Efficacy and safety of subcutaneous immunotherapy with polymerized allergen mixtures in polyallergic patients - ARES observational study.

BACKGROUND: Administration of allergen mixtures of many components comprises the most common approach for American allergists regarding the management of polyallergic patients. European allergists, however, are more reluctant to this type of treatment due to the potential drawbacks of mixing extracts. RESEARCH DESIGN AND METHODS: To assess the efficacy and safety of subcutaneous immunotherapy (SCIT) with polymerized allergen mixtures without dilutional effect in polyallergic patients.This observational, prospective, multicenter study included patients (between 5 and 60 years) with respiratory allergic diseases that had been prescribed with SCIT with mixtures of two pollen or mite extracts. Changes in Symptoms and Medication Score (SMS) and in rhinitis quality of life questionnaire (RQLQ), subjective clinical improvement, treatment satisfaction and tolerability were assessed after the 1-year treatment. RESULTS: A total of 115 patients were included in the assessment. Mean global SMS decreased from 3.5 (SD = 1.1) to 1.6 (SD = 1.2) points, with a mean absolute reduction of 1.6 (SD = 1.3) points in the RQLQ score (p < 0.001, Wilcoxon test). General subjective clinical improvements and a good treatment satisfaction and tolerability were observed. CONCLUSION: SCIT with polymerized allergen mixtures from either pollen or mite extracts proved to be an effective and safe treatment option for polyallergic patients suffering from allergic respiratory diseases.

Induction of cyclooxygenase-2 expression by allergens in lymphocytes from allergic patients.

Cyclooxygenase (COX) is a key enzyme in prostaglandin (PG) synthesis. Up-regulation of COX-2 expression is responsible for increased PG release during inflammatory conditions and is thought to be also involved in allergic states. In this study, we demonstrate that in human T, B and natural killer lymphocytes from allergic patients, COX-2 expression became induced upon cell challenge with specific allergens and that this process is presumably IgE dependent and occurs after CD23 receptor ligation. This induction took place at both mRNA and protein levels and was accompanied by PGD2 release. IgE-dependent lymphocyte treatment elicited, in parallel, an activation of the MAPK p38 and extracellular signal-regulated kinase 1/2, an enhancement of calcineurin (CaN) activity, and an increase of the DNA-binding activity of the nuclear factor of activated T cells and of NF-kappaB, with a concomitant decrease in the levels of the cytosolic inhibitor of kappaB, IkappaB. In addition, specific chemical inhibitors of MAPK, such as PD098059 and SB203580, as well as MG-132, an inhibitor of proteasomal activity, abolished allergen-induced COX-2 up-regulation, suggesting that this process is mediated by MAPK and NF-kappaB. However, induction of COX-2 expression was not hampered by the CaN inhibitor cyclosporin A. We also examined the effect of a selective COX-2 inhibitor, NS-398, on cytokine production by human lymphocytes. Treatment with NS-398 severely diminished the IgE-dependently induced production of IL-8 and TNF-alpha. These results underscore the relevant role of lymphocyte COX-2 in allergy and suggest that COX-2 inhibitors may contribute to the improvement of allergic inflammation through the reduction of inflammatory mediator production by human lymphocytes.