Topical Irrigation Therapy for CRS

Overall Objectives:

To evaluate the physiological differences between quinine-saline irrigations vs.
saline-placebo irrigations for acute exacerbation of uncomplicated chronic rhinosinusitis
following endoscopic sinus surgery. A secondary objective is to determine if the use of
quinine is efficacious as an alternative therapy to treat bacterial rhinosinusitis.

Background:

Sinusitis is a common disorder accounting for an estimated 13 million physician office visits
in the United States each year. The aggregated cost of sinusitis is approximately $8 billion
annually, affecting an estimated 16% of the population in the United States. Despite multiple
attempted treatments, including an estimated 550,000 surgeries per year, the disease
continues to be a major health problem, both in expenditures and poor quality of life. Recent
analysis of data from the National Ambulatory Medical Care Survey and the National Hospital
Ambulatory Medical Care Survey from 2006 to 2010 showed that rhinosinusitis accounted for
more outpatient antibiotic prescriptions in adults than any other diagnosis.

Chronic rhinosinusitis (CRS) represents a considerable subset of this population and accounts
for a significant portion of expenditures and the vast majority of surgeries. It is defined
as signs and symptoms of sinusitis lasting more than 12 weeks. Unlike the organisms
responsible for acute rhinosinusitis, difficult to treat bacteria such as Pseudomonas
aeruginosa, Staphylococcus aureus and Stenotrophomonas multiformia are often offending
pathogens in CRS. Their prevalence increases in those patients who have already had sinus
surgery and continue to get recurring sinus infections. Staph aureus and gram-negative
organisms have been shown to account for roughly 60% of infections in those patients who have
previously undergone endoscopic sinus surgery. Due to increasing drug resistance as well as
the potential for biofilm formation, there has been an increasing pressure from both patients
and clinicians alike to develop alternative treatments to systemic antibiotics. One commonly
used alternative in patients who have had previous sinus surgery is topical saline irrigation
with and without other topical preparations. Topical irrigations have much greater paranasal
sinus penetration in post surgical patients. Commonly used topical preparations include:
saline alone or saline mixed with mupirocin, gentamicin, tobramycin, ceftazadine, betadine,
manuka honey, baby shampoo, budesonide or mometasone.

The investigators have recently identified a novel arm of upper airway innate immunity
mediated by bitter taste receptors. When a subset of airway bitter taste receptors are
activated they stimulate the respiratory epithelium to generate nitric oxide, an important
component of sinus innate immunity that increases mucociliary clearance as well as diffuses
into the mucus where it is bactericidal. A topical therapy to activate these taste receptors
may help the sinuses clear infections through this natural innate defense mechanism. While
the investigators have identified multiple bitter compounds that stimulate this response,
quinine piqued our interest as it activates multiple bitter taste receptors and has already
been used in the human nose.

Inclusion Criteria:

1. Patients who have undergone Functional Endoscopic Sinus Surgery (FESS)

2. Purulent drainage on nasal endoscopy

3. Male or female subjects, 18 years of age or older

4. Patients seen at the Dept. of Otorhinolaryngology clinic at Hospital of the University
of Pennsylvania (HUP), a tertiary care clinic

Exclusion Criteria:

1. Pregnant women

2. Immunocompromised patients

3. Granulomatous diseases with rhinologic manifestations (Wegner's, Sarcoid,
Churg-Strauss)

4. Primary ciliary dyskinesia