# Mitochondrial DNA biomarkers to assess responses to changes in personal environmental exposures in pediatric urban asthma

> **NIH NIH R21** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $217,322

## Abstract

Urban children are exposed disproportionately to air pollution and indoor allergens that trigger asthma
symptoms. To better address this public health problem, we propose to leverage two established and
comparable urban cohorts: 1) randomized controlled trial (RCT) “Environmental Control as Add-on Therapy in
Childhood Asthma” (ECATCh) that is determining the efficacy of adding individually tailored, multi-faceted
home environmental control strategy (ECS) to titration of controller medication (TCM) over 6 months among
predominantly African American children with persistent asthma, and 2) observational case control “Traffic
Associated Air Pollution Asthma Study” (TAPAS) over 6 months among African American and Dominican
children with and without asthma. We propose to determine the contribution of novel mitochondrial (mt) DNA
biomarkers that capture responses to multiple environmental stressors, and are more sensitive to the dynamics
of dysregulation, on lung function and airway inflammation. Our objective is to elucidate the dynamic interplay
between reductions in multiple inflammatory urban exposures, attributable changes in mtDNA content
and methylation of mitochondrial regulatory genes, and improvements in asthma outcomes over time. In two
well-defined cohorts representing minority urban pediatric populations, we hypothesize that reversal of
mitochondrial damage following personalized ECS and other time-related changes in multiple
environmental exposures is associated with improved lung function and airway inflammation. We
predict that intermediate mitochondrial biomarkers following changes in diverse personal environmental
exposures may link directly to clinical outcomes. Using two repeat measures of buccal mtDNA content and
buccal genomic DNA methylation of displacement loop and other regions important to mitochondrial function,
we propose to: 1) Determine differences in mitochondrial biomarkers among ECATCh asthma cases, TAPAS
asthma cases, and TAPAS nonasthmatic controls, and the associations of mitochondrial biomarkers with
exhaled nitric oxide (eNO) and lung function within asthma cases, measured concurrently and as changes over
6 months. 2) Determine associations of repeat mitochondrial biomarkers with repeat residential measures of
fine particulate matter (PM)2.5 and other asthmogenic exposures, and 3) Explore whether 6-month treatment
with personalized multi-faceted ECS plus TCM vs TCM alone (i.e. ECATCh RCT group assignment) of
persistent asthmatics changes mitochondrial biomarkers. Significant associations from these two cohorts will
be replicated in our single-faceted environmental intervention RCT “Mouse Allergen and Asthma Intervention
Trial” (MAAIT). This proposal intends to capture the pivotal role of novel mitochondrial biomarkers in measuring
the dynamic biological responses following induction and remediation of oxidative damage, triggered by a
child’s changing personal environment. These results could direct more effective pe...

## Key facts

- **NIH application ID:** 9991853
- **Project number:** 5R21ES029607-03
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** RACHEL L MILLER
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $217,322
- **Award type:** 5
- **Project period:** 2019-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9991853

## Citation

> US National Institutes of Health, RePORTER application 9991853, Mitochondrial DNA biomarkers to assess responses to changes in personal environmental exposures in pediatric urban asthma (5R21ES029607-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9991853. Licensed CC0.

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