Allergen exposure chambers: harmonizing current concepts and projecting the needs for the future - an EAACI Position Paper

International audienceBACKGROUND:Allergen exposure chambers (AECs) are clinical facilities allowing for controlled exposure of subjects to allergens in an enclosed environment. AECs have contributed towards characterizing the pathophysiology of respiratory allergic diseases and the pharmacological properties of new therapies. In addition, they are complementary to and offer some advantages over traditional multicentre field trials for evaluation of novel therapeutics. To date, AEC studies conducted have been monocentric and have followed protocols unique to each centre. Because there are technical differences among AECs, it may be necessary to define parameters to standardize the AECs so that studies may be extrapolated for driving basic immunological research and for marketing authorization purposes by regulatory authorities.METHODS:For this task force initiative of the European Academy of Allergy and Clinical Immunology (EAACI), experts from academia and regulatory agencies met with chamber operators to list technical, clinical and regulatory unmet needs as well as the prerequisites for clinical validation.RESULTS:The latter covered the validation process, standardization of challenges and outcomes, intra- and interchamber variability and reproducibility, in addition to comparability with field trials and specifics of paediatric trials and regulatory issues.CONCLUSION:This EAACI Position Paper aims to harmonize current concepts in AECs and to project unmet needs with the intent to enhance progress towards use of these facilities in determining safety and efficacy of new therapeutics in the future

Dose-response relationship of a new Timothy grass pollen allergoid in comparison with a 6-grass pollen allergoid

Background: Subcutaneous allergen immunotherapy with grass pollen allergoids has been proven to be effective and safe in the treatment of patients with allergic rhinoconjunctivitis. Based on the extensive cross-reactivity among Pooideae species, it has been suggested that grass pollen extracts could be prepared from a single species, rather than from a multiple species mixture. Objective: To find the optimal dose of a Phleum pratense (P. pratense) allergoid preparation and compare its efficacy and safety to a 6-grass pollen allergoid preparation. Methods: In this double-blind, placebo-controlled study (EudraCT: 2011-00067458), three doses of P. pratense allergoid (1800 therapeutic units (TU), standard-dose 6000 TU and 18 000 TU) were compared with placebo and the marketed 6-grass pollen allergoid (6000 TU). In a pre-seasonal dosing regimen, 102 patients were randomized to five treatment groups and received nine subcutaneous injections. The primary efficacy endpoint was the change in weal size (late-phase reaction [LPR]) in response to the intracutaneous testing (ICT) before and after treatment, comparing the active allergoids to placebo. Secondary outcomes were the change in Total Nasal Symptom Score (TNSS) assessed in the allergen exposure chamber (AEC), the changes in P. pratense-serum-specific IgG(4) and the incidence of adverse events (AEs). Results: All three doses of the P. pratense and the 6-grass pollen allergoid preparations were significantly superior to placebo for the primary outcome, whereas there were no significant differences in the change in TNSS. Compared to the standarddose, the high-dose of P. pratense did not produce any additional significant benefit, but showed a slight increase in AEs. Yet this increase in AEs was lower than for the 6-grass pollen preparation. Conclusions & Clinical relevance: The standard-dose of the new P. pratense allergoid was comparable to the marketed 6-grass pollen preparation at equal dose for the parameters measured

Assessing the impacts of mining activities on zooplankton functional diversity

Abstract Aim Mining activities generate countless environmental impacts, including heavy-metal contamination, sorting and increased turbidity. In aquatic ecosystems these impacts can drastically affect the initial links of the food chain, such as zooplankton. Methods To evaluate how the different mining activities can influence the structure and functional diversity of zooplankton, we investigated the geochemical characteristics of the water and sediment in two small impoundments impacted by different mining activities (kaolin and iron extraction). We also explored zooplankton composition, species diversity and functional diversity (feeding guilds taxa). Results As expected, the water and the sediment of both of the reservoirs showed high concentrations of trace elements, particularly Al, Ba, Fe, Mg, Mn, Sr and Zn. Zooplankton biomass and diversity were markedly reduced (< 12 &#956;g.DW.L-1 and H&#8217; < 1.5, respectively), and negatively correlated with turbidity and total suspended solids. Small microphages dominated the trophic composition of zooplankton, and an alternation of trophic guilds was not observed, since the dynamics of raptorial organisms was essentially linked to the temporal fluctuation of a single species of rotifer (Polyarthra cf. dolichoptera). Conclusions In addition to changes in the aquatic habitat and zooplankton composition, the functional niches were also affected by the mining impacts. The use of the functional diversity analysis can emerge as a valuable approach to understand how zooplankton communities respond to drastic environmental changes