Saliva and Serum Inflammatory Biomarkers in Periodontitis: A Study in Older Women

描述（由申请人提供）：本申请涉及广泛的挑战领域（03）生物标志物的发现和验证，以及特定的挑战主题，03- de -101：与口腔或颅面疾病相关的生物标志物的开发，改进或验证。本研究的目的是测量唾液和血清中的一系列炎症生物标志物，以检查非侵入性唾液生物标志物在多大程度上可以用于表征血清中测量的相同生物标志物。我们建议评估唾液和血清样本中的炎症生物标志物，这些样本来自两项联邦资助和已完成的骨质疏松症和牙周病相关性研究（DOD #OS950077; R01DE013505）中先前收集和冷冻的样本。唾液和血液样本在基线时（DOD研究）使用标准化协议收集、处理和存储，并在相同的参与者中再次收集，预计大约5年后（R01）。参与者是绝经后的妇女从布法罗大学临床中心的NIH妇女健康倡议观察性研究中招募到这两个辅助研究。这些储存的样本是一种独特的资源，将用于测量一组炎症生物标志物，因为它们在口腔和全身健康中具有潜在的重要性。储存的样本在两个时间点（基线和5年后）在诊所就诊时收集。研究人员在同一天收集了这些参与者的唾液和血清，并立即进行了冷冻储存。在这些访问中，根据标准化方案进行口腔检查，以评估口腔和牙周健康指标（CAL、ACH、出血、牙菌斑、牙石、牙齿脱落、DMFT、口腔骨密度）。评估骨密度（DXA）、身体成分和其他物理指标。收集了参与者的人口统计、个人习惯、生活方式因素、社会心理因素、饮食摄入、身体活动、药物/补充剂使用、职业、家族史、健康习惯和病史等方面的信息。本研究的主要目的是测量存储唾液样本中的炎症生物标志物，并确定这些生物标志物的唾液水平在多大程度上能够表征存储血清样本中测量的相同生物标志物（N=920）。我们还建议确定这些生物标志物的水平及其相互关系随时间变化的程度（在基线和5年后收集，N=400）。此外，我们将确定丹参和血清中的基线标志物在多大程度上能够表征基线时流行的牙周病，并预测新牙周病的发病率和现有牙周病的进展（N=920）。由于几个原因，这些数据非常重要和重要。首先，如果我们能够利用唾液表征这些生物标志物的血清水平，这将提供一种评估老年妇女全身性炎症的新颖且无创的方法，这可能有许多应用。其次，这里收集的信息将使我们能够开发预测模型，用于牙周病的发生和现有疾病的进展。第三，尽管本研究的重点是利用生物标志物来表征牙周病，但唾液中测量的唾液生物标志物可以更广泛地用于其他被认为与炎症相关的慢性疾病。例如，在这个队列中，我们将能够探索预测骨密度和骨质疏松症的唾液生物标志物，这在这个队列中是很有特点的。我们可能能够探索其他慢性疾病的关系，这些疾病也被评估为WHI常规结果收集的一部分。最后，由于该队列具有许多变量的特征，因此根据年龄、BMI、身体组成、饮食、吸烟、牙龈下细菌的存在等因素可以很容易地探索效果的改变。利用这些生物标志物数据获得临床和科学理解的机会是巨大的，应该会产生重大影响。目前，在大量具有良好特征的前瞻性女性队列中，描述唾液和血清中炎症生物标志物特征的已发表数据非常有限，其中基线和纵向生物样本以及口腔和整体健康的详细表型信息都是可用的。这项提议的研究将大大增加这方面的文献。重要的是，这项研究与2009-2013年NIDCR战略计划非常一致，包括“整合分子、临床和人口健康，以改善诊断和优化结果”，并强调需要从“系统角度”“了解健康和疾病”，“需要将这些进步与最先进的临床和流行病学方法相结合……”。这项拟议的研究将以一种经济有效的方式，利用生物样本和从先前联邦政府支持的研究中收集的其他数据，扩大我们对唾液炎症非侵入性评估效用的科学理解。最终，这些信息可以用来告知我们炎症作为牙周和其他慢性疾病发生和发展的一种机制的作用。研究相关性：本研究的目的是测量920名绝经后妇女现有唾液和血清样本中的炎症生物标志物，以检查非侵入性唾液炎症生物标志物在多大程度上可以用于表征血清中测量的相同生物标志物，然后确定它们与流行和发生的牙周病的关联。这项拟议的研究将以一种经济有效的方式，利用生物样本和从以前的研究中收集的其他数据，扩大我们对唾液炎症非侵入性评估效用的科学理解。最终，这些信息可以用来告知我们炎症作为牙周和其他慢性疾病发生和发展的一种机制的作用。

DESCRIPTION (provided by applicant): This application addresses broad Challenge Area (03) Biomarker Discovery and Validation, and specific Challenge Topic, 03-DE-101: Development, Refinement, or Validation of Biomarkers Relevant to Oral or Craniofacial Disorders. The goal of this proposed study is to measure a series of inflammatory biomarkers in saliva and serum to examine to what extent non-invasive salivary biomarkers can be used to characterize those same biomarkers measured in serum. We propose to assess inflammatory biomarkers in saliva and serum samples that are available from previously collected and frozen samples from two funded and completed federally supported studies investigating the association of osteoporosis and periodontal disease (DOD #OS950077; R01DE013505). Samples of saliva and blood were collected, processed and stored using standardized protocols at baseline (DOD study) and again in the same participants prospectively approximately 5 years later (R01). Participants were postmenopausal women recruited into these 2 ancillary studies from the University at Buffalo clinical center of the NIH Women's Health Initiative Observational Study. These stored samples are a unique resource that will be used to measure a panel of inflammatory biomarkers selected for their potential importance in both oral and systemic health. The stored samples were collected at two time points (baseline and 5 years later) at clinic visits. Both saliva and serum blood were collected from these participants on the same day and immediately processed for frozen storage. At these same visits, oral examinations were conducted according to standardized protocols to assess indices of oral and periodontal health (CAL, ACH, bleeding, plaque, calculus, tooth loss, DMFT, oral bone density). Assessments of bone density (DXA), body composition and other physical measures were obtained. Information was collected on participant demographics, personal habits, lifestyle factors, psychosocial factors, dietary intake, physical activity, medication/supplement use, occupation, family history, health practices and medical history. The primary aim of this proposed study is to measure a panel of biomarkers of