2015
Celli BR, Decramer M, Wedzicha JA, Wilson KC, Agustí AA, Criner GJ, MacNee W, Make BJ, Rennard SI, Stockley RA, Vogelmeier C, Anzueto A, Au DH, Barnes PJ, Burgel P-R, Calverley PM, Casanova C, Clini EM, Cooper CB, Coxson HO, Dusser DJ, Fabbri LM, Fahy B, Ferguson GT, Fisher A, Fletcher MJ, Hayot M, Hurst JR, Jones PW, Mahler DA, Maltais F, Mannino DM, Martinez FJ, Miravitlles M, Meek PM, Papi A, Rabe KF, Roche N, Sciurba FC, Sethi S, Siafakas N, Sin DD, Soriano JB, Stoller JK, Tashkin DP, Troosters T, Verleden GM, Verschakelen J, Vestbo J, Walsh JW, Washko GR, Wise RA, Wouters EFM, ZuWallack RL.
An official American Thoracic Society/European Respiratory Society statement: research questions in COPD. Eur Respir Rev 2015;24(136):159-72.
AbstractChronic obstructive pulmonary disease (COPD) is a leading cause of morbidity, mortality and resource use worldwide. The goal of this official American Thoracic Society (ATS)/European Respiratory Society (ERS) Research Statement is to describe evidence related to diagnosis, assessment, and management; identify gaps in knowledge; and make recommendations for future research. It is not intended to provide clinical practice recommendations on COPD diagnosis and management. Clinicians, researchers and patient advocates with expertise in COPD were invited to participate. A literature search of Medline was performed, and studies deemed relevant were selected. The search was not a systematic review of the evidence. Existing evidence was appraised and summarised, and then salient knowledge gaps were identified. Recommendations for research that addresses important gaps in the evidence in all areas of COPD were formulated via discussion and consensus. Great strides have been made in the diagnosis, assessment and management of COPD, as well as understanding its pathogenesis. Despite this, many important questions remain unanswered. This ATS/ERS research statement highlights the types of research that leading clinicians, researchers and patient advocates believe will have the greatest impact on patient-centred outcomes.
Celli BR, Decramer M, Wedzicha JA, Wilson KC, Agustí A, Criner GJ, MacNee W, Make BJ, Rennard SI, Stockley RA, Vogelmeier C, Anzueto A, Au DH, Barnes PJ, Burgel P-R, Calverley PM, Casanova C, Clini EM, Cooper CB, Coxson HO, Dusser DJ, Fabbri LM, Fahy B, Ferguson GT, Fisher A, Fletcher MJ, Hayot M, Hurst JR, Jones PW, Mahler DA, Maltais F, Mannino DM, Martinez FJ, Miravitlles M, Meek PM, Papi A, Rabe KF, Roche N, Sciurba FC, Sethi S, Siafakas N, Sin DD, Soriano JB, Stoller JK, Tashkin DP, Troosters T, Verleden GM, Verschakelen J, Vestbo J, Walsh JW, Washko GR, Wise RA, Wouters EFM, ZuWallack RL.
An Official American Thoracic Society/European Respiratory Society Statement: Research questions in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2015;191(7):e4-e27.
AbstractBACKGROUND: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity, mortality, and resource use worldwide. The goal of this Official American Thoracic Society (ATS)/European Respiratory Society (ERS) Research Statement is to describe evidence related to diagnosis, assessment, and management; identify gaps in knowledge; and make recommendations for future research. It is not intended to provide clinical practice recommendations on COPD diagnosis and management.
METHODS: Clinicians, researchers, and patient advocates with expertise in COPD were invited to participate. A literature search of Medline was performed, and studies deemed relevant were selected. The search was not a systematic review of the evidence. Existing evidence was appraised and summarized, and then salient knowledge gaps were identified.
RESULTS: Recommendations for research that addresses important gaps in the evidence in all areas of COPD were formulated via discussion and consensus.
CONCLUSIONS: Great strides have been made in the diagnosis, assessment, and management of COPD as well as understanding its pathogenesis. Despite this, many important questions remain unanswered. This ATS/ERS Research Statement highlights the types of research that leading clinicians, researchers, and patient advocates believe will have the greatest impact on patient-centered outcomes.
Nardelli P, Khan KA, Corvò A, Moore N, Murphy MJ, Twomey M, O'Connor OJ, Kennedy MP, San José Estépar R, Maher MM, Cantillon-Murphy P.
Optimizing parameters of an open-source airway segmentation algorithm using different CT images. Biomed Eng Online 2015;14:62.
AbstractBACKGROUND: Computed tomography (CT) helps physicians locate and diagnose pathological conditions. In some conditions, having an airway segmentation method which facilitates reconstruction of the airway from chest CT images can help hugely in the assessment of lung diseases. Many efforts have been made to develop airway segmentation algorithms, but methods are usually not optimized to be reliable across different CT scan parameters.
