F. Hampel1, P. Ratner2, J. Diaz3, H. Sacks4; 1Central Texas Health Re- search, New Braunfels, TX, 2Sylvana Research Associates, San Antonio,. TX, 3Allergy ...
Abstracts S155
J ALLERGY CLIN IMMUNOL VOLUME 123, NUMBER 2
Polymorphisms in the MET/HGF Gene Complex are Associated with Severe Chronic Rhinosinusitis R. Castano1, L. M. Endam1, A. Mouhim1, Y. Bosse2, M. Desrosiers1; 1 Hotel-Dieu de Montreal, Montreal, QC, Canada, 2Centre de Recherche, Hoˆpital Laval, Quebec, QC, Canada. RATIONALE: Genome-wide transcriptional profiling of nasal polyps obtained from individuals with chronic rhinosinusitis (CRS) has identified an overexpresssion of the met proto-oncogene (MET) receptor gene. The MET receptor belongs to the tyrosine kinase family of oncogenes and binds its ligand, hepatocyte growth factor (HGF) protein. The MET/HGF signalling complex is involved in various cellular responses including proliferative, morphogenic and angiogenic activities. The goal of the current study was to determine whether polymorphisms in the MET and HGF genes were associated with CRS. METHODS: The genes encoding the MET/HGF complex were analyzed in a case-control association study including 206 adult patients with surgery-unresponsive CRS and 196 postal-code matched controls. Genotyping was performed on a set of 34 and 3 tagging single nucleotide polymorphisms (SNPs) for MET and HGF genes, respectively. RESULTS: Statistically significant allelic associations with CRS were noted for 5 SNPs in the MET gene (rs33850, p 5 0.004; rs17526983, p 5 0.01; rs33857, p 5 0.03; rs722134, p 5 0.03 and rs1621, p 5 0.05) and for 2 SNPs in the HGF gene (rs10273273, p 5 0.04; rs6956973, p 5 0.05). CONCLUSIONS: Polymorphisms in the MET and HGF genes are associated with CRS. This finding, combined with the available functional studies demonstrating an overexpression of the MET gene in nasal polyps of patients with CRS, support the implication of these genes in the pathogenesis of sinus disease.
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Experimentally Induced Allergic Rhinitis Induces Anxietylike Behavior and Altered Social Interaction in Rodents L. Tonelli, M. Katz, C. Kovacsis, T. Gould, T. Postolache; University of Maryland, Baltimore, Baltimore, MD. RATIONALE: Epidemiological and clinical human studies report higher incidence of anxiety and increased emotional reactivity in individuals suffering from respiratory allergies however, it is not known if this association is causative or secondary to other behavioral traits associated with allergies. METHODS: To evaluate if respiratory allergies are capable of promoting anxiety-like behavior in rodents, allergic rhinitis to ovoalbumin (OVA) or pollen was induced in mice and rats respectively following standard sensitization and challenge protocols. After challenge, the animals were evaluated in the open field, elevated plus maze and resident intruder tests. Cytokines and corticotropin releasing factor expression were assessed by real-time RT-PCR in different brain regions. Plasma corticostereone concentrations were determined by radioimmunoassay. RESULTS: Mice and rats sensitized and exposed to their respective antigen showed increased anxiety-like behavior as measured by the elevated plus maze and open field test without any overt behavioral signs of sickness. Moreover, they showed reduced social interaction in the resident intruder test. T-helper 2 (TH2) cytokines were induced in both rats and mice in the olfactory bulbs and prefrontal cortex. CRF was increased in the prefrontal cortex but remained unchanged in the temporal cortex and hypothalamus. No differences were observed in corticosterone concentrations. CONCLUSIONS: These results show that inflammatory processes of allergic rhinitis induce anxiety across rodent species and with two different antigens tested. These effects were paralleled by the expression of TH2 cytokines and CRF in the olfactory bulbs and prefrontal cortex without affecting HPA-axis responses. Funding: Supported by grants R21MH075905, R21MH075891 and R01MH074891.
