Immunological Factors and Risk of Vulvodynia

免疫因素和外阴痛的风险

• 批准号: 7730036
• 负责人: BERNARD L HARLOW
• 金额: $ 96.65万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7730036
• 关键词: Address; Affect; Age; Ants; Area; Awareness; Biological; Biological Markers; Biological Markers; Blood specimen; Boston; C-reactive protein; Case-Control Studies; Censuses; Characteristics; Childhood; Chronic; Clinic; Clinical; Communities; Community Health; Critical Pathways; DSM-IV; Data; Data Collection; Development; Diagnosis; Digit structure; Directories; Education; Emotional; Environmental Exposure; Epidemiology; Etiology; Event; Frequencies; General Population; Genes; Genetic; Genetic Polymorphism; Genitourinary system; Goals; Gynecologic; Health; Hispanics; Hygiene; IL8 gene; Immunologic Factors; Infection; Infertility; Inflammation; Inflammation Mediators; Inflammatory; Inflammatory Response; Interleukin-1; Interleukin-6; Interview; Interviewer; Learning; Measures; Medical; Methods; Modeling; Morbidity - disease rate; Motor Vehicles; Nerve Fibers; Nerve Growth Factors; Neurogenic Inflammation; Neuropeptides; Pain; Pathway interactions; Patient Self-Report; Pattern; Population; Pregnancy; Prevalence; Prevention strategy; Process; Proteins; Public Health; Published Directory; Questionnaires; Race; Recording of previous events; Reporting; Research; Research Personnel; Risk; Risk Factors; Sampling; Scientist; Screening procedure; Self-Administered; Structure; Substance P; Symptoms; Syndrome; Techniques; Telephone; Testing; Trauma; Uninsured; Vagina; Validity and Reliability; Victimization; Vulvodynia; Woman; administrative database; aged; bactericide; base; care seeking; case control; cytokine; experience; improved; inflammatory marker; interest; men; metropolitan; nervous system disorder; novel; peripheral blood; population based; psychologic; reproductive; response; toll-like receptor 4; vulvar pain

Vulvodynia (VVD) is debilitating chronic vulvar pain that occurs in the absence of visible findings or clinically identifiable neurological disease. Between 2000 and 2005, we estimated the prevalence ofvulvodynia and examined factors associated with its largely unknown etiology (NIH-ROI-HD38428). We learned that nearly 16% of reproductive aged women self-report current or past history of vulvar pain lasting >3 months (an estimated 14 million U.S. women annually), less than 50% seek treatment, few receive an adequate diagnosis, and Hispanic women are more likely to report vulvar pain. Regarding etiology, we learned that women with VVD compared to controls have a) higher levels of neurogenic inflammation markers, b) more psychological trauma and psychiatric morbidity antecedent to vulvar pain symptoms, c) a more prevalent history of environmental exposures that act on immuno-inflammatory response (IIR), and d) significant abnormalities in the characteristics of their vaginal microflora. Furthermore, recent studies have suggested that women with VVD may have an alteration in genes that regulate cytokine expression. Collectively, these findings suggest that VVD is the result oran altered IIR mechanism that occurs as a consequence orreproductive, gynecologic, environmental, or psychological exposures, with abnormal vaginal microflora and genetic polymorphisms as potential modifiers o[the effects o{interest. To test this etiological hypothesis we propose to screen a multiracial sample of approximately 24,000 women from the administrative databases of 4 community health clinics that closely resembles the surrounding general population. Through screening procedures, we expect to identify 325 women with VVD who mayor may not have been previously diagnosed. After clinicalconfirmation, these cases will be frequency-matched to 325 randomly-sampled controls. Data collection and analyses will determine I) whether reproductive, gynecological and environmental exposures influence the odds ofVVD, 2) whether psychological trauma and psychiatric morbidity influence the odds ofVVD, and 3) whether markers of immuno-inflammation and nerve fiber proliferation are directly associated with the odds ofVVD, and the extent to which genetic and microbiological markers modify associations in I and 2 above. A recent congressional report has cited the need for new educational initiatives to create more awareness of VVD, but the repolt also indicates that the ability to implement improved treatment and prevention strategies hinges on our understanding ofVVD etiology. Our proposed study is unique in that it uses an epidemiological approach with adequate statistical power to confirm specific antecedent risk factors among a diverse sample of women at risk ofVVD (who mayor may not have sought care for their condition), while also measuring biological markers and related psychological processes that inform the plausibility of potential etiological pathways. We have also built into our study sophisticated analytical techniques to address the extent to which biases inherent in observational case-control studies could potentially influence our associations. Three important enhanced research goals have been added to be accomplished during the first 2 years of this study. We will determine I) whether demographic characteristics of women identified through community clinic-based administrative databases are comparable to that of census data drawn from the general population surrounding the community clinic, 2) whether the prevalence of vulvar pain symptoms in a sample of women derived from community clinic-based administrative databases that includes insured and uninsured subjects is comparable to that of similarly aged women sampled through a true population-based assessment done in the Boston Metropolitan Area, and 3) what factors contribute toward women choosing to or not choosing to palticipate in studies that involved stigmatizing conditions such as vulvodynia. These enhanced research aims have enormous impact on all scientists involved in population-based studies that previously used approaches such as random digit dialing and motor vehicle registration directories that are now no long viable for identifying population-based subjects. It will also help determine what factors contribute toward successful recruitment of subjects for important studies of stigmatizing conditions which can be extremely prevalent among women.

