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

摘要 囊性纤维化是高加索人最常见的常染色体隐性遗传病。受损的 粘液纤毛清除使患有慢性支气管炎的人易患慢性呼吸道感染，导致进行性感染。 肺损伤和过早死亡。我们和其他人已经证明口腔细菌会感染个体的肺部。 在高浓度条件下，使用CF。龋齿和牙周炎与更多的 口腔内的致病细菌，通常是促炎细菌，可吸入。牙菌斑菌群可导致 肺炎，例如在机械通气的患者中。鉴于口腔呼吸道感染的更广泛证据 链接，令人惊讶的是，在慢性阻塞性肺疾病中口腔疾病和呼吸健康之间的联系从来没有 评估，即使有一个看似合理的微生物机制。这一提议的总体假设 口腔疾病，被定义为龋齿和牙周炎，是潜在的可改变的肺部疾病的诱因 参见在这个为期5年的观察U01中，我们将招募210名年龄在12岁到30岁之间的青少年和青壮年 三年：西雅图儿童医院、北卡罗来纳大学教堂山分校和密歇根大学 阿拉巴马州的伯明翰。这项研究将在24个月内进行3次考察访问。我们将获得数量和 口腔疾病风险因素的定性数据；对龋齿和牙周炎进行标准化评估； 评估呼吸道健康结果；并收集痰、唾液和菌斑进行微生物组分析。这个 目的是：(1)描述青少年和青少年口腔疾病的患病率和发病率 并找出相应的危险因素，重点是如何改善关键口腔 健康行为；(2)评估口腔疾病和健康行为之间的横向和纵向关联 呼吸结果；以及(3)探索连接口腔和呼吸健康的微生物组途径。这个 拟议的研究将是迄今为止规模最大、第一个纵向的CF口腔健康研究，也是第一个评估的研究 慢性阻塞性肺疾病患者与口腔疾病相关的呼吸结局。我们的长期目标是发展行为 青少年和青壮年CF预防和保护口腔疾病的随机临床试验 呼吸健康。我们还试图阐明解释系统性健康后果的机制。 口腔疾病。更广泛地说，我们的方法为改善口腔健康提供了一个框架 通过关键的流行病学调查和循证干预，使人口受到危害。

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.