Publications

2015
Come CE, Washko GR. CT Scanning in COPD - Is it Time to Move On?. Chronic Obstr Pulm Dis 2015;2(3):201-203.
Doyle TJ, Patel AS, Hatabu H, Nishino M, Wu G, Osorio JC, Golzarri MF, Traslosheros A, Chu SG, Frits ML, Iannaccone CK, Koontz D, Fuhrman C, Weinblatt ME, El-Chemaly SY, Washko GR, Hunninghake GM, Choi AMK, Dellaripa PF, Oddis CV, Shadick NA, Ascherman DP, Rosas IO. Detection of Rheumatoid Arthritis-Interstitial Lung Disease Is Enhanced by Serum Biomarkers. Am J Respir Crit Care Med 2015;191(12):1403-12.Abstract
RATIONALE: Interstitial lung disease (ILD), a leading cause of morbidity and mortality in rheumatoid arthritis (RA), is highly prevalent, yet RA-ILD is underrecognized. OBJECTIVES: To identify clinical risk factors, autoantibodies, and biomarkers associated with the presence of RA-ILD. METHODS: Subjects enrolled in Brigham and Women's Hospital Rheumatoid Arthritis Sequential Study (BRASS) and American College of Rheumatology (ACR) cohorts were evaluated for ILD. Regression models were used to assess the association between variables of interest and RA-ILD. Receiver operating characteristic curves were generated in BRASS to determine if a combination of clinical risk factors and autoantibodies can identify RA-ILD and if the addition of investigational biomarkers is informative. This combinatorial signature was subsequently tested in ACR. MEASUREMENTS AND MAIN RESULTS: A total of 113 BRASS subjects with clinically indicated chest computed tomography scans (41% with a spectrum of clinically evident and subclinical RA-ILD) and 76 ACR subjects with research or clinical scans (51% with a spectrum of RA-ILD) were selected. A combination of age, sex, smoking, rheumatoid factor, and anticyclic citrullinated peptide antibodies was strongly associated with RA-ILD (areas under the curve, 0.88 for BRASS and 0.89 for ACR). Importantly, a combinatorial signature including matrix metalloproteinase 7, pulmonary and activation-regulated chemokine, and surfactant protein D significantly increased the areas under the curve to 0.97 (P = 0.002, BRASS) and 1.00 (P = 0.016, ACR). Similar trends were seen for both clinically evident and subclinical RA-ILD. CONCLUSIONS: Clinical risk factors and autoantibodies are strongly associated with the presence of clinically evident and subclinical RA-ILD on computed tomography scan in two independent RA cohorts. A biomarker signature composed of matrix metalloproteinase 7, pulmonary and activation-regulated chemokine, and surfactant protein D significantly strengthens this association. These findings may facilitate identification of RA-ILD at an earlier stage, potentially leading to decreased morbidity and mortality.
Diaz AA, Diaz O. Effects of Mild Chronic Obstructive Pulmonary Disease on Gas Exchange during Cycling and Walking. Am J Respir Crit Care Med 2015;192(9):1137-8.
Díaz AA, Pinto-Plata V, Hernández C, Peña J, Ramos C, Díaz JC, Klaassen J, Patino CM, Saldías F, Díaz O. Emphysema and DLCO predict a clinically important difference for 6MWD decline in COPD. Respir Med 2015;109(7):882-9.Abstract
BACKGROUND: Exercise impairment is a central feature of chronic obstructive pulmonary disease (COPD), and a minimal clinically important difference (MCID) for 6-min walk distance (6MWD) decline (>30 m) has been associated with increased mortality. The predictors of the MCID are not fully known. We hypothesize that physiological factors and radiographic measures predict the MCID. METHODS: We assessed 121 COPD subjects during 2 years using clinical variables, computed tomographic (CT) measures of emphysema, and functional measures including diffusion lung capacity for carbon monoxide (DLCO). The association between an MCID for 6MWD and clinical, CT, and physiologic predictors was assessed using logistic analysis. The C-statistic was used to assess the predictive ability of the models. RESULTS: Forty seven (39%) subjects had an MCID. In an imaging-based model, log emphysema and age were the best predictors of MCID (emphysema Odds Ratio [OR] 2.47 95%CI [1.28-4.76]). In a physiologic model, DLCO, age, and male gender were selected the best predictors (DLCO OR 1.19 [1.08-1.31]). The C-statistic for the ability of these models to predict an MCID was 0.71 and 0.75, respectively. CONCLUSION: In COPD patients the burden of emphysema on CT scan and DLCO predict a clinically meaningful decline in exercise capacity.
