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

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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.