Occupational exposure, inflammatory processes and chemosensation

嗅觉障碍会增加人们对火灾、摄入变质食物和接触化学毒素的危险的易感性，并可能导致营养问题和生活质量下降。这些风险在工作场所会加剧。然而，超过10%的美国劳动力(约1400万人)每天都有职业接触化学品或颗粒物，其中多达40%的人报告了慢性鼻炎或鼻炎的症状，这些症状是嗅觉丧失的已知先兆。尽管如此，对患者嗅觉功能的评价 易感的职业队列很少进行，因此，人们对化学诱导的人类嗅觉功能障碍的流行率和潜在机制知之甚少。由于化学暴露继发嗅觉障碍的机制可能是多因素的，包括解剖学变化(如充血、息肉)、粘液纤毛运输的变化以及炎性介质对嗅神经上皮的直接影响，因此该建议采取多管齐下的方法，对预期和持续化学暴露个体的化学感觉功能、鼻部炎症过程和气流模式进行全面、纵向的临床评估。利用当前资助期开发的技术和我们在个体化患者模型中对嗅觉传输和沉积进行数值模拟的能力的进步，我们建议研究三个暴露于假定的嗅觉毒物的队列。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 暴露个人鼻子中发生的物理和生化炎症变化(目标2)。除了临床队列，我们还将开发一个基于工作类型的嗅觉功能数据库，方法是对被转介到宾夕法尼亚大学职业医学诊所的接触过化学物质的个人进行筛查。在目标3中，我们将使用我们的计算模型来评估鼻流中炎性变化的影响，这些变化是化学物质暴露和鼻窦疾病(In)引起的继发性嗅觉甩动的原因。 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做法提供参考，对他们来说，接触化学物质似乎会增加与年龄相关的感觉衰退的严重程度。通过对广泛的相关特征的评估，结果还将支持对可能缓解或加剧炎症过程的功能性化学感觉影响的风险因素的合理预测，炎症过程在各种慢性健康和暴露条件下的普通人群中普遍存在。

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.