Clinical efficacy and safety of preseasonal sublingual immunotherapy with grass pollen carbamylated allergoid in rhinitic patients. A double-blind, placebo-controlled study.

BACKGROUND: The aim of this study was to confirm the clinical efficacy and safety of a preseasonal sublingual immunotherapy (SLIT) in a group of allergic patients with seasonal rhinoconjunctivitis with or without mild intermittent or mild persistent asthma. The immunotherapy was administered through the oral mucosa with a monomeric carbamylated allergoid (allergoid SLIT) for grass pollens. A secondary endpoint was to evaluate the effect of the allergoid SLIT on nasal reactivity. METHODS AND RESULTS: A single-center, randomized, double-blind, placebo-controlled study was performed. Patients were selected and randomly allocated to two groups: one group received active treatment (allergoid SLIT) for 2 years and the other received placebo. Both groups received the necessary drug treatment throughout the trial. Thirty-three outpatients (20 men and 13 women, mean age: 30 years; range: 19-43) attending our center were enrolled in the study. Symptoms and medications were scored on diary cards during the pollen season. An allergen nasal challenge was performed at baseline and after 2 years of SLIT to evaluate nasal reactivity. Because the clinical scores were non-normally distributed, the Mann-Whitney and the Chi-square tests for intergroup comparisons and the Wilcoxon test for intragroup comparisons were used. The results were evaluated after 1 and 2 years of treatment. Between the first and second years of treatment, no changes in the scores for the placebo group were found, while for the active vaccine group significant decreases were found in rhinorrhea (p < 0.03), sneezing (p < 0.03), and conjunctivitis (p < 0.02). Symptom scores after nasal challenge decreased (p < 0.03) after 2 years' treatment. Nasal steroid use significantly decreased in the active treatment group during May and June in both the years of treatment (p < 0.02). Only two mild local adverse events were reported in the active group and none was reported in the placebo group. CONCLUSIONS: The results of this study show that the allergoid SLIT is safe and effective in decreasing symptom scores and drug use in rhinitic patients allergic to grass pollen.

Monoid sublingual immunotherapy.

Sublingual monoid immunotherapy with monomeric allergoids has been largely used in Europe in the last few years. An open trial of allergoid in tablets has been done in rhinitic patients allergic to house dust mites, grass pollens and Parietaria with clear improvement in clinics and drug consumption scores. In a second phase a double blind placebo controlled trial of grass pollens allergoids have been done in hay fever patients with significant decrease on the scores of rhinorrea, sneezing and conjunctivitis nasal steroid consumption and clinical score after serial nasal challenges. Monomeric allergoids are an efficace and safe immunotherapy in allergic rhinitis.

Effect of allergen immunotherapy on soluble adhesion molecules.

UNLABELLED: The level of soluble adhesion molecules in the serum reflects the degree of systemic inflammation but the dynamics of these molecules in the pathogenesis of allergic diseases and their evolution during treatment, remains to be established. OBJECTIVE: To determine the evolution of the levels of soluble forms of serum intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1) during immunotherapy to Dermatophagoides pteronyssinus in patients with allergic rhinitis and/or asthma. POPULATION: We included in this study 23 patients with perennial allergic rhinitis and/or asthma to Dermatophogoides pteronyssinus. 17 patients (6 males, 11 females, 13-48 years; mean: 27.2 years) were treated for one year with specific immunotherapy using standardized slow-release D. pteronyssinus extract (Lofarma, Milan, Italy). The other 6 patients (control group; 2 males, 4 females, 20-37 years; mean: 26.5 years) received only symptomatic treatment. METHODS: Serum sICAM-1 and sVCAM-1 were measured by ELISA method (R&D system). Blood samples were collected from each immunotherapy-treated patient at two timings: before immunotherapy (T0) and after one year of immunotherapy (T1). The two blood samples from each control patient (T0 and T1) were also collected one year apart. RESULTS: Before Immunotherapy (T0), the mean serum level of sICAM-1 was 336.0 ng/ml. After one year of immunotherapy (T1) it decreased to 325.2 ng/ml but this difference was not statistically significant. Mean serum level of sVCAM-1 was 655.5 ng/ml before immunotherapy (T0), decreasing significantly (p < 0.05) to 568.2 ng/ml (T1). In the control group both sICAM-1 and sVCAM-1 had no significant changes (sICAM-1: 363.1 ng/ml (T0) and 374.7 ng/ml (T1); sVCAM-1: 611.5 ng/ml (T0) and 649.8 ng/ml (T1). CONCLUSIONS: These results suggest that specific immunotherapy with D. pteronyssinus induces a decrease in serum sVCAM-1 but not in sICAM-1 levels. The decreased expression of sVCAM-1 after immunotherapy is probably related to a decrease in the inflammatory reactions.

