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INTRODUCTION
Xylitol is a five-carbon sugar alcohol that has
gained relative prominence in the past decade as a naturally occurring antibacterial agent. It is generally not
believed to possess its own antibacterial properties;
rather it appears to enhance the bodys own innate bactericidal mechanisms.1,2
Based on these findings, we sought to explore the
therapeutic potential of xylitol irrigations in treating
chronic rhinosinusitis, a condition that has been estimated to affect nearly 14% of the population, with
significant associated quality-of-life impairment.3,4 Saline irrigation, which has been shown to be beneficial for
patients with rhinosinusitis,5 served as an accepted
standard treatment for comparison. We conducted a prospective, randomized, crossover study to compare the
therapeutic value of saline versus xylitol irrigations in
patients with chronic rhinosinusitis.
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Patients
Eligible subjects were adults with chronic rhinosinusitis
who had undergone bilateral endoscopic sinus surgery to
include at a minimum maxillary antrostomy and anterior ethmoidectomy. Sinus patency was confirmed endoscopically to
ensure adequate exposure to the irrigation solutions. Subjects
were excluded if they had a history of immunocompromise,
cystic fibrosis (CF), primary ciliary dyskinesia, active smoking,
treatment with antifungal medications, an active bacterial
infection requiring antibiotics, history of head and neck irradiation, active pregnancy, or granulomatous disease. Subjects who
were taking other ancillary sinus medications, such as nasal
steroids and antihistamines, were eligible as long as they maintained regular use throughout the study period.
Materials
Xylitol. Pharmaceutical-grade xylitol (Acros Organics,
Fair Lawn, NJ) was premeasured and packaged in the hospital
pharmacy into unlabeled, sealed packets each containing 12 mg
of the sugar. Subjects were given 10 of these packets and
instructed to dissolve the contents of one packet in 240 mL of
water (5% wt/vol) in a sinus irrigation bottle, followed by bilateral sinus irrigation once daily. They were instructed to use one
packet daily for 10 days total.
Saline. Standard buffered isotonic individual-use salt
packets (NeilMed, Santa Rosa, CA) were repackaged into unlabeled, sealed packets to maintain blinding. Each subject was
given 10 of these packets as well and instructed to dissolve the
contents into sinus irrigation bottles with 240 mL of water,
with subsequent bilateral irrigation. One packet was to be used
daily for 10 days.
The unlabeled packets of the xylitol and saline were
placed respectively into two separate coded envelopes. Each
subject was instructed to begin the trial with 3 days of no irrigation to allow for an initial washout period from any prior
saline irrigation use. Then they were instructed to perform 10
days of once-daily irrigations with the first envelopes irrigants,
followed by another 3-day washout period, and ending with 10
days of once-daily irrigation with the other irrigant. The order
of irrigation was randomized using a random-number generator
in a double-blinded fashion. Each subject was also given a prepaid, addressed envelope in which to return their outcomes
surveys by mail at the conclusion of the study.
Outcomes Measures
Sino-Nasal Outcome Test 20. The Sino-Nasal Outcome
Test 20 (SNOT-20) was given to all subjects to be completed at
home on the first and final day of each irrigation course as the
primary outcome measure. The test has a maximum score of
100 points based on the responses to 20 items.
Visual Analog Scale. Also given to all subjects at enrollment for their self-completion on the first and final days of each
irrigation course, a single Visual Analog Scale (VAS) was collected as a secondary outcome survey. It was measured as a
mark made by the subject on a 100-mm line to represent their
overall sinonasal well-being, where the lowest extreme of the
line (0) indicates the worst possible feeling, and the highest
extreme end (10) represents best possible feeling. The mark
was made in response to the question of how you think your
nose/sinuses are feeling overall.
Statistical Analysis
SAS Enterprise Guide 4.2 (SAS, Cary, NC) was used for
data analysis. The differences between pre- and posttreatment
SNOT-20 and VAS scores were compared between the two treatments for all collected data, utilizing a mixed-effects model.
This method was also used to evaluate the effects of different
treatment orders.
RESULTS
During the recruitment period, 23 subjects were
screened and met criteria for inclusion in this study.
Three subjects who met the inclusion criteria declined
enrollment. Twenty subjects were recruited after providing their informed consent and signing appropriate
institutional review board documentation.
Although all subjects served as their own controls,
comparison of their demographics when grouped by
sequence of treatment (saline then xylitol vs xylitol then
saline) showed generally good matching. There were 10
subjects in each group. The average age was 44 years in
both groups. The male-to-female ratio of the saline then
xylitol group was 3:7; it was 7:3 in the other group. Nine
(90%) in each group used nasal steroids. Five (50%) of
Laryngoscope 121: November 2011
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DISCUSSION
Support for the therapeutic role of xylitol in chronic
rhinosinusitis comes from basic science research on the
airway surface liquid (ASL). The ASL, which coats the
apical surface of airway epithelia, is known to contain
multiple innate antimicrobial agents such as lactoferrin
and lysozyme, among others, which function to combat
the persistent influx of microbes on the surface of
the airway.1,6 Studies have shown that in respiratory
epithelium affected by inflammation, irritation, and CF,
the ASL chloride concentration is higher than normal.68
In laboratory settings, the antibacterial properties of
normal ASL diminish with increasing chloride
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CONCLUSION
Xylitol is a safe, natural five-carbon sugar that is
gaining interest in many fields for promising data showing efficacy against chronic bacterial infections. We have
shown that it is a well-tolerated sinonasal irrigant when
mixed with water in a 5% wt/vol formulation, with only
a few complaints regarding its inherently sweet taste
and one isolated report of transient stinging. In our
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Acknowledgment
The authors thank Dr. Jayakar Nayak for his critical
feedback on the project and Dr. Raymond Balise, Biostatistician of the Stanford Department of Health Research and
Policy for assistance with the statistical analysis. We are
also indebted to Dr. Martha Hamilton and the Stanford
Hospital Central Pharmacy staff for their accommodation
during the packaging of our supplies.
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