Late-Breaking Abstracts 795J ALLERGY CLIN IMMUNOL

VOLUME 121, NUMBER 3

CONCLUSIONS: The majority of children with peanut allergy devel-oped sensitization to multiple tree nuts and sesame by 4 yrs of age, despiteadvice on stringent dietary avoidance.

LB18 The Association between Frequent Large Local Reac-tions and Systemic Reactions to Immunotherapy within aPractice Utilizing a No-dose Adjustment Protocol forLocal Reactions

M. S. Tankersley, C. W. Calabria; Wilford Hall Medical Center, SanAntonio, TX.RATIONALE: Prior studies have demonstrated local reactions do notpredict systemic reactions. However, a recent study demonstrated anincrease in large local reactions among systemic reactors in practicesusing routine local reaction dose adjustments. The present study investi-gates this association between large local and systemic reactions within apractice not dose adjusting for local reactions.METHODS: A retrospective analysis of an electronic immunotherapydatabase was performed over 12 months at a single site which did not doseadjust for large local reactions. A large local reaction was defined as � thesize of the patient’s palm. P values were calculated using the Fisher’sexact test.RESULTS: Three hundred sixty patients received a total of 9,678 injec-tions. For all injections, the large local reaction rate was 0.4% and thesystemic reaction rate was 0.5%. Among 46 systemic reactors (12.7% ofpatients), the large local reaction rate was 0.74% of injections, com-pared to 0.32% of injections among 314 non-systemic reactors(p=0.024). Similarly, among 24 patients experiencing 38 large localreactions (6.7% of patients), the systemic reaction rate was 1.22% ofinjections, compared to 0.45% of injections among 336 non-large localpatients (p=0.0046).CONCLUSIONS: Although large local reactions do not predict systemicreactions, patients with large local reactions experience a higher frequen-cy of systemic reactions during their immunotherapy course. Similarly,systemic reactors have a higher frequency of large local reactions duringtheir immunotherapy course. In light of a similar previous study, this asso-ciation occurs irrespective of whether a dose adjustment protocol is uti-lized for large local reactions.

LB16 Treatment of Acute Abdominal and Facial Attacks ofHereditary Angioedema (HAE) with Human C1 EsteraseInhibitor (C1-INH): Results of a Global, Multicenter, Randomized, Placebo-controlled, Phase II/III Study(I.M.P.A.C.T.1)

J. A. Bernstein1, R. Levy2, R. L. Wasserman3, A. Bewtra4, D. Hurewitz5,K. Obtulowicz6, A. Reshef7, P. C. Kiessling8, T. J. Craig9; 1BernsteinClinical Research Center, Cincinnati, OH, 2Family Allergy and AsthmaCenter, Atlanta, GA, 3DallasAllergyImmunology, Dallas, TX, 4CreightonUniversity School of Medicine, Omaha, NE, 5Allergy Clinic of Tulsa,Inc., Tulsa, OK, 6Jagiellonian University Hospital, Krakow, POLAND,7The Chaim Sheba Medical Center, Tel Hashomer, ISRAEL, 8CSLBehring, Marburg, GERMANY, 9Penn State University, Hershey, PA.RATIONALE: C1-inhibitor replacement therapy, globally recognized asthe gold standard treatment for acute attacks of hereditary angioedema(HAE), is currently not licensed in many countries including the US.METHODS: I.M.P.A.C.T.1 is a double-blind, placebo-controlled PhaseII/III study that enrolled 125 HAE patients with acute, moderate/severe,abdominal or facial attacks to assess the efficacy and safety of Berinert®

P (CSL Behring, Marburg, Germany), a virus-inactivated and purified C1-INH concentrate, administered at two different doses compared toplacebo. The main study endpoints were time to onset of symptom relieffrom HAE attacks, proportion of subjects with worsening clinical HAEsymptoms, and safety.RESULTS: Subjects administered C1-INH 20 U/kg exhibited a highlysignificant reduction in the median time to onset of HAE symptom relief(30 minutes) compared to subjects receiving placebo (1.5 hours),(p=0.003). Additionally, the proportion of subjects with worsening HAEsymptoms after start of study drug administration was significantly lowerin the Berinert® P 20 U/kg treated group (p=0.001). No drug-related serious adverse events (SAEs) were reported and treatment was well tolerated.CONCLUSIONS: The results of this Phase II/III study confirm that C1-INH replacement therapy is highly effective and well tolerated for thetreatment of acute abdominal and facial attacks in patients with HAE.

