Objective evaluation of conductive olfactory losses & nasal obstruction symptoms

项目摘要 鼻窦疾病是美国最常见的医疗条件之一， 估计有13%的成年人，或超过2900万人。鼻塞和嗅觉丧失是 疾病的两个主要症状;然而，该领域目前缺乏明确的，客观的 了解导致这些症状的机制，这限制了有效的疾病 管理例如，患者对鼻塞的抱怨与患者的症状之间的相关性很差， 与实际物理障碍的客观测量不一致。嗅觉丧失 被广泛认为是由气流阻塞引起的;然而，没有工具能够 来量化或预测这种机制。 我们建议开发和验证一种新的客观诊断工具， 症状，基于两个假设（a）认为鼻塞（缺乏通畅性）是 由于物理鼻部状况和/或不充分的感觉导致的鼻冷却不足， 反馈，以及（B）空气/气味剂流具体到嗅觉器官传导不足 区域有助于嗅觉损失。为了验证这些假设并寻求临床工具，我们 将进行研究，并集中在三个目标。在目标1中，我们将使用个性化计算 基于患者CT扫描的流体动力学（CFD）鼻模型，以评估粘膜不足 由于现有的气道异常导致的冷却，并确定这是否与患者 症状评级。我们将用鼻扩张器进一步暂时干扰患者的鼻气道 和减充血剂，并测试我们的方法是否可以预测感知症状的变化。在 目的2，我们将广泛评估三叉神经冷敏感性的症状， 鼻塞，并确定是否异常三叉神经冷敏感（包括 TRPM 8途径）有助于症状。TRPM 8是冷传入神经的主要成分 也被化学激活的途径，这提供了一个独特的双重解释工具， 潜在地拓宽了我们对鼻腔炎症中化学感受功能的理解， 疾病在目标3中，我们将专门针对嗅觉丧失的鼻息肉患者，跟踪 他们的治疗进展，并确定如果CFD预测的空气传输和气味吸附 嗅觉区的速度与嗅觉功能的丧失和恢复相关。 本研究的结果可以验证如何将一种或几种联合收割机 测量成为一个有效的临床工具，以区分因果因素，导致 患者的传导症状，以潜在地识别最影响症状的部位， 并指导今后的有效治疗或手术。

Project Summary Nasal sinus disease is one of the most common medical conditions in the US, affecting an estimated 13% of adults, or more than 29 million people. 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 limits effective disease management. For example, patients' complaints of nasal obstruction correlate poorly or inconsistently with objective measurements of actual physical obstruction. Olfactory loss has been widely believed to be induced in part by airflow blockage; however, no tool has been able to quantify or predict such a mechanism. We propose to develop and validate a novel objective diagnostic tool for nasal obstructive symptoms, based on two hypotheses (a) that perception of nasal obstruction (lack of patency) is due to lack of nasal cooling caused by physical nasal conditions, and/or inadequate sensory feedback, and (b) that insufficient conduction of air/odorant flow specifically to the olfactory region contributes to olfactory losses. To test these hypotheses and pursue a clinical tool, we will conduct a study and focus on three aims. In Aim 1, we will use individualized computational fluid dynamics (CFD) nasal models based on patient CT scans to assess insufficient mucosal cooling due to existing airway abnormalities, and determine if this correlates with patient symptom ratings. We will further perturb patients' nasal airway temporarily with a nasal dilator and decongestant and test whether our approach can predict perceptual symptom changes. In Aim 2, we will broadly assess the trigeminal cool sensitivity of patients with the symptom of nasal obstruction, and determine whether abnormal trigeminal cool sensitivity (including the TRPM8 pathway) contributes to symptoms. TRPM8 is a major component of the cool afferent pathway that is also activated chemically, which offers a unique dual investigatory tool and potentially broadens our understanding of chemosensory functions in nasal inflammatory disease. In Aim 3, we will specifically target nasal polyp patients with olfactory losses, track their treatment progress, and determine if the CFD-predicted air transport and odorant sorption rate to the olfactory region correlate with olfactory function losses and recovery. The outcomes from this research may validate how to combine one or several measurements into an effective clinical tool to differentiate the causal factors leading to a patient's conductive symptoms, to potentially identify the site that most affects the symptom, and to guide move effective treatment or surgery in the future.