# Prognostic Markers of Emphysema Progression

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $730,139

## Abstract

Project Summary/Abstract
Chronic Obstructive Pulmonary Disease (COPD) affects up to 24 million people in the United States and is
projected to be the 3rd leading cause of death worldwide by 2020 with a total cost of $50 billion. COPD has
been traditionally dichotomized into the clinical phenotypes of emphysema and chronic bronchitis, but its
underlying mechanisms are poorly understood. In particular, emphysema is defined as abnormal, permanent
dilation of the distal airspaces. The development and progression of this pathologic process are associated
with a decline in lung function and progressive clinical impairment. Computed tomographic (CT) imaging of the
chest is increasingly being leveraged to quantify the disease and its progression objectively. Current
approaches to quantify emphysema progression are limited and discard most of the spatial and temporal
information in CT scans obtained at inspiration and expiration. In this proposal, we plan on developing
computational components to prognosticate emphysema progression that builds upon image density markers
and lung mechanical strain characteristics conditioned on their underlying emphysema subtypes. This proposal
leverages our previous experience in computational emphysema subtyping to discover, validate and translate
a novel panel of prognostic markers tailored around the postulated mechanisms of emphysema progression:
inflammation injury and mechanical strain. To reach this goals, we will (1) develop an advanced emphysema
subtyping approach using novel deep learning architectures, (2) develop a fast mass preserving large
displacement registration approach to enable the discovery of local elastic properties of lung tissue between
inspiratory and expiration CT scans, (3) discover new subtype-specific biomarker features based on image
density relations and mechanical properties using unsupervised deep learning techniques within a common
statistical framework, and (4) validate the prognostic value of the proposed biomarkers and their association
with decline end-points and clinical outcomes to enable its clinical interpretation and translation. In addition to
that, will be explored alternative prognostic models based on advanced machine learning techniques and
performed a model comparison study to define the most prognostic model for emphysema progression. Our
analysis will process 12,300 scans corresponding to 5,517 subjects with baseline and follow-up data from the
COPDGene cohort –one of the largest cohort in COPD containing CT images at inspiration and expiration,
respiratory and genetic measurements. The proposed methodology will provide reproducible, automatic and
low-cost prognostic in-vivo biomarkers of emphysema progression that may enable the discovery of new
therapies and translate them into clinical practice.

## Key facts

- **NIH application ID:** 9865706
- **Project number:** 1R01HL149877-01
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Raul San Jose Estepar
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $730,139
- **Award type:** 1
- **Project period:** 2020-03-15 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9865706

## Citation

> US National Institutes of Health, RePORTER application 9865706, Prognostic Markers of Emphysema Progression (1R01HL149877-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9865706. Licensed CC0.

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