# Phenotyping Asthma for Bronchial Thermoplasty: Airway Smooth Muscle Structure and Function

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2021 · $723,611

## Abstract

Project Summary
Asthma currently affects over 300 million individuals worldwide and the prevalence is continually increasing.
Approximately 10% of asthmatics have uncontrolled or poorly controlled symptoms and it is this population that
urgently need improved targeted therapies and management strategies in order to reduce the high morbidity
and socio-economic burden, estimated to be 14.7 billion dollars annually in the United States alone. The exact
mechanisms behind the pathophysiology of asthma remain uncertain. Airway smooth muscle (ASM) is known
to play a critical and multifaceted role, yet our knowledge on the role of ASM in asthma is limited due to an
inability to directly visualize and study the 3D structure of ASM, and the relationship to functional
bronchoconstriction in patients. The real-time evaluation of ASM is critical in furthering our understanding of
the pathophysiology of asthma, for classifying asthma phenotypes, for tailoring treatment, and for assessing
and monitoring the response to therapy. In this award we will develop a custom optical imaging platform based
on polarization-sensitive optical coherence tomography (PS-OCT) that will enable the accurate quantification of
ASM hyperplasia and hypertrophy, epithelial disruption and hypertrophy, subepithelial fibrosis, mucosal
thickness increases, mucus metaplasia, in vivo. We will develop and validate novel dual-layer calibrating
catheters that will enable accurate assessment of tissue fiber orientation and birefringence signal intensity. We
will additionally develop and validate automated calibration and processing software that will provide real-time
visualization of ASM in vivo. These technological advancements will enable us to begin to answer important
questions linking remodeling changes in airway wall structure with physiologic function. We will conduct a
preclinical study in a sheep model of allergic asthma to test our hypothesis that remodeling plays both a
protective and provocative role in bronchoconstriction, and that the presence of inflammation greatly increases
bronchoconstriction. We will further translate this technology into the clinical setting in a multicenter clinical trial
aimed at using our PS-OCT imaging system to phenotype asthma and to predict the response to bronchial
thermoplasty. The unprecedented ability to study both the 3D structure of airway smooth muscle (ASM) and it’s
function in vivo is likely to transform the study of asthma in patients in phenotyping populations, for therapy
guidance, and in research endeavors aimed at studying the true role of ASM in asthma.

## Key facts

- **NIH application ID:** 10205149
- **Project number:** 5R01HL133664-05
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Melissa J Suter
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $723,611
- **Award type:** 5
- **Project period:** 2017-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10205149

## Citation

> US National Institutes of Health, RePORTER application 10205149, Phenotyping Asthma for Bronchial Thermoplasty: Airway Smooth Muscle Structure and Function (5R01HL133664-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10205149. Licensed CC0.

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