Asthma and Nocturnal Hypoxemia in Sickle Cell Anemia II

描述（由研究者提供）：这是一份延续申请，旨在继续我们在睡眠和哮喘队列（SAC）研究（HL 079937）中的工作，我们于2006年5月开始入组受试者。我们的总体目标是阐明哮喘危险因素和睡眠呼吸障碍（SDB）对镰状细胞病（SCD）发病率的影响，并更好地了解肺部疾病进展的生物学基础。在SAC研究中，我们建立了一个由251名SCD儿童组成的独特队列，这些儿童接受了肺功能测试（PFT）和完整的多导睡眠图（PSG），这是世界上最大的SCD儿童队列。目前，该队列的平均前瞻性随访期仅为2.1年，时间不足以评估哮喘风险因素与SCD相关发病率（因疼痛或ACS住院）之间的关系。目前，我们还不清楚哮喘危险因素、SDB和肺功能异常之间的关系。我们建议对现有队列再进行4年随访，以评估这些关系是否具有足够的统计把握度。此外，我们的转化研究工作集中在建立一个临床前转基因SCD小鼠模型的肺部疾病，强烈牵连纤维细胞，作为一个关键组成部分，肺纤维化和肺功能异常。该项目将有三个相互关联的目的：1）确定哮喘风险因素（父母哮喘史和空气过敏原皮肤试验阳性）是否与疼痛和ACS发作的发生率增加相关。目的2，确定SDB与阻塞性肺疾病的存在或进展的关系。目的3，探讨循环纤维细胞百分比和表型与肺功能异常演变的纵向关系。总之，临床和基础科学家高度互动合作的结果将允许对SCD中肺部和睡眠疾病的自然史和发病机制的新见解，为未来的靶向治疗提供坚实的基础。

DESCRIPTION (provided by investigator): This is a renewal application to continue our work on the Sleep and Asthma Cohort (SAC) Study, HL079937, in which we started enrolling subjects in May 2006. Our overall goal is to elucidate the effects that asthma risk factors and sleep disordered breathing (SDB) have on sickle cell disease (SCD) morbidity and to better understand the biological basis progression of lung disease. In the SAC Study, we established a unique cohort of 251 children with SCD, who have received both pulmonary function testing (PFT) and full polysomnography (PSG), the largest cohort of children with SCD with this extensive evaluation in the world. Currently, the cohort has a mean prospective follow- up period of only 2.1 years, a time insufficient to assess the relationship between asthma risk factors on SCD-related morbidity (hospitalization for pain or ACS). At present, we do not know the relationship between asthma risk factors, SDB, and lung function abnormalities. We propose following the existing cohort for additional 4 years to assess these relationships with adequate statistical power. Further, our translational research efforts have focused on establishing a pre-clinical transgenic SCD mouse model of lung disease that strongly implicates fibrocytes, as a key component to pulmonary fibrosis and abnormal lung function. 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.