VO2max & HRQoL in Children With Sickle Cell Disease

Study Overview
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Brief Summary
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Sickle cell disease is the most common inherited genetic disorder, accounting for 300,000 births worldwide per year. It is caused by an autosomal recessive mutation of the β-globin gene, responsible for an abnormal hemoglobin, the main protein in red blood cells, responsible for transporting oxygen from the lungs to the tissues. The abnormal hemoglobin, known as Sickle or S, deforms the red blood cell, causing chronic hemolytic anemia, organ damage (heart, spleen, etc.) and vaso-occlusive crises. Therapeutic progress and specialised patient follow-up have considerably improved the vital and functional prognosis of children and adolescents with sickle cell disease. Physical fitness, measured during a cardiorespiratory exercise test (CPET), is used to determine maximal oxygen uptake (VO2max). Patients with sickle cell disease have a multifactorial limitation of exercise tolerance, which may affect their physical fitness. Authors have shown that VO2max is impaired in children and adolescents with sickle cell disease, independently of their baseline hemoglobin level. Yet VO2max is a key determinant of health-related quality of life (HRQoL) in patients being monitored for a chronic disease. In the past, our team has contributed to the assessment of HRQoL in several groups of pediatric patients suffering from chronic disease (congenital heart disease, PAH). To date, the link between impaired physical fitness and HRQoL has not been demonstrated in sickle cell children. The pathophysiological determinants of reduced physical capacity and exercise tolerance in sickle cell patients have also not been fully elucidated. Studying these factors will enable us to propose appropriate treatment in the future, with the aim of improving physical fitness and HRQoL in children and adolescents with sickle cell disease.

Detailed Description
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This prospective case-control study included sickle cell children and healthy controls from 6 to 17 years old. Patients refuse the use of medical data will be excluded. After description of the study sample, we will first compare the VO2max Z-score between cases and controls. We will correlate the VO2max to PedsQL self- and proxy-related and Ricci and Gagnon scores (use of the coefficient of correlation rhô). Then we will compare others CPET parameters and will determine associated factors of VO2max with others resting data : hematological, respiratory, cardiologic, anthropometric, educational (use of the coefficient of correlation rhô, and multivariate linear regression model).

Official Title
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Aerobic Physical Fitness and Health-related Quality of Life in Children With Sickle Cell Disease.

Conditions
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Sickle Cell, Children

Participation Criteria
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Eligibility Criteria
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Sickle cell children Inclusion Criteria: Child from 6 to 17 years old, with a confirmed diagnosis of sickle cell disease (i.e., homozygous HbS/S or heterozygous HbS/C mutations), during their routine follow-up, having performed : a hematology consultation : physical examination, blood test a cardiology consultation : electrocardiogram, transthoracic echocardiography a respiratory plethysmography a CPET and to fill in the study questionnaires. Exclusion Criteria: Parents' refusal to use medical data. Healthy children Inclusion Criteria: Child from 6 to 17 years old having performed a cardio-respiratory exercise test for chest pain, dyspnea on exertion, heart murmur and whose results do not find: Congenital heart disease (normal echocardiography and ECG) Respiratory disease (normal FEV1 and FVC) Child having performed a maximal cardio-respiratory stress exercise until exhaustion. Exclusion Criteria: Child taking long-term drug treatment Child with chronic disease Parents' refusal to use medical data.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cases: Children with sickle cell disease<br>Children aged 6 to 17 years with a confirmed diagnosis of sickle cell disease (i.e., homozygous HbS/S or heterozygous HbS/C mutations) | |
| Controls: Healthy children referred for a non-severe functional symptom linked to exercise<br>Children aged 6 to 17 years with a completely normal check-up, including physical examination, ECG, echocardiography, and spirometry. Children with any chronic disease, medical condition, or medical treatment and those requiring any further specialized medical consultation were not eligible. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference between aerobic fitness evaluated by VO2max, expressed in Z-score between cases and controls |  | 1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation between aerobic fitness and quality of life in cases group | To analyze this, we will correlate the VO2max Z-score and the assessment of health-related quality of life (measured by PedQL 4.0). | 1 day | 
| Correlation between aerobic fitness and physical activity level, in cases group | To analyze this, we will correlate the VO2max Z-score and the assessment of physical activity level (measured by Ricci and Gagnon questionnaire). | 1 day | 
| Correlation between aerobic fitness and educational level (knowledge about disease), in cases group | To analyze this, we will correlate the VO2max Z-score and the assessment of educational level (local disease knowledge questionnaire). | 1 day | 
| Correlation between aerobic fitness and VO2max limiting factors in cases group: demographic, genetic mutation, clinical (comorbidities, respiratory function, cardiac function, anemia, CPET data) | To analyze this, we will correlate the VO2max Z-score and demographic data, genetic mutation, spirometry, plethysmography, trans-thoracic echocardiography, hemoglobin level, other CPET data. | 1 day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardiopulmonary exercise test, VO2max, Sickle cell disease, Child, Heath-related quality of life, Cardiopulmonary rehabilitation