# The Airway Functional Genomics of Bronchodilator Drug Response in Minority Children with Asthma

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $790,190

## Abstract

ABSTRACT
Asthma is the most common chronic disease among children. Asthma prevalence, mortality, and drug
response vary by race/ethnicity and genetic ancestry. In the U.S., asthma prevalence is highest among Puerto
Ricans (36.5%), intermediate among African Americans (13.0%) and whites (12.1%), and lowest in Mexicans
(7.5%). These disparities extend to asthma mortality, which is four-fold higher in Puerto Ricans and African
Americans compared to Mexican Americans. Albuterol is the most commonly prescribed asthma medication in
the world and is the mainstay of acute asthma management. Among low income and minority populations in the
U.S., albuterol is often the only medication used regardless of asthma severity. Poor drug response contributes
to racial/ethnic disparities in asthma morbidity and mortality. Disturbingly, Americans with the highest asthma
prevalence and death rate also have the lowest drug response. Chronic albuterol use can decrease acute
airway smooth muscle response to albuterol and increase airway inflammation through beta-agonist signaling
in the airway epithelium, suggesting that chronic albuterol use may alter acute response through genomic and
epigenomic modification of airway cells. Furthermore, acute bronchodilator drug response (BDR) to albuterol is
a complex phenotype with an estimated heritability of 28.5%, indicating genetic factors contribute to BDR
variability. Genome-wide and whole genome association analyses have revealed population-specific common
and rare variants in non-coding regions of the genome associated with the extremes of BDR. The roles of
genomic regulatory regions and population-specific variants in BDR have yet to be fully investigated. To this
end, we have created an investigative system involving airway-specific cell types, patient-derived cells, and
detailed clinical data to generate an encyclopedia of genes, regulatory regions, and pathways involved in BDR
to albuterol. We will integrate RNA-seq, ChIP-seq, ATAC-seq, and whole genome sequencing data with
detailed clinical data to identify trans-ethnic and population-specific variants contributing to differential
expression and chromatin structure patterns in response to albuterol exposure. Furthermore, we will
functionally characterize the regulatory regions that underlie acute and chronic albuterol BDR in multi-ethnic
children with asthma using CRISPR-Cas9 activation/inhibition assays. These analyses will allow us to determine
on a genomic scale the functional consequences of acute and chronic albuterol treatment on airway cells, and
provide insight into potential targetable genes, regulatory elements, and pathways for improved asthma
therapies in at-risk populations.

## Key facts

- **NIH application ID:** 10434093
- **Project number:** 5R01HL117004-08
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Nadav Ahituv
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $790,190
- **Award type:** 5
- **Project period:** 2013-08-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10434093

## Citation

> US National Institutes of Health, RePORTER application 10434093, The Airway Functional Genomics of Bronchodilator Drug Response in Minority Children with Asthma (5R01HL117004-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10434093. Licensed CC0.

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