# The Pro-Inflammatory Effects of Acute Exercise in Children with Sickle Cell Anemia

> **NIH NIH R01** · LURIE CHILDREN'S HOSPITAL OF CHICAGO · 2021 · $445,812

## Abstract

PROJECT SUMMARY
Children with sickle cell anemia (SCA) suffer from complications that lead to significantly reduced physical
functioning and exercise capacity. Despite the known benefits of regular physical activity across the lifespan,
evidence-based recommendations for exercise prescription do not exist for children with SCA. Inflammation
and endothelial dysfunction represent major contributors to disease pathophysiology and complications in SCA.
For many children with SCA, the health benefits of physical activity are unrealized due to concerns that the
well-described inflammatory effects of acute exercise may precipitate or exacerbate complications such as
vaso-occlusive pain or exercise-induced bronchoconstriction (EIB). We have previously shown that compared
to controls without SCA, children with SCA have 30% lower fitness levels and engage less often in vigorous
physical activity and organized sports. However, children with SCA tolerate maximal cardiopulmonary exercise
testing (CPET) without adverse effects and show similar patterns in their acute inflammatory response to
maximal CPET. Although our preliminary data suggest that increasing physical activity may be beneficial rather
than harmful in children with SCA, the pro-inflammatory effects associated with repeated bouts of moderate to
vigorous exercise remain poorly understood. Our long term goal is to address the safety and health impact of
regular exercise in children with SCA. For this proposal, we will evaluate the effect of acute exercise and
exercise intensity on circulating systemic pro-inflammatory mediators and airway bronchoconstriction in SCA.
We hypothesize that regular exercise at moderate to vigorous intensity is safe for children with SCA and do not
precipitate SCA-related symptoms. In this multicenter study, 70 non-asthmatic children with SCA and 70
controls without SCA will first undergo maximal CPET, then be randomized to exercise challenge by controlled
intensity interval training (CIIT) at either moderate or vigorous intensity (8 exercise bouts at 50-55% or 80-85%
peak workload, respectively). Our Aims are to: 1) Determine the influence of exercise intensity on the acute
inflammatory response to exercise, defined by an increase in soluble vascular cell adhesion molecule (VCAM)
and other adhesion molecules, and 2) Define the effect of moderate to vigorous exercise on forced expiratory
volume in 1 second (FEV1) and acute bronchoconstriction in children with SCA. We will also explore exercise-
induced changes in gene and microRNA expression in peripheral blood mononuclear cells as well as the role
of hyperventilation in bronchoconstriction using eucapnic voluntary hyperventilation testing. For the first time in
SCA, our group of investigators in hematology, exercise science and exercise immunology will provide the
critical prerequisite toward developing evidence-based guidelines for exercise prescription as a transformative
strategy to maintain physical functioning and ...

## Key facts

- **NIH application ID:** 10141282
- **Project number:** 5R01HL136480-05
- **Recipient organization:** LURIE CHILDREN'S HOSPITAL OF CHICAGO
- **Principal Investigator:** Robert Ie Liem
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $445,812
- **Award type:** 5
- **Project period:** 2017-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10141282

## Citation

> US National Institutes of Health, RePORTER application 10141282, The Pro-Inflammatory Effects of Acute Exercise in Children with Sickle Cell Anemia (5R01HL136480-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10141282. Licensed CC0.

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