Leukotriene receptor antagonists (Montelukast) in the treatment of asthma crisis: preliminary results of a double-blind placebo controlled randomized study.

OBJECTIVE: Evaluate the efficacy of oral Montelukast 10 mg as an add-on therapy to the usual emergency therapy of an asthma crisis in an emergency room (ER). POPULATION: Twenty adults that sought medical attention in the ER of our Hospital and in whom, on admission, it appeared unnecessary to give systemic steroids. METHODS: All patients received the usual therapy of the asthma crisis. Simultaneously it was randomly administered a capsule containing 10 mg Montelukast or placebo, in a double-blind protocol. In both groups we evaluated the evolution of Peak-Flow values, the duration of stay in the ER as well as the need for additional therapy with systemic aminophylline or steroids, representing an insufficient response to the initial treatment. Student's T test was used to evaluate the statistical differences between these two groups. RESULTS: Both the Montelukast (MK) and Placebo (PL) groups were comparable regarding age and sex distribution, Peak-Flow values and Arterial O2 values on admission. During therapy, MK group had a shorter duration of ER stay (MK = 2.5 h; PL = 2.9 h) and a better evolution of Peak-Flow values (medium increase of 55% from baseline versus 44% in PL group). However these differences did not reach statistical significance. In the MK group one patient needed systemic steroids and 4 received systemic aminophylline while in the PL group 4 patients received systemic steroids and 8 aminophylline. This difference was significant (p = 0.03). We did not observe any significant side effects during therapy. CONCLUSIONS: Despite a small trend favourable to Montelukast we did not observe significant differences between groups regarding duration of stay or Peak-Flow evolution during therapy in ER, most probably due to the small sample size. However patients in the MK group needed significantly less systemic therapy with aminophylline or steroids. These data, in view of the very good safety profile of Montelukast, allow us to conclude that this is a useful additional therapy, which should be considered in the ER treatment of the asthma crisis.

Effect of specific immunotherapy versus loratadine on serum adhesion molecules.

OBJECTIVE: To evaluate comparatively the effect on serum ICAM-1 and VCAM-1 values of specific immunotherapy versus loratadine in the treatment of allergic rhinitis. POPULATION: 65 patients with mild to moderate House Dust Mite allergic rhinitis. METHODS: Patients were divided into three groups, according to patients' preference: a control group with patients receiving only rescue therapy (antihistamines and/or nasal cromoglycate when needed); an antihistamine group with patients receiving daily loratadine 10 mg (and nasal cromoglycate as rescue therapy); an immunotherapy group with patients receiving subcutaneous house dust mite specific immunotherapy (and antihistamines or nasal cromoglycate when needed). In all groups we measured soluble ICAM-1 and VCAM-1 serum levels before the start of the study period and at the end of the study period. The duration of the study was one year for the control group and for the immunotherapy group. In patients taking daily antihistamines we measured serum adhesion molecules one month after the beginning of the therapy. We used Student's T test for statistical analysis. RESULTS: Patients in the control group didn't have significant variations in serum ICAM-1 (p = 0.239) or VCAM-1 (p = 0.38) levels. Patients receiving loratadine showed significant decreases in serum VCAM-1 levels (p = 0.0012) but not in serum ICAM-1 levels (p = 0.224). Patients receiving immunotherapy also showed a similar pattern, with significant decreases in serum VCAM-1 levels (p = 0.012) but not in serum ICAM-1 levels (p = 0.254). CONCLUSIONS: Specific house dust mite immunotherapy and regular daily loratadine therapy are able to lower significantly serum levels of soluble VCAM-1. However, this effect, which can be interpreted as an anti-inflammatory action, is not applied to soluble ICAM-1 levels, which raises the possibility of a differential action of these therapies on the mechanisms of allergic inflammation. Patients on rescue medication alone did not show any significant differences in these parameters.