ORL的360研究计beplay苹果手机能用吗划将新的实验室发现转化为患者护理

自2008年抵达纪念馆赫尔曼 - 德克萨斯医学中心和麦戈文医学院以来，艾伯·卢恩（Amber Luong），医学博士，FACS博士，她的大部分注意力集中在构建一项翻译的耳鼻喉科研究计划上。beplay苹果手机能用吗如今，这些努力正在为慢性鼻孔炎（CRS）患者提供更好的结局，因为耳鼻喉科治疗和颈部手术的医生迅速将新型治疗方法从实验室转移到通过临床试验的直接患者护理。

“We don’t fully understand the disease process of chronic rhinosinusitis, a condition diagnosed in more than 30 million Americans annually,” says Dr. Luong, an associate professor and research director in the department of Otorhinolaryngology who also directs a laboratory at the Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases. “The disease accounts for about $6 billion annually in treatment costs, making it one of the most costly non-fatal diseases to manage. We have knowledge of some of the potential triggers for CRS – viruses, bacteria and fungal exposure – but we aren’t certain which of the triggers affects individual patients. Our research goal is to develop directed curative treatment options for CRS through a better understanding of the triggers and molecular mechanisms that are important in the disease process. Learning more about CRS will give us a better idea of how to treat the cause of the disorder rather than just the symptoms, which is the focus of most current treatment. We’re not stopping with basic science. We’re taking our laboratory discoveries all the way through to patient care.”

The department’s robust translational research program stems from Dr. Luong’s training in the National Institutes of Health-sponsored Medical Scientist Training Program at UT Southwestern Medical Center, where she received her MD/PhD Two Nobel laureates, Michael S. Brown, MD, and Joseph L. Goldstein, MD, served as mentors for her PhD work during the eight-year program.

“他们是榜样的伟大，”卢恩博士说。“这里有两名医生，他们从照顾个别患者到进行研究以获取新知识，以帮助数百名患者。beplay苹果手机能用吗我第一次理解了以独特的方式结合临床医学和基础科学研究的医学生涯的可能性。beplay苹果手机能用吗作为医生科学家，您可以在患者中表现出疾病过程，每个人都非常不同，并利用治疗患者的知识和经验来构建研究问题并解释实验室中的结果，反之亦然。beplay苹果手机能用吗我作为科学家获得的信息使我考虑了治疗或对人类疾病的理解的适用性。通过汇集这两个世界，转化医学诞生了。”

她希望与临床治疗融合基础科学的愿望导致了几项开创性研究的发表，重点是理解过敏真菌鼻炎的病理生理学，作为研究副窦免疫失调的模型。IL-33作为慢性鼻孔炎的途径；鼻内辣椒素作为诊断工具和非过敏性刺激性鼻炎的作用；真菌可以刺激慢性鼻孔炎的分子途径。麦戈文医学院和贝勒医学院的研究人员进行的一项研究beplay苹果手机能用吗首次证明了先天性淋巴样细胞在2型2型介导的炎症性疾病中的功能重要性（1）。

“该研究的目的是研究上皮细胞衍生的细胞因子白细胞介素-33（IL-33）和IL-33反应性的先天淋巴样细胞在慢性鼻鼻涕的病理生理学中的作用。”“从动物模型的先前研究中，我们知道IL-33在2型免疫反应的开发和调节中起着关键作用，这是由IL-33响应性的先天淋巴样细胞介导的，但直到现在，直接几乎没有直接这些细胞在人类2型介导的炎性疾病中的重要作用的证据。我们能够证明，与鼻息肉（一种2型2型介导的炎症过程）在慢性鼻鼻炎中患病的粘膜中先天淋巴样细胞的百分比显着升高，并且这些细胞代表了IL-13的一致且潜在的重要来源。到IL-33刺激。”

Luong博士的研究是识别IL-33途径很重要的人类疾病的少数研究之一。目前，她和该部门的其他讲道医生正在积极招募参与者，以进行随机，双盲，安慰剂对照的临床试验，研究了阻断IL-33分子的方法，以管理具有鼻息肉的CRS。

In the same study, the researchers also found that epithelial cells release IL-33 upon challenge with fungus. Later, Dr. Luong was a collaborator in a related study at Baylor College of Medicine, the results of which were published in Science in 2013 (2). Led by David Corry, MD, a professor in the departments of Pathology & Immunology and Medicine-Pulmonary and Critical Care at Baylor, the research team described how fungus signals through epithelial and immune cells to trigger a type 2 inflammatory response leading to airway hypersensitivity.