LB17 The Pattern and Progression of Multiple Tree Nut Allergyin Preschool Children

K. J. Allen1, M. Ho2, W. Wong2, R. Heine1, C. Hosking3, D. Hill1;1Department of Allergy and Immunology, Murdoch Childrens ResearchInstitute, Royal Children’s Hospital, Parkville, AUSTRALIA, 2Depart-ment of Pediatrics and Adolescent Medicine, The University of HongKong, Hong Kong SAR, CHINA, 3John Hunter Children’s Hospital,Newcastle, AUSTRALIA.RATIONALE: Cross-sectional studies indicate that multiple tree nut co-sensitization is common in peanut allergic children. Little is known aboutthe development of new tree nut allergies in the context of strict nut avoid-ance. We aimed to determine the pattern and progression of tree nut andsesame co-sensitization, using a longitudinal cohort of young childrenwith peanut allergy.METHODS: Consecutive patients less than 2 years of age with peanutallergy were identified and baseline SPT to peanuts, cashew, hazelnut, andsesame, and peanut-specific serum IgE antibody levels were documented.All patients were advised to strictly avoid all peanut, tree nuts, and sesameand were followed up yearly for up to 10 years. At median age 4 year, apanel of 9 tree nuts together with peanut and sesame, was conducted.RESULTS: 297 children were diagnosed with peanut allergy during thestudy period. At the initial assessment (mean age 14 months), 133 (45%)of patients were sensitized to 1 or more tree nuts, and 74 (25%) to sesame.Of 225 who had a complete preschool nut assessment (aged 3-5 yrs), 145(65%) were sensitized to at least one tree nut. Of these, 109 (75%) weresensitized to more than 1 tree nut, despite strict dietary avoidance of allpeanuts, tree nuts and sesame from the time of diagnosis of peanut allergy.

LB19 Effect of Air Pollution on Asthma Severity and Control

P. Huynh, K. Kwong, A. Ratanayake, T. Morphew, C. Jones; Universityof Southern California, Los Angeles, CA.RATIONALE: Whether exposure to air pollution adversely affects base-line asthma severity and the ability to achieve asthma control isunknown.METHODS: In this cohort study, we followed 765 Hispanic childrenfrom 7 distinct southern California communities enrolled in our pediatricasthma disease management program (PADMAP) for 1 year. The com-munities are defined by the Air Quality Management District (AQMD)and represent a wide range of ambient exposure to carbon monoxide,ozone, and nitrogen dioxide. Linear regression was used to examine therelationship of air pollution to baseline asthma severity and long-termasthma control.RESULTS: Baseline asthma severity is directly correlated to air pollu-tant levels of carbon monoxide (1 hour maximum R value of 0.72, 8 hourmaximum R value of 0.80). Baseline asthma severity was also directlycorrelated with nitrogen dioxide levels (1 hour maximum R value of0.80, 8 hour maximum R value of 0.73). Ozone levels however did notshow any appreciable correlation to baseline asthma severity. We alsofound no correlation between the ability to achieve asthma control andair pollutant levels of carbon monoxide, ozone, and nitrogen dioxide. Thelevels of air pollution did not have an effect on the ability to achieve asth-ma control.

796 Late-Breaking Abstracts J ALLERGY CLIN IMMUNOL

MARCH 2008

CONCLUSIONS: Our data support the novel concept that CD34+ cellsare not only precursors but also potent effectors of allergic inflammation.

