ASTHMA AND NOCTURNAL HYPOXEMIA IN SICKLE CELL ANEMIA

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Our overall goal is to elucidate the physiologic, genetic, and molecular aspects of two common co-morbid conditions, asthma and nocturnal oxygen desaturation, that increase the incidence rate of pain in sickle cell anemia (SCA). In separate studies, we have shown children with SCA and either asthma or nocturnal desaturation have an increased pain rate when compared to children without the condition. Also, our group demonstrated that in a murine model of SCA there was significant susceptibility to hypoxia-induced pulmonary vasocongestion when compared to mice without SCA. Unfortunately, we do not know the interrelationship if any, between asthma, nocturnal desaturation and lung disease in SCA.We will test three global hypotheses: 1) phenotypic and genotypic features of asthma are risk factors for pain and ACS episodes in children with SCA; 2) nocturnal desaturation in children with SCA modifies the effect of asthma on morbidity in SCA; and 3) chronic airway inflammation and nocturnal hypoxia, separately and together, increase HbSS-induced lung injury in a murine SCA model. Taken together, the results of this highly interactive collaboration of clinical and basic scientists will permit new insights into the mechanisms of lung disease, thus providing a strong foundation for targeted therapy for this vulnerable group.