Validation of the Global Allergy and Asthma European Network (GA2LEN) chamber for trials in allergy: Innovation of a mobile allergen exposure chamber.

BACKGROUND: Field clinical trials of pollen allergy are affected by the impossibility of predicting and determining individual allergen exposure because of many factors (eg, pollen season, atmospheric variations, pollutants, and lifestyles). Environmental exposure chambers, delivering a fixed amount of allergen in a controlled environmental setting, can overcome these limitations. Environmental exposure chambers are currently already used in phase 2, 3, and even 4 trials. Unfortunately, few chambers exist in the world, and this makes it difficult to perform large, multicenter clinical trials. The new Global Allergy and Asthma European Network (GA2LEN) mobile exposure chamber is a step forward because the mobility of the chamber makes it convenient for patients to participate in clinical testing. OBJECTIVE: This study was made to validate the reproducibility, sensitivity, and specificity of the results obtained in the new GA2LEN chamber. METHODS: Seventy-two adult patients (19-61 years old) with allergic rhinitis with or without asthma caused by grass pollen were included in different clinical validation tests. Total symptom scores and total nasal symptom scores were recorded at time zero (0) and every 10 minutes during exposures, along with nasal and respiratory parameters. RESULTS: Exposure tests confirmed the reproducibility between subsequent runs and the sensitivity (P < .00001 vs patients exposed to placebo) and specificity (very low score in nonallergic subjects) in the GA2LEN chamber. No adverse reactions were recorded during the tests. CONCLUSIONS: The mobility of the GA2LEN chamber provides a new, potentially effective, and safe way of generating reliable data in allergy multicenter clinical trials.

Probiotics and allergies: myth or reality?

During the last years, along with the growing knowledge about the role and importance of the intestinal flora, interest remarkably increased in probiotic bacteria supplementation. It has indeed been demonstrated that the intestinal microbiota is very important in the regulation of several functions of the organism, even those far from the gastro-enteric system. Among them, great interest was stimulated by the proven capability of the intestinal microbiota to regulate the immune system, in particular to rebalance the TH1/Th2 ratio. Consequence thereof is the assumption that the administration of probiotic bacteria may induce clinical benefits in allergic pathologies. Many clinical studies have been carried out that considered the possibility of preventing allergic sensitizations, and preventing and treating atopic dermatitis and allergic rhinitis. Many studies demonstrated that the administration of probiotics is able to prevent the onset of allergic sensitizations and improve the symptoms of atopic dermatitis and allergic rhinitis; however, studies were published, too, that achieved negative outcomes. The overall evaluation of results is, however, difficult, as the strains used and the study design are markedly heterogeneous. Future investigations with a better standardization will be able to better explain the role of the intestinal flora in atopy, and the role of probiotics in the treatment of allergic diseases.

How air pollution influences clinical management of respiratory diseases. A case-crossover study in Milan.

BACKGROUND: Environmental pollution is a known risk factor for multiple diseases and furthermore increases rate of hospitalisations. We investigated the correlation between emergency room admissions (ERAs) of the general population for respiratory diseases and the environmental pollutant levels in Milan, a metropolis in northern Italy. METHODS: We collected data from 45770 ERAs for respiratory diseases. A time-stratified case-crossover design was used to investigate the association between air pollution levels and ERAs for acute respiratory conditions. The effects of air pollutants were investigated at lag 0 to lag 5, lag 0-2 and lag 3-5 in both single and multi-pollutant models, adjusted for daily weather variables. RESULTS: An increase in ozone (O(3)) levels at lag 3-5 was associated with a 78% increase in the number of ERAs for asthma, especially during the warm season. Exposure to carbon monoxide (CO) proved to be a risk factor for pneumonia at lag 0-2 and in the warm season increased the risk of ERA by 66%. A significant association was found between ERAs for COPD exacerbation and levels of sulphur dioxide (SO(2)), CO, nitrate dioxide (NO(2)), and particulate matter (PM(10) and PM(2.5)). The multipollutant model that includes all pollutants showed a significant association between CO (26%) and ERA for upper respiratory tract diseases at lag 0-2. For chronic obstructive pulmonary disease (COPD) exacerbations, only CO (OR 1.19) showed a significant association. CONCLUSIONS: Exposure to environmental pollution, even at typical low levels, can increase the risk of ERA for acute respiratory diseases and exacerbation of obstructive lung diseases in the general population.

