Reduced fitness and abnormal cardiopulmonary responses to maximal exercise testing in children and young adults with sickle cell anemia.

Robert I Liem,Adrienne P Savant,Bo Fernhall,Stephanie A Pelligra,Mark Rodeghier,Madhuri Reddy,Alexis A Thompson

doi:10.14814/phy2.12338

Robert I Liem, Adrienne P Savant + Show 5 more

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https://doi.org/10.14814/phy2.12338

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Abstract

Physiologic contributors to reduced exercise capacity in individuals with sickle cell anemia (SCA) are not well understood. The objective of this study was to characterize the cardiopulmonary response to maximal cardiopulmonary exercise testing (CPET) and determine factors associated with reduced exercise capacity among children and young adults with SCA. A cross-sectional cohort of 60 children and young adults (mean 15.1 ± 3.4 years) with hemoglobin SS or S/β0 thalassemia and 30 matched controls (mean 14.6 ± 3.5 years) without SCA or sickle cell trait underwent maximal CPET by a graded, symptom-limited cycle ergometry protocol with breath-by-breath, gas exchange analysis. Compared to controls without SCA, subjects with SCA demonstrated significantly lower peak VO2 (26.9 ± 6.9 vs. 37.0 ± 9.2 mL/kg/min, P < 0.001). Subjects demonstrated slower oxygen uptake (ΔVO2/ΔWR, 9 ± 2 vs. 12 ± 2 mL/min/watt, P < 0.001) and lower oxygen pulse (ΔVO2/ΔHR, 12 ± 4 vs. 20 ± 7 mL/beat, P < 0.001) as well as reduced oxygen uptake efficiency (ΔVE/ΔVO2, 42 ± 8 vs. 32 ± 5, P < 0.001) and ventilation efficiency (ΔVE/ΔVCO2, 30.3 ± 3.7 vs. 27.3 ± 2.5, P < 0.001) during CPET. Peak VO2 remained significantly lower in subjects with SCA after adjusting for age, sex, body mass index (BMI), and hemoglobin, which were independent predictors of peak VO2 for subjects with SCA. In the largest study to date using maximal CPET in SCA, we demonstrate that children and young adults with SCA have reduced exercise capacity attributable to factors independent of anemia. Complex derangements in gas exchange and oxygen uptake during maximal exercise are common in this population.

Highlights

Sickle cell anemia (SCA) is a common inherited blood disorder associated with abnormal hemoglobin production and characterized by chronic hemolysis, a proinflammatory state and endothelial dysfunction (Solovey et al 1997; Reiter et al 2002; Hebbel et al 2004; Brittain and Parise 2007)
This study demonstrated several important findings that strengthen our understanding of cardiopulmonary fitness and exercise responses among children and young adults with SCA
We showed that cardiopulmonary exercise testing (CPET) at maximal exertion is safe and did not directly cause vasoocclusive pain either during or after testing

Summary

Introduction

Sickle cell anemia (SCA) is a common inherited blood disorder associated with abnormal hemoglobin production and characterized by chronic hemolysis, a proinflammatory state and endothelial dysfunction (Solovey et al 1997; Reiter et al 2002; Hebbel et al 2004; Brittain and Parise 2007). The disease impact on physical function among affected individuals is significant. Both adults and children with SCA, either directly or by proxy, consistently report poor physical functioning on health-related quality of life surveys (Panepinto et al 2005). Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

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