Evaluation and validation of a bee venom sting challenge performed by a micro-syringe.

BACKGROUND: The honeybee sting challenge is considered a reliable procedure to evaluate the efficacy of specific immunotherapy, but it is difficult and unpractical to perform in clinical practice, because live insects are required. OBJECTIVE: To assess the feasibility and reliability of a challenge test using a micro-syringe, and compared the procedure with sting challenge. METHODS: Patients on bee venom immunotherapy and without systemic reactions at field sting were enrolled. They underwent a sting challenge with live bee, and large local reactions were assessed up to 48 hours. Those patients displaying systemic reactions at the sting challenge were excluded from the syringe challenge for ethical reasons. The syringe challenge was done by injecting 0.5 µL fresh unfiltered bee venom at 2 mm depth (the length of the sting left by a bee). The same follow-up as at the first challenge was performed. Bee-specific immunoglobulin E (IgE) and tryptase were measured after each challenge. RESULTS: Nineteen patients underwent the sting challenge with live bees. Four had immediate systemic reactions (urticaria or asthma) and were excluded from the second challenge. The remaining 15 patients with large local reaction underwent the syringe challenge. No significant difference was seen in the maximum area of the large local reactions between the challenge with live bees and the syringe challenge. Also, no change was seen in tryptase and specific antibodies. CONCLUSION: This preliminary study suggests that the micro-syringe challenge with honeybee venom is feasible and produces results indistinguishable from those of the traditional sting challenge.

Long-lasting effects of sublingual immunotherapy according to its duration: a 15-year prospective study.

BACKGROUND: Data on the long-term effects of sublingual immunotherapy (SLIT) are sparse, and the optimal duration of treatment is a matter of debate. OBJECTIVE: We sought to prospectively evaluate the long-term effect of SLIT given for 3, 4, or 5 years and to compare the effect of those different durations. METHODS: In this prospective open controlled study we followed up patients with respiratory allergy who were monosensitized to mites for 15 years. The subjects were divided in 4 groups receiving drug therapy alone or SLIT for 3, 4, or 5 years. Clinical scores, skin sensitizations, methacholine reactivity, and nasal eosinophil counts were evaluated every year during the winter months. The clinical effect was considered to persist until clinical scores remained at less than 50% of the baseline value, and then patients underwent another course of SLIT. RESULTS: Seventy-eight patients were enrolled, and 59 completed the study. In the 12 control subjects no relevant change in clinical scores was seen throughout the study. In the patients receiving SLIT for 3 years, the clinical benefit persisted for 7 years. In those receiving immunotherapy for 4 or 5 years, the clinical benefit persisted for 8 years. New sensitizations occurred in all the control subjects over 15 years and in less than a quarter of the patients receiving SLIT (21%, 12%, and 11%, respectively). The second course of vaccination induced a benefit more rapidly than the first course. The behavior of bronchial hyperreactivity and nasal eosinophils paralleled the clinical score. CONCLUSION: Under the present conditions, it can be suggested that a 4-year duration of SLIT is the optimal choice because it induces a long-lasting clinical improvement similar to that seen with a 5-year course and greater than that of a 3-year vaccination.

Sublingual immunotherapy for Alternaria-induced allergic rhinitis: a randomized placebo-controlled trial.

BACKGROUND: Respiratory allergy due to Alternaria is a relevant clinical problem, and specific immunotherapy may represent a viable treatment option. Sublingual immunotherapy (SLIT) is safe and effective, but data for Alternaria are lacking. OBJECTIVE: To assess the efficacy of standardized SLIT in patients sensitized to Alternaria in a randomized, prospective, double-blind, placebo-controlled trial. METHODS: Patients with rhinitis with or without intermittent asthma and ascertained allergy to Alternaria were enrolled. After a baseline season, SLIT or matched placebo was given for 10 months. Symptoms and rescue medication intake were recorded on diary cards between June and October. Skin prick testing was performed and specific IgE, IgG4, and precipitin levels were measured at baseline and at the end of the study. RESULTS: Twenty-seven patients (age range, 14-42 years) were randomized, and 26 completed the study. The baseline characteristics were homogeneous in the 2 groups. After treatment, patients receiving SLIT had a significant improvement in symptoms and a reduction in medication intake vs placebo and vs the run-in season, whereas no change was seen in the placebo group. Skin prick test reactivity significantly decreased only in the SLIT group. No change was seen in specific IgG4 levels in the 2 groups, whereas Alt a 1 specific IgE levels significantly increased in the active group. One patient in the active group reported oral itching and conjunctivitis at the beginning of treatment. CONCLUSION: SLIT seems effective and safe and may represent a valuable therapeutic option in respiratory allergy due to Alternaria.

