Understanding Oral Diseases in Cystic Fibrosis to Develop Tailored Preventive Dental Interventions

摘要 囊性纤维化（CF）是白种人中最常见的限制生命的常染色体隐性遗传病。受损 粘膜纤毛清除使CF个体易患慢性呼吸道感染，导致进行性呼吸道感染。 肺损伤和过早死亡我们和其他人已经证明，口腔细菌感染肺部的个人 高浓度的CF。龋齿和牙龈炎与增加的 可吸入的致病性且通常是促炎性的口腔内细菌。牙菌斑植物群会导致 肺炎，例如机械通气患者。鉴于更广泛的证据表明， 链接，令人惊讶的是，CF中口腔疾病和呼吸系统健康之间的联系从未被发现。 尽管存在合理的微生物机制，但仍进行了评价。这项提议的总体假设是， 口腔疾病，定义为龋齿和牙龈炎，是肺部疾病的潜在可改变因素， 参见在这项为期5年的观察性U 01中，我们将招募210名12至30岁的青少年和年轻成人CF 在3个地点工作了3年：西雅图儿童医院、北卡罗来纳州查佩尔山大学和 亚拉巴马对伯明翰。本研究将在24个月内进行3次研究访视。我们将获得定量和 关于口腔疾病风险因素的定性数据;对龋齿和牙龈炎进行标准化评估; 评估呼吸系统健康结果;收集痰液、唾液和菌斑进行微生物组分析。的 目的：（1）描述青少年口腔疾病的患病率和发病率 成人CF，并确定相应的危险因素，重点是如何改善关键的口腔 健康行为;（2）评估口腔疾病与健康行为之间的横向和纵向关联， 呼吸结果;（3）探索连接口腔和呼吸健康的微生物组途径。的 拟议的研究将是迄今为止最大的和第一个纵向CF口腔健康研究， CF中与口腔疾病相关的呼吸结局。我们的长期目标是发展行为 青少年和年轻成人CF预防口腔疾病和保护的随机临床试验 呼吸道健康我们还试图阐明解释全身健康后果的机制， 口腔疾病更广泛地说，我们的方法提供了一个框架，以改善口腔健康的医学 通过关键的流行病学调查和循证干预措施，

Abstract Cystic fibrosis (CF) is the most common life-limiting autosomal recessive disease in Caucasians. Impaired mucociliary clearance predisposes individuals with CF to chronic respiratory infections, resulting in progressive lung damage and premature death. We and others have shown that oral bacteria infect the lungs in individuals with CF at high concentrations. Caries and gingivitis are associated with an increased abundance of pathogenic and often proinflammatory intraoral bacteria that can be aspirated. Dental plaque flora can cause pneumonia, for example in mechanically-ventilated patients. Given the broader evidence of oral-respiratory links, it is surprising that the association between oral diseases and respiratory health in CF has never been evaluated, even though there is a plausible microbiological mechanism. The overall hypothesis of this proposal is that oral diseases, defined as caries and gingivitis, are potentially modifiable contributors to lung disease in CF. In this 5-year observational U01, we will enroll 210 adolescents and young adults with CF ages 12 to 30 years at 3 sites: Seattle Children’s Hospital, the University of North Carolina Chapel Hill, and the University of Alabama at Birmingham. The study will involve 3 study visits over 24 months. We will obtain quantitative and qualitative data on risk factors for oral diseases; perform a standardized assessment of caries and gingivitis; evaluate respiratory health outcomes; and collect sputum, saliva, and plaque for microbiome analyses. The Aims are to: (1) Describe the prevalence and incidence of oral diseases in adolescents and young adults with CF and identify corresponding risk factors with an emphasis on how to improve key oral health behaviors; (2) Evaluate cross-sectional and longitudinal associations between oral diseases and respiratory outcomes; and (3) Explore microbiome pathways that link oral and respiratory health. The proposed study will be the largest and first longitudinal CF oral health study to date, and the first to evaluate respiratory outcomes associated with oral diseases in CF. Our long-term objective is to develop behavioral randomized clinical trials for adolescents and young adults with CF to prevent oral diseases and protect respiratory health. We also seek to elucidate mechanisms that explain the systemic health consequences of oral diseases. More broadly, our approach provides a framework for improving the oral health of medically compromised populations through critical epidemiologic inquiry and evidence-based interventions.