METHODS: In this paper, we present a simple and reliable semi-automatic algorithm which can segment tracheal and bronchial anatomy using the open-source 3D Slicer platform. The method is based on a region growing approach where trachea, right and left bronchi are cropped and segmented independently using three different thresholds. The algorithm and its parameters have been optimized to be efficient across different CT scan acquisition parameters. The performance of the proposed method has been evaluated on EXACT'09 cases and local clinical cases as well as on a breathing pig lung phantom using multiple scans and changing parameters. In particular, to investigate multiple scan parameters reconstruction kernel, radiation dose and slice thickness have been considered. Volume, branch count, branch length and leakage presence have been evaluated. A new method for leakage evaluation has been developed and correlation between segmentation metrics and CT acquisition parameters has been considered.
RESULTS: All the considered cases have been segmented successfully with good results in terms of leakage presence. Results on clinical data are comparable to other teams' methods, as obtained by evaluation against the EXACT09 challenge, whereas results obtained from the phantom prove the reliability of the method across multiple CT platforms and acquisition parameters. As expected, slice thickness is the parameter affecting the results the most, whereas reconstruction kernel and radiation dose seem not to particularly affect airway segmentation.
CONCLUSION: The system represents the first open-source airway segmentation platform. The quantitative evaluation approach presented represents the first repeatable system evaluation tool for like-for-like comparison between different airway segmentation platforms. Results suggest that the algorithm can be considered stable across multiple CT platforms and acquisition parameters and can be considered as a starting point for the development of a complete airway segmentation algorithm.
Araki T, Nishino M, Zazueta OE, Gao W, Dupuis J, Okajima Y, Latourelle JC, Rosas IO, Murakami T, O'Connor GT, Washko GR, Hunninghake GM, Hatabu H.
Paraseptal emphysema: Prevalence and distribution on CT and association with interstitial lung abnormalities. Eur J Radiol 2015;84(7):1413-8.
AbstractOBJECTIVE: To investigate the prevalence and distribution of paraseptal emphysema on chest CT images in the Framingham Heart Study (FHS) population, and assess its impact on pulmonary function. Also pursued was the association with interstitial lung abnormalities.
MATERIALS AND METHODS: We assessed 2633 participants in the FHS for paraseptal emphysema on chest CT. Characteristics of the participants, including age, sex, smoking status, clinical symptoms, and results of pulmonary function tests, were compared between those with and without paraseptal emphysema. The association between paraseptal emphysema and interstitial lung abnormalities was investigated.
RESULTS: Of the 2633 participants, 86 (3%) had pure paraseptal emphysema (defined as paraseptal emphysema with no other subtypes of emphysema other than paraseptal emphysema or a very few centrilobular emphysema involved) in at least one lung zone. The upper zone of the lungs was almost always involved. Compared to the participants without paraseptal emphysema, those with pure paraseptal emphysema were significantly older, and were more frequently male and smokers (mean 64 years, 71% male, mean 36 pack-years, P<0.001) and had significantly decreased FEV1/FVC% (P=0.002), and diffusion capacity of carbon monoxide (DLCO) (P=0.002). There was a significant association between pure paraseptal emphysema and interstitial lung abnormalities (P<0.001).
CONCLUSIONS: The prevalence of pure paraseptal emphysema was 3% in the FHS population, predominantly affects the upper lung zone, and contributes to decreased pulmonary function. Cigarette smoking, aging, and male gender were the factors associated with the presence of paraseptal emphysema. Significant association between paraseptal emphysema and interstitial lung abnormalities was observed.
Araki T, Nishino M, Gao W, Dupuis J, Putman RK, Washko GR, Hunninghake GM, O'Connor GT, Hatabu H.
Pulmonary cysts identified on chest CT: are they part of aging change or of clinical significance?. Thorax 2015;70(12):1156-62.
AbstractOBJECTIVE: To investigate the prevalence and natural course of pulmonary cysts in a population-based cohort and to describe the CT image characteristics in association with participant demographics and pulmonary functions.
MATERIALS AND METHODS: Chest CT scans of 2633 participants (mean age 59.2 years; 50% female) of the Framingham Heart Study (FHS) were visually evaluated for the presence of pulmonary cysts and their image characteristics. These findings were correlated with participant demographics and results of pulmonary function tests as well as the presence of emphysema independently detected on CT. The interval change was investigated by comparison with previous CT scans (median interval 6.1 years).
RESULTS: Pulmonary cysts were seen in 7.6% (95% CI 6.6% to 8.7%; 200/2633). They were not observed in participants younger than 40 years old, and the prevalence increased with age. Multiple cysts (at least five) were seen in 0.9% of all participants. Participants with pulmonary cysts showed significantly lower body mass index (BMI) (p<0.001). Pulmonary cysts were most likely to appear solitary in the peripheral area of the lower lobes and remain unchanged or slightly increase in size over time. Pulmonary cysts showed no significant influence on pulmonary functions (p=0.07-0.6) except for diffusing capacity of the lung for carbon monoxide (DLCO) (p=0.03) and no association with cigarette smoking (p=0.1-0.9) or emphysema (p=0.7).