inflammation in stored saliva samples and determine to what extent salivary levels of these biomarkers are able to characterize these same biomarkers measured in samples of stored serum (N=920). We also propose to determine to what extent the levels of these biomarkers and their relationship to each other change over time (collected at baseline and 5 years later, N=400). In addition, we will determine to what extent baseline markers in salvia and in serum are able to characterize prevalent periodontal disease at baseline, and predict incidence of new and progression of existing periodontal disease (N=920). These data are critically important and significant for several reasons. First, if we are able to characterize serum levels of these biomarkers using saliva, this would provide a novel and non-invasive method of assessing systemic inflammation in older women, which could have many applications. Second, the information collected here will allow us to develop prediction models for incident periodontal disease and also for progression of existing disease. Third, although the focus of this proposed study is to utilize the biomarkers to characterizing periodontal disease, the salivary biomarkers measured in saliva could be used more generally in other chronic diseases thought to be associated with inflammation. For example, in this cohort we would be able to explore salivary biomarkers in the prediction of bone density and osteoporosis which is well characterized in this cohort. We may be able to explore the relation in other chronic diseases that are also assessed as part of routine outcomes collection in WHI. Last, since the cohort is well- characterized according to many variables, effect modification according to factors such as age, BMI, body composition, diet, smoking, presence of subgingival bacteria, and others could easily be explored. The opportunity to use these biomarker data to gain clinical and scientific understanding is enormous and should have substantial impact. There is currently very limited published data available characterizing inflammatory biomarkers in saliva and serum in large well characterized prospective cohorts of women, where both baseline and longitudinal biologic samples are available along with detailed phenotypic information on oral and overall health. This proposed study will add substantially to that body of literature. Importantly, this study aligns well with the 2009-2013 NIDCR Strategic Plan including "integration of molecular, clinical and population health to improve diagnostics and optimize outcomes" and the emphasis on the need to "understand health and disease" from a "systems perspective" that "will require melding these advances with state-of-the-science clinical and epidemiological approaches...". The proposed study will, in a cost efficient way, utilize biologic samples and other data collected from previous federally supported research to expand our scientific understanding of the utility of non- invasive assessments of inflammation in saliva. Ultimately, this information can be used to inform our understanding of the role of inflammation as one mechanism by which periodontal and other chronic diseases occur and progress. Study Relevance: The aim of this study is to measure a panel of inflammatory biomarkers in existing samples of saliva and serum collected from 920 well-characterized postmenopausal women to examine to what extent non-invasive salivary inflammatory biomarkers can be used to characterize those same biomarkers measured in serum, and then determine their association with prevalent and incident periodontal disease. The proposed study will, in a cost efficient way, utilize biologic samples and other data collected from previous research to expand our scientific understanding of the utility of non-invasive assessments of inflammation in saliva. Ultimately, this information can be used to inform our understanding of the role of inflammation as one mechanism by which periodontal and other chronic diseases occur and progress.