COPDGene® 2019: Redefining the Diagnosis of Chronic Obstructive Pulmonary Disease

Background:Chronic obstructive pulmonary disease (COPD) remains a major cause of morbidity and mortality. Present-day diagnostic criteria are largely based solely on spirometric criteria. Accumulating evidence has identified a substantial number of individuals without spirometric evidence of COPD who suffer from respiratory symptoms and/or increased morbidity and mortality. There is a clear need for an expanded definition of COPD that is linked to physiologic, structural (computed tomography [CT]) and clinical evidence of disease. Using data from the COPD Genetic Epidemiology study (COPDGene®), we hypothesized that an integrated approach that includes environmental exposure, clinical symptoms, chest CT imaging and spirometry better defines disease and captures the likelihood of progression of respiratory obstruction and mortality. Methods:Four key disease characteristics - environmental exposure (cigarette smoking), clinical symptoms (dyspnea and/or chronic bronchitis), chest CT imaging abnormalities (emphysema, gas trapping and/or airway wall thickening), and abnormal spirometry - were evaluated in a group of 8784 current and former smokers who were participants in COPDGene® Phase 1. Using these 4 disease characteristics, 8 categories of participants were identified and evaluated for odds of spirometric disease progression (FEV1 > 350 ml loss over 5 years), and the hazard ratio for all-cause mortality was examined. Results:Using smokers without symptoms, CT imaging abnormalities or airflow obstruction as the reference population, individuals were classified as Possible COPD, Probable COPD and Definite COPD. Current Global initiative for obstructive Lung Disease (GOLD) criteria would diagnose 4062 (46%) of the 8784 study participants with COPD. The proposed COPDGene® 2019 diagnostic criteria would add an additional 3144 participants. Under the new criteria, 82% of the 8784 study participants would be diagnosed with Possible, Probable or Definite COPD. These COPD groups showed increased risk of disease progression and mortality. Mortality increased in patients as the number of their COPD characteristics increased, with a maximum hazard ratio for all cause-mortality of 5.18 (95% confidence interval [CI]: 4.15-6.48) in those with all 4 disease characteristics. Conclusions:A substantial portion of smokers with respiratory symptoms and imaging abnormalities do not manifest spirometric obstruction as defined by population normals. These individuals are at significant risk of death and spirometric disease progression. We propose to redefine the diagnosis of COPD through an integrated approach using environmental exposure, clinical symptoms, CT imaging and spirometric criteria. These expanded criteria offer the potential to stimulate both current and future interventions that could slow or halt disease progression in patients before disability or irreversible lung structural changes develop

Pulmonary Vascular Morphology as an Imaging Biomarker in Chronic Thromboembolic Pulmonary Hypertension

Abstract. Patients with chronic thromboembolic pulmonary hypertension (CTEPH) have morphologic changes to the pulmonary vasculature. These include pruning of the distal vessels, dilation of the proximal vessels, and increased vascular tortuosity. Advances in image processing and computer vision enable objective detection and quantification of these processes in clinically acquired computed tomographic (CT) scans. Three-dimensional reconstructions of the pulmonary vasculature were created from the CT angiograms of 18 patients with CTEPH diagnosed using imaging and hemodynamics as well as 15 control patients referred to our Dyspnea Clinic and found to have no evidence of pulmonary vascular disease. Compared to controls, CTEPH patients exhibited greater pruning of the distal vasculature (median density of small-vessel volume: 2.7 [interquartile range (IQR): 2.5–3.0] vs. 3.2 [3.0–3.8]; P = 0.008), greater dilation of proximal arteries (median fraction of blood in large arteries: 0.35 [IQR: 0.30–0.41] vs. 0.23 [0.21–0.31]; P = 0.0005), and increased tortuosity in the pulmonary arterial tree (median: 4.92% [IQR: 4.85%–5.21%] vs. 4.63% [4.39%–4.92%]; P = 0.004). CTEPH was not associated with dilation of proximal veins or increased tortuosity in the venous system. Distal pruning of the vasculature was correlated with the cardiac index (R = 0.51, P = 0.04). Quantitative models derived from CT scans can be used to measure changes in vascular morphology previously described subjectively in CTEPH. These measurements are also correlated with invasive metrics of pulmonary hemodynamics, suggesting that they may be used to assess disease severity. Further work in a larger cohort may enable the use of such measures as a biomarker for diagnostic, phenotyping, and prognostic purposes

