# Arsenic related cystic fibrosis

> **NIH NIH R01** · BOSTON CHILDREN'S HOSPITAL · 2021 · $364,637

## Abstract

PROJECT SUMMARY/ABSTRACT
Environmental arsenic exposure is associated with increased rates of pneumonia, bronchiectasis, and
diabetes. The underlying biochemical pathways that link arsenic exposure to lung disease and diabetes are
difficult to study, but the symptoms of arsenic toxicity overlap with those of cystic fibrosis, a rare autosomal
recessive disease most common in people of Northern European ancestry. Accumulating evidence suggests
that arsenic toxicity and cystic fibrosis share a common mechanism: dysfunction of the cystic fibrosis
transmembrane regulator (CFTR). CFTR is a chloride channel that regulates intracellular fluid transport in the
lungs, pancreas, and other organs. Studies in cell culture show that arsenic causes degradation of CFTR, and
our recent epidemiological study demonstrates that humans exposed to arsenic also exhibit CFTR dysfunction.
It is critical to understand these specific mechanisms in order to develop effective preventive and therapeutic
interventions.
In this proposal, we plan to study whether CFTR dysfunction in adults with high arsenic exposure contributes to
diminished lung function and diabetes. We propose a comprehensive set of studies that leverage an
established study population in rural Bangladesh, a country that is currently experiencing an epidemic of
arsenic poisoning through contaminated drinking water. We hypothesize that arsenic influences diminished
lung function and risk of diabetes by inducing CFTR dysfunction. We will use established biochemical
techniques, including sweat test and Western Blot of peripheral blood mononuclear cells, to assess CFTR
function. In this application, we present preliminary data that suggest that sweat chloride, a noninvasive
measure that is easy to obtain, is elevated among individuals with high arsenic exposure. We will now test
whether sweat chloride concentration can be used to identify individuals at higher risk for low respiratory
function and diabetes related to arsenic exposure. Our analyses will employ causal mediation analysis to
investigate whether diseases related to arsenic can be attributed to CFTR dysfunction.
These studies explore mechanisms by which arsenic may increase risk of lung disease and diabetes in
humans, and use a unique population of adults with high arsenic exposure in order to test hypotheses. Our
long-range goals are to develop novel screening strategies to identify populations at high risk for lung disease
and diabetes due to environmental exposure, and to direct the development of more effective preventive
interventions.

## Key facts

- **NIH application ID:** 10088446
- **Project number:** 5R01ES027825-04
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** Maitreyi Mazumdar
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $364,637
- **Award type:** 5
- **Project period:** 2018-02-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10088446

## Citation

> US National Institutes of Health, RePORTER application 10088446, Arsenic related cystic fibrosis (5R01ES027825-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10088446. Licensed CC0.

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