Explanatory models of CF Survival, Infection and Intermediate Clinical Outcomes

 描述(由申请人提供)：该项目将使用囊性纤维化(CF)基金会患者登记(CFFPR)来探索囊性纤维化引起的基因突变、呼吸道感染、临床疾病和生存之间的潜在因果关系。CFFPR包含1986年至2011年期间在美国经过认证的CF护理中心就诊的超过200万例患者的数据，涉及4.5万名患者。我们的努力将集中在三个具体的目标上：(1)基于临床相关因素建立一个关于CF存活率的解释模型；(2)评估CF突变、存活率和中间疾病结局之间的关系；(3)突变、呼吸道感染、临床疾病和存活率之间的模型反馈。更好地了解从基因突变到存活率下降的潜在途径可能有助于临床医生制定个性化的治疗计划。一些对特定疾病、并发症或感染有特殊易感性的患者可能会从强调特定治疗中受益。对于探索新药的研究人员，我们的模型可能会确定要招募的特定患者组，或者至少在控制组和试验组之间取得平衡。最后，更好 对病理生理学的理解可能会鼓励在CF中探索新的方向，我们的方法可能会对存在大量临床数据集的其他遗传病的研究人员感兴趣。

 DESCRIPTION (provided by applicant): The project will use the Cystic Fibrosis (CF) Foundation Patient Registry (CFFPR) to explore potentially causal relationships between CF causing genetic mutations, airway infections, clinical disease and survival. The CFFPR contains data from over 2 million encounters involving 45,000 patients seen at certified CF care centers in the United States from 1986 through 2011. Our efforts will focus on three specific aims: (1) Develop an explanatory model of survival in CF based on clinically relevant factors; (2) Assess associations between CF mutations, survival and intermediate disease outcomes; (3) Model feedback among mutations, airway infection, clinical disease and survival. Better understanding of the potential pathways that lead from genetic mutation to decreased survival may help clinicians craft individualized treatment plans. Some patients with special vulnerabilities to specific disease complications or infections may benefit from emphasizing specific treatments. For investigators exploring novel medications, our models may identify particular groups of patients to recruit or at least to balance between control and experimental groups. Finally, better pathophysiologic understanding may encourage new directions for exploration in CF, and our methods may be of interest to investigators of other genetic diseases where substantial clinical data sets exist.