Objective evaluation of conductive olfactory losses & nasal obstruction symptoms

描述（由申请人提供）：鼻窦疾病是美国最常见的疾病之一，估计影响13%的成年人，或约3000万人，每年造成58亿美元的医疗保健费用（2009年国家健康访谈调查，CDC）。鼻塞和嗅觉丧失是该疾病的两个主要症状;然而，该领域目前缺乏对引起这些症状的机制的明确，客观的理解，这阻碍了有效的治疗。例如，患者对鼻塞的抱怨与实际物理阻塞的客观测量结果相关性差或不一致。人们普遍认为嗅觉丧失部分是由气流阻塞引起的;然而，没有工具能够量化或预测这种传导机制。在没有经过验证的临床工具的情况下，目前对这些症状的评估和治疗主要依赖于患者的主观反馈和医生的个人培训和经验。我们建议客观地评估鼻阻塞症状下的传导成分，基于两个假设：（a）鼻阻塞的感知（缺乏通畅性）可能不是由阻塞本身引起的，而是由缺乏鼻冷却引起的，并且这种感觉可能由于鼻气道中的三叉神经反馈不足而恶化，以及（B）专门流向嗅觉区域的空气/气味剂流量不足会导致传导性嗅觉损失。为了验证这些假设并寻求临床工具，我们将研究几种类型的慢性鼻塞或嗅觉丧失患者：鼻甲肥大，鼻中隔偏曲，特发性鼻塞和鼻息肉。在目标1中，我们将使用基于容易获得的办公室CT扫描的个性化CFD模型来捕获由于气道异常导致的粘膜冷却不足，并确定这是否单独或与传统的鼻内窥镜测量组合预测患者在治疗/手术后的几个时间点的鼻塞投诉。将使用鼻扩张器和减充血剂暂时扰乱患者的鼻气道，以测试我们的方法是否可以预测感知症状的变化。在目标2中，我们将广泛评估具有鼻塞症状的患者的三叉神经冷敏感性，并确定异常三叉神经冷敏感性（包括TRPM 8通路）是否有助于症状。TRPM 8是冷传入通路的主要组成部分，也被化学激活，这提供了一个独特的双重解释工具，并可能扩大我们对鼻腔炎症性疾病中化学感觉功能的理解。两个目标的变量将结合起来，形成鼻塞症状的最终评价工具。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/手术进展，并确定CFD预测的气流和嗅觉区域的气味吸附率是否与嗅觉丧失和恢复相关。 本研究的结果可以验证如何将联合收割机组合成有效的临床工具，以评估导致患者传导症状的因果因素，以潜在地识别最影响症状的部位，并帮助患者和临床医生规划有效的、消息灵通的、个性化的治疗/手术策略，每年可能节省数百万美元的医疗保健费用，同时提高患者满意度。

DESCRIPTION (provided by applicant): 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 healthcare costs 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 has been widely believed to be induced in part by airflow blockage; however, no tool has been able to quantify or predict such conductive mechanism. Without validated clinically tools, current evaluation and treatment on these symptoms rely primarily on the patient's subjective feedback and the doctor's personal training and experience. We propose to objectively evaluate the conductive components underling nasal obstructive symptoms, based on two hypotheses (a) that perception of nasal obstruction (lack of patency) may be caused not by obstruction per se but by lack of nasal cooling, and that such perception can be worsened by inadequate trigeminal feedback in the nasal airways, and (b) that insufficient air/odorant flow specifically to the olfactory region causes conductive olfactory losses. To test these hypotheses and pursue a clinical tool, we will study several types of patients with chronic complaints of nasal obstruction or smell loss: turbinate hypertrophy, septal deviation, idiopathic nasal obstruction, and nasal polyps. In Aim 1, we will use individualized CFD models based on easily obtained office CT scans to capture the insufficient mucosal cooling due to airway abnormalities and determine if this alone or in combination with conventional rhinometric measurements predicts patient complaints of nasal obstruction at several time points post treatment/surgery. A nasal dilator and decongestant will be used to temporarily perturb patients' nasal airways, to 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. Variables from both aims will be combined to form the final evaluation tool for nasal obstruction symptom. In Aim 3, we will specifically target nasal polyp patients with olfactory losses, track their treatment/surgery progress, and determine if the CFD-predicted airflow and odorant sorption rate to the olfactory region correlate with olfactory losses and recovery. The outcomes from this research may validate how to combine one or several measurements into an effective clinical tool to evaluate the causal factors leading to a patient's conductive symptoms, to potentially identify the site that most affects the symptom, and to assist patients and clinicians n planning effective, well-informed, personalized treatment/surgery strategies, potentially saving millions of healthcare dollars annually while improving patient satisfaction.