Barnes M L, Menzies D, Nair A R, Hopkinson P J, Lipworth B J
Asthma and Allergy Research Group, Department of Medicine and Therapeutics, Ninewells Hospital and Perth Royal Infirmary, University of Dundee, Dundee DD1 9SY, Scotland, UK.
Clin Exp Allergy. 2007 May;37(5):696-703. doi: 10.1111/j.1365-2222.2007.02713.x.
The aim of this proof-of-concept study was to assess whether nasal adenosine monophosphate (AMP) challenge may be used to quantify dose response to topical fluticasone propionate (FP) in persistent allergic rhinitis (PER).
Eligible subjects with PER entered a randomized double-blind crossover study of 2 weeks of intranasal FP at 100 microg or 400 microg daily, with a 2-week placebo washout period before each randomized treatment. Measurements after each washout or treatment comprised: peak nasal inspiratory flow (PNIF) response to nasal AMP (the primary outcome), domiciliary PNIF, the mini rhinoconjunctivitis quality of life questionnaire (miniRQLQ), symptom scores, nasal nitric oxide levels and overnight urinary cortisol:creatinine ratios.
Thirteen patients completed per protocol. Maximal PNIF response to AMP was attenuated 0.9% (95% confidence interval -7.1 to 9.0, P=NS) by FP 100 microg, and 12.9% (4.8-20.9, P=0.009) by FP 400 microg. The 400-100 microg difference was 12.0% U (2.6-21.3, P=0.049). None of the other outcomes were responsive enough to detect any significant treatment effects. The standardized response means to FP 400 microg were 81% for AMP challenge, 54% for domiciliary PNIF, 53% for miniRQLQ, 24% for symptom scores and 18% for nasal nitric oxide. No adrenal suppression was detected at either dose.
FP exhibited dose-related suppression of nasal airway hyperresponsiveness to AMP challenge, but without associated detectable adrenal suppression at the higher dose. Moreover, the AMP response demonstrated the highest signal to noise ratio compared with other outcome measures in PER.
本概念验证研究的目的是评估鼻内单磷酸腺苷(AMP)激发试验是否可用于量化持续性变应性鼻炎(PER)患者对局部应用丙酸氟替卡松(FP)的剂量反应。
符合条件的PER患者进入一项随机双盲交叉研究,接受为期2周的每日100μg或400μg鼻内FP治疗,每次随机治疗前有2周的安慰剂洗脱期。每次洗脱或治疗后的测量包括:对鼻内AMP的鼻吸气峰流量(PNIF)反应(主要结局)、家庭PNIF、小型鼻结膜炎生活质量问卷(miniRQLQ)、症状评分、鼻一氧化氮水平和过夜尿皮质醇:肌酐比值。
13例患者按方案完成研究。100μg FP使AMP的最大PNIF反应减弱0.9%(95%置信区间-7.1至9.0,P=无统计学意义),400μg FP使其减弱12.9%(4.8-20.9,P=0.009)。400μg与100μg的差异为12.0%(2.6-21.3,P=0.049)。其他结局均无足够的反应性以检测到任何显著的治疗效果。400μg FP的标准化反应均值在AMP激发试验中为81%,家庭PNIF中为54%,miniRQLQ中为53%,症状评分中为24%,鼻一氧化氮中为18%。两种剂量均未检测到肾上腺抑制。
FP对AMP激发试验引起的鼻气道高反应性表现出剂量相关的抑制作用,但高剂量时未伴有可检测到的肾上腺抑制。此外,与PER的其他结局指标相比,AMP反应显示出最高的信噪比。