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，影响了大约13%的成年人，约3000万人，每年造成58亿美元的医疗费用（2009年美国国家健康访谈调查，CDC）。鼻塞和嗅觉丧失是本病的两个主要症状；然而，该领域目前缺乏对引起这些症状的机制的清晰、客观的认识，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相关性很差或不一致。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导电机制。由于缺乏有效的临床工具，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。基于两种假设，我们建议客观地评估鼻塞症状下的传导成分，(a)鼻塞的感觉（缺乏通畅）可能不是由阻塞本身引起的，而是由鼻冷却不足引起的，并且这种感觉可能因鼻气道三叉神经反馈不足而恶化，(b)专门流向嗅觉区域的空气/气味流量不足导致传导性嗅觉丧失。为了验证这些假设并寻求临床工具，我们将研究几种慢性鼻塞或嗅觉丧失的患者：鼻甲肥大、鼻中隔偏曲、特发性鼻塞和鼻息肉。在Aim 1中，我们将使用基于易于获得的办公室CT扫描的个体化CFD模型来捕捉由于气道异常导致的粘膜冷却不足，并确定单独或与常规鼻测量相结合是否可以预测患者在治疗/手术后几个时间点的鼻塞主诉。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Aim 2中，我们将广泛评估鼻塞症状患者的三叉神经冷敏感性，并确定三叉神经冷敏感性异常（包括TRPM8通路）是否与症状有关。TRPM8是冷传入通路的一个主要组成部分，它也被化学激活，这提供了一个独特的双重研究工具，并有可能拓宽我们对鼻炎性疾病化学感觉功能的理解。这两个目标的变量将结合起来，形成鼻塞症状的最终评估工具。在Aim 3中，我们将专门针对嗅觉丧失的鼻息肉患者，跟踪其治疗/手术进展，并确定cfd预测的气流和嗅觉区域的气味吸收率是否与嗅觉丧失和恢复相关。这项研究的结果可能会验证如何将一种或几种测量方法结合成一种有效的临床工具，以评估导致患者传导性症状的因果因素，潜在地确定对症状影响最大的部位，并帮助患者和临床医生制定有效的、信息充分的、个性化的治疗/手术策略，在提高患者满意度的同时，每年可能节省数百万美元的医疗保健费用。

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.