COPD is a heterogeneous lung condition characterized by progressive loss of lung function causing increasing breathlessness and loss of quality of life. While the predominant mechanism of lung injury in the US is cigarette smoke exposure, the condition is due to an admixture of emphysema and airways disease. This unpredictable mix of tissue pathology is indiscernible by conventional spirometric measures of lung function. This has lead to the recruitment of very large numbers of subjects into clinical studies to include the various subsets of disease. Recently, the NHLBI put forth a consensus statement specifying the need for new techniques to """"""""phenotype"""""""" the pulmonary component of COPD, including image-based analysis. Our overall hypothesis is that airway characteristics in subjects with COPD are independent predictors of disease pathophysiology and clinical indices of lung function.
Aim 1 of this application is to analyze chest CT scans from 3 independent cohorts and correlate the structural characteristics with clinical and spirometric parameters.
Aim 2 involves the histologic validation of our novel CT derived metrics of airways disease defined in Aim 1.
In Aim 3, our novel CT measures of airway disease will be applied to a prospectively collected cohort of subjects from the Genetic Epidemiology of COPD Investigation (1 RO1 HL089897 and 1 RO1 HL089856-01A1). In subjects enrolled locally, I will perform physiologic measures of airway inspiratory resistance, compliance and conductance using techniques pioneered at Brigham and Women's Hospital. Validation of these measures of airway disease and investigation of their interdependence with the CT assessed burden of emphysema may provide a non-invasive tool to be used as a biomarker for clinical investigation in chronic obstructive pulmonary disease.
The aims of this research proposal are possible through the active collaboration of Dr. John J. Reilly, MD, a well recognized clinical investigator in COPD, Dr. Edwin Silverman MD, PhD, the national co-primary investigator of the Genetic Epidemiology of COPD Investigation and a well recognized specialist in clincial/genetics research of COPD, and Dr. Ron Kikinis, MD, an expert in quantitative image analysis and interpretation. (End of Abstract) ? ? ? ?
|Kurugol, Sila; Come, Carolyn E; Diaz, Alejandro A et al. (2015) Automated quantitative 3D analysis of aorta size, morphology, and mural calcification distributions. Med Phys 42:5467-78|
|Gazourian, Lee; Rogers, Angela J; Ibanga, Ruby et al. (2014) Factors associated with bronchiolitis obliterans syndrome and chronic graft-versus-host disease after allogeneic hematopoietic cell transplantation. Am J Hematol 89:404-9|
|Castaldi, Peter J; Cho, Michael H; San José Estépar, Raúl et al. (2014) Genome-wide association identifies regulatory Loci associated with distinct local histogram emphysema patterns. Am J Respir Crit Care Med 190:399-409|
|Martinez, Carlos H; Okajima, Yuka; Murray, Susan et al. (2014) Impact of self-reported gastroesophageal reflux disease in subjects from COPDGene cohort. Respir Res 15:62|
|Ross, James C; Díaz, Alejandro A; Okajima, Yuka et al. (2014) AIRWAY LABELING USING A HIDDEN MARKOV TREE MODEL. Proc IEEE Int Symp Biomed Imaging 2014:554-558|
|Washko, G R; Diaz, A A; Kim, V et al. (2014) Computed tomographic measures of airway morphology in smokers and never-smoking normals. J Appl Physiol (1985) 116:668-73|
|Come, Carolyn E; Diaz, Alejandro A; Curran-Everett, Douglas et al. (2013) Characterizing functional lung heterogeneity in COPD using reference equations for CT scan-measured lobar volumes. Chest 143:1607-1617|
|Gazourian, Lee; Coronata, Anna Maria F; Rogers, Angela J et al. (2013) Airway dilation in bronchiolitis obliterans after allogeneic hematopoietic stem cell transplantation. Respir Med 107:276-83|
|Díaz, Alejandro A; Morales, Arturo; Díaz, Juan C et al. (2013) CT and physiologic determinants of dyspnea and exercise capacity during the six-minute walk test in mild COPD. Respir Med 107:570-9|
|Ross, James C; Kindlmann, Gordon L; Okajima, Yuka et al. (2013) Pulmonary lobe segmentation based on ridge surface sampling and shape model fitting. Med Phys 40:121903|
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