Chest
Volume 143, Issue 2, February 2013, Pages 478-484
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Original Research
Pulmonary Physiology
The Impact of Sickle Cell Disease on Exercise Capacity in Children

https://doi.org/10.1378/chest.12-0611Get rights and content

Background

Little is known about pulmonary vascular complications in children with sickle cell disease (SCD). We hypothesized that transfer factor (diffusing capacity of the lung for carbon monoxide [DLCO]) may be used as a surrogate for the size of the pulmonary vascular bed and that pulmonary vascular abnormalities in children with SCD may limit exercise capacity.

Methods

Fifty stable patients with SCD aged 10 to 18 years and 50 healthy control subjects matched for race and age were recruited. Incremental ergometer cardiopulmonary exercise testing was performed using respiratory mass spectrometry for exhaled gas analysis. A rebreathing maneuver was used to measure functional residual capacity, effective pulmonary blood flow (Qpeff), and DLCO, and helium dilution was used to calculate minute ventilation, oxygen consumption, and CO2 production.

Results

In the 89 evaluable subjects, there were no ventilatory differences between SCD and control subjects. Qpeff was consistently 15% to 20% greater in subjects with SCD than control subjects at all stages, but DLCO corrected for both surface area and hemoglobin was only about 7% to 10% greater in subjects with SCD at all stages. As a result, the DLCO/Qpeff ratio was considerably lower in SCD at all stages. Arteriovenous oxygen content difference was about one-third less in SCD at all stages.

Conclusions

Contrary to our hypothesis, failure to maintain a sufficient Qpeff to compensate for anemia led to exercise limitation. The ratio of pulmonary capillary blood volume to flow is reduced throughout, implying subtle pulmonary vascular disease; however, this was not a factor limiting exercise.

Section snippets

Exercise Physiology

Noninvasive RMS permits the measurement of physiologic variables during both rest and exercise. Using a rebreathing protocol, the disappearance of acetylene and oxygen determines the effective pulmonary blood flow (Qpeff) (defined as being in contact with ventilated alveoli), effective stroke volume (Qpeff/heart rate), and oxygen consumption, respectively. Their ratio (Fick principle) determines the arteriovenous content difference (AVO).

Similarly, the disappearance of carbon monoxide (CO)

Results

Demographics are summarized in Table 1. Of 100 subjects recruited, four did not attend, two had oxygen saturation < 91% at rest, and five were excluded for persistent mouth leak; therefore, 89 of 100 (44 patients and 45 control subjects) had analyzable exercise data. All 89 reached the 25 W/m2 stage. Patients were well matched for age, but male patients were significantly shorter than control subjects, and female patients had a later puberty. Patients by definition had a lower Hb and higher

Statement of Principal Findings

Children with SCD have a greater than normal Qpeff at rest, on exercise, and during recovery, achieved by raising both stroke volume and heart rate, presumably to compensate for chronic anemia. This compensation was incomplete, as oxygen dispatch was consistently slightly reduced. DLCO corrected for hemoglobin and surface area was consistently slightly greater in subjects with SCD, making the ratio of DLCO to Qpeff about 40% to 50% less in subjects with SCD. Given that recruitment and

Acknowledgments

Author contributions: Dr Rosenthal acts as guarantor of the manuscript.

Dr Chaudry: contributed to recruiting all subjects, supervised all exercise tests, and wrote the drafts of the manuscript.

Dr Bush: contributed to writing and supervision of the project.

Dr Rosenthal: contributed to advising on the exercise protocol, supervised the analyses, assisted with writing, and supervised the project.

Dr Crowley: contributed to conceiving and designing the project and assisted with writing and

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  • Cited by (0)

    Funding/Support: This study was funded by the St. George's Healthcare National Health Service Trust Charitable Trustees (UK) and The Sobell Foundation (UK). It was supported by the National Institute for Health Research Respiratory Disease Biomedical Research Unit at the Royal Brompton and Harefield National Health Service Foundation Trust and Imperial College London.

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.

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