Statistical segmentation of carotid plaque neovascularization

In several studies, intraplaque neovascularization (IPN) has been linked with plaque vulnerability. The recent development of contrast enhanced ultrasound enables IPN detection, but an accurate quantification of IPN is a big challenge due to noise, motion, subtle contrast response, blooming of contrast and artifacts. We present an algorithm that automatically estimates the location and amount of contrast within the plaque over time. Plaque pixels are initially labeled through an iterative expectation-maximization (EM) algorithm. The used algorithm avoids several drawbacks of standard EM. It is capable of selecting the best number of components in an unsupervised way, based on a minimum message length criterion. Next, neighborhood information using a 5×5 kernel and spatiotemporal behavior are combined with the known characteristics of contrast spots in order to group components, identify artifacts and finalize the classification. Image sequences are divided into 3-seconds subgroups. A pixel is relabeled as an artifact if it is labeled as contrast for more than 1.5 seconds in at least two subgroups. For 10 plaques, automated segmentation results were validated with manual segmentation of contrast in 10 frames per clip. Average Dice index and area ratio were 0.73±0.1 (mean±SD) and 98.5±29.6 (%) respectively. Next, 45 atherosclerotic plaques were analyzed. Time integrated IPN surface area was calculated. Average area of IPN was 3.73±3.51 mm2. Average area of 45 plaques was 11.6±8.6 mm2. This method based on EM contrast segmentation provides a new way of IPN quantification.</p

COPDGene® 2019: Redefining the Diagnosis of Chronic Obstructive Pulmonary Disease.

BackgroundChronic obstructive pulmonary disease (COPD) remains a major cause of morbidity and mortality. Present-day diagnostic criteria are largely based solely on spirometric criteria. Accumulating evidence has identified a substantial number of individuals without spirometric evidence of COPD who suffer from respiratory symptoms and/or increased morbidity and mortality. There is a clear need for an expanded definition of COPD that is linked to physiologic, structural (computed tomography [CT]) and clinical evidence of disease. Using data from the COPD Genetic Epidemiology study (COPDGene®), we hypothesized that an integrated approach that includes environmental exposure, clinical symptoms, chest CT imaging and spirometry better defines disease and captures the likelihood of progression of respiratory obstruction and mortality.MethodsFour key disease characteristics - environmental exposure (cigarette smoking), clinical symptoms (dyspnea and/or chronic bronchitis), chest CT imaging abnormalities (emphysema, gas trapping and/or airway wall thickening), and abnormal spirometry - were evaluated in a group of 8784 current and former smokers who were participants in COPDGene® Phase 1. Using these 4 disease characteristics, 8 categories of participants were identified and evaluated for odds of spirometric disease progression (FEV1 &gt; 350 ml loss over 5 years), and the hazard ratio for all-cause mortality was examined.ResultsUsing smokers without symptoms, CT imaging abnormalities or airflow obstruction as the reference population, individuals were classified as Possible COPD, Probable COPD and Definite COPD. Current Global initiative for obstructive Lung Disease (GOLD) criteria would diagnose 4062 (46%) of the 8784 study participants with COPD. The proposed COPDGene® 2019 diagnostic criteria would add an additional 3144 participants. Under the new criteria, 82% of the 8784 study participants would be diagnosed with Possible, Probable or Definite COPD. These COPD groups showed increased risk of disease progression and mortality. Mortality increased in patients as the number of their COPD characteristics increased, with a maximum hazard ratio for all cause-mortality of 5.18 (95% confidence interval [CI]: 4.15-6.48) in those with all 4 disease characteristics.ConclusionsA substantial portion of smokers with respiratory symptoms and imaging abnormalities do not manifest spirometric obstruction as defined by population normals. These individuals are at significant risk of death and spirometric disease progression. We propose to redefine the diagnosis of COPD through an integrated approach using environmental exposure, clinical symptoms, CT imaging and spirometric criteria. These expanded criteria offer the potential to stimulate both current and future interventions that could slow or halt disease progression in patients before disability or irreversible lung structural changes develop