Treatment of RSV Bronchiolitis with NSAIDs

描述（由申请人提供）：呼吸道合胞病毒（RSV）是导致1岁以下儿童死亡的主要病毒，也是移植患者和老年人发病率和死亡率上升的原因。RSV引起上呼吸道和下呼吸道感染，偶尔导致严重的细支气管炎和肺炎。目前还没有针对呼吸道合胞病毒安全有效的疫苗。抗rsv免疫疗法虽然在预防方面是有效的，但在治疗方面并没有提供任何临床有益的结果，这表明rsv诱导的病理主要是对感染的炎症反应的结果，而不是直接的病毒作用。抗病毒和抗炎联合治疗可能是对抗RSV感染最安全有效的治疗方法。COX-2及其产物前列腺素和凝血烷的表达与许多炎症过程的发展有关。我们最近在棉花大鼠（先前RSV免疫预防研究选择的动物模型）中的研究有力地支持了我们的假设，即RSV感染期间诱导COX-2在RSV诱导的炎症和病理中起关键作用，相反，抑制COX-2活性是RSV诱导的毛细支气管炎的有益治疗。本应用程序旨在确定COX-2特异性非甾体抗炎药（NSAID）治疗rsv诱导的肺部病理的有效性和安全性。我们的假设是，抑制RSV感染期间产生的COX-2活性将在急性RSV疾病期间具有治疗益处，防止炎症和病理的发展。实验将集中在原发呼吸道合胞病毒疾病上，有两个目标。首先是确定在原发RSV感染的急性期，COX-2抑制本身是否可以作为一种有效和安全的治疗方案。第二个将是确定cox -2特异性抑制剂治疗是否可以与抗病毒治疗相辅相成，以改善RSV疾病的最终结局。这些研究将涉及rsv感染动物的治疗与肺部组织病理学和炎症的相关性。

DESCRIPTION (provided by applicant): Respiratory Syncytial virus (RSV) is the leading viral cause of death in children under 1 year and is an increasing cause of morbidity and mortality in transplant patients and the elderly. RSV causes upper and lower respiratory tract infections, occasionally leading to severe bronchiolitis and pneumonia. There is no safe and effective vaccine against RSV. Anti-RSV immunotherapy, although effective in prophylactic settings, does not provide any clinically beneficial outcome when applied therapeutically, indicating that RSV-induced pathology is mostly the result of the inflammatory response to infection rather than a direct viral effect. A combined antiviral and anti-inflammatory therapy might represent the most safe and efficient treatment against RSV infection. The expression of COX-2 and its products, prostaglandins and thromboxanes, has been correlated with the development of many inflammatory processes. Our recent studies in the cotton rat, the animal model of choice for previous studies of RSV immunoprophylaxis, strongly support our hypothesis that induction of COX-2 during RSV infection plays a pivotal role during RSV-induced inflammation and pathology and, conversely, that inhibition of COX-2 activity is a beneficial treatment for RSV-induced bronchiolitis. This application is designed to determine efficacy and safety profiles for COX-2 specific, non-steroidal anti-inflammatory drug (NSAID) treatment of RSV-induced lung pathology. Our hypothesis is that inhibition of COX-2 activity generated during RSV infection will be of therapeutic benefit during acute RSV disease, preventing the development of inflammation and pathology. The experiments will focus on primary RSV disease, with two goals in mind. The first will be to determine if COX-2 inhibition can by itself be an effective and safe treatment regimen during the acute phase of primary RSV infection. The second will be to determine whether treatment with COX-2-specific inhibitors can be complemented with antiviral therapy to improve the final outcome of RSV disease. These studies will involve correlating treatment of RSV-infected animals with pulmonary histopathology and inflammation.