Occupational exposure, inflammatory processes and chemosensation

职业暴露、炎症过程和化疗敏感性

• 批准号: 7644890
• 负责人: PAMELA HELEN DALTON
• 金额: $ 33.8万
• 依托单位: MONELL CHEMICAL SENSES CENTER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7644890
• 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

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.

嗅觉功能障碍增加了对火灾、摄入变质食物和接触化学毒素的危险的易感性，并且它可以导致营养问题并降低生活质量。这些风险在工作场所更加突出。然而，超过10%的美国劳动力（约1400万人）每天职业性暴露于化学品或颗粒物，并且这些个体中多达40%报告慢性鼻炎症或鼻炎的症状，这些症状是嗅觉丧失的已知前兆。尽管如此，嗅觉功能的评估， 易感职业队列很少进行，因此，对人类化学品诱导的嗅觉功能障碍的患病率和潜在机制知之甚少。由于继发于化学品暴露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）、粘膜纤毛运输的变化和炎症介质对嗅觉神经上皮的直接影响，该建议采取多管齐下的方法，为具有前瞻性和持续性化学暴露的个体提供化学感觉功能、鼻腔炎症过程和气流模式的全面、纵向临床评价。利用在当前资助期内开发的技术和我们在个性化患者模型中数值模拟嗅觉运输和沉积能力的进步，我们建议研究暴露于假定嗅觉毒物的三个队列。我们将在暴露前、暴露期间和暴露后的多个时间点评估化学感觉功能（目标1），并开发 暴露个体鼻子中发生的物理和生物化学炎症变化（目标2）。除了临床队列，我们将开发一个基于工作类型的嗅觉功能的数据库，通过筛选被转介到宾夕法尼亚大学职业医学诊所的化学品暴露个体。在目标3中，我们将使用我们的计算模型来评估鼻腔气流中的炎症变化的影响，这些炎症变化是化学暴露和鼻窦疾病继发嗅觉障碍的原因（在2008年）。 项目1）。这些研究结果将为预测和减轻职业性化学暴露对化学感觉功能的影响提供重要的资源。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，对他们来说，化学品暴露似乎会增加与年龄相关的感觉下降的严重程度。通过对广泛的相关特征进行评估，结果还将支持对可能减轻或加剧炎症过程的功能性化学感受影响的风险因素的合理预测，这些炎症过程在各种慢性健康和暴露条件下的一般人群中普遍存在。