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Efficacy and Safety of Azelastine Hydrocloride and Fluticasone Propionate Combined in a Single Nasal Spray Delivery Device in Patients with Seasonal Allergic Rhinitis F. Hampel1, P. Ratner2, J. Diaz3, H. Sacks4; 1Central Texas Health Research, New Braunfels, TX, 2Sylvana Research Associates, San Antonio, TX, 3Allergy and Asthma Research Center, P.A., San Antonio, TX, 4Meda Pharmaceuticals, Somerset, NJ. RATIONALE: A proof of concept study in patients with SAR indicated that combination therapy with commercially available azelastine nasal spray and commercially available fluticasone nasal spray significantly improved nasal symptoms compared to either agent alone. As a result, the current study was conducted with the combination of azelastine and fluticasone administered in a single delivery device. METHODS: The study was a randomized, double-blind, placebo-controlled trial in patients with moderate-to-severe SAR conducted during the 2007/2008 Texas Mountain Cedar season. A total of 610 patients were randomized to treatment with: (1) azelastine (Astelin) nasal spray, (2) fluticasone (Flonase) nasal spray, (3) combination azelastine/fluticasone (MP 29-02) nasal spray, or (4) placebo nasal spray. All treatments were given 1 spray per nostril twice daily. The primary efficacy variable was the change from baseline in the 12-hour reflective total nasal symptom score (TNSS), consisting of nasal congestion, sneezing, itchy nose, and runny nose. RESULTS: All three active groups were statistically superior (P < .05) to placebo, and the combination was statistically superior (P < .001) to either agent alone. The TNSS improved 31.3% with combination azelastine/fluticasone, 20.8% with fluticasone, 16.3% with azelastine, and 9.0% with placebo. Dysgeusia (7.2%), epistaxis (3.9%), and headache (2.6%) were the only adverse events reported by more than 2% of patients treated with combination therapy. CONCLUSIONS: Therapy with azelastine nasal spray and fluticasone nasal spray in combination provided significant clinical benefit compared to either agent alone. Providing the two drugs in a single delivery device should benefit patients who require combination therapy to effectively manage their allergic rhinitis.
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Sublingual Immunotherapy (SLIT) for House Dust Mites (HDM) in respiratory allergy: update of metanalysis results G. W. Canonica1, G. Passalacqua1, E. Villa1, C. E. Baena-Cagnani2, E. Compalati1; 1Allergy & Respiratory Diseases DIMI, Genoa University, Genova, Italy, 2Catholic University of Cordoba, Cordoba, Argentina. RATIONALE: Recent meta-analyses documented the efficacy and safety of SLIT in allergic rhinitis (AR) and asthma (AA). SLIT was found to be globally effective although sub-analyses for single allergens provided uncertain results mainly for the low number of patients included. Our aim is to investigate the efficacy of SLIT with HDM extracts in both AR and AA by updating the results of previous metanalyses. METHODS: Main databases were searched up to March 31th, 2008, for randomized double blind placebo controlled trials (DBPCRT), assessing the efficacy of SLIT in AR and AA sustained by HDM sensitization, not included in previous metanalyses. The new data available were integrated with the results of existing metanalyses. RevMan 4.2.8 program was used. RESULTS: For AR, 1 new study fulfilled the selection criteria; a significant reduction in symptoms of AR (p 5 0.04) was found in 273 patients (adults and children),140 receiving SLIT and 133 placebo. Similar results was found for asthma symptoms (p 5 0.02) in 476 patients (adults and children), 214 patients receiving SLIT, 209 placebo. Reduction in rescue medication use resulted for both AR (p 5 0.04) in 175 patients and AA (p 5 0.02) in 397 patients. A relevant heterogeneity due to widely differing scoring systems was detected. CONCLUSIONS: These data confirm the efficacy of SLIT with HDM extract in allergic patients suffering from AR and AA compared to placebo, but the small population explored suggests that further data, coming from homogeneous and standardized trials, are relevant for better understanding this issue.
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