CONCLUSIONS: Pulmonary cysts identified on chest CT may be a part of the aging changes of the lungs, occurring in asymptomatic individuals older than 40 years, and are associated with decreased BMI and DLCO. Multiple pulmonary cysts may need to be evaluated for the possibility of cystic lung diseases.
DuBrock HM, Bankier AA, Silva M, Litmanovich DE, Curry MP, Washko GR.
Pulmonary Vessel Cross-sectional Area before and after Liver Transplantation: Quantification with Computed Tomography. Acad Radiol 2015;22(6):752-9.
AbstractRATIONALE AND OBJECTIVES: Pulmonary vascular complications of liver disease have a substantial impact on morbidity and mortality in patients who undergo liver transplant. The effect of liver transplantation on the pulmonary vasculature in patients without pulmonary vascular disease, however, has not been described. This study was undertaken to characterize the regional effect of liver transplant on the cross-sectional area (CSA) of pulmonary vessels.
MATERIALS AND METHODS: We performed a single-center, retrospective, cohort study of patients who had a liver transplant between 2002 and 2012 and who had chest computed tomography scans within 1 year before and after transplant. Using ImageJ software, we measured the CSA of small pulmonary vessels (0-5 mm(2)) and the total lung CSA to calculate the percent CSA of pulmonary vessels <5 mm (%CSA<5) at the level of the aortic arch, carina, and right inferior pulmonary vein (RIPV). Pretransplant and posttransplant, %CSA<5 were compared, and associations of pretransplant %CSA<5 with clinical parameters were measured.
RESULTS: There was a significant decrease in %CSA<5 at the level of the RIPV (0.19% [interquartile range {IQR}, 0.15-0.26] before vs. 0.15% [IQR, 0.12-0.21] after; P = .0003), with a median change of -16.2% (IQR, -39.3 to 3.9) posttransplant. Changes at the level of the aortic arch and carina were not significant. Pretransplant RIPV %CSA<5 was not significantly correlated with severity of liver disease or oxygenation but was inversely correlated with percent change in %CSA<5 (r = -0.39; P = .0039).
CONCLUSIONS: This is the first study to describe a significant regional change in the pulmonary vessels of patients without known pulmonary vascular disease who undergo liver transplant.
Come CE, Kramer MR, Dransfield MT, Abu-Hijleh M, Berkowitz D, Bezzi M, Bhatt SP, Boyd MB, Cases E, Chen AC, Cooper CB, Flandes J, Gildea T, Gotfried M, Hogarth KD, Kolandaivelu K, Leeds W, Liesching T, Marchetti N, Marquette C, Mularski RA, Pinto-Plata VM, Pritchett MA, Rafeq S, Rubio ER, Slebos D-J, Stratakos G, Sy A, Tsai LW, Wahidi M, Walsh J, Wells MJ, Whitten PE, Yusen R, Zulueta JJ, Criner GJ, Washko GR.
A randomised trial of lung sealant versus medical therapy for advanced emphysema. Eur Respir J 2015;46(3):651-62.
AbstractUncontrolled pilot studies demonstrated promising results of endoscopic lung volume reduction using emphysematous lung sealant (ELS) in patients with advanced, upper lobe predominant emphysema. We aimed to evaluate the safety and efficacy of ELS in a randomised controlled setting.Patients were randomised to ELS plus medical treatment or medical treatment alone. Despite early termination for business reasons and inability to assess the primary 12-month end-point, 95 out of 300 patients were successfully randomised, providing sufficient data for 3- and 6-month analysis.57 patients (34 treatment and 23 control) had efficacy results at 3 months; 34 (21 treatment and 13 control) at 6 months. In the treatment group, 3-month lung function, dyspnoea, and quality of life improved significantly from baseline when compared to control. Improvements persisted at 6 months with >50% of treated patients experiencing clinically important improvements, including some whose lung function improved by >100%. 44% of treated patients experienced adverse events requiring hospitalisation (2.5-fold more than control, p=0.01), with two deaths in the treated cohort. Treatment responders tended to be those experiencing respiratory adverse events.Despite early termination, results show that minimally invasive ELS may be efficacious, yet significant risks (probably inflammatory) limit its current utility.
Jaramillo JD, Wilson C, Stinson DS, Stinson DJ, Lynch DA, Bowler RP, Lutz S, Bon JM, Arnold B, McDonald M-LN, Washko GR, Wan ES, DeMeo DL, Foreman MG, Soler X, Lindsay SE, Lane NE, Genant HK, Silverman EK, Hokanson JE, Make BJ, Crapo JD, Regan EA.
Reduced Bone Density and Vertebral Fractures in Smokers. Men and COPD Patients at Increased Risk. Ann Am Thorac Soc 2015;12(5):648-56.
AbstractRATIONALE: Former smoking history and chronic obstructive pulmonary disease (COPD) are potential risk factors for osteoporosis and fractures. Under existing guidelines for osteoporosis screening, women are included but men are not, and only current smoking is considered.