Sublingual immunotherapy for large local reactions caused by honeybee sting: a double-blind, placebo-controlled trial.

BACKGROUND: Sublingual immunotherapy (SLIT) proved effective and safe in respiratory allergy, and thus its use in hymenoptera allergy can be hypothesized. OBJECTIVE: We sought to assess, in a proof-of-concept study, whether SLIT might potentially be beneficial in hymenoptera allergy. The sting challenge in large local reactions (LLRs) was used to test this hypothesis. METHODS: We performed a randomized, double-blind, placebo-controlled study involving patients with LLRs who were monosensitized to honeybee. After the baseline sting challenge, they were randomized to either SLIT or placebo for 6 months. The treatment (Anallergo, Florence, Italy) involved a 6-week build-up period, followed by maintenance with 525 microg of venom monthly. The sting challenge was repeated after 6 months. RESULTS: Thirty patients (18 male patients; mean age, 44.5 years) were enrolled, and 26 completed the study, with 1 dropout in the active group and 3 dropouts in the placebo group. In the active group the median of the peak maximal diameter of the LLRs decreased from 20.5 to 8.5 cm (P = .014), whereas no change was seen in the placebo group (23.0 vs 20.5 cm, P = not significant). The diameter was reduced more than 50% in 57% of patients. One case of generalized urticaria occurred in a placebo-treated patient at sting challenge. No adverse event caused by SLIT was reported. CONCLUSION: Honeybee SLIT significantly reduced the extent of LLRs, and its safety profile was good. Although LLRs are not an indication for immunotherapy, this proof-of-concept study suggests that SLIT in hymenoptera allergy deserves further investigation. Trials involving systemic reactions and dose-ranging studies are needed.

Comparison of the medium molecular weight venom fractions from five species of common social wasps by MALDI-TOF spectra profiling.

The average spectral profiles and the exact mass weight (MW) of biomolecules present in the medium fraction (from 900 to 3000 Da) of the venom of five social wasps (three European and one North American Polistes and the European hornet Vespa crabro) were determined by matrix assisted laser desorption ionization time of flight (MALDI-TOF) MS. Data were obtained analyzing the venom of single specimens (N = 46) and elaborated with the ClinProTools 2.0 (CPT) software to search for differences among the five species examined. Interesting differences in the spectral profiles were found, allowing the discrimination of venoms belonging to the different species, and their possible use as a quality control method in venom immunotherapy (VIT) for allergic patients.

Characterization of the major allergens purified from the venom of the paper wasp Polistes gallicus.

Allergic reactions to vespid stings are one of the major causes of IgE-mediated anaphylaxis. Vespa and Vespula venoms are closely related; Polistes venom is more distantly related and its allergens are less well studied. There is limited cross-reactivity between Polistes and the other vespid venoms because of differences in the epitopes on the allergen molecules. In this study, the major allergens of Polistes gallicus are isolated and characterized. P. gallicus venom contains four major allergens: phospholipase, antigen 5 (Ag5), hyaluronidase and protease that were characterized by mass spectrometry and specific binding to IgE. The complete amino acid sequence of Ag5 and the sequence of the N-terminal region of phospholipase were also determined. The alignment of Ag5 from P. gallicus (European species) and Polistes annularis (American species) shows an 85% identity that increases to 98% within the same subgenus. This could suggest the presence of specific epitopes on Ag5 molecule being the variations on the superficial loops. The features of the P. gallicus allergens could explain the partial cross-reactivity found between the American and European Polistes venoms, and suggest that the use of European Polistes venoms would improve the diagnostic specificity and the therapy of European patients and of North American patients sensitized by European Polistes.

Long-term comparison of sublingual immunotherapy vs inhaled budesonide in patients with mild persistent asthma due to grass pollen.

