Novel mechanisms and therapeutic approaches for nasal obstruction and olfactory losses

鼻塞和嗅觉丧失的新机制和治疗方法

• 批准号: 10587159
• 负责人: KAI ZHAO
• 金额: $ 39.38万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-26 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10587159
• 关键词: Adult; Affect; Afferent Pathways; Air; Air Movements; Anosmia; Blinded; Breathing; Centers for Disease Control and Prevention (U.S.); Chemicals; Chronic; Client satisfaction; Clinical; Clip; Data; Devices; Disease; Disease Management; Enrollment; Environment; Etiology; Eye; Feedback; Functional disorder; Future; Goals; Health Expenditures; Healthcare; Hearing Aids; Hypertrophy; Impairment; Individual; Inferior nasal concha; Knowledge; Lead; Learning; Legal patent; Link; Liquid substance; Maps; Measurement; Medical; Methods; Modeling; Mucous Membrane; National Health Interview Survey; Nose; Obstruction; Odors; Olfactory Pathways; Operative Surgical Procedures; Outcome; Outcomes Research; Pathway interactions; Patients; Pattern; Perception; Peripheral; Persons; Publishing; Quality of life; Route; Savings; Sensory; Series; Sinus; Structure; Structure of mucous membrane of nose; Suicide attempt; Surgeon; Symptoms; Syndrome; Testing; Therapeutic; Training; Treatment outcome; Trigeminal System; airway obstruction; base; effective therapy; efficacy testing; experience; improved; invention; mechanical stimulus; nasal obstruction; notch protein; novel; novel therapeutics; patient population; patient subsets; personalized decision; personalized medicine; prevent; reduce symptoms; sensory feedback; sensory input; sensory stimulus; standard of care; surgery outcome; symptom treatment; tool; treatment strategy

Project Summary Nasal sinus disease is one of the most common medical conditions in the US, affecting an estimated 13% of adults, or some 30 million people, and responsible for $5.8 billion in health care expenditures annually (National Health Interview Survey 2009, CDC). Nasal obstruction and smell loss are two of the major symptoms of the disease; however, the field currently lacks a clear, objective understanding to the mechanisms causing these symptoms, which thwarts effective treatment. For example, patients’ complaints of nasal obstruction correlate poorly or inconsistently with objective measurements of actual physical obstruction. Olfactory loss is widely believed to be induced in part by airflow blockage that prevents sufficient ambient odor from reaching the olfactory region; however, no tool has been able to evaluate and target such conductive causes. Without validated clinically tools, current treatment of these symptoms relies primarily on the patient’s subjective feedback and the doctor’s personal training and experience, which can lead to inconsistent and unsatisfactory outcomes. Through a series of preliminary studies, we demonstrated that the symptom of nasal obstruction may be caused not by obstruction per se but by poor sensing of airflow during breathing, through the trigeminal cool-sensitive (TRPM8) pathway, and that such sensing may be worsened by impaired trigeminal function. However, which trigeminal sensory regions and what nasal airflow anomalies are most critical to disrupt the sensing of airflow are still unknown. To establish a more direct link, in Aim 1 of this proposal, we will examine the critical trigeminal sensory regions and critical nasal airflow distortions that may better predict airflow perception and obstruction symptoms. TRPM8 is a major component of the cool afferent pathway that is also activated chemically, which offers a unique dual investigatory tool to broaden our understanding of chemosensory function in nasal sinus disease and open up new therapeutic directions. So in Aim 2, we will investigate the efficacy of a novel patent-pending “nasal aid” to improve patients’ symptoms by modulating nasal airflow and trigeminal sensory feedback and to improve future treatment outcomes based on what we have learned and will continue to learn about the airflow trigeminal perception mechanisms. We have also shown in a series of published studies that complicated relationships exist between nasal obstruction and olfactory function. Based on these findings, in Aim 3 we propose to explore how to potentially improve olfactory function in patients with likely conductive olfactory loss, by enhancing nasal odor/air flow to the olfactory region (another pending US patent), analogous to hearing aids or eye glasses that amplify peripheral sensory stimuli. The outcomes from this research may potentially validate several novel clinical tools to better identify factors that most affect patients’ obstructive symptoms and to relieve symptoms by modulating nasal airflow patterns. The ultimate goal is to assist patients and clinicians in planning effective, well-informed, personalized treatment strategies, potentially saving millions of health care dollars annually while improving patient satisfaction.

项目概要 鼻窦疾病是美国最常见的疾病之一，影响着人们 据估计 13% 的成年人，即约 3000 万人，造成了 58 亿美元的健康损失 每年的护理支出（2009 年全国健康访谈调查，CDC）。鼻塞 和嗅觉丧失是该病的两个主要症状；但该领域目前缺乏 对引起这些症状的机制有一个清晰、客观的了解，这会阻碍 有效的治疗。例如，患者对鼻塞的抱怨相关性较差或 与实际物理障碍的客观测量不一致。嗅觉丧失是 人们普遍认为部分是由于气流阻塞阻止了足够的环境气味引起的 到达嗅觉区域；然而，没有工具能够评估和定位此类 传导原因。如果没有经过验证的临床工具，目前对这些症状的治疗依赖于 主要取决于患者的主观反馈以及医生的个人培训和经验， 这可能会导致不一致和不令人满意的结果。 通过一系列的初步研究，我们证明鼻炎症状 阻塞可能不是由阻塞本身引起的，而是由在运行过程中气流感应不良引起的。 呼吸，通过三叉神经冷敏感（TRPM8）通路，并且这种传感可能 因三叉神经功能受损而恶化。然而，哪些三叉神经感觉区域和 哪些鼻气流异常对于扰乱气流感知最关键仍然未知。 为了建立更直接的联系，在本提案的目标 1 中，我们将检查关键的三叉神经 感觉区域和关键的鼻气流扭曲可以更好地预测气流感知 和梗阻症状。 TRPM8 是冷传入通路的主要组成部分 也通过化学方式激活，这提供了一种独特的双重调查工具来扩大我们的研究范围 了解鼻窦疾病的化学感应功能并开辟新的治疗方法 方向。因此，在目标 2 中，我们将研究一种正在申请专利的新型“鼻腔辅助器”的功效 通过调节鼻气流和三叉神经感觉反馈来改善患者的症状 根据我们所学到的并将继续学习的知识来改善未来的治疗结果 关于气流三叉神经感知机制。 我们还在一系列已发表的研究中表明，存在复杂的关系 鼻塞和嗅觉功能之间的关系。基于这些发现，我们在目标 3 中提出 探索如何潜在地改善可能具有传导性的患者的嗅觉功能 嗅觉丧失，通过增强鼻腔气味/气流到嗅觉区域（另一个悬而未决的美国 专利），类似于放大外围感官刺激的助听器或眼镜。 这项研究的结果可能会验证几种新颖的临床工具 更好地识别最影响患者阻塞症状的因素并缓解症状 通过调节鼻气流模式。最终目标是帮助患者和临床医生 规划有效、消息灵通、个性化的治疗策略，可能节省数百万美元 每年节省医疗保健费用，同时提高患者满意度。