Toews M, Wachinger C, Estepar RSJ, Wells WM. A Feature-Based Approach to Big Data Analysis of Medical Images. Inf Process Med Imaging 2015;24:339-50.Abstract
This 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.
Batmanghelich NK, Saeedi A, Cho M, Estepar RSJ, Golland P. Generative Method to Discover Genetically Driven Image Biomarkers. Inf Process Med Imaging 2015;24:30-42.Abstract
We present a generative probabilistic approach to discovery of disease subtypes determined by the genetic variants. In many diseases, multiple types of pathology may present simultaneously in a patient, making quantification of the disease challenging. Our method seeks common co-occurring image and genetic patterns in a population as a way to model these two different data types jointly. We assume that each patient is a mixture of multiple disease subtypes and use the joint generative model of image and genetic markers to identify disease subtypes guided by known genetic influences. Our model is based on a variant of the so-called topic models that uncover the latent structure in a collection of data. We derive an efficient variational inference algorithm to extract patterns of co-occurrence and to quantify the presence of heterogeneous disease processes in each patient. We evaluate the method on simulated data and illustrate its use in the context of Chronic Obstructive Pulmonary Disease (COPD) to characterize the relationship between image and genetic signatures of COPD subtypes in a large patient cohort.
Cho MH, Castaldi PJ, Hersh CP, Hobbs BD, Barr GR, Tal-Singer R, Bakke P, Gulsvik A, San José Estépar R, van Beek EJR, Coxson HO, Lynch DA, Washko GR, Laird NM, Crapo JD, Beaty TH, Silverman EK. A Genome-Wide Association Study of Emphysema and Airway Quantitative Imaging Phenotypes. Am J Respir Crit Care Med 2015;192(5):559-69.Abstract
RATIONALE: Chronic obstructive pulmonary disease (COPD) is defined by the presence of airflow limitation on spirometry, yet subjects with COPD can have marked differences in computed tomography imaging. These differences may be driven by genetic factors. We hypothesized that a genome-wide association study (GWAS) of quantitative imaging would identify loci not previously identified in analyses of COPD or spirometry. In addition, we sought to determine whether previously described genome-wide significant COPD and spirometric loci were associated with emphysema or airway phenotypes. OBJECTIVES: To identify genetic determinants of quantitative imaging phenotypes. METHODS: We performed a GWAS on two quantitative emphysema and two quantitative airway imaging phenotypes in the COPDGene (non-Hispanic white and African American), ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints), NETT (National Emphysema Treatment Trial), and GenKOLS (Genetics of COPD, Norway) studies and on percentage gas trapping in COPDGene. We also examined specific loci reported as genome-wide significant for spirometric phenotypes related to airflow limitation or COPD. MEASUREMENTS AND MAIN RESULTS: The total sample size across all cohorts was 12,031, of whom 9,338 were from COPDGene. We identified five loci associated with emphysema-related phenotypes, one with airway-related phenotypes, and two with gas trapping. These loci included previously reported associations, including the HHIP, 15q25, and AGER loci, as well as novel associations near SERPINA10 and DLC1. All previously reported COPD and a significant number of spirometric GWAS loci were at least nominally (P < 0.05) associated with either emphysema or airway phenotypes. CONCLUSIONS: Genome-wide analysis may identify novel risk factors for quantitative imaging characteristics in COPD and also identify imaging features associated with previously identified lung function loci.
Washko GR. Imaging to predict therapeutic outcomes. Am J Respir Crit Care Med 2015;191(7):724-5.
