# Respiratory Diseases, Genetics, and Rheumatoid Arthritis Risk

> **NIH NIH R03** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $89,500

## Abstract

Project Summary
Rheumatoid arthritis (RA) is a systemic autoimmune disease affecting nearly 1% of adults that causes a
painful, destructive inflammatory arthritis with long-term serious consequences including chronic pain,
disability, accumulation of morbidities, and excess mortality. Cyclic citrullinated peptide (CCP) and rheumatoid
factor (RF) are elevated in the serum of two-thirds of RA patients. Seropositive RA patients are more likely to
develop serious respiratory outcomes including interstitial lung disease and chronic obstructive pulmonary
disease (COPD). Patients with seropositive RA have 3-fold excess respiratory mortality compared to the
general population. Lung involvement is known to be an important contributor to excess RA morbidity and
mortality, however less is known about its role in RA risk. Previous studies suggest that mucosal surfaces of
the lung may be an initiating site, after smoking or exposure to other inhalants, where CCP and RF may be
formed years before joint symptoms first develop. Therefore, patients with respiratory diseases such as asthma
and COPD may be more likely to develop RA.
These investigations will study whether individuals with respiratory diseases are more likely to develop RA. In
the first aim, we will perform a prospective cohort study within the Nurses’ Health Studies, two longitudinal
studies with up to 40 years of follow-up where we have we have already identified women who developed RA
and collected data including RA serologic status. We will investigate whether women with asthma or COPD are
more likely to develop RA overall, and by serologic status, compared to women without these diseases while
adjusting for important confounders or mediators such as smoking. In the second aim, we will perform a case-
control study in the Partners Biobank and replicated in the Nurses’ Health Studies to test whether genetic
factors related to respiratory diseases and function are related to RA risk. The Partners Biobank is a large
research repository recruited from patients seen at Brigham and Women’s Hospital, Massachusetts General
Hospital, and affiliated satellite clinics in Boston, Massachusetts. We will analyze genotype data that has
already been collected in the Partners Biobank and the Nurses’ Health Studies.
Dr. Jeffrey Sparks (the PI) is an Assistant Professor of Medicine at Brigham and Women’s Hospital and
Harvard Medical School. He has made significant progress in his ongoing K23 studies funded by NIAMS that
are investigating RA-specific factors and subsequent respiratory outcomes. These proposed studies will
complement those findings by using RA as the outcome instead of the exposure thereby describing a bi-
directional association between respiratory diseases and RA. These will be secondary analyses of data
already collected in datasets that the PI has access to and familiarity with analyzing. Together, the results of
these studies will provide strong preliminary data supporting an R01 application to...

## Key facts

- **NIH application ID:** 9970420
- **Project number:** 5R03AR075886-02
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Jeffrey Andrew Sparks
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $89,500
- **Award type:** 5
- **Project period:** 2019-07-03 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9970420

## Citation

> US National Institutes of Health, RePORTER application 9970420, Respiratory Diseases, Genetics, and Rheumatoid Arthritis Risk (5R03AR075886-02). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/9970420. Licensed CC0.

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