Improving Topical Drug Delivery for Treatment of Chronic Rhinosinusitis

 描述：慢性鼻窦炎(CRS)每年影响1100多万美国人，每年造成86亿美元的损失。CRS可以用外用药物和口服抗生素治疗，但药物治疗无效导致美国每年有25.7万例手术。虽然手术改变了解剖结构，但它没有解决导致这种疾病的炎症介质。因此，手术前后都需要口服抗生素和抗炎药物，但由于成本和全身副作用，长期使用可能不可行。局部用药可能会将高浓度的这些药物输送到鼻黏膜，同时将全身副作用降至最低。然而，即使在手术后，这些强效药物往往也无法帮助患者，可能部分原因是向受影响地区的药物输送不足。此外，在CRS人群中还没有研究患者使用局部药物的说明，尽管这种药物经常被开给这一人群。拟议研究的长期目标是通过优化医疗治疗从根本上改善CRS的治疗，特别是最大限度地增加受CRS影响的鼻腔区域的局部药物输送。通过改进和优化CRS的医疗治疗，潜在地可以实现对社会和患者的下游好处-例如，改进鼻窦手术患者选择标准，降低医疗相关成本，降低与鼻窦手术相关的发病率，最终提高患者的幸福感和满意度。在这个项目中，我们将重点改善鼻喷剂的使用，鼻喷剂是CRS最常用的局部用药。在一项前瞻性的临床研究中，我们将把计算流体动力学(CFD)建模与鼻腔复制品和CRS患者的实验相结合，以量化CRS患者在功能性内窥镜鼻窦手术(FESS)前后鼻腔目标部位的气溶胶颗粒输送。FESS是CRS最常见的外科治疗方法。我们的中心假设是：(1)存在头部位置、喷嘴位置和呼吸技术的组合，可以增加FESS前后的靶部位颗粒沉积(TSPD)(“最佳使用条件”)，而不是根据医生针对这些因素(“当前使用条件”)的医生建议(“当前使用条件”)获得的FESS，以及(2)与当前使用条件下的TSPD相比，CFD衍生的最佳使用条件将增加鼻复制品和CRS患者的TSPD。这项拟议的研究预计将制定说明和规范，以改进鼻腔喷雾剂和雾化器的使用，使目标位置的颗粒沉积最大化。这些信息将有助于改善CRS的医疗管理，潜在地为患有这种流行疾病的患者带来更好的结果。此外，这项研究将为随后的随机对照临床试验奠定基础，该试验将测量CRS患者在最大限度地给予雾化局部药物后的临床结果。

 DESCRIPTION: Chronic rhinosinusitis (CRS) affects over 11 million Americans each year at an annual cost of $8.6 billion. CRS is treated with topical medications and oral antibiotics, but faild response to medical therapy results in 257,000 surgeries annually in the U.S. While surgery alters anatomy, it does not address the inflammatory mediators contributing to this disease. Oral antibiotic and anti-inflammatory medicines are, therefore, needed before and after surgery, but long-term use may not be feasible due to cost and systemic side-effects. Topical medications potentially deliver high concentrations of these drugs to nasal mucosa while minimizing systemic side-effects. However, these potent drugs often fail to help patients even after surgery, possibly due in part to insufficient drug delivery to affected areas. Furthermore, patient instructions for using topical drugs have not been studied in a CRS population, even though this medication is frequently prescribed for this population. The long-term objective of the proposed research is to fundamentally improve CRS treatment by optimizing medical treatment, specifically, maximizing topical drug delivery in areas of the sinonasal cavity affected by CRS. By improving and optimizing medical treatment of CRS, downstream benefits to society and patients can potentially be realized - e.g. refined criteria for patient selection for sinus surger, decreased healthcare related costs, and decreased morbidities related to sinus surgery, and ultimately increased patient well-being and satisfaction. In this project, we will focus on improving the use of nasal sprays, the topical medication most frequently prescribed for CRS. We will combine computational fluid dynamics (CFD) modeling with experiments in nasal replicas and in CRS patients in a prospective clinical study to quantify aerosol particle delivery to target sites in the sinonasal cavities of CRS patients before and after functional endoscopic sinus surgery (FESS), the most frequent surgical treatment for CRS. Our central hypotheses are that (1) there are combinations of head positions, nozzle positions, and breathing techniques that increase target-site particle deposition (TSPD) ("optimal use conditions") before and after FESS over TSPD obtained using physician recommendations for these factors ("current use conditions"), and (2) CFD-derived optimal use conditions will increase TSPD in nasal replicas and in CRS patients compared to TSPD under current use conditions. The proposed research is expected to develop instructions and specifications for improved use of nasal sprays and nebulizers that maximize target-site particle deposition. This information will help improve medical management of CRS, potentially leading to better outcomes for patients who suffer from this prevalent disease. In addition, this research will be the basis for a subsequent randomized, controlled, clinical trial that will measure clinical outcomes in CRS patients after maximal delivery of aerosolized topical medications.