OBJECTIVES: To demonstrate the impact of COPD and smoking history on the risk of osteoporosis and vertebral fracture in men and women.
METHODS: Characteristics of participants with low volumetric bone mineral density (vBMD) were identified and related to COPD and other risk factors. We tested associations of sex and COPD with both vBMD and fractures adjusting for age, race, body mass index (BMI), smoking, and glucocorticoid use.
MEASUREMENTS AND MAIN RESULTS: vBMD by calibrated quantitative computed tomography (QCT), visually scored vertebral fractures, and severity of lung disease were determined from chest CT scans of 3,321 current and ex-smokers in the COPDGene study. Low vBMD as a surrogate for osteoporosis was calculated from young adult normal values. Male smokers had a small but significantly greater risk of low vBMD (2.5 SD below young adult mean by calibrated QCT) and more fractures than female smokers. Low vBMD was present in 58% of all subjects, was more frequent in those with worse COPD, and rose to 84% among subjects with very severe COPD. Vertebral fractures were present in 37% of all subjects and were associated with lower vBMD at each Global Initiative for Chronic Obstructive Lung Disease stage of severity. Vertebral fractures were most common in the midthoracic region. COPD and especially emphysema were associated with both low vBMD and vertebral fractures after adjustment for steroid use, age, pack-years of smoking, current smoking, and exacerbations. Airway disease was associated with higher bone density after adjustment for other variables. Calibrated QCT identified more subjects with abnormal values than the standard dual-energy X-ray absorptiometry in a subset of subjects and correlated well with prevalent fractures.
CONCLUSIONS: Male smokers, with or without COPD, have a significant risk of low vBMD and vertebral fractures. COPD was associated with low vBMD after adjusting for race, sex, BMI, smoking, steroid use, exacerbations, and age. Screening for low vBMD by using QCT in men and women who are smokers will increase opportunities to identify and treat osteoporosis in this at-risk population.
Kinsey MC, San José Estépar R, Wei Y, Washko GR, Christiani DC.
Regional Emphysema of a Non-Small Cell Tumor Is Associated with Larger Tumors and Decreased Survival Rates. Ann Am Thorac Soc 2015;12(8):1197-205.
AbstractRATIONALE: Chronic obstructive pulmonary disease is associated with a worse overall survival in non-small cell lung cancer. Lung emphysema is one component of chronic obstructive pulmonary disease. We hypothesized that emphysema of the tumor region may result in larger tumors and a poorer overall survival.
METHODS: We evaluated 304 cases of non-small cell lung cancer from a prospectively enrolled cohort. The lung was divided into equal volumetric thirds (upper, middle, or lower region). Emphysema was defined as percentage of low-attenuation areas less than -950 Hounsfield units (%LAA-950) and measured for each region. Whole-lung %LAA-950 was defined as the emphysema score of the entire lung parenchyma, whereas regional %LAA-950 was the score within that particular region (upper, middle, or lower). The emphysema score of the region in which the tumor occurred was defined as the tumor %LAA-950. Tumor diameter was measured while blinded to characteristics of the lung parenchyma. A proportional hazards model was used to control for multiple factors associated with survival.
MEASUREMENTS AND MAIN RESULTS: Increasing tumor %LAA-950 was associated with larger tumors (P = 0.024). Survival, stratified by stage, was significantly worse in those with tumor %LAA-950 greater than or equal to the 50th percentile versus less than the 50th percentile (P = 0.046). Whole-lung %LAA-950 and regional %LAA-950 (e.g., regional emphysema without tumor occurring in the region) were not significantly associated with survival. There were no differences in presenting symptoms or locations of mediastinal or distant metastasis by emphysema score. Increasing tumor %LAA-950 was associated with an increased risk of death (adjusted hazard ratio, 1.36; confidence interval, 1.09-1.68; P = 0.006) after adjustment for age, sex, smoking status, histology, stage, performance status, chemotherapy, radiation, and surgery. Sensitivity analyses revealed no significant difference in the effect size or test of significance for each of the following conditions: (1) exclusion of cases with central tumor location, (2) exclusion of cases where surgery was performed, (3) exclusion of cases where radiation therapy was performed, (4) exclusion of cases where epidermal growth factor receptor tyrosine kinase inhibitors were administered, and (5) inclusion of only stage IV disease.
CONCLUSIONS: Increasing emphysema of the region in which a non-small cell lung cancer tumor occurs is associated with increasing tumor size and worse overall survival.
Gjerdevik M, Grydeland TB, Washko GR, Coxson HO, Silverman EK, Gulsvik A, Bakke PS.
The Relationship of Educational Attainment with Pulmonary Emphysema and Airway Wall Thickness. Ann Am Thorac Soc 2015;12(6):813-20.
AbstractRATIONALE: Low educational attainment is a risk factor of chronic obstructive pulmonary disease (COPD). There is limited knowledge on the relationship between educational level and computed tomography measures of emphysema and airway wall thickness (AWT).
