Occupational exposure, inflammatory processes and chemosensation

职业暴露、炎症过程和化疗敏感性

基本信息

批准号：
7455184
负责人：
PAMELA HELEN DALTON
金额：
$ 31.54万
依托单位：
MONELL CHEMICAL SENSES CENTER
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-07-01 至 2009-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7455184
关键词：
3-Dimensional Acoustic Rhinometry Acute Adverse effects Age Ammonia Animals Anterior Area Biochemical Biochemical Markers Biological Markers Biopsy Blood flow Case Study Cell physiology Cells Cereals Characteristics Chemical Agents Chemical Exposure Chemicals Chlorine Chronic Clinic Clinical Clinical Research Compost Computer Simulation Computer software Condition Congestive Corrosives Daily Data Databases Deposition Development Disease Dose Dust Elderly Elevation Environment Epithelial Epithelium Esthesia Etiology Evaluation Exhibits Exposure to Fire - disasters Food Formaldehyde Functional disorder Funding General Population Goals Health Human Image Impairment Individual Inferior nasal concha Inflammation Inflammatory Ingestion Inhalation Exposure Irritants Lead Lesion Liquid substance Literature Location Measures Mediating Mediator of activation protein Methacrylates Minerals Modeling Mucociliary Clearance Mucous Membrane Mucous body substance Nasal Lavage Fluid Nasal cavity Nature Nose Nutritional Occupational Occupational Exposure Occupational Medicine Occupations Olfactory Epithelium Operative Surgical Procedures Outcome Participant Particulate Patients Pattern Pennsylvania Perception Physicians Policies Predisposition Prevalence Process Quality of life Range Rate Recording of previous events Recovery Recruitment Activity Reporting Research Personnel Resources Rhinitis Rhinomanometry Risk Risk Factors Rodent Saccharin Sampling Screening procedure Secondary to Sensory Severities Simulate Sinus Solvents Source Swelling Symptoms Techniques Testing Time Tissues Toxic effect Toxicology Toxin Universities Viscosity Wood material Work Workplace X-Ray Computed Tomography age related base clinically significant cohort cytokine dalton density experience hazard neuroepithelium olfactory disorder olfactory receptor polyposis pressure programs prospective receptor research clinical testing response rhinosinusitis toxicant uptake vapor young adult

项目摘要

Olfactory dysfunction increases susceptibility to the hazards of fire, ingestion of spoiled food and exposure to chemical toxins, and it can lead to nutritional problems and reduce the quality of life. These risks are heightened in the workplace. Yet, more than 10% of the U.S. workforce approximately 14 million people) has daily occupational exposure to chemicals or particulates and as many as 40% of these individuals report symptoms of chronic nasal inflammation or rhinitis that are known precursors of olfactory loss. Despite this, the evaluation of olfactory function in susceptible occupational cohorts is rarely performed and consequently, little is known about the prevalence of and mechanisms underlying chemical-induced olfactory dysfunction in humans. Because the mechanisms of olfactory dysfunction secondary to chemical exposure are likely to be multi-factorial, including anatomical changes (e.g., congestion, polyposis), changes in mucociliary transport and direct effects of inflammatory mediators on the olfactory neuroepithelium, this proposal takes a multi-pronged approach to provide a comprehensive, longitudinal clinical evaluation of the chemosensory function, nasal inflammatory processes and airflow patterns among individuals with prospective and ongoing chemical exposures. Using techniques developed in the current funding period and advances in our ability to numerically model olfactory transport and deposition in individualized patient models, we propose to study three cohorts with exposure to putative olfactory toxicants. We will evaluate chemosensory function at multiple timepoints before, during and after exposure (Aim 1) and develop profiles of the physical and biochemical inflammatory changes that occur in the noses of exposed individuals (Aim 2). In addition to the clinical cohorts, we will develop a database of olfactory function based on job type by screening individuals with chemical exposures who are referred to the University of Pennsylvania Occupational Medicine Clinic. In Aim 3, we will use our computational model to evaluate the impact of inflammatory changes in nasal airflow which are responsible for olfactory toss secondary to chemical exposures and nasal-sinus disease (in Project 1). Results of these studies will provide an important resource for predicting and mitigating the effects from occupational chemical exposure on chemosensory function. These findings will inform policies and practices to protect the sensory function and health of both young adults and the elderly, for whom chemical exposure appears to increase the severity of age-related sensory declines. Through evaluation of a wide range of relevant characteristics, the outcome will also support reasoned predictions about risk factors that may mitigate or exacerbate the functional chemosensory impact of inflammatory processes, which are prevalent in the general population from a variety of chronic health and exposure conditions.

嗅觉功能障碍会增加对火灾危害，摄入宠坏食物和暴露于化学毒素的敏感性，并且可能导致营养问题并降低生活质量。这些风险在工作场所增加。然而，超过10％的美国劳动力大约有1400万人）每天接触化学物质或颗粒物，其中多达40％的人报告了慢性鼻部炎症或鼻炎的症状，这些症状是嗅觉损失的已知前体。尽管如此，对嗅觉功能的评估易感职业队列很少进行，因此，关于人类化学引起的嗅觉功能障碍的流行率和机制知之甚少。因为继发于化学暴露于化学的嗅觉功能障碍的机制可能是多因素的，包括解剖学变化（例如，充血，息肉病），粘膜循环的变化，炎症介体对嗅觉神经上皮的直接影响，对嗅觉性神经上皮的方法进行了多种量化的态度，该方法对本质上的范围进行了多种功能，该方法是全面的。有前瞻性和持续化学暴露的个体的鼻炎症过程和气流模式。利用当前资金期间开发的技术以及我们在个性化患者模型中对嗅觉运输和沉积进行数字化运输和沉积的能力的进步，我们建议研究三个同类群体，暴露于推定的嗅觉上。我们将在暴露之前，之中和之后在多个时间点上评估化学感应函数（AIM 1），并发展暴露个体的鼻子发生的物理和生化炎症变化（AIM 2）。除临床队列外，我们还将通过筛查被转诊至宾夕法尼亚大学职业医学诊所的化学暴露个人来开发基于工作类型的嗅觉功能数据库。在AIM 3中，我们将使用我们的计算模型来评估鼻气流中炎症变化的影响，这些变化是导致嗅觉折腾继发于化学暴露和鼻音疾病的（在项目1）。这些研究的结果将为预测和减轻职业化学暴露对化学水敏功能的影响提供重要资源。这些发现将为保护年轻人和老年人的感觉功能和健康的政策和实践提供信息，对于他们来说，化学暴露似乎会增加与年龄相关的感觉下降的严重程度。通过评估广泛的相关特征，该结果还将支持有关危险因素的合理预测，这些预测可能会减轻或加剧炎症过程的功能化学感应影响，而炎症过程的功能性化学感应影响，这些影响在普通人群中因各种慢性健康和暴露条件而普遍存在。