# Predictive Models of Beryllium Sensitization and Chronic Beryllium Disease

> **NIH NIH R01** · NATIONAL JEWISH HEALTH · 2023 · $2,413,505

## Abstract

PROJECT SUMMARY/ABSTRACT
Beryllium (Be) is used in a several industries and US is the largest exporter of Be in the world. Despite
mitigation strategies, Be exposure at workplace results in Be sensitization (BeS) and Chronic Beryllium
Disease (CBD). CBD is an important understudied organ-specific immune-mediated disease characterized by
granulomatous lung inflammation, fibrosis, and death. Hence, CBD is a public health concern resulting in
promulgation of new exposures standards recently. BeS develops in up to 20% of Be-exposed individuals and
progresses to CBD 50-100% of these at-risk individuals. The goal of this study is to define the novel lung
compartment-specific gene-protein pathways, which will narrow the existing gap in understanding of Be lung
disease and form the basis of a clinically viable models (classifiers) to identify BeS, CBD and predict
progression of BeS to CBD. This projects hypothesis is that systematic characterization of lung compartment-
specific changes will identify novel pathways linked to BeS, CBD and the progression of BeS to CBD. The
investigators posit that the proteins in these pathways would provide clinically viable models (classifiers) that
will discriminate between healthy controls, BeS, and CBD. In Aim 1, the study will determine the systems level,
lung compartment-specific, gene-protein changes linked to BeS and CBD by analyzing BAL cells from a
Discovery Cohort (CBD=50, BeS=50, healthy controls=25). This aim will Identify the transcriptional and global
protein changes using contemporary high-resolution mass-spectrometry coupled with advanced computational
biology and bioinformatics. A combination of single cell RNA sequencing and innovative expression
deconvolution will define cell-specific transcriptional changes implicated in BeS and CBD. Furthermore, the
research team will integrate transcription and protein expression to identify the biological pathways associated
with Be-induced lung disease. The study uses the same Discovery Cohort, and an independent Validation
Cohort of subjects already enrolled in Aim 2, to develop and validate a comprehensive BAL fluid classifier of
BeS and CBD. Specifically, the Discovery Cohort will be used to construct and internally validate a
multicomponent classifier that discriminates healthy controls. In addition, this classifier will be externally
validated in the Validation Cohort of CBD (n=50), BeS (n=50), and healthy controls (n=25). In Aim 3, the study
evaluates the stability of the classifier of BeS and CBD and develops predictive models of progression from
BeS to CBD in subjects with longitudinal clinical data and BAL fluid already available. A group of BeS cases
who on follow-up developed CBD will be compared to BeS cases who do not develop CBD to build a model
that predicts BeS progression. At the completion of this project, the study findings will be poised to translate to
clinical care for the rapid detection of CBD and BeS. Further, it will identify novel pathw...

## Key facts

- **NIH application ID:** 10736862
- **Project number:** 1R01ES034767-01A1
- **Recipient organization:** NATIONAL JEWISH HEALTH
- **Principal Investigator:** Maneesh Bhargava
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $2,413,505
- **Award type:** 1
- **Project period:** 2023-09-10 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10736862

## Citation

> US National Institutes of Health, RePORTER application 10736862, Predictive Models of Beryllium Sensitization and Chronic Beryllium Disease (1R01ES034767-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10736862. Licensed CC0.

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