Occupational exposure, inflammatory processes and chemosensation

职业暴露、炎症过程和化疗敏感性

• 批准号: 6819583
• 负责人: PAMELA HELEN DALTON
• 金额: $ 30.2万
• 依托单位: MONELL CHEMICAL SENSES CENTER
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-15 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6819583
• 关键词: chemical hypersensitivity; chemosensitizing agent; clinical research; computational neuroscience; environmental exposure; histology; human subject; immunocytochemistry; inflammation; irritation /irritant; mass spectrometry; mathematical model; mucus; occupational disease /disorder; occupational hazard; occupational health /safety; olfactory disorder; olfactory nerve; olfactory stimulus; pathologic process; patient oriented research; respiratory airflow measurement; respiratory epithelium; rhinitis; sensory mechanism; sinusitis; taste disorders

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、摄入变质食物和接触化学毒素的敏感性，还会导致营养问题，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）每天都有接触化学物质或颗粒的职业，其中多达40%的人报告有慢性鼻炎或鼻炎的症状，这些症状是嗅觉丧失的先兆。尽管如此，嗅觉功能的评估