通过其蛋白酶活性，真菌裂解结合和激活类似收费的受体的纤维蛋白原释放降解产物4.研究人员发现，Toll样受体4不会直接激活T细胞，而是导致IL-13受体的表达，即beplay苹果手机能用吗引起哮喘的典型症状，并暗示真菌感染与哮喘之间存在联系。在与Corry博士的另一项合作研究中，Luong博士表明，在患病的鼻窦腔中，真菌负荷升高，但在未切除的腔体中也可以找到。然而，只有在患病鼻腔腔中特异性发现的真菌物种的免疫记忆在CRS患者而不是健康对照的患者中才明显，这与真菌在某些CRS患者的病理生理学中的积极作用联系起来（3）。今天，在纪念赫尔曼 - 特克萨斯医学中心正在进行的临床试验正在研究在典型的术后治疗中添加抗真菌剂，以治疗具有真菌敏感性的CRS患者。

她说：“因为我们的基础科学工作表明真菌刺激了慢性鼻鼻涕和哮喘中的免疫反应，所以对我们来说，抗真菌剂会通过消除推动免疫反应的东西来帮助我们。”“这是我们360方向的另一个例子，将基础科学迅速转化为患者护理。”

Luong博士和她的研究团队还正在研beplay苹果手机能用吗究使用鼻内辣椒素作为诊断工具的使用，并将其作为非过敏性刺激性鼻炎（NAIR）的治疗方法。NAIR患者患有鼻充血，鼻部刺激，鼻炎和打喷嚏的症状，以应对鼻刺激性。直到最近，医生还没有可靠的客观手段来诊断NAIR。这是排除的诊断。他们以辣椒素为鼻内挑战，将血流的变化与NAIR和健康对照受试者之间的光学隆旋法进行了比较。此外，研究表明，多次鼻内暴露于高剂量的辣椒素可以作为NAIR的治疗方法（4）。

“Study participants with NAIR showed a significant increase in blood flow relative to patients who don’t have this diagnosis,” she says. “Today, we’re continuing the development of this diagnostic tool and conducting a randomized blinded clinical trial in which we’re objectively identifying patients with NAIR and then randomizing patients to treatment with a high dose of capsaicin administered in five doses a day, each given one hour apart, or to placebo. We’re evaluating them at one month and three months to determine if the diagnostic response to capsaicin disappears, suggesting a positive treatment for NAIR.

“实验室这样的突破意味着开证imately we’ll be able to help many more patients,” she adds. “It’s very rewarding to successfully treat one patient, but it’s also great to be able to help many patients through research. Our translational research program is a grand project: we’re looking for a cure for chronic sinus disease. Our long-term goal is to put ourselves out of business.”

参考

1. Shaw JL, Fakhri S, Citardi MJ, Porter PC, Corry DB, Kheradmand F, Liu Y-J, Luong A.IL-33-responsive Innate Lymphoid Cells Are an Important Source of IL-13 in Chronic Rhinosinusitis with Nasal Polyps.American Journal of Respiratory and Critical Care Medicine. 2013 Aug 15:188(4):432-9.
2. Millien VO, Lu W, Shaw J, Xuan X, Mak G, Roberts L, Song L-Z, Knight JM, Creighton CJ, Luong A, Kheradmand F, Corry DB.蛋白酶对纤维蛋白原的切割通过Toll样受体4引起过敏反应。科学。2013年8月16日； 341（6147）：792-6。
3. Porter PC，Lim DJ，Maskatia ZK，Mak G，Tsai CL，Citardi MJ，Fakhri S，Shaw JL，Fothergil A，Kheradmand F，Corry DB，Luong A.Airway surface mycosis in chronic TH2-associated airway disease.Journal of Allergy and Clinical Immunology. 2014 Aug;134(2):325-31.
4. Lambert EM, Patel CB, Fakhri S, Citardi MJ, Luong A.Optical rhinometry in nonallergic irritant rhinitis: a capsaicin challenge study.International Forum of Allergy and Rhinology. 2013 Oct;3(10):795-800. [Epub 2013 Jun 3]

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