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.

Public Health Relevance

Chronic rhinosinusitis (CRS) is the most prevalent chronic condition in the U.S., affecting over 11 million Americans resulting in 257,000 surgeries annually. Nasal sprays are routinely used to administer topical medication to patients with CRS but are not always effective. The extent to which this failure is due to suboptimal drug delivery t affected areas is unknown, even though this information is critical to maximizing benefits from these medications while reducing the need for systemic drugs and additional surgery. Furthermore, patient instructions for using nasal sprays have not been studied in a CRS population, even though this medication is frequently prescribed for these patients. The proposed project will use three- dimensional computer modeling and experimental studies in nasal replicas and in CRS patients to maximize the deposition of nasal spray particles in areas of the nasal passages affected by CRS, before and after surgery to treat CRS symptoms. The results are expected to aid development of new instructions for use and specifications of nasal sprays 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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL122154-04
Application #
9462213
Study Section
Gene and Drug Delivery Systems Study Section (GDD)
Program Officer
Gan, Weiniu
Project Start
2015-04-01
Project End
2019-03-31
Budget Start
2018-04-01
Budget End
2019-03-31
Support Year
4
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Keeler, Jarrod A; Patki, Aniruddha; Woodard, Charles R et al. (2016) A Computational Study of Nasal Spray Deposition Pattern in Four Ethnic Groups. J Aerosol Med Pulm Drug Deliv 29:153-66