# Transcriptomic and Pharmacogenetic Asthma Endotypes in Minority Children

> **NIH NIH R01** · NATIONAL JEWISH HEALTH · 2020 · $765,609

## Abstract

PROJECT SUMMARY
Asthma affects 5% of the world population. In the U.S., asthma death rates are four-fold higher in Latinos and
African Americans compared to Whites. Childhood asthma is a complex disease historically defined by partially
overlapping clinical features. However, the heterogeneity observed in clinical disease and airway pathology
suggests that the standard definition of asthma is composed of multiple clinical subgroups each with a distinct
pathogenesis (i.e. endotypes). Gene expression profiling of bronchial airway brushings identified the type 2-
high asthma endotype, defined by excessive airway inflammation driven by type 2 cytokines. We found that the
type 2-high asthma endotype can be identified by gene expression profiling of minimally invasive nasal airway
epithelium brushings. We also found high nasal expression of the type 2 cytokine, IL-13, was associated with
higher risk of asthma attacks among Puerto Ricans, who have the highest asthma morbidity and mortality in
the U.S. The populations with the highest asthma morbidity also have the poorest response to the most
common asthma medication, albuterol. We hypothesize that specific molecular airway endotypes will define
children with severe asthma and poor drug response and that these endotypes will have a strong genetic
basis. To investigate this hypothesis the following aims are proposed: (1) Determine the expression endotypes
of childhood asthma that underlie poor albuterol drug response and severe disease, using minimally invasive
samples. Molecular endotyping with be performed by computational analysis of whole transcriptome
sequencing data generated from 745 asthmatic and healthy children. Correlates of airway endotypes will be
identified using peripheral blood gene expression. (2) Determine how IL-13 modifies airway cell responses to
albuterol and HRV infection, and the genetic control of these responses. A powerful in vitro airway epithelial
model will be used to determine if type 2 inflammation of the airway epithelium modifies transcriptional
response to albuterol (most common asthma medication) and human rhinovirus (HRV) infection (most common
trigger of asthma attacks). (3) Determine the genetic basis of and validate poor drug response and severe
asthma endotypes in ethnically diverse children. We will perform the first genetic screen of type 2-high and
other asthma endotypes. We will examine data from 4,379 minority children with asthma to determine how
asthma endotypes influence response to albuterol and risk for severe asthma. Our goal is to understand the
genetic basis of racial/ethnic differences in asthma severity and lung function. Results from this proposal will
inform public health policy and clinical practice and aide in the mechanistic understanding of asthma severity
(morbidity), which may lead to more targeted therapies. Data generated from our proposal will become a
valuable resource for the medical and scientific communities.

## Key facts

- **NIH application ID:** 9925294
- **Project number:** 5R01HL135156-04
- **Recipient organization:** NATIONAL JEWISH HEALTH
- **Principal Investigator:** Esteban Gonzalez Burchard
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $765,609
- **Award type:** 5
- **Project period:** 2017-05-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9925294

## Citation

> US National Institutes of Health, RePORTER application 9925294, Transcriptomic and Pharmacogenetic Asthma Endotypes in Minority Children (5R01HL135156-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9925294. Licensed CC0.

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