Chronic obstructive pulmonary disease (COPD) is a heterogeneous lung condition characterized by progressive loss of lung function with subsequent increasing breathlessness and worsening quality of life. The condition is due to an admixture of emphysema and airways remodeling. This unpredictable mixture of tissue pathology is indiscernible with conventional spirometric measures of lung function. Computed tomography (CT) is increasingly being used to characterize emphysema and airway disease in COPD. However, classic CT measures of the airways are limited for assessing airway remodeling. The applicant has developed novel CT metrics of airways that provide insight into both the mechanical properties of airways and their disappearance in advanced emphysema. In this career development proposal, the applicant hypothesizes that CT airway characteristics can independently predict clinical manifestations and disease progression in COPD.
Aim 1 of this application involves the histologic validation of two novel CT metrics of airways. The goal of Aim 2 is to analyze chest CT scans from the COP Gene Study and correlate airway distensibility (a measure of the change in airway inner diameter from end tidal breathing to full inspiration) and total airway count (a measure of proximal airway drop out) with spirometric parameters, clinical manifestations of disease, and exercise capacity.
In Aim 3, the applicant will measure total airway count on CT scans from the ECLIPSE Study and then determine the ability of total airway count to predict decline in lung function, COPD exacerbations, and mortality. These CT-based airway metrics have the potential to be used as non-invasive biomarkers for clinical investigation in COPD.
The aims of this research proposal are possible through the active collaboration of Dr. Bartolome Celli, M.D., an internationally renowned clinical investigator in COPD and Dr. George Washko M.D., M.M.Sc., a prominent physician investigator in quantitative CT imaging.

Public Health Relevance

Chronic Obstructive Pulmonary Disease (COPD) is a progressive, debilitating lung condition mainly caused by cigarette smoking. Computerized Tomography (CT) is an imaging tool used to investigate pulmonary structure in great detail. In carrying out the research outlined in the following proposal, we plan to perform refined measurements made possible by CT images to better anticipate symptoms of this condition and to more accurately predict characteristics of lung function deterioration.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01HL118714-02
Application #
8666048
Study Section
Special Emphasis Panel (ZHL1)
Program Officer
Tigno, Xenia
Project Start
2013-06-01
Project End
2018-05-31
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02115
Martinez, Carlos H; Diaz, Alejandro A; Meldrum, Catherine et al. (2016) Age and Small Airway Imaging Abnormalities in Subjects With and Without Airflow Obstruction in SPIROMICS. Am J Respir Crit Care Med :
Martinez, Carlos H; Diaz, Alejandro A; Parulekar, Amit D et al. (2016) Age-Related Differences in Health-Related Quality of Life in COPD: An Analysis of the COPDGene and SPIROMICS Cohorts. Chest 149:927-35
Wells, J Michael; Estepar, Raul San Jose; McDonald, Merry-Lynn N et al. (2016) Clinical, physiologic, and radiographic factors contributing to development of hypoxemia in moderate to severe COPD: a cohort study. BMC Pulm Med 16:169
Harmouche, Rola; Ross, James C; Diaz, Alejandro A et al. (2016) A Robust Emphysema Severity Measure Based on Disease Subtypes. Acad Radiol 23:421-8
Diaz, Alejandro A; Estépar, Raul San José; Washko, George R (2016) Computed Tomographic Airway Morphology in Chronic Obstructive Pulmonary Disease. Remodeling or Innate Anatomy? Ann Am Thorac Soc 13:4-9
Diaz, Alejandro A; Petersen, Hans; Meek, Paula et al. (2016) Differences in Health-Related Quality of Life Between New Mexican Hispanic and Non-Hispanic White Smokers. Chest 150:869-876
Bhatt, Surya P; Soler, Xavier; Wang, Xin et al. (2016) Association between Functional Small Airway Disease and FEV1 Decline in Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med 194:178-84
Putman, Rachel K; Hatabu, Hiroto; Araki, Tetsuro et al. (2016) Association Between Interstitial Lung Abnormalities and All-Cause Mortality. JAMA 315:672-81
Diaz, Alejandro A; Rahaghi, Farbod N; Ross, James C et al. (2015) Understanding the contribution of native tracheobronchial structure to lung function: CT assessment of airway morphology in never smokers. Respir Res 16:23
Martinez, Carlos H; Mannino, David M; Curtis, Jeffrey L et al. (2015) 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 148:151-8

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