Effect of IVL745, a VLA-4 antagonist, on allergen-induced bronchoconstriction in patients with asthma

Background: Very late antigen (VLA-4) antagonists have been proposed as potential therapies for diseases in which cell recruitment and accumulation are causative. Asthma, which is characterized by airway inflammation involving the accumulation of eosinophils and mononuclear cells, is one such disease.Objective: We sought to assess the effect of IVL745, a VLA-4 antagonist, on the early and late asthmatic response (LAR) and on markers of airway inflammation after allergen inhalation.Methods: The study was of a placebo-controlled, double-blind, randomized, 2-way crossover design. Sixteen subjects with mild-to-moderate asthma controlled with short-acting ?2-agonists only and with a LAR to inhaled allergen participated in the study. At one treatment period they took 20 mg of IVL745 and one treatment period placebo. Both treatments were taken twice daily for 7 days, with a single dose on day 8. Treatments were separated by a washout period of at least 2 weeks. On day 7 of each treatment period, sputum was induced and collected, and exhaled nitric oxide (NO) was measured. On day 8, an inhaled bolus allergen challenge was performed, and blood was taken for pharmacokinetics. On day 9, exhaled NO was measured, and a methacholine challenge was done. On day 10, sputum was induced and collected. Adverse events, peak expiratory flow (PEF), use of short-acting ?2-agonists, and asthma symptoms were recorded daily throughout the study.Results: There was no statistically significant difference between IVL745 and placebo in the effect on the LAR after allergen challenge, as measured by the area under the curve of the percentage change in FEV1 from the prechallenge baseline (mean [SEM], ?81.99 [18.80] after IVL745 and ?72.58 [21.29] after placebo; 95% CI of difference, ?36 to 16.8; P = .46) or by the maximum percentage change from the prechallenge baseline (mean [SEM], ?23.44 [4.73] after IVL745 and ?21.30 [5.17] after placebo; 95% CI of difference, ?11 to 6.29; P = .60). There was a statistically significant decrease in the percentage of eosinophils in sputum on day 7 of treatment with IVL745 (mean [SEM], 7.32 [1.46]) compared with placebo (mean [SEM], 15.00 [1.92]; 95% CI of difference, ?13 to ?1.2; P = .02). There was no statistically significant difference between IVL745 and placebo with respect to the early asthmatic response, methacholine hyperresponsiveness, exhaled NO, postallergen sputum, symptoms, inhaled ?2-agonist use, or PEF.Conclusion: In patients with mild-to-moderate atopic asthma, IVL745 did not affect the early and late response to inhaled allergen or markers of airway inflammation, except for a modest reduction in sputum eosinophils

L'épandage aérien des produits antiparasitaires. Rapport du groupe de travail institutionnel en charge de la saisine AFSSE

The French Minister of Ecology and Sustainable Development asked to the French Agency of environmental sanitary security (AFSSE) a report on impacts and sanitary risks of aerial applications of pesticides on population health and ecosystems. Yhis question is a consequence of the 05/03/04 modification of the 25/02/75 directive on aérial application of pesticides for crop protection.Le Ministère de l'écologie et du développement durable ainsi que le Ministère de la santé et de la protection sociale ont demandé l'avis de l'Agence française de sécurité sanitaire environnementale (AFSSE) concernant les risques sanitaires pour la population ainsi que les conséquences pour les écosystèmes de l'épandage aérien de produits anti-parasitaires. Cette saisine fait suite à la modification par la Direction générale de l'alimentation, par un arrêté en date du 5 mars 2004, de l'arrêté du 25 février 1975 relatif à l'utilisation par voie aérienne de produits anti-parasitaires à des fins de protection des végétaux