哮喘联盟

   摘要
   背景：哮喘治疗需要有效的抗炎疗法，但如果没有糖皮质激素引起的全身不良反应更好。
   目的：研究旨在评估吸入性非甾体糖皮质激素受体激动剂AZD5423对过敏原诱发的反应的影响。
   方法：一项双盲、四阶段的交叉研究，20例轻度过敏性哮喘受试者随机接受为期7天的AZD5423雾化治疗(75 或300 μg，一天一次)、布地奈德都保（200 μg，一天两次）或安慰剂治疗。第6天给予过敏原刺激。
   结果：给予过敏原刺激后连续监测7小时早期和晚期哮喘反应的FEV1。过敏原刺激前和刺激后7小时、24小时检测痰液炎症细胞，过敏原刺激前和刺激后24小时检测乙酰甲胆碱气道反应。与安慰剂组（FEV1下降14%）相比，AZD5423可以显著减轻晚期哮喘反应期间的FEV1下降（两种剂量均下降8.7%）(P < 0.05)，布地奈德（FEV1下降12.5%）与安慰剂相比无显著差异（P> 0.05）。但对早期哮喘反应期间的FEV1下降无影响。AZD5423 300μg和75 μg可以显著降低过敏原引起的痰液中嗜酸性粒细胞的数量（与安慰剂相比，过敏原刺激后7小时分别降低63%和61%，24小时分别降低46%和34%(P值均＜0.05）。与安慰剂相比，布地奈德不减少过敏原引起的痰液中嗜酸性粒细胞的数量。与安慰剂比相比，300ug AZD5423可以显著降低过敏原刺激24小时后的气道高反应性(P<0.05)。两种剂量AZD5423的耐受性均良好。
   结论：使用吸入非甾体糖皮质激素受体激动剂AZD5423 治疗7天，可以有效降低轻度哮喘患者过敏原引起的气道反应。
 

（杨冬 审校）
Am J Respir Crit CareMed. 2015Jan15;191(2):161-7.doi:10.1164/rccm.201404-0623OC.
 

A nonsteroidal glucocorticoid receptor agonist inhibits allergen-induced late asthmatic responses.
 

Gauvreau GM1, Boulet LP, Leigh R, Cockcroft DW, Killian KJ, Davis BE, Deschesnes F, Watson RM, Swystun V,Mårdh CK, Wessman P, Jorup C, Aurivillius M, O'Byrne PM.

Author information
 

Abstract
RATIONALE:Effective antiinflammatory therapies are needed for the treatment of asthma, but preferably without the systemic adverse effects of glucocorticosteroids.
OBJECTIVES:We evaluated the effect of an inhaled nonsteroidal glucocorticoid receptor agonist, AZD5423, on allergen-induced responses.
METHODS:Twenty subjects with mild allergic asthma were randomized to receive 7 days of treatment with nebulized AZD5423 (75 or 300 μg) once daily, budesonide 200 μg twice daily via Turbuhaler, or placebo in a double-blind, four-period, crossover design study. Allergen challenge was performed on Day 6.
MEASUREMENTS AND MAIN RESULTS:FEV1 was measured repeatedly for 7 hours after allergen challenge for early and late asthmatic responses. Sputum inflammatory cells was measured before and at 7 and 24 hours after allergen challenge, and methacholine airway responsiveness was measured before and 24 hours after allergen challenge. AZD5423 significantly attenuated the fall in FEV1 during the late asthmatic response (both doses led to an 8.7% fall) versus placebo (14% fall) (P < 0.05) with no effect of budesonide (12.5% fall) versus placebo (P > 0.05). There was no effect on the fall in FEV1 during early asthmatic response.
AZD5423 300 and 75 μg significantly attenuated allergen-induced sputum eosinophilia by 63 and 61% at 7 hours, respectively, and by 46 and 34% at 24 hours after allergen challenge, respectively, versus placebo (all P < 0.05). Budesonide did not reduce allergen-induced sputum eosinophilia versus placebo. AZD5423 at 300 μg significantly attenuated allergen-induced airway hyperresponsiveness at 24 hours after allergen challenge versus placebo (P < 0.05). Both doses of AZD5423 were well tolerated.
CONCLUSIONS:Seven-day treatment with inhalation of the nonsteroidal glucocorticoid receptor agonist AZD5423 effectively reduced allergen-induced responses in subjects with mild allergic asthma. Clinical trialregistered with www.clinicaltrials.gov (NCT01225549).
 

Am J Respir Crit CareMed. 2015Jan15;191(2):161-7.doi:10.1164/rccm.201404-0623OC.