Clinical efficacy and safety of a depigmented and glutaraldehyde polymerized therapeutic vaccine of Parietaria judaica.

BACKGROUND: The inhalation of Parietaria judaica pollen is a common cause of allergic respiratory diseases in the Mediterranean area. The objective of this study was to investigate the safety and clinical efficacy of a chemically modified (depigmented and glutaraldehyde-polymerized) vaccine of Parietaria judaica. METHODS AND RESULTS: Thirty patients with a well-documented clinical history of seasonal rhinitis and clinical sensitivity to Parietaria judaica pollen were included in a randomized trial during 12 months. The study was conducted following good clinical practices and appropriate consent forms were signed. Patients were divided into 2 groups of 15 individuals; group A received the modified extract and group C did not receive specific immunotherapy. Any adverse event was recorded to assess safety. Symptom scores, symptomatic medication use and the results of specific nasal challenges (before and after 12 months of treatment) were recorded to evaluate clinical efficacy. The treatment schedule consisted of an incremental phase of 5 injections and a maintenance dosage of 0.5 ml per month. Each patient received 14 injections during this period. All the patients completed the trial and no adverse reactions related to immunotherapy were recorded. A significant difference (p < 0.001) in symptom scores and overall use of symptomatic medication was observed between the two groups, being both scores lower in group A. No significant differences in nasal sensitivity existed before treatment among the 2 groups. However, after 12 months, a significant difference (p < 0.05) was observed only in group A patients, who showed a significant improvement in specific nasal challenges. CONCLUSIONS: Immunotherapy with depigmented and glutaraldehyde-polymerized extract of Parietaria judaica pollen is safe and effective to treat patients with allergic rhinitis and clinical sensitivity to this pollen.

Biosynthesis inhibitors for leukotrienes in bronchial asthma.

This article reviews the literature on the effects of leukotrienes in asthma. In particular, the ability of recently developed synthesis inhibitors to attenuate the asthma causing effects of leukotrienes is examined. MEDLINE (1966-1996), EMBASE (Excerpta Medica; 1974-1996), and other biomedical and drug directory databases were searched to identify English-language articles (basic science, clinical trial research, and review articles) and abstracts of conference proceedings on biosynthesis inhibitors for leukotrienes and related terms. Leukotrienes are endogenous molecules formed by the breakdown of a membrane constituent, arachidonic acid, via the 5-Lipoxygenase enzyme pathway. This pathway ultimately produces several species of leukotrienes with various biologic activities, including generalized inflammatory effects associated with asthma: increased vascular permeability, enhanced mucous production, and decreased mucociliary transport. The biosynthesis inhibitors for leukotrienes attenuated the response to inhaled leukotrienes and allergen challenges (MK-0591; MK-886; AA-681; A-64077; ZD-2138). These agents produced beneficial effects in cold, exercise (A-64077) and aspirin-induced asthma (A-64077; ZD-2138), as well as clinical asthma. Many of these medications appear to be effective in the treatment of asthma (BAYX-1005; MK-0591; MK-886; AA-681; A-64077; ZD-2138; U-60257; FR-110302; BI-6239; A-78773; ABT-761; L-746530; L-699333; ZM-230487). Further clinical research is needed to determine which patients would benefit most from their use.

Leukotrienes and their antagonists in allergic disorders.

Cysteinyl leukotrienes are important mediators of asthma, and inhibition of their effects may represent a potential breakthrough in the therapy of allergic rhinitis and asthma. Strategies for inhibition of cysteinyl leukotriene receptors and inhibition of 5-lipoxygenase activity. The leukotrienes antagonists, with particular reference to asthma and allergic rhinitis, is reviewed in this paper. In studies in asthmatic patients, these compounds can inhibit bronchoconstriction in response to exercise, aspirin and allergen. Results from clinical studies using receptor antagonists, such as LY-171883, SK&F-104353, ICI-204219, ONO-1078, MK-751, MK-0679, demonstrate beneficial effects, with improvement in symptoms and forced expiratory volume in one second (FEV1), and a reduction in the use of beta 2-adrenergic relief medication. NZ-107 was studied for its effect on airway inflammation caused by intratracheal injection of LTB4 or IL-5, or by inhalation of PAF, and by cell activation. Analysis of the BAL fluid revealed that both induced eosinophilia and neutrophilia were suppressed. Surprisingly, although PAF and superoxide generation were inhibited in macrophages and eosinophils, NZ-107 had no effect on neutrophil activation. U-75302 was studied in guinea pigs and inhibited LTB4 induced chemotaxis of eosinophils in vitro and antigen-induced lung eosinophilia in vivo. Further studies are needed to clarify the exact mechanism by which these compounds provide beneficial effects.

Antiallergic properties of antihistamines.

Histamine is a major mediator of the allergic reaction, and histamine H1-receptor antagonists have a long history of clinical efficacy in a variety of allergic disorders. The pathogenesis of allergic disease is complex, involving not only histamine and mast cell-derived tryptase, but also eosinophil and neutrophil derived mediators, cytokines, and intercellular adhesion molecules (ICAM-1). A number of "in vitro" and "in vivo" studies have been performed to assess the clinical effectiveness of antihistamines in inhibiting the allergen-induced inflammatory process in the skin and mucosa. In vitro human studies have shown that high concentration of second generation antihistamines can block inflammatory mediator release from basophils and mast cells, and reduce ICAM-1 expression in epithelial cell lines. In vivo studies have also shown an effect on the allergen-induced inflammatory reaction; both oral and intranasal antihistamines cause a reduction in nasal symptoms and inflammatory cell influx. Analysis of secretory fluids and tissues after challenge indicates that antihistamines interfere with mediator release. Recruitment of inflammatory cells to the site of the allergic insult is also disturbed by antihistamines of second-generation, suggesting that these drugs may inhibit upregulation of molecules involved in cell adhesion and migration, and perhaps they may interfere with the cytokine cascade through their ability of stabilizing mast cells and of limiting the incursion of inflammatory cells. This article reviews available human data on the antiallergic effects of antihistamines.