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1. Determinants of Medical and Surgical Treatment Outcomes in Chronic Sinusitis

This is an NIH funded multi-institutional outcomes based investigation. The purpose of this study is to find out what effects medical or surgical treatment have on disease-specific quality of life and to look at which factors (microscopic and macroscopic) predict improvement of patient disease and well-being. Dr. Alt is also interested in examining the relationship between the immune system’s inflammatory markers and chronic sinusitis-specific disease severity; thereby, further elucidating how microscopic aspects of disease relate to macroscopic clinical measures. This is being accomplished by harvesting serum and surgical tissue during endoscopic sinus surgery. He is building a comprehensive tissue repository that can be examined for specific immune markers.

2. Chronic Rhinosinusitis and Sleep Dysfunction

This is funded through the joint support of the American Rhinologic Society and the American Academy of Otolaryngologic Allergy. The purpose of this study is to assess both the impact that chronic rhinosinusitis has on sleep dysfunction and how we can improve sleep through treatment. This will be assessed using both objective (WatchPat) and subjective (validated sleep questionnaires) measures.

3. Assessment of Pain in Chronic Rhinosinusitis

Relationship between Pain, Sleep, and Quality of Life: Facial pain is a common complaint in patients with chronic rhinosinusitis (CRS) and may be enhanced, in part, due to an overall poor well-being. The purpose of this study is to determine how pain relates to CRS-disease specific severity and quality of life in this patient population.

4. Genetic Associations in Chronic Rhinosinusitis

The goal of this project is to establish a saliva repository with the purpose of providing a platform for possible, future genetic analysis and future pilot projects for grant funding mechanisms focused on original genetic research for chronic rhinosinusitis (CRS).

5. Genetic and Familial Risk of Chronic Rhinosinusitis with and without Nasal Polyposis

Dr. Alt is using data from the Utah Population Database (UPDB) to determine the familial patterns of chronic rhinosinusitis (CRS) with nasal polyposis (CRSwNP) and without nasal polyps (CRSsNP) in relatives of patients diagnosed with CRS. He hypothesizes that relatives of patients with CRS have an increased incidence of CRS compared to the Utah population.

6. Peri-Operative Measures in Patients with Obstructive Sleep Apnea (OSA) Undergoing Sinonasal Surgery

The goal of this study is to better understand peri-operative measures in patients with obstructive sleep apnea (OSA) undergoing sinonasal surgery. Specifically, this study examines oxygen saturation levels and the need for supplemental oxygen during the first night following surgery, as well as the tolerance of continuous positive airway pressure (CPAP) therapy in the weeks following surgery.

7. Basic Science

Chronic rhinosinusitis (CRS) is a common and debilitating health condition afflicting 11.1 million Americans, which corresponds to a prevalence of 4.9%. This condition results in 18.3 million office visits and a direct annual cost of $8.6 billion with staggering effects on societal burden with 11.5 million missed workdays. Despite the prevalence of CRS, an effective treatment that eliminates chronic inflammation has been elusive. Due to the chronicity of the disease, and the relatively poor response to initial medical therapies, more than 500,000 sinus surgeries are performed annually, to address this inflammation. The unrealized costs secondary to disease severity metrics such as missed workdays and sleep dysfunction have not been measured, although are undoubtedly substantial. The impact of our research is therefore far reaching: 1) providing a non-surgical option, 2) reducing health care costs, and 3) providing a self-administered therapy.

7a. Animal Models: Animal models have enhanced our insight into the pathophysiology of many human diseases. They are also indispensable in testing new therapeutic options. One of the remaining barriers to understanding sinus inflammation and treatment strategies is an acceptable non-infectious and non-allergenic animal model that accurately mimics chronic sinonasal inflammation. We are developing a mouse model of sinonasal inflammation that is more physiologically accurate. The model builds upon prior investigations that have demonstrated that elevated levels of innate peptides are associated with profound inflammation in the sinuses. We are also actively exploring the role inflammation plays in olfactory loss.

7b. Therapeutics: The semi-synthetic glycosaminoglycan ethers (SAGEs) are inflammation-modulating sulfated polysaccharides derived from hyaluronic acid (HA). We have previously shown that SAGEs are anti-inflammatory by inhibiting RAGE (receptor for advanced glycation end-products) and its activating ligands. SAGE may also play a role in controlling inflammation in chronic rhinosinusitis as it demonstrates excellent tissue protection. We are actively investigating the possibility of using SAGE in animal and human clinical trials.

Jeremiah Alt, MD, PhD

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