# The Role of IL-5 and Local Nasal Polyp Immunoglobulin Production in Aspirin-Exacerbated Respiratory Disease

> **NIH NIH K23** · BRIGHAM AND WOMEN'S HOSPITAL · 2021 · $197,640

## Abstract

This proposal details a five-year plan to prepare the candidate, Kathleen M. Buchheit, MD, for a career
as an independent translational investigator positioned to impact our understanding of allergic and
immunologic disease. The proposed investigations focus on the role of interleukin (IL)-5 and local
immunoglobulins driving respiratory tract inflammation and mast cell activation in aspirin-exacerbated
respiratory disease (AERD). AERD is characterized by asthma, severe chronic rhinosinusitis with nasal
polyposis, excessive cysteinyl leukotriene and prostaglandin production, and respiratory reactions to
cyclooxygenase-1 inhibitors. The candidate has observed that patients with AERD have a unique
population of plasma cells that express high levels of IL-5 receptor at both the transcript and protein
levels. Additionally, she has discovered that subjects with AERD have aberrant local nasal polyp
immunoglobulin production, which correlates with nasal polyp severity, and also demonstrate elevated
nasal polyp IgE and IgG4 as compared to aspirin-tolerant patients. Employing cellular and molecular
techniques, the candidate will test the hypotheses that a unique subset of IL-5 receptor-driven nasal
polyp plasma cells drives production of pathogenic immunoglobulins in the respiratory tract in AERD,
and that the pathogenic immunoglobulin production can be mitigated by targeting IL-5 with
mepolizumab. These studies will advance our understanding of the pathogenesis of AERD leading to
the identification of novel therapeutic targets for this disease. During the period of support the candidate
will leverage her clinical experience in the treatment of nasal polyposis and AERD, the regional and
national referral patient base at her institution’s AERD center, and her laboratory skills while she further
develops skills in mechanistically-focused clinical study design, computational biostatistics for high-
dimensional data analysis, team leadership, and scientific writing. Dr. Buchheit will work under the
mentorship of Tanya Laidlaw, MD and Joshua Boyce, MD, experts in AERD and mechanisms of
inflammation. Additionally, Dr. Buchheit has assembled a team of extraordinary physician-scientists
including Drs. Shiv Pillai, Frances Eun-Hyung Lee, Soumya Raychaudhuri, and Peter Weller, who have
committed their time, resources, and expertise to facilitate her career development and research goals.
Their mentorship and the scientific and clinical environment at BWH, along with the translational work
and career development plan, will position the candidate to secure independent NIH funding and to
establish herself as a physician-scientist with a focus on mechanistic clinical trials in AERD and chronic
rhinosinusitis.

## Key facts

- **NIH application ID:** 10160767
- **Project number:** 5K23AI139352-03
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Kathleen Mary Buchheit
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $197,640
- **Award type:** 5
- **Project period:** 2019-06-19 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10160767

## Citation

> US National Institutes of Health, RePORTER application 10160767, The Role of IL-5 and Local Nasal Polyp Immunoglobulin Production in Aspirin-Exacerbated Respiratory Disease (5K23AI139352-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10160767. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*