CONCLUSIONS: The results of this study indicate that children livingin high areas of air pollution have higher baseline asthma severity. How-ever, once they are involved in a pediatric management program, the abil-ity to control their asthma is not affected by levels of air pollution.

LB20 Recombinant Peanut Allergens: Specific IgEs for Diagnosis

G. KANNY1, F. CODREANU1, S. JACQUENET2, C. ASTIER1, M. MORISSET1, D. MONERET-VAUTRIN1, C. Roland3, B. BIHAIN2; 1Nancy University, Nancy, FRANCE, 2Genclis, Nancy, FRANCE, 3Phadia, Uppsala, SWEDEN.RATIONALE: This study evaluated the diagnosis value of recombinantallergens to peanut.METHODS: Specific IgE to peanut (F13), recombinant allergens (rAra h1, rAra h 2, rAra h 3, rAra h 8) using ImmunoCAP system (Phadia, Sweden) were measured in 94 patients allergic to peanut (positive oralfood challenge), 39 controls allergic to grass and birch pollens and 50non-atopic.RESULTS: Patients allergic to peanut have sIgE to peanut (94), rAra h 2(93), rAra h 1 (74), rAra h 3 (62), rAra h 8 (45). Pollinic controls havesIgE to peanut (22), rAra h 2 (1), rAra h 1 (0), rAra h 3 (1), rAra h 8 (33).sIgE were negative in non atopic controls.The sensitivity and specificity were respectively 100% and 44% forpeanut, 99% and 97% for rArah 2.The reactogenic dose in oral challenge tests was 1876�2060 mg formono-sensitized to rAra h 2; 1567�1883 mg for co-sensitized to rAra h1 and rAra h 2 ; 620�329 mg for polysensitized to rAra h 1, rAra h 2 andrAra h 3.CONCLUSIONS: This study confirms the high sensitivity and specifici-ty of sIgE to rAra h 2. It is of particular interest for the diagnosis of peanutallergy in pollinic patients where the level of false positives for sIgE topeanut reached 56%. sIgE to rAra h 8 were detected in 85% of polliniccontrols, linked to the cross-reactivity with pollen allergens. The polysen-sitization is associated with a lower reactogenic threshold.

LB21 CD34+ Precursor Cells are Potent Effectors of AllergicInflammation

Z. Allakhverdi1, D. E. Smith2, M. R. Comeau2, G. J. Delespesse1;1CHUM Research Center, Montreal, QC, CANADA, 2InflammationResearch, Amgen, Seattle, WA.RATIONALE: Eosinophils, basophils and mast cells, the key effectors ofallergic diseases, are derived from common CD34+ myeloid precursorcells. The CD34+ cells are equipped with the appropriate chemokinereceptors and adhesion molecules allowing homing to inflammatory sites.We here provide evidence that in addition to being the precursors of clas-sical effectors, the CD34+ cells may behave as very potent effector cellsthat rapidly release high levels of proinflammatory cytokines/chemokinesin response to epithelial cell-derived cytokines, such as IL-33 and TSLP.METHODS: CD34+ progenitors were isolated from umbilical cord bloodand cultured in the presence of SCF/IL-3 with TSLP and/or IL-33 for 24hand the pellets and the supernatants were analyzed by real-time PCR orELISA.RESULTS: Freshly isolated CD34+ cells express TSLP and IL-33 recep-tor mRNA. Upon stimulation with TSLP and/or IL-33, the CD34+ cellsexpress IL-5, IL-13 and GM-CSF mRNAs and release high levels of sev-eral pro-inflammatory cytokines/chemokines such as IL-5, IL-6, IL-13,GM-CSF, CXCL8, CCL1, CCL17 and CCL22. The response is dose-dependent and specific, as it is blocked by neutralizing antibody to TSLPor by soluble ST2-Fc. Moreover, two color flow cytometry analysisreveals that all the cells producing IL-5 (or IL-13) are CD34+. Theresponse is rapid and is maximal after 18 h. In vivo significance of thesedata is supported by the finding of CD34+/IL-13+ cells in biopsies ofatopic dermatitis patients but not in controls.