外阴痛 (VVD) 是一种使人衰弱的慢性外阴疼痛，在没有明显发现或临床可识别的神经系统疾病的情况下发生。 2000 年至 2005 年间，我们估计了外阴痛的患病率，并检查了与其很大程度上未知的病因相关的因素 (NIH-ROI-HD38428)。我们了解到，近 16% 的育龄女性自我报告当前或既往有持续超过 3 个月的外阴疼痛史（估计每年有 1400 万美国女性），不到 50% 的人寻求治疗，很少有人得到充分的诊断，而西班牙裔女性更有可能报告外阴疼痛。关于病因学，我们了解到，与对照组相比，患有 VVD 的女性 a) 神经源性炎症标志物水平更高，b) 外阴疼痛症状之前有更多的心理创伤和精神发病率，c) 更普遍的环境暴露史，这些环境暴露史会影响免疫系统。炎症反应 (IIR)，以及 d) 阴道微生物群特征显着异常。此外，最近的研究表明，患有 VVD 的女性可能存在调节细胞因子表达的基因发生改变。总的来说，这些研究结果表明，VVD 是由于生殖、妇科、环境或心理暴露而发生的 IIR 机制改变的结果，异常的阴道微生物群和遗传多态性是潜在的影响因素。为了检验这一病因学假设，我们建议从 4 个社区卫生诊所的管理数据库中筛选大约 24,000 名女性的多种族样本，这些样本与周围的一般人群非常相似。通过筛查程序，我们预计会识别出 325 名患有 VVD 的女性，她们之前可能没有被诊断过。临床确认后，这些病例将与 325 个随机抽样的对照进行频率匹配。数据收集和分析将确定：1）生殖、妇科和环境暴露是否影响 VVD 的发生率；2）心理创伤和精神疾病发病率是否影响 VVD 的发生率；3）免疫炎症和神经纤维增殖的标志物是否与 VVD 直接相关。 VVD 的几率，以及遗传和微生物标记改变上述 I 和 2 中关联的程度。最近的一份国会报告指出，需要采取新的教育举措来提高人们对 VVD 的认识，但该报告还表明，实施改进的治疗和预防策略的能力取决于我们对 VVD 病因的理解。我们提出的研究的独特之处在于，它使用具有足够统计能力的流行病学方法来确认处于 VVD 风险的不同女性样本（她们可能或可能没有寻求治疗）的特定先行风险因素，同时还测量生物标志物和相关的心理过程，告知潜在病因途径的合理性。我们还在我们的研究中融入了复杂的分析技术，以解决观察性病例对照研究中固有的偏差可能影响我们的关联的程度。在本研究的头两年内增加了三个重要的增强研究目标。我们将确定：1）通过基于社区诊所的管理数据库确定的女性人口特征是否与从社区诊所周围的一般人群中提取的人口普查数据具有可比性，2）女性样本中外阴疼痛症状的患病率是否得出来自基于社区诊所的行政数据库（包括参保和未参保受试者）的数据与通过在波士顿大都市区进行的真实人口评估中抽样的类似年龄女性的数据相当，以及 3) 哪些因素导致女性选择或不选择参与涉及外阴痛等污名化病症的研究。这些增强的研究目标对所有参与基于人群的研究的科学家产生了巨大影响，这些科学家以前使用随机数字拨号和机动车辆登记目录等方法，但现在这些方法不再适用于识别基于人群的受试者。它还将有助于确定哪些因素有助于成功招募受试者进行重要研究，这种情况在女性中极为普遍。