Mizolastine provides effective symptom relief in patients suffering from perennial allergic rhinitis: a double-blind, placebo-controlled study versus loratadine.

BACKGROUND: Mizolastine is a nonsedating H1 histamine receptor antagonist with additional antiallergic properties currently marketed in Europe for the treatment of seasonal and perennial allergic rhinitis (PAR) and urticaria. OBJECTIVE: This multicenter, randomized, double-blind, parallel-group study was conducted to evaluate the efficacy and safety of mizolastine in PAR compared with loratadine and placebo. METHODS: After a 1-week placebo run-in period, 428 adult PAR patients received placebo (146 of 428), mizolastine 10 mg (141 of 428), or loratadine 10 mg (141 of 428) once daily for 28 days. Symptoms were evaluated by patients and physicians using a total nasal score, evaluating itching, rhinorrhea, nasal blockade, and sneezing severity. RESULTS: Mizolastine treatment resulted in a significantly greater decrease in patient-rated total nasal score than placebo after 2 weeks (D14; -42%, P < 0.001) and at the end of the treatment period (-46%, P = 0.01), and significantly greater than that observed with loratadine at D14 (P = 0.031). No significant difference in change in total nasal score was observed between loratadine and placebo at 2- and 4-week visits. The global safety was satisfactory and the incidence of adverse events was similar in the three treatment groups. CONCLUSIONS: Mizolastine provides effective symptom relief in PAR together with a satisfactory safety profile. Improvement with mizolastine was significantly greater than placebo throughout the study despite a large placebo effect. Also mizolastine's effects were greater those observed with loratadine after 2 weeks of treatment.     

Anaphylaxis to muscle-relaxant drugs: study of cross-reactivity by skin tests.

Intradermal skin tests (two dilutions) carried out systematically with 5 muscle-relaxant drugs were used to study the cross-reactivity between these drugs in 131 patients who had suffered from anaphylaxis. The skin tests were positive for at least 2 drugs in 65.6% of the cases. We observed a significant concordance (positive-positive or negative-negative skin tests) between pancuronium and vecuronium (p less than 0.01) and a significant correlation between the skin test diameters obtained with these 2 drugs (p less than 0.02 for wheals and p less than 0.01 for flares). Conversely, the lack of concordance between pancuronium and suxamethonium was significant (p less than 0.05). When comparing all the concordances obtained with each pair of drugs, it appeared that the concordance between pancuronium and vecuronium was significantly higher than all others. For other concordances, 2 main factors seemed to play a role: the N+ of the ammonium ions included in a ring as in pancuronium and the presence of a 'choline-like' side chain as in suxamethonium. But there was no significant correlation between skin test diameters. Altogether, these results suggest that in vivo there is no 'true' cross-reactivity between the drugs except frequently between pancuronium and vecuronium. In all other cases, the patients have probably specific IgE antibodies for each drug, all these antibodies being able to recognize the ammonium determinant; this common property may be insufficient to induce a clinical allergy.     

Safety of various dosage regimens during induction of sublingual immunotherapy. A preliminary study

BACKGROUND: Sublingual immunotherapy (SLIT) has been demonstrated to be a viable alternative to injection immunotherapy. Administration of high doses of allergens to ensure efficacy has been shown to be well tolerated. The aim of the present study was the first step to address the issue of fast-induction regimens using various induction SLIT regimens in paediatric and adult patients. METHODS: Sixty-four patients (age range 5-46 years) with grass pollen rhinoconjunctivitis were enrolled in an 8-month double-blind, placebo-controlled trial of SLIT. Sixty-three patients were randomized to four groups and evaluated at the end of the study. One group received placebo (n = 16) and the other three groups (n = 47) received five grass pollen extracts according to three different induction regimens: regimen 1 starting with 3 IR tablets (n = 15), regimen 2 starting with 10 IR (n = 16) and regimen 3 starting with 30 IR (n = 16). The maintenance phase was made with sublingual-swallow drops at the same concentration of 300 IR/ml for all the patients. Adverse events were recorded on diary cards. RESULTS: During induction phase, 25/47 patients in the SLIT groups had adverse reactions in comparison to 2/16 patients in the placebo group (p < 0.05). The rate of adverse reactions was 33.3% (11.8-61.6) (95% CI) for regimen 1, 31.3% (11.0-58.7) for regimen 2, 43.8% (19.8-70.1) for regimen 3 and 12.5% (1.6-38.3) for placebo. Fifty-seven reactions were local reactions involving the oral region (54 SLIT, 3 placebo) and 13 were systemic reactions (all in the SLIT groups). 11/13 reactions were mild (gastrointestinal disorders, rhinoconjunctivitis), 1/13 consisted of moderate asthma and 1/13 consisted of severe abdominal pain. No urticaria, angioedema or life-threatening events were observed. CONCLUSIONS: These preliminary data showed that various induction regimens for SLIT are generally well tolerated and could allow a fast build-up phase of SLIT.     

Mast cells and basophils in asthma

Airway inflammation may contribute to the nonspecific bronchial hyperreactivity, which is a prominent feature in chronic asthma. Many stimuli such as allergens in allergic asthma, virus and irritants may induce an early reaction and in some cases a late reaction. An increase of nonspecific bronchial hyperreactivity is well demonstrated after this late reaction but no after the early one. Although a variety of inflammatory cells may be located within the respiratory tract, the late phase is generally considered as a direct consequence of the effects of mediators released from mast cells activated during the early reaction. Eosinophils and other inflammatory cells are attracted by chemotactic mediators such as PGD2. However the pathophysiology of chronic asthma remains uncertain because the heterogeneity of mast cells and the complexity of intercellular regulations. The role of basophils has been suggested mainly because their number increases during the late phase of allergic process. On the other hand, histamine and LTC4, but not PGD2, are found during the late phase: it is well established that basophils do not release PGD2. Two recent hypothesis have focused interest on basophils: the higher releasability property of basophils obtained from allergic and asthmatic patients, whatever their serum IgE and the presence of histamine releasing factors acting only on one kind of IgE (IgE+) which is apparently found in severe asthmatic patients. It may be probable that other cells, such as epithelial cells, play also a prominent role in chronic asthma.     

Mizolastine in primary acquired cold urticaria

BACKGROUND: Treatment of primary acquired cold urticaria (CU) is quite difficult because of variable clinical effectiveness and side effects of classic antihistamines. OBJECTIVE: The objective of the study was to assess the efficacy and safety of mizolastine, an antihistaminic with antiallergic properties, versus placebo in primary acquired CU. METHODS: This study was a phase II, multicenter, randomized, double-blind, crossover, placebo-controlled study of mizolastine (10 mg, once daily) versus placebo in 28 patients with primary acquired CU. Efficacy was measured by the cold-stimulation time test, the wheal response, and pruritus intensity after an ice-cube test. RESULTS: Mizolastine delayed the cold-induced wheal reaction, reduced wheal response at 3 and 10 minutes, and reduced pruritus intensity. Statistically significant differences were observed versus placebo for the cold-stimulation time test, wheal response at 3 and 10 minutes, and pruritus intensity (P =.006,.015,.009, and.005, respectively). No clinically relevant adverse events were reported. CONCLUSIONS: Mizolastine (10 mg, once daily) was shown to be superior to placebo for both delaying and reducing the cold-induced wheal reaction without significant adverse events. Results suggest that mizolastine may be effective in the treatment of CU.