# Immunometabolic phenotypes in adult severe asthma and disease progression

> **NIH NIH U01** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $3,355,708

## Abstract

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:** 10022504
- **Project number:** 5U01HL146002-02
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** MARK A ARONICA
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $3,355,708
- **Award type:** 5
- **Project period:** 2019-09-23 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10022504

## Citation

> US National Institutes of Health, RePORTER application 10022504, Immunometabolic phenotypes in adult severe asthma and disease progression (5U01HL146002-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10022504. Licensed CC0.

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