1013 Montelukast Augments Bacterial Sinusitis in AllergicMice

R. M. Naclerio1, P. Khoury1, F. M. Baroody1, J. J. Klemens1, K. Thomp-

son2; 1Otolaryngology-Head and Neck Surgery, University of Chicago,

Chicago, IL, 2Pathology, University of Chicago, Chicago, IL.

RATIONALE: In mice, allergic rhinitis augments the response to Strep-tococcus (S.) pneumoniae-induced acute sinusitis. We investigated the

effects of cysteinyl leukotriene antagonism on the severity of bacterial

infection, the response to histamine challenge, and the inflammatory cell

infiltration.

METHODS: We performed 3 parallel, placebo-controlled experiments to

examine the effects of montelukast. First, mice were ovalbumin (OVA)-sen-

sitized and OVA-challenged to show the effects on allergic inflammation;

second, we evaluated the effect of S. pneumoniae infection; third, we used

mice that were both allergic and infected. Treatment was given starting

two days after sensitization until the day prior to euthanasia. Three days

after the second intraperitoneal injection, the mice were inoculated

intranasally with S. pneumoniae in the infected groups and with PBS in

the non-infected groups. Nasal hypersensitivity was measured with hista-

mine challenges prior to the first sensitization and on the day prior to

euthanasia. Mice were euthanized on the fifth day after infection: nasal

lavage was performed for bacterial culture, and inflammatory cells in the

sinuses were quantified.

RESULTS: Compared to placebo, infected only mice treated with mon-

telukast tended to have increased bacterial counts from nasal lavage.

Allergic and infected mice had significantly higher bacterial counts and

reduced responsiveness to histamine after montelukast (p<0.05). All three

montelukast treated groups had significantly decreased eosinophil and

T-lymphocyte counts.

CONCLUSIONS: Montelukast reduces the manifestations of allergic

rhinitis in mice. Surprisingly, montelukast led to an increase in bacterial

growth in infected mice. This suggests an effect of the cysteinyl

leukotrienes on the innate response to bacterial infection.

Funding: Merck

1014 Drowsiness and Sedation: A Comparison Between Levoce-tirizine and Desloratadine Using Post-Marketing Observa-tional Data.

D. Layton1,2, L. W. Wilton1,2, A. Boshier1,2, V. Cornelius1, S. Harris3, S.

A. W. Shakir1,2; 1Drug Safety Research Unit, Southampton, UNITED

KINGDOM, 2Faculty of Science, University of Portsmouth, Portsmouth,

UNITED KINGDOM, 3Public Health Sciences & Medical Statistics,

Southampton University Hospital Trust, Southampton, UNITED KING-

DOM.

RATIONALE: To investigate the frequency of drowsiness/sedation

reported for levocetirizine and desloratadine during their immediate

post-marketing periods in England, from Prescription-event Monitoring

studies.

METHODS: Exposure data were derived from dispensed prescriptions

written by primary care physicians for desloratadine (Mar-May 2001) and

levocetirizine (Nov 2001-Nov 2002). Outcome data were derived from

questionnaires posted to prescribers at least 6 months after the date of the

first prescription for each patient. The crude OR (95% CI) was calculated

for incident reports of drowsiness/sedation for levocetirizine vs deslorata-

dine (as reference cohort) during the first 30 days observation, using uni-

variate modelling. Age, sex, reported prescribing indication [Allergic

Rhinitis (AR) with/without asthma, Other] and pattern of use on the OR

was examined. A time-to-event analysis was performed.

RESULTS: Cohort demographics were similar [both cohorts: mean age

39 years (SD 0.2), 60% women]. The incidence of drowsiness/sedation

for desloratadine and levocetirizine was low [9 (0.1%), 46 (0.4%); 50%

occurring by 7 or 14 days observation, respectively]. Time-to-event esti-

mates differed (Log rank test, p<0.0001). Age and sex were not con-

founding variables, whilst pattern of use could not be examined. The

crude OR of drowsiness/sedation was 4.9 (95% CI 2.4,10.0 ; n=24195)

overall. The crude OR in patients with prescribing indication AR without

asthma was 6.7 (95%CI 2.4, 19.2; n=12844); other indication category

ORs were non-significant. Results were similar for drowsiness/sedation

combined with other selected CNS depressant events.

CONCLUSIONS: Our study suggests a 5-fold significant increase in the

odds of drowsiness/sedation for users of levocetirizine vs desloratadine in

the first month of observation.

Funding: Schering Plough

1015 Sinus and Mastoid Involvement in Cystic Fibrosis and theEfficacy of Surgical Intervention

A. A. Horwitz1, G. Graff1, R. Vender1, L. Sachs2, T. Craig1; 1Hershey

Medical Center, Hershey, PA, 2Harrisburg Hospital, Harrisburg, PA.

RATIONALE: Diffuse sinus involvement has been well documented in

Cystic Fibrosis (CF) and is often associated with hypoplasia of the frontal

sinuses. Our previous work had noted a lack of involvement of the mas-

toids. The intent of this study was to confirm the unique pattern of sinus

and mastoid involvement in CF and evaluate the effectiveness of sinus

surgery in CF patients.

METHODS: All sinus CT scans of patients with the diagnosis of CF

from 1993-2005 were reviewed. We assessed for medial deviation, mas-

toid involvement, frontal sinus hypoplasia, nasal polyps, the effects of

surgical intervention, and presence of the triad (medial deviation,

paranasal sinus opacification, and frontal sinus hypoplasia).

RESULTS: Lack of mastoid involvement was noted in 92%. The full

triad was present in 79%. Surgical intervention was evident in 50%; how-

ever, radiographic benefit of surgery was only noted in 11%.

CONCLUSIONS: It appears that the majority of CF patients have the

triad and mastoid sparing. The combination of diffuse sinus involvement,

frontal sinus hypoplasia, and sparing of the mastoids should raise suspi-

cion for CF. Surgical intervention does not appear to have radiographic

benefit in CF patients.

Funding: Hershey Medical Center

1016 Radiofrequency for the Treatment of Allergic RhinitisRefractory to Medical Therapy

D. Matesic1, J. B. Bitner2, R. O. Gustafson2, J. F. Pallanch2; 1Allergic

Diseases, Mayo Clinic and Foundation, Rochester, MN, 2Otolaryngology,

Mayo Clinic and Foundation, Rochester, MN.

RATIONALE: The optimal treatment for allergic rhinitis refractory to

medications is lacking. We propose radiofrequency tissue ablation as a

useful alternative to alleviate nasal obstruction in these patients.

METHODS: A prototype patient with chronic and poorly responsive

allergic rhinitis is presented. In an outpatient setting and under local anes-

thesia, radiofrequency was delivered via two punctures per turbinate.

Postsurgical changes in nasal symptoms were closely followed.

RESULTS: Nasal symptomatology was markedly reduced post radiofre-

quency application. No perioperative problems or later complications

were reported. The patient experienced a lasting benefit from this proce-

dure.

CONCLUSIONS: When conservative therapy has failed to relieve the

symptoms of allergic rhinitis, radiofrequency turbinate reduction should

be considered.

S262 Abstracts J ALLERGY CLIN IMMUNOL

FEBRUARY 2006

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