BACKGROUND: Few studies have compared the effects of immunotherapy and inhaled steroids. The main limitation of such studies is the long duration required to fully appreciate the effects of immunotherapy. OBJECTIVE: To compare the effects of inhaled budesonide and sublingual immunotherapy (SLIT) in mild persistent asthma for up to 5 years. METHODS: Patients with mild persistent asthma and rhinitis due to grass pollen were enrolled in an open randomized controlled trial. After a run-in season, they were randomized to either budesonide, 800 microg/d, in the pollen season or continuous grass SLIT for 5 years. All patients received rescue medications. Symptoms were evaluated by diary cards filled out from May to July at baseline and after 3 and 5 years. In-season nasal eosinophils and bronchial hyperresponsiveness were also assessed. RESULTS: Fifty-one patients were enrolled and 46 completed the study. The bronchial symptom scores and the use of bronchodilators decreased significantly in both groups, but the improvement was greater in the SLIT patients at 3 and 5 years. The nasal symptom score and the intake of nasal steroids decreased only in the SLIT group, and the difference vs the budesonide group was always significant. In the SLIT group vs the budesonide group, a statistically significant decrease of nasal eosinophils was found at 3 and 5 years (P < .01). The bronchial hyperresponsiveness improved significantly only in the SLIT group. CONCLUSION: In patients with grass pollen-induced asthma, in the long term SLIT was equally effective as inhaled budesonide in treating bronchial symptoms and provided an additional benefit in treating rhinitis symptoms and bronchial hyperresponsiveness.

Effects of sublingual immunotherapy for multiple or single allergens in polysensitized patients.

BACKGROUND: Sublingual immunotherapy (SLIT) has proven efficacy in treating respiratory allergy. OBJECTIVE: To compare the clinical and functional effects and the effect on nasal eosinophils of SLIT with either single or combination allergens. METHODS: We performed an open-labeled, controlled, 4 parallel-group randomized study with 58 patients sensitized to birch and grasses only who had rhinitis and bronchial hyperreactivity in both pollen seasons. Patients were recruited for the study from January 1, 1999, to June 30, 2001. The patients received SLIT for birch, SLIT for grass, SLIT for birch and grass, or drugs only. Symptom and medication scores, forced expiratory volume in 1 second, bronchial hyperreactivity, and nasal eosinophil counts were evaluated in both pollen seasons at baseline and after 2 and 4 years. RESULTS: Ten patients dropped out and 48 completed the study. No change in all the considered parameters vs baseline was seen in patients treated with drugs only. Those patients receiving SLIT for grass or birch had a significant clinical improvement and nasal eosinophil reduction vs baseline and vs patients who did not receive SLIT in the target season (P < .01) but also in the unrelated pollen season (P < .05). The patients receiving SLIT for grass and birch improved as well, and their improvement in clinical symptoms and inflammation was significantly greater than in patients treated with SLIT for the single allergens. Minor changes were seen in the forced expiratory volume in 1 second, since it remained within the reference range in the whole population. CONCLUSION: In patients sensitized to grass and birch, SLIT with the 2 allergens provided the best clinical results. Nevertheless, SLIT with birch only or grass only also provided a measurable improvement in the grass season and birch season, respectively.

Clinical, functional, and immunologic effects of sublingual immunotherapy in birch pollinosis: a 3-year randomized controlled study.

BACKGROUND: Sublingual immunotherapy (SLIT) has been proved effective in allergic rhinitis, but there are few studies assessing its effects on inflammation and on the lower airways. OBJECTIVE: We sought to evaluate at the same time the effects of SLIT on rhinitis symptoms, nasal inflammation, and lower airways function in patients with birch pollinosis. METHODS: Adult patients with rhinitis and asthma monosensitized to birch were evaluated during a run-in pollen season and then randomized to receive openly either drugs alone or drugs plus SLIT and reevaluated in the subsequent 4 pollen seasons. Rhinitis symptoms and consumption of bronchodilators were assessed by means of diary card. A nasal smear for eosinophil count was carried out in and out of pollen seasons, and pulmonary function tests with methacholine challenge were performed at each season. RESULTS: Of 79 enrolled patients, 27 dropped out, with a significantly higher rate of dropouts in the control group. There was a decrease in symptoms and bronchodilator use in the SLIT group versus the control group, becoming significant at the second and third pollen seasons, respectively ( P < .01 at all times). Nasal eosinophils decreased significantly in the active group, starting from the third pollen season ( P < .01). In the SLIT group a significant increase in FEV 1 , specific airways conductance, and maximal expiratory flow at 25% of forced vital capacity was seen starting from the second year and was associated with an increase in the methacholine threshold dose ( P < .01). The differences were significant also at the intragroup comparison over time. CONCLUSION: SLIT achieved a significant clinical benefit in birch pollinosis, reduced the eosinophil infiltration in nasal mucosa, and significantly improved pulmonary function during the pollen seasons.