Steroid-sparing effects with allergen-specific immunotherapy in children with asthma: a randomized controlled trial.

BACKGROUND: Asthma control is now recognized as the main goal of asthma therapy. Guidelines recommend finding the lowest effective dose of inhaled corticosteroids in children with persistent asthma. OBJECTIVE: The aim of this study was to investigate the efficacy of an allergen-specific immunotherapy with a high-dose hypoallergenic mite preparation (allergoid) as steroid-sparing agent in children with allergic asthma. METHODS: Sixty-five children with asthma (Global Initiative for Asthma treatment levels II and III; 6-17 years old), after reaching asthma control with inhaled steroids during a 5-month baseline period, were randomized for subcutaneous mite allergoid immunotherapy (SCIT) plus fluticasone propionate (FP) or FP therapy alone for 2 years. During 2 subsequent 5-month winter periods, steroid therapy was adjusted according to predefined dose steps, determining and comparing the changes in FP dosages and the lowest FP dose sufficient to maintain asthma control. Immunologic and functional investigations were also carried out. RESULTS: Children treated with house dust mite SCIT plus FP were able to significantly reduce the FP dose by more steps (P < .05), compared with the control group on FP alone. The mean daily dose in the immunotherapy group decreased from 330.3 µg in the baseline period to 151.5 µg after 2 treatment years, whereas in the control group the dose decreased from 290.6 µg to 206.3 µg. Compared with the control group, significant improvement was also observed in morning peak expiratory flow (P = .0315). Significantly increased levels of specific IgG(1) (P = .0001) and IgG(4) (P < .0001) were also observed. CONCLUSION: Adding a mite allergoid SCIT to pharmacologic treatment is an effective and safe strategy to reduce corticosteroid doses while maintaining disease control in children with mite-induced allergic asthma.

Giant ragweed specific immunotherapy is not effective in a proportion of patients sensitized to short ragweed: analysis of the allergenic differences between short and giant ragweed.

BACKGROUND: Short ragweed and giant ragweed pollen allergens are considered largely cross-reactive, and it is generally believed that 1 species is sufficient for skin testing and immunotherapy. However, in the area north of Milan (a zone widely invaded only by short ragweed), about 50% of patients submitted to injection specific immunotherapy with giant ragweed showed little or no clinical response, but showed an excellent outcome if they were shifted to short ragweed specific immunotherapy. OBJECTIVE: To investigate allergenic differences between short and giant ragweed. METHODS: IgE reactivity to short ragweed of sera from 16 patients allergic to ragweed was assessed by immunoblot before and after absorption with short and giant ragweed. Moreover, 41 ragweed-monosensitive patients underwent skin prick test with both ragweed species. RESULTS: In several cases, preabsorption of sera with giant ragweed extract was unable to inhibit IgE reactivity fully against both a 43-kd allergen and other allergens at different molecular weights in short ragweed. On skin prick test, short ragweed induced larger wheals than giant ragweed in the majority of patients, and 6 of 41 (15%) patients were strongly short ragweed-positive but giant ragweed-negative. The immunoblot with the serum from 1 of these subjects showed a strong IgE reactivity to short ragweed at about 43 kd in the absence of any reactivity to giant ragweed. CONCLUSION: Short and giant ragweed are not allergenically equivalent. Allergenic differences involve both the major allergens Amb a 1-2/Amb t 1-2 and some minor allergens. In patients allergic to ragweed, both diagnosis in vivo and immunotherapy should always be performed by using the ragweed species present in that specific geographic area.