# Rheumatoid Arthritis-associated Parenchymal Lung Disease: Clinical and Molecular Phenotypes

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2022 · $708,294

## Abstract

PROJECT SUMMARY / ABSTRACT
Rheumatoid arthritis (RA) is a systemic inflammatory disorder affecting approximately 1.5 million people in the
United States. Although parenchymal lung disease, which encompasses interstitial lung disease (ILD) and
emphysema, is a common lung complication of RA with increasing prevalence and mortality, no strategies
currently exist for early detection or risk stratification of progressive disease. This is an area of unmet need that
could lead to improved opportunities for intervention and a decrease in the considerable morbidity and
mortality of RA-associated parenchymal lung disease.
 In this proposal, we aim to fully characterize early parenchymal lung disease in RA and establish risk
factors for progressive disease. We hypothesize that clinical and molecular risk factors can predict the
development and progression of RA-associated parenchymal lung disease, including preclinical ILD (preILD)
and emphysema, and that the molecular profile of progressive RA-preILD will overlap with fibrotic RA-ILD. To
test this hypothesis, we will propose the following: In Specific Aim 1, we will determine the prevalence and
progression of RA-associated preILD and emphysema using visual and objective radiologic approaches and
correlate these measurements with functional capacity, respiratory symptoms, and health-related quality of life
assessments. In Specific Aim 2, we will define clinical and molecular determinants that predict the
development and progression of RA emphysema and compare the molecular profile of emphysema with
preILD to provide mechanistic insight into the divergent patterns of parenchymal lung injury caused by RA. In
Specific Aim 3, we will demonstrate that progressive RA-preILD and fibrotic RA-ILD have similar molecular
signatures, suggesting phenotypic and mechanistic overlap. To achieve the aims of this proposal, a
longitudinal cohort of 200 RA patients without a history of ILD will be followed for up to 6 years with detailed
clinical, functional, radiologic, and molecular phenotyping.
 The successful completion of this research will provide us with a better understanding of the early
characteristics and natural history of RA-associated ILD and emphysema and establish novel non-invasive
ways to identify those at risk for progressive disease. This will enable closer monitoring and earlier
opportunities for intervention, potentially leading to decreased morbidity and mortality in individuals afflicted
with RA-associated parenchymal lung disease.

## Key facts

- **NIH application ID:** 10446060
- **Project number:** 1R01HL155522-01A1
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Tracy Jennifer Doyle
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $708,294
- **Award type:** 1
- **Project period:** 2022-04-15 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10446060

## Citation

> US National Institutes of Health, RePORTER application 10446060, Rheumatoid Arthritis-associated Parenchymal Lung Disease: Clinical and Molecular Phenotypes (1R01HL155522-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10446060. Licensed CC0.

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