# Immunometabolic phenotypes in adult severe asthma and disease progression

> **NIH NIH U01** · BRIGHAM AND WOMEN'S HOSPITAL · 2022 · $235,989

## Abstract

PARENT GRANT ABSTRACT
The proposed experiments will test the hypothesis: Extensive longitudinal and immunometabolic phenotyping
will advance our understanding of the heterogeneous mechanisms for SA and inform future therapeutic
development and clinical management strategies. Specifically, comprehensive phenotyping will reveal distinct
biological mechanisms and clinical outcomes for SA patients with persistent type 2 inflammation, non-type 2
disease, and defective resolution. Severe asthma (SA) is characterized by persistent airway inflammation, airway
hyper-responsiveness, and decreased lung function despite glucocorticoids. Here, we are proposing to extend
the NHLBI Severe Asthma Research Program (SARP) for a translational, longitudinal mechanistic study of SA.
This longitudinal study design represents an essential “next step” to provide information on the stability of SA
endophenotypes and their relationship to disease severity and progression. Investigation into SA airway
inflammation has uncovered heterogeneous pathobiology. Approximately 50% of patients are characterized by
increased type 2 (T2) inflammation; discoveries that led recently to new T2 targeted therapies. There remains a
continuing and critical need to further elucidate mechanisms underlying the distinct pathobiology in
subpopulations of SA to provide molecular phenotyping for risk stratification, new therapeutic development,
especially for non-T2 inflammation, and precision clinical management. Over the last 6 years, SARP has
recruited a large US cohort of SA patients. Subjects were comprehensively characterized at baseline and then
monitored over three years of longitudinal follow up, leading to significant new insights into clinical, structural,
functional and immunometabolic disturbances in SA. In work in progress, analyses of 3-year longitudinal follow-
up has established 3 principal immunophenotypes: (1) persistent T2 inflammation, (2) intermittent T2
inflammation, and (3) persistent non-T2 inflammation. The immunophenotypes had both similarities and
differences at presentation with differences evolving further over 3 years of longitudinal follow up (e.g., changes
in bronchodilator responsiveness, risk for exacerbations; vide infra). In addition to lung specific inflammation,
many SA patients have systemic inflammation, metabolic dysfunction and defects in resolution mechanisms. To
address our main hypothesis, we propose a national, multicenter collaborative study with a mechanistic
translational approach with 4 specific aims to rigorously and comprehensively investigate the molecular and
cellular origin of SA immunometabolic phenotypes and their relationship to disease progression.

## Key facts

- **NIH application ID:** 10622745
- **Project number:** 3U01HL146002-04S1
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** MARK A ARONICA
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $235,989
- **Award type:** 3
- **Project period:** 2019-09-23 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10622745

## Citation

> US National Institutes of Health, RePORTER application 10622745, Immunometabolic phenotypes in adult severe asthma and disease progression (3U01HL146002-04S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10622745. Licensed CC0.

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