OBJECTIVES: We hypothesized that low educational attainment is associated with increased emphysema and AWT in ever-smokers with and without COPD.
METHODS: We included 462 and 485 ever-smokers with and without COPD in a cross-sectional study, aged 40-86 years. The sample was divided into groups reflecting educational attainment: primary, secondary, and university. We performed linear regression to examine associations between educational attainment and both emphysema and AWT separately for those with and without COPD. We adjusted for sex, age, smoking status, age of onset of smoking, pack-years, height, and body mass index.
MEASUREMENTS AND MAIN RESULTS: Compared with university education, in subjects with COPD, primary education was associated with a 68.1% (95% confidence interval = 14.2-147.6%; P = 0.01) relative increase in emphysema and secondary education was associated with a 50.6% (95% confidence interval = 5.7-114.6%; P = 0.02) relative increase. There was a nonsignificant trend toward an association between lower educational attainment and increased emphysema among those without COPD (P = 0.18), yet greater age appeared to modify this association (P = 0.01). We did not detect significant linear relationships between educational attainment and AWT in subjects with or without COPD.
CONCLUSIONS: Lower educational attainment was associated with increased emphysema among adults with COPD. Among those without COPD, this association was more pronounced with increasing age. No significant linear relationship between educational attainment and AWT was found. Clinicians treating adults with emphysema should keep in mind that factors related to low education beyond that of smoking and occupational dust exposure might be of importance to the disease.
Patil V, Gupta R, San José Estépar R, Lacson R, Cheung A, Wong JM, Popp JA, Golby A, Ogilvy C, Vosburgh KG.
Smart stylet: the development and use of a bedside external ventricular drain image-guidance system. Stereotact Funct Neurosurg 2015;93(1):50-8.
AbstractBACKGROUND: Placement accuracy of ventriculostomy catheters is reported in a wide and variable range. Development of an efficient image-guidance system may improve physician performance and patient safety.
OBJECTIVE: We evaluate the prototype of Smart Stylet, a new electromagnetic image-guidance system for use during bedside ventriculostomy.
METHODS: Accuracy of the Smart Stylet system was assessed. System operators were evaluated for their ability to successfully target the ipsilateral frontal horn in a phantom model.
RESULTS: Target registration error across 15 intracranial targets ranged from 1.3 to 4.6 mm (mean 3.1 mm). Using Smart Stylet guidance, a test operator successfully passed a ventriculostomy catheter to a shifted ipsilateral frontal horn 20/20 (100%) times from the frontal approach in a skull phantom. Without Smart Stylet guidance, the operator was successful 4/10 (40%) times from the right frontal approach and 6/10 (60%) times from the left frontal approach. In a separate experiment, resident operators were successful 2/4 (50%) times when targeting the shifted ipsilateral frontal horn with Smart Stylet guidance and 0/4 (0%) times without image guidance using a skull phantom.
CONCLUSIONS: Smart Stylet may improve the ability to successfully target the ventricles during frontal ventriculostomy.
Martinez CH, Mannino DM, Curtis JL, Han MLK, Diaz AA.
Socioeconomic Characteristics Are Major Contributors to Ethnic Differences in Health Status in Obstructive Lung Disease: An Analysis of the National Health and Nutrition Examination Survey 2007-2010. Chest 2015;148(1):151-158.
AbstractBACKGROUND: Understanding ethnic differences in health status (HS) could help in designing culturally appropriate interventions. We hypothesized that racial and ethnic differences exist in HS between non-Hispanic whites and Mexican Americans with obstructive lung disease (OLD) and that these differences are mediated by socioeconomic factors.
METHODS: We analyzed 826 US adults aged ≥ 30 years self-identified as Mexican American or non-Hispanic white with spirometry-confirmed OLD (FEV₁/FVC < 0.7) who participated in the National Health and Nutrition Examination Survey 2007-2010. We assessed associations between Mexican American ethnicity and self-reported HS using logistic regression models adjusted for demographics, smoking status, number of comorbidities, limitations for work, and lung function and tested the contribution of education and health-care access to ethnic differences in HS.
RESULTS: Among Mexican Americans with OLD, worse (fair or poor) HS was more prevalent than among non-Hispanic whites (weighted percentage [SE], 46.6% [5.0] vs 15.2% [1.6]; P < .001). In bivariate analysis, socioeconomic characteristics were associated with lower odds of reporting poor HS (high school graduation: OR, 0.24 [95% CI, 0.10-0.40]; access to health care: OR, 0.50 [95% CI, 0.30-0.80]). In fully adjusted models, a strong association was found between Mexican American ethnicity (vs non-Hispanic white) and fair or poor HS (OR, 7.52; 95% CI, 4.43-12.78; P < .001). Higher education and access to health care contributed to lowering the Mexican American ethnicity odds of fair or poor HS by 47% and 16%, respectively, and together, they contributed 55% to reducing the differences in HS with non-Hispanic whites.
CONCLUSIONS: Mexican Americans with OLD report poorer overall HS than non-Hispanic whites, and education and access to health care are large contributors to the difference.
