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疾病。受损 粘液纤毛清除功能使 CF 患者易患慢性呼吸道感染，从而导致进行性进展 肺部损伤和过早死亡。我们和其他人已经证明口腔细菌会感染个体的肺部 与高浓度的CF。龋齿和牙龈炎与牙齿数量的增加有关 可以吸出的致病性且通常促炎的口腔内细菌。牙菌斑菌群可引起 肺炎，例如机械通气患者的肺炎。鉴于口腔呼吸系统的更广泛证据 联系，令人惊讶的是，CF 中口腔疾病与呼吸系统健康之间的关联从未被研究过。 尽管存在合理的微生物机制，但仍进行了评估。本提案的总体假设 被定义为龋齿和牙龈炎的口腔疾病是肺部疾病的潜在可改变因素 CF。在这项为期 5 年的 U01 观察中，我们将招募 210 名年龄在 12 至 30 岁之间患有 CF 的青少年和年轻人 在 3 个地点工作多年：西雅图儿童医院、北卡罗来纳大学教堂山分校和北卡罗来纳大学 阿拉巴马州在伯明翰。该研究将涉及 24 个月内的 3 次研究访问。我们将获得定量和 关于口腔疾病危险因素的定性数据；对龋齿和牙龈炎进行标准化评估； 评估呼吸系统健康结果；并收集痰液、唾液和菌斑进行微生物组分析。的 目的是： (1) 描述青少年口腔疾病的患病率和发病率 患有 CF 的成人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) 评估口腔疾病与口腔疾病之间的横断面和纵向关联 呼吸系统结果； (3) 探索连接口腔和呼吸系统健康的微生物组途径。的 拟议的研究将是迄今为止最大的、第一个纵向 CF 口腔健康研究，也是第一个评估 与 CF 口腔疾病相关的呼吸结果。我们的长期目标是培养行为 针对患有 CF 的青少年和年轻人预防口腔疾病和保护的随机临床试验 呼吸系统健康。我们还试图阐明解释系统健康后果的机制 口腔疾病。更广泛地说，我们的方法为改善医学上的口腔健康提供了一个框架 通过严格的流行病学调查和循证干预措施来帮助受影响的人群。

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.