LB22 Nasal Immunization With A Novel Nanonemulsion Adjuvant Modifies Th2-polarized Immune Responses

J. R. Baker, Jr., K. W. Janczak, A. U. Bielinska; University of Michigan,Ann Arbor, MI.RATIONALE: Th2 immune responses are associated with allergy andwhile immunotherapeutic approaches have been used to shift immuneresponses from Th2 to Th1 phenotypes, they require long immunizationprotocols. We have developed a novel nasal vaccine system employing ananoemulsion (NE) that can simply be mixed with antigen and applied tothe nares to produce mucosal immunity and a systemic Th1-biasedimmune response. We hypothesized that a single administration of antigenin NE could re-direct an established Th2-type immune response.METHODS: To elicit a Th2 immune response, CD-1 mice were immu-nized intramuscularly with alum-adsorbed hepatitis B virus surface anti-gen (HBsAg). Analysis of serum IgG subclass and cytokine expressionconfirmed prevalence of IgG1 subclass antibodies and Th2 pattern ofcytokine expression. The mice were then given a single, intranasal immu-nization with HBsAg mixed with NE adjuvant.RESULTS: Titers of IgG2a and IgG2b subclass antibodies rose in miceafter NE nasal immunization and their splenic lymphocytes producedIFN-� in response to HBsAg. Antigen was found throughout the immunesystem within 24 hours after nasal administration, suggesting dendriticcell engagement. Of interest, there was no local inflammatory response inthe nares after NE immunized animals, and no local production of IL-12or other TH1 associated cytokines. NE also provided thermal stability forprotein antigens, avoiding the need for refrigeration of the vaccine afterformulation.CONCLUSIONS: These findings suggest potential importance for NEdelivery systems in the development of therapeutic vaccines to modifyTH2 immune responses.

LB23 Secondhand cigarette smoke may combine with commonrespiratory viruses to trigger exaggerated inflammationin CRS

D. L. Hamilos1, M. Yamin1, E. Holbrook2, N. Busaba2, S. Gray2, K. J. Powell1, R. Harold1, A. Sridhar1; 1Massachusetts General Hospital,Division of Rheumatology, Allergy & Immunology, Boston, MA, 2Mass-achusetts Eye and Ear Infirmary (MEEI), Boston, MA.BACKGROUND: Chronic rhinosinusitis (CRS) is characterized by per-sistent mucosal inflammation and frequent exacerbations. We hypothesizethat the innate epithelial response to common respiratory viral pathogensmay be abnormal leading to persistent inflammation in CRS. This mayinvolve Toll-like (TLR) receptors.METHODS: Nasal middle turbinate biopsies were obtained from 7healthy controls (HC) and 7 CRS patients. Primary nasal epithelial cells(PNEC) were cultured in LHC9 serum free medium. After reaching 80-90% confluence, PNEC were exposed to medium alone or cigarettesmoke extract (CSE) 5% (v/v) for 1 hour, washed, then stimulated for 24hours with double-stranded (ds)-RNA. For comparison, PNEC were stim-ulated with TNF- 100 ng/ml for 24 hours. After harvesting, gene expres-sion was quantified by RT-PCR relative to GAPDH.RESULTS: Baseline mRNA expression of TNF-, IL-1�, IL-6, IL-8,GRO-, �-defensin-2 (HBD2), RANTES, IFN�, IFN1 and IFN2/3revealed no differences between HC and CRS subjects. The combinationof CSE+dsRNA induced exaggerated RANTES (12115-fold versus 1500-fold, P = .03) and HBD-2 (1120-fold versus 12.5-fold, P = .05) productionin CRS subjects. By comparison, there were no differences in RANTESor HBD2 induction by CSE, dsRNA or TNF- alone. No other genes weredifferentially induced. No differences in TLR3 or IL-17 receptor mRNA