Diaz AA, Rahaghi FN, Ross JC, Harmouche R, Tschirren J, San José Estépar R, Washko GR.
Understanding the contribution of native tracheobronchial structure to lung function: CT assessment of airway morphology in never smokers. Respir Res 2015;16(1):23.
AbstractBACKGROUND: Computed tomographic (CT) airway lumen narrowing is associated with lower lung function. Although volumetric CT measures of airways (wall volume [WV] and lumen volume [LV]) compared to cross sectional measures can more accurately reflect bronchial morphology, data of their use in never smokers is scarce. We hypothesize that native tracheobronchial tree morphology as assessed by volumetric CT metrics play a significant role in determining lung function in normal subjects. We aimed to assess the relationships between airway size, the projected branching generation number (BGN) to reach airways of <2mm lumen diameter -the site for airflow obstruction in smokers- and measures of lung function including forced expiratory volume in 1 second (FEV1) and forced expiratory flow between 25% and 75% of vital capacity (FEF 25-75).
METHODS: We assessed WV and LV of segmental and subsegmental airways from six bronchial paths as well as lung volume on CT scans from 106 never smokers. We calculated the lumen area ratio of the subsegmental to segmental airways and estimated the projected BGN to reach a <2mm-lumen-diameter airway assuming a dichotomized tracheobronchial tree model. Regression analysis was used to assess the relationships between airway size, BGN, FEF 25-75, and FEV1.
RESULTS: We found that in models adjusted for demographics, LV and WV of segmental and subsegmental airways were directly related to FEV1 (P <0.05 for all the models). In adjusted models for age, sex, race, LV and lung volume or height, the projected BGN was directly associated with FEF 25-75 and FEV1 (P = 0.001) where subjects with lower FEV1 had fewer calculated branch generations between the subsegmental bronchus and small airways. There was no association between airway lumen area ratio and lung volume.
CONCLUSION: We conclude that in never smokers, those with smaller central airways had lower airflow and those with lower airflow had less parallel airway pathways independent of lung size. These findings suggest that variability in the structure of the tracheobronchial tree may influence the risk of developing clinically relevant smoking related airway obstruction.
Martinez CH, Mannino DM, Jaimes FA, Curtis JL, Han MLK, Hansel NN, Diaz AA.
Undiagnosed Obstructive Lung Disease in the United States. Associated Factors and Long-term Mortality. Ann Am Thorac Soc 2015;12(12):1788-95.
AbstractRATIONALE: Understanding factors associated with undiagnosed obstructive lung disease and its impact on mortality could inform the ongoing discussions about benefits and risks of screening and case finding.
OBJECTIVES: To define factors associated with undiagnosed obstructive lung disease and its long-term mortality.
METHODS: Cross-sectional analysis of participants, aged 20 to 79 years, in two National Health and Nutritional Examination Surveys (NHANES), NHANES III (1988-1994) and NHANES 2007-2012, with longitudinal follow-up of NHANES III participants.
MEASUREMENTS AND MAIN RESULTS: We classified participants with spirometry-confirmed obstructive disease, based on the fixed ratio definition (FEV1/FVC < 0.7), as "diagnosed" (physician diagnosis of either asthma or chronic obstructive pulmonary disease), and "undiagnosed" (no recorded physician diagnosis). For the longitudinal analysis of NHANES III participants, mortality was the outcome of interest. We tested the contribution of self-reported health status and comorbidity burden (exposure) to the odds of being undiagnosed using logistic models adjusted for demographics, smoking status, and lung function. We estimated hazard ratios (HRs) for all-cause mortality for diagnosed and undiagnosed subjects participating in NHANES III who had spirometry using Cox- proportional regression analysis. Among those with spirometry-defined obstruction, 71.2% (SE, 1.8) in NHANES III and 72.0% (SE, 1.9) in NHANES 2007-2012 were undiagnosed. In multivariate models, undiagnosed obstructive disease was consistently associated in both surveys with self-reported good/excellent health status, lower comorbidity burden, higher lung function, and being of racial/ethnic minority. Among NHANES III participants (median follow up, 14.5 yr), both undiagnosed (HR, 1.23; 95% confidence interval, 1.08-1.40) and correctly diagnosed participants (HR, 1.74; 95% confidence interval, 1.45-2.09) had higher risk for all-cause mortality than participants without obstruction.
CONCLUSIONS: Undiagnosed obstructive lung disease is common among American adults and remained unchanged over 2 decades. Although undiagnosed subjects appear healthier than those with a diagnosis, their risk of death was increased compared with subjects without obstruction. These findings need to be considered when judging the implications of case-finding programs for obstructive lung disease.
Mulshine JL, Avila R, Yankelevitz D, Baer TM, San Jose Estépar R, Ambrose LF, Aldige CR.
Lung Cancer Workshop XI. Journal of Thoracic OncologyJournal of Thoracic Oncology 2015;10:762-767.
