|
Overview
|
The project will have three inter-related Aims: 1) To determine if asthma risk factors (parental history of asthma and positive skin test for an aeroallergen) are associated with an increase incidence of pain and ACS episodes. Aim 2, to determine relationship between SDB and the presence of, or progression to, obstructive lung disease. Aim 3, to determine the longitudinal relationship between the percentage and phenotypes of circulating fibrocytes and evolution of abnormal lung function. Together, the results of this highly interactive collaboration of clinical and basic scientists will permit new insights into the natural history and pathogenesis of lung and sleep disease in SCD, providing a strong foundation for future targeted therapy.
|
|
Focus Areas
|
1. Asthma phenotypes, as defined by bronchodilator response, obstructive pattern on spirometry, and doctor diagnosis of asthma
2. Restrictive lung disease (reduced total lung capacity determined on lung volume testing)
3. Characterize pulmonary function (based on Spirometry, bronchodilator response, in children with SCD
4. Determine linear growth curves in children with SCD with and without asthma
5. Determine the relative importance of sleep-disordered breathing and asthma in predicting nocturnal oxygen desaturation in children, adolescents and adults with SCD
6. Determine the relationship between asthma and sleep disordered breathing
7. Determine which patterns of nocturnal oxygen desaturation are risk factors for ACS
8. Evaluate the lung function of healthy normal control children using spirometry and lung volume testing to compare to the lung function of the children with SCD
9. Impact of hydroxyurea on lung growth in adults and children with SCD
|
|
Outcomes
|
1. Increased incidence of either vaso-occlusive pain episodes requiring hospitalization and treatment with opioids (Aim 1A) and/or acute chest syndrome (ACS) (Aim 1B) and progression of lung function abnormalities
2. Sleep disordered breathing (SDB) as measured by apnea, hypopnea and desaturation indices
3. Circulating fibrocyte number and activated phenotype (expression of pSmad2/3 or a-SMA)
|