Asthma and Nocturnal Hypoxemia in Sickle Cell Anemia II

描述（由研究者提供）：这是一份续期申请，以继续我们在睡眠和哮喘队列（SAC）研究中的工作，编号h079937，我们在2006年5月开始招募受试者。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的生物学基础进展。在SAC研究中，我们建立了一个独特的队列，包括251名SCD儿童，他们接受了肺功能测试（PFT）和全多道睡眠描画（PSG），这是世界上最大的SCD儿童队列，进行了广泛的评估。目前，该队列的平均前瞻性随访期仅为2.1年，这段时间不足以评估哮喘危险因素与scd相关发病率（因疼痛或ACS住院）之间的关系。目前尚不清楚哮喘危险因素、SDB与肺功能异常之间的关系。我们建议对现有队列再进行4年的跟踪研究，以充分评估这些关系。此外，我们的转化研究工作集中在建立一种与纤维细胞密切相关的肺疾病的临床前转基因SCD小鼠模型，纤维细胞是肺纤维化和肺功能异常的关键成分。该项目将有三个相互关联的目标：1)确定哮喘危险因素（父母哮喘史和空气过敏原皮肤试验阳性）是否与疼痛和ACS发作的发生率增加有关。目的2：确定SDB与阻塞性肺疾病的存在或进展之间的关系。目的3，确定循环纤维细胞百分比和表型与肺功能异常演变之间的纵向关系。总之，临床和基础科学家的高度互动合作的结果将为SCD肺部和睡眠疾病的自然历史和发病机制提供新的见解，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. PUBLIC HEALTH RELEVANCE: Pulmonary complications are a leading cause of morbidity and mortality in sickle cell disease; yet, the natural history, risk factors and underlying mechanisms of progressive lung disease are poorly defined. The overall goal of this applications is to identify the laboratory and clinical determinants of how lung disease progresses from normal in early childhood to asthma and later to a severe lung disease that requires oxygen