AbstractThe Prevent Cancer Foundation Lung Cancer Workshop XI: Tobacco-Induced Disease: Advances in Policy, Early Detection and Management was held in New York, NY on May 16 and 17, 2014. The two goals of the Workshop were to define strategies to drive innovation in precompetitive quantitative research on the use of imaging to assess new therapies for management of early lung cancer and to discuss a process to implement a national program to provide high quality computed tomography imaging for lung cancer and other tobacco-induced disease. With the central importance of computed tomography imaging for both early detection and volumetric lung cancer assessment, strategic issues around the development of imaging and ensuring its quality are critical to ensure continued progress against this most lethal cancer.
Kinsey MC, San Jose Estépar R, Wei Y, Washko GR, Christiani DC.
Regional Emphysema of a Non-Small Cell Tumor Is Associated with Larger Tumors and Decreased Survival. Annals ATSAnnals ATS 2015;
AbstractRATIONALE:COPD is associated with a worse overall survival in NSCLC. Lung emphysema is one component of COPD. We hypothesized that emphysema of the tumor region may result in larger tumors and a poorer overall survival.METHODS:We evaluated 304 cases of NSCLC from a prospectively enrolled cohort. The lung was divided into equal volumetric thirds (upper, middle, or lower region). Emphysema was defined as percentage of low attenuation areas less than -950 Hounsfield units (%LAA-950) and measured for each region. Whole-lung %LAA-950 was defined as the emphysema score of the entire lung parenchyma while regional %LAA-950 was the score within that particular region (upper, middle, or lower). The emphysema score of the region in which the tumor occurred was defined as the tumor %LAA-950. Tumor diameter was measured while blinded to characteristics of the lung parenchyma. A proportional hazards model was used to control for multiple factors associated with survival.RESULTS:Increasing tumor %LAA-950 was associated with larger tumors (P=0.024). Survival, stratified by stage, was significantly worse in those with tumor %LAA-950 greater than or equal to the 50th percentile vs. less than the 50th percentile (P=0.046). Whole-lung %LAA-950 and regional %LAA-950 (e.g. regional emphysema without tumor occurring in the region) were not significantly associated with survival. There were no differences in presenting symptoms or locations of mediastinal or distant metastasis by emphysema score. Increasing tumor %LAA-950 was associated with an increased risk of death (HRadj 1.36 [1.09, 1.68], P=0.006) after adjustment for age, sex, smoking status, histology, stage, performance status, chemotherapy, radiation, and surgery. Sensitivity analyses revealed no significant difference in the effect size or test of significance for each of the following conditions: 1) exclusion of cases with central tumor location, 2) exclusion of cases where surgery was performed, 3) exclusion of cases where radiation therapy was performed, 4) exclusion of cases where epidermal growth factor receptor tyrosine kinase inhibitors were administered, and 5) inclusion of only stage IV disease.CONCLUSIONS:Increasing emphysema of the region in which a NSCLC tumor occurs is associated with increasing tumor size and worse overall survival.
Patil V, Gupta R, San Jose Estépar R, Lacson R, Cheung A, Wong JM, Popp JA, Golby A, Ogilvy C, Vosburgh KG.
Smart stylet: the development and use of a bedside external ventricular drain image-guidance system. Stereotactic and functional neurosurgeryStereotactic and functional neurosurgery 2015;93:50-58.
AbstractBACKGROUND:Placement accuracy of ventriculostomy catheters is reported in a wide and variable range. Development of an efficient image-guidance system may improve physician performance and patient safety.OBJECTIVE:We evaluate the prototype of Smart Stylet, a new electromagnetic image-guidance system for use during bedside ventriculostomy.METHODS:Accuracy of the Smart Stylet system was assessed. System operators were evaluated for their ability to successfully target the ipsilateral frontal horn in a phantom model.RESULTS:Target registration error across 15 intracranial targets ranged from 1.3 to 4.6 mm (mean 3.1 mm). Using Smart Stylet guidance, a test operator successfully passed a ventriculostomy catheter to a shifted ipsilateral frontal horn 20/20 (100%) times from the frontal approach in a skull phantom. Without Smart Stylet guidance, the operator was successful 4/10 (40%) times from the right frontal approach and 6/10 (60%) times from the left frontal approach. In a separate experiment, resident operators were successful 2/4 (50%) times when targeting the shifted ipsilateral frontal horn with Smart Stylet guidance and 0/4 (0%) times without image guidance using a skull phantom.CONCLUSIONS:Smart Stylet may improve the ability to successfully target the ventricles during frontal ventriculostomy. © 2015 S. Karger AG, Basel.
Diaz AA, Young TP, Kurugol S, Eckbo E, Muralidhar N, Chapman JK, Kinney GL, Ross JC, San Jose Estépar R, Harmouche R, Black-Shinn JL, Budoff M, Bowler RP, Hokanson J, Washko GR, Washko GR.
Abdominal Visceral Adipose Tissue is Associated with Myocardial Infarction in Patients with COPD. Chronic obstructive pulmonary diseases (Miami, Fla.)Chronic obstructive pulmonary diseases (Miami, Fla.) 2015;2:8-16.
