Respiratory allergic disease represents a global health problem, 30% of the population suffers from allergic rhinoconjunctivitis and 20% suffer from asthma. Allergy immunotherapy induce immunological tolerance and thereby modify the response to allergens and sublingual immunotherapy (SLIT) offers the possibility of home administration of allergen therapy, but adherence is more uncertain. The aim of the study was to investigate the adherence with GRAZAX in adults and children ≥ 5 years during three consecutive years of treatment. This was a non-interventional, prospective, observational, multi-center, open-label study to investigate adherence, quality of life, safety and tolerability of GRAZAX in adult and pediatric patients in a real-life setting. During the 3-years study period estimation of adherence was done regularly. Quality of life as well as symptom score was also assessed. In total, 399 patients (236 adults and 163 children) were included in the study. At baseline, 100% suffered from moderate-severe eyes and nose symptoms, and 31% had asthma in the grass pollen season. Overall, 55% completed a 3-years treatment period, whereas 37% stopped before end of study and 8% were lost to follow up. After 3 years, the adherence rate decreased from 98.2% (first month), 93.7% (first year), 93.2% (second year) and 88.9% (third year) and adverse events were the main reason for pre-term termination. The study suggests a good adherence to treatment in a real life setting among the patients finalizing 3-years SLIT therapy. The treatment was effective both on symptoms and HRQL.
Early asthmatic responses (EAR) and late asthmatic responses (LAR) to allergen are induced by the local release of a series of bronchoconstrictor mediators, including leukotrienes and histamine. Both anti-leukotrienes and other anti-asthma drugs, such as inhaled glucocorticoids, have been shown to reduce both EAR and LAR. The aim of the present study was to directly compare the effects of regular treatment with an oral anti-leukotriene, montelukast (Mont; 10 mg once daily, for 8 days), and an inhaled glucocorticoid [fluticasone propionate (FP) 250 microg twice daily for 8 days] on the EAR and LAR to an inhaled allergen challenge. Patients with a documented EAR and LAR at a screening visit were randomized to these treatments, or placebo, in a double-blind, double-dummy, crossover fashion. Allergen challenge at a dose causing both an EAR and LAR was given on the eighth day of treatment. The maximum fall in FEV1 during the EAR was 17.8% during placebo treatment, 8.3% during Mont and 16.3% during FP (P <0.05 for Mont vs placebo). The maximum fall during the EAR was 13.8% during placebo treatment, 11.8% during Mont and 2% during FP treatment (P <0.05 for FP vs placebo and FP vs Mont). PC20 methacholine was significantly higher 24 h after allergen challenge during FP-treatment compared with Mont (P <0.05). Both montelukast and fluticasone reduced the relative amount of sputum eosinophils after allergen compared with placebo treatment. This study shows that anti-leukotrienes are effective to attenuate the EAR, whereas inhaled glucocorticoids are more effective than anti-leukotrienes in attenuating the EARs and improves bronchial hyperresponsiveness to a greater extent. In conclusion, inhaled glucocorticoids have overall greater efficacy than oral anti-leukotrienes to attenuate allergen-induced airway responses in mild asthmatic patients.
Background: The synthetic vasoactive intestinal peptide (VIP) analogue Ro 25-1553 is a selective VIP-PACAP type 2 (VPAC 2 ) receptor agonist that causes a bronchodilatory effect in guinea pigs in vivo. The effect of Ro 25-1553 given by inhalation to patients with asthma was studied and compared with that of a long acting β 2 adrenoceptor agonist. Methods: Twenty four patients with moderate stable asthma participated in a double blind, randomised, placebo controlled, crossover study. The primary variable was bronchodilatory effect (increase in forced expiratory volume in 1 second, FEV 1 ) after inhalation of Ro 25-1553 (100 µg or 600 µg) and formoterol (4.5 µg), respectively. Putative side effects were characterised by monitoring sitting blood pressure, serum potassium, electrocardiography and echocardiography. Results: Inhalation of 600 µg Ro 25-1553 caused a rapid bronchodilatory effect (geometric mean increase in FEV 1 compared with placebo) within 3 minutes of 6% (95% CI 4 to 9), as did inhalation of formoterol (8% (95% CI 5 to 10)). The corresponding maximum bronchodilatory effect during 24 hours was similar for 600 µg Ro 25-1553 (7% (95% CI 4 to 10)) and the reference bronchodilator formoterol (10% (95% CI 7 to 12)). However, for both doses of Ro 25-1553 the bronchodilatory effect was attenuated 5 hours after inhalation whereas formoterol still had a bronchodilatory effect 12 hours after inhalation. Neither Ro 25-1553 nor formoterol produced any clinically relevant side effects. No drug related difference in adverse events was observed. Conclusion: Inhalation of a synthetic selective VPAC 2 receptor agonist constitutes a promising approach for bronchodilation in patients with asthma.
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