Rice MB, Ljungman PL, Wilker EH, Dorans KS, Gold DR, Schwartz J, Koutrakis P, Washko GR, O'Connor GT, Mittleman MA. Long-term exposure to traffic emissions and fine particulate matter and lung function decline in the Framingham heart study. Am J Respir Crit Care Med 2015;191(6):656-64.Abstract
RATIONALE: Few studies have examined associations between long-term exposure to fine particulate matter (PM2.5) and lung function decline in adults. OBJECTIVES: To determine if exposure to traffic and PM2.5 is associated with longitudinal changes in lung function in a population-based cohort in the Northeastern United States, where pollution levels are relatively low. METHODS: FEV1 and FVC were measured up to two times between 1995 and 2011 among 6,339 participants of the Framingham Offspring or Third Generation studies. We tested associations between residential proximity to a major roadway and PM2.5 exposure in 2001 (estimated by a land-use model using satellite measurements of aerosol optical thickness) and lung function. We examined differences in average lung function using mixed-effects models and differences in lung function decline using linear regression models. Current smokers were excluded. Models were adjusted for age, sex, height, weight, pack-years, socioeconomic status indicators, cohort, time, season, and weather. MEASUREMENTS AND MAIN RESULTS: Living less than 100 m from a major roadway was associated with a 23.2 ml (95% confidence interval [CI], -44.4 to -1.9) lower FEV1 and a 5.0 ml/yr (95% CI, -9.0 to -0.9) faster decline in FEV1 compared with more than 400 m. Each 2 μg/m(3) increase in average of PM2.5 was associated with a 13.5 ml (95% CI, -26.6 to -0.3) lower FEV1 and a 2.1 ml/yr (95% CI, -4.1 to -0.2) faster decline in FEV1. There were similar associations with FVC. Associations with FEV1/FVC ratio were weak or absent. CONCLUSIONS: Long-term exposure to traffic and PM2.5, at relatively low levels, was associated with lower FEV1 and FVC and an accelerated rate of lung function decline.
Mulshine JL, Avila R, Yankelevitz D, Baer TM, Estépar RSJ, Ambrose LF, Aldigé CR. Lung Cancer Workshop XI: Tobacco-Induced Disease: Advances in Policy, Early Detection and Management. J Thorac Oncol 2015;10(5):762-7.Abstract
The 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.
Rahaghi FN, Come CE, Ross J, Harmouche R, Diaz AA, Estepar RSJ, Washko G. Morphologic Response of the Pulmonary Vasculature to Endoscopic Lung Volume Reduction. Chronic Obstr Pulm Dis 2015;2(3):214-222.Abstract
INTRODUCTION: Endoscopic Lung Volume Reduction has been used to reduce lung hyperinflation in selected patients with severe emphysema. Little is known about the effect of this procedure on the intraparenchymal pulmonary vasculature. In this study we used CT based vascular reconstruction to quantify the effect of the procedure on the pulmonary vasculature. METHODS: Intraparenchymal vasculature was reconstructed and quantified in 12 patients with CT scans at baseline and 12 weeks following bilateral introduction of sealants in the upper lobes. The volume of each lung and each lobe was measured, and the vascular volume profile was calculated for both lower lobes. The detected vasculature was further labeled manually as arterial or venous in the right lower lobe. RESULTS: There was an increase in the volume of the lower lobes (3.14L to 3.25L, p=0.0005). There was an increase in BV5, defined as the volume of blood vessels with cross sectional area of less than 5mm, (53.2ml to 57.9ml, p=0.03). This was found to be correlated with the increase in lower lobe volumes (R=0.65, p=0.02). The changes appear to be symmetric for veins and arteries with a correlation coefficient of 0.87 and a slope of near identity. CONCLUSION: In the subjects studied, there was an increase, from baseline, in BV5 in the lower lobes that correlated with the change in the volume of the lower lobes. The change appeared to be symmetric for both arteries and veins. The study illustrates the use of intraparenchymal pulmonary vascular reconstruction to study morphologic changes in response to interventions.
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 COPD. Eur Respir J 2015;45(4):879-905.Abstract
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. 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 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.Abstract
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. 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.Abstract
BACKGROUND: 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.Abstract
BACKGROUND: 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.Abstract
OBJECTIVE: 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.Abstract
OBJECTIVE: 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.Abstract
RATIONALE 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.Abstract
Uncontrolled 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.Abstract
RATIONALE: 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.

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