AbstractBACKGROUND:Cardiovascular diseases are frequent and a major cause of death in patients with chronic obstructive pulmonary disease (COPD). In the general population, various fat depots including abdominal visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and liver fat have been linked to increased risk of cardiovascular diseases. We hypothesize that these adipose tissue compartments are associated with myocardial infarction (MI) in patients with COPD.METHODS:We collected measures of VAT and SAT areas and liver attenuation on the computed tomography scan of the chest from 1267 patients with COPD. MI was a self-reported physician-diagnosed outcome. The association between fat depots and self-reported history of MI was assessed by logistic regression analysis in which the patients within the 2 lowest tertiles of VAT and SAT areas were the reference group.RESULTS:Eighty three patients (6.6%) reported a history of MI at the time of enrollment. Compared to patients who did not have an MI episode, those who had a prior MI had a higher VAT area (mean ± SD, 303.4 ± 208.5 vs. 226.8 ± 172.6 cm(2); P=0.002) with no differences in SAT area and liver fat. After adjustment for age, gender, obesity, pack years of smoking, hypertension, high cholesterol, and diabetes, patients within the upper tertile (vs. those in the lower tertiles) of VAT area had increased odds of MI (odds ratio [OR] 1.86, 95% confidence interval [CI] 1.02 - 3.41).CONCLUSION:Increased abdominal visceral fat is independently associated with a history of MI in individuals with COPD.
Paper González G, Jimenez-Carretero D, Rodríguez-López S, Kumamaru KK, George E, San Jose Estépar R, Rybicki FJ, Ledesma-Carbayo MJ.
Automated axial right ventricle to left ventricle diameter ratio computation in computed tomography pulmonary angiography. PloS onePloS one 2015;10:e0127797.
AbstractBACKGROUND AND PURPOSE:Right Ventricular to Left Ventricular (RV/LV) diameter ratio has been shown to be a prognostic biomarker for patients suffering from acute Pulmonary Embolism (PE). While Computed Tomography Pulmonary Angiography (CTPA) images used to confirm a clinical suspicion of PE do include information of the heart, a numerical RV/LV diameter ratio is not universally reported, likely because of lack in training, inter-reader variability in the measurements, and additional effort by the radiologist. This study designs and validates a completely automated Computer Aided Detection (CAD) system to compute the axial RV/LV diameter ratio from CTPA images so that the RV/LV diameter ratio can be a more objective metric that is consistently reported in patients for whom CTPA diagnoses PE.MATERIALS AND METHODS:The CAD system was designed specifically for RV/LV measurements. The system was tested in 198 consecutive CTPA patients with acute PE. Its accuracy was evaluated using reference standard RV/LV radiologist measurements and its prognostic value was established for 30-day PE-specific mortality and a composite outcome of 30-day PE-specific mortality or the need for intensive therapies. The study was Institutional Review Board (IRB) approved and HIPAA compliant.RESULTS:The CAD system analyzed correctly 92.4% (183/198) of CTPA studies. The mean difference between automated and manually computed axial RV/LV ratios was 0.03±0.22. The correlation between the RV/LV diameter ratio obtained by the CAD system and that obtained by the radiologist was high (r=0.81). Compared to the radiologist, the CAD system equally achieved high accuracy for the composite outcome, with areas under the receiver operating characteristic curves of 0.75 vs. 0.78. Similar results were found for 30-days PE-specific mortality, with areas under the curve of 0.72 vs. 0.75.CONCLUSIONS:An automated CAD system for determining the CT derived RV/LV diameter ratio in patients with acute PE has high accuracy when compared to manual measurements and similar prognostic significance for two clinical outcomes.
Toews M, Wachinger C, San Jose Estépar R, Wells WM.
A Feature-Based Approach to Big Data Analysis of Medical Imaging. Information processing in medical imaging : proceedings of the .. conferenceInformation processing in medical imaging : proceedings of the .. conference 2015;24:339-350.
AbstractThis paper proposes an inference method well-suited to large sets of medical images. The method is based upon a framework where distinctive 3D scale-invariant features are indexed efficiently to identify approximate nearest-neighbor (NN) feature matches in O(log N) computational complexity in the number of images N. It thus scales well to large data sets, in contrast to methods based on pair-wise image registration or feature matching requiring O(N) complexity. Our theoretical contribution is a density estimator based on a generative model that generalizes kernel density estimation and K-nearest neighbor (KNN) methods. The estimator can be used for on-the-fly queries, without requiring explicit parametric models or an off-line training phase. The method is validated on a large multi-site data set of 95,000,000 features extracted from 19,000 lung CT scans. Subject-level classification identifies all images of the same subjects across the entire data set despite deformation due to breathing state, including unintentional duplicate scans. State-of-the-art performance is achieved in predicting chronic pulmonary obstructive disorder (COPD) severity across the 5-category GOLD clinical rating, with an accuracy of 89% if both exact and one-off predictions are considered correct.