high perfusion where mortality was unchanged (RR, 0.97; P = 0.62). Similarly, among 404 of 1,045 patients with upper lobe-predominant emphysema and high exercise capacity, the 278 with low upper zone perfusion had lower mortality with LVRS (RR, 0.70; P = 0.02) unlike the remaining 126 with high perfusion (RR, 1.05; P = 1.00). Among the 357 patients with non-upper lobe-predominant emphysema (75 with low and 282 with high exercise capacity) there was no improvement in survival with LVRS and measurement of upper zone perfusion did not contribute new prognostic information.
CONCLUSIONS: Compared with optimal medical management, LVRS reduces mortality in patients with upper lobe-predominant emphysema when there is low rather than high perfusion to the upper lung.
Arnold FW, Brock GN, Peyrani P, Rodríguez EL, Díaz AA, Rossi P, Ramirez JA.
Predictive accuracy of the pneumonia severity index vs CRB-65 for time to clinical stability: results from the Community-Acquired Pneumonia Organization (CAPO) International Cohort Study. Respir Med 2010;104(11):1736-43.
AbstractBACKGROUND: The Pneumonia Severity Index (PSI) and CRB-65 are scores used to predict mortality in patients with community-acquired pneumonia (CAP). It is unknown how well either score predicts time to clinical stability in hospitalized patients with CAP. Thus, it is also not known which score predicts time to clinical stability better.
METHODS: A secondary analysis of 3087 patients from the Community-Acquired Pneumonia Organization (CAPO) database was performed. Time-dependent receiver-operator characteristic (ROC) curves for time to clinical stability were calculated for the PSI and CRB-65 scores at day seven of hospitalization. Secondary outcomes were to assess the relationship of the PSI and CRB-65 to in-hospital mortality and length of stay (LOS). ROC curves for LOS and mortality were calculated.
RESULTS: The area under the ROC curve (AUC) for time to clinical stability by day seven was 0.638 (95% CI 0.613, 0.660) when using the PSI, and 0.647 (95% CI 0.619, 0.670) while using the CRB-65. The difference in AUC values was not statistically significant (95% CI for difference of -0.03 to 0.01). However, the difference in the AUC values for discharge within 14 days (0.651 for PSI vs 0.63 for CRB-65, 95% CI for difference 0.001-0.049), and 28-day in-hospital mortality (0.738 for PSI vs 0.69 for CRB-65, 95% CI for difference 0.02-0.082) were both statistically significant.
CONCLUSIONS: This study demonstrates a moderate ability of both the PSI and CRB-65 scores to predict time to clinical stability, and found that the predictive accuracy of the PSI was equivalent to that of the CRB-65 for this outcome.