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）基金会患者登记处（CFFPR）来探索CF引起的基因突变、气道感染、临床疾病和生存之间的潜在因果关系。CFFPR包含了1986年至2011年在美国认证的CF护理中心就诊的45，000名患者的200多万次接触的数据。我们的努力将集中在三个具体目标：（1）开发一个解释模型的生存CF的基础上临床相关因素;（2）评估CF突变，生存和中间疾病的结果之间的关联;（3）模型之间的反馈突变，气道感染，临床疾病和生存。更好地了解从基因突变到生存率降低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特别脆弱的患者可能会从强调特定治疗中受益。对于探索新药物的研究人员来说，我们的模型可以识别特定的患者群体，或者至少在对照组和实验组之间进行平衡。最后，更好 病理生理学的理解可能会鼓励新的方向探索CF，我们的方法可能是感兴趣的其他遗传性疾病的研究人员在大量的临床数据集存在。

 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.