# Penetrating the “Black box”:  Prediction of early Bronchiolitis obliterans in Pediatric Hematopoietic Stem Cell Transplant Recipients

> **NIH NIH R01** · CINCINNATI CHILDRENS HOSP MED CTR · 2021 · $649,585

## Abstract

Abstract
Bronchiolitis obliterans syndrome (BOS) is an obstructive lung disease caused by a combination of inflammation
and immune response that is irreversible in its late stage. Children with BOS are typically diagnosed late
because they are unable to perform spirometry, and morbidity and mortality are high. The long-term goal of this
work is to improve survival and reduce morbidity from BOS by identifying strategies for accurate screening and
prediction of BOS in children and young adults after HSCT and using these tools to identify novel drug targets
for early intervention or prevention of BOS. The objective of this application is to validate novel predictive plasma
protein biomarkers and establish a dynamic prediction model for BOS for early diagnosis, risk stratification and
disease trajectory prediction for BOS after HSCT. We will achieve these goals through the following specific
aims: 1) Validate longitudinal predictive performance of newly discovered plasma biomarkers of BOS risk in
samples from banked and prospective studies by mass spectrometry and ELISA in both pediatric and adult
cohorts. 2) Optimize and validate our dynamic prediction algorithm using pulmonary function and clinical data as
well as biomarker levels (needed when no spirometry can be obtained) as covariates to project risks of BOS and
rapid BOS lung-function decline to inform treatment decisions. There are currently no biomarkers or predictive
tools for BOS so this work is entirely novel. The use of a dynamic prediction algorithm in this clinical setting is
innovative allowing for the first time the ability to predict and diagnose early lung disease in HSCT subjects prior
to the clinical diagnosis of BOS. Identification of BOS risk and stratification of screening and treatment
procedures according to risk and predicted disease course would allow us to modify post-transplant care and
reduce morbidity and mortality. We will use our data to inform prospective clinical trials of both early active
treatment prior to development of early fibrosis and to test novel prophylactic therapies to reduce incidence in
high risk individuals. Our studies will provide blood biomarkers that can be used as frequently as necessary
without requiring active participation from small and often very sick children. Our preliminary biomarker and
HSCT specific algorithm data demonstrate detection of BOS as soon as 2 weeks to 6 months prior to clinical
diagnosis of BOS. This work is both significant and vital because improvements in HSCT techniques and
supportive care have led to improved survival. Improved survival increases the number of children at risk for late
complications of HSCT that are associated with life-changing morbidity and late mortality and there is urgent
need to address these issues. This work will advance prediction and early diagnosis of BOS, as well as providing
the framework for future prevention and treatment trials.

## Key facts

- **NIH application ID:** 10293181
- **Project number:** 1R01HL153108-01A1
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** Kasiani Myers
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $649,585
- **Award type:** 1
- **Project period:** 2021-07-15 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10293181

## Citation

> US National Institutes of Health, RePORTER application 10293181, Penetrating the “Black box”:  Prediction of early Bronchiolitis obliterans in Pediatric Hematopoietic Stem Cell Transplant Recipients (1R01HL153108-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10293181. Licensed CC0.

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