Asthma and Allergy Research Group, Division of Cardiovascular and Diabetes Medicine, Ninewells Hospital and Medical School, The University of Dundee, Dundee, Scotland.
Asthma and Allergy Research Group, Division of Cardiovascular and Diabetes Medicine, Ninewells Hospital and Medical School, The University of Dundee, Dundee, Scotland.
Chest. 2012 Dec;142(6):1553-1561. doi: 10.1378/chest.12-1310.
International guidelines advocate a standard approach to asthma management for all, despite its heterogeneity. "Personalized" treatment of inflammatory asthma phenotypes confers superior benefits. We wished to evaluate dose response to inhaled corticosteroids (ICSs) in patients with asthma with an elevated fractional exhaled nitric oxide (Feno) phenotype using domiciliary measurements.
We performed a randomized, crossover trial in 21 patients with mild to moderate persistent asthma receiving ICSs with elevated Feno (>30 parts per billion [ppb]) that increased further (>10 ppb) after ICS washout. Patients were randomized to 2 weeks of either fluticasone propionate 50 μg bid (FP100) or 250 μg bid (FP500). The primary outcome was response in diurnal domiciliary Feno levels. Secondary outcomes included mannitol challenge, serum eosinophilic cationic protein (ECP), blood eosinophil count, and asthma control questionnaire.
We found significant dose-related reductions of diurnal Feno compared with baseline - morning Feno: baseline = 71 ppb (95% CI, 61-83 ppb); FP100 = 34 ppb (95% CI, 29-40 ppb), P < .001; FP500 = 27 ppb (95% CI, 22-33 ppb), P < .001; and significant dose separation for morning, P < .05, and evening, P < .001. Time-series Feno displayed exponential decay: FP100 R² = 0.913, half-life = 69 h (95% CI, 50-114 h); FP500 R² = 0.966, half-life = 55 h (95% CI, 45-69 h), as well as diurnal variation. The Asthma Control Questionnaire showed significant improvements exceeding the minimal important difference (>0.5) with values in keeping with controlled asthma (<0.75) after each dose: FP100 = 0.48 (95% CI, 0.24-0.71), P = .004; FP500 = 0.37 (95% CI, 0.18-0.57), P = .001. All other secondary inflammatory related outcomes (mannitol, ECP, and eosinophils) showed significant improvements from baseline but no dose separation.
There is a significant dose response of diurnal Feno to ICS in patients with asthma with an elevated Feno phenotype, which translates into well-controlled asthma. Further interventional studies are warranted using domiciliary Feno in this specific phenotype.
ClinicalTrials.gov; No.: NCT00995657; URL: clinicaltrials.gov.
国际指南主张对所有患者采用标准化的哮喘管理方法，尽管其存在异质性。针对炎症性哮喘表型的“个体化”治疗可带来更好的获益。我们希望评估在使用家庭测量仪时，呼出一氧化氮分数（Feno）升高的哮喘患者对吸入性皮质激素（ICS）的剂量反应。
我们对 21 例接受 ICS 治疗且 Feno 升高（>30 皮克/每十亿[ppb]）的轻至中度持续性哮喘患者进行了一项随机交叉试验，这些患者在 ICS 冲洗后 Feno 进一步升高（>10 ppb）。患者被随机分配接受两周的丙酸氟替卡松 50 μg 每日两次（FP100）或 250 μg 每日两次（FP500）治疗。主要结局是日间家庭 Feno 水平的变化。次要结局包括甘露糖醇挑战、血清嗜酸性阳离子蛋白（ECP）、血嗜酸性粒细胞计数和哮喘控制问卷。
我们发现与基线相比，Feno 有显著的剂量相关性降低-清晨 Feno：基线=71 ppb（95%CI，61-83 ppb）；FP100=34 ppb（95%CI，29-40 ppb），P<.001；FP500=27 ppb（95%CI，22-33 ppb），P<.001；清晨和傍晚的 Feno 均有显著的剂量分离，P<.05 和 P<.001。时间序列 Feno 显示出指数衰减：FP100 R²=0.913，半衰期=69 h（95%CI，50-114 h）；FP500 R²=0.966，半衰期=55 h（95%CI，45-69 h），以及日间变化。哮喘控制问卷显示出显著的改善，超过了最小有意义差异（>0.5），且分值与控制良好的哮喘相符（<0.75），在每次给药后均如此：FP100=0.48（95%CI，0.24-0.71），P=.004；FP500=0.37（95%CI，0.18-0.57），P=.001。所有其他与炎症相关的次要结局（甘露糖醇、ECP 和嗜酸性粒细胞）均显示出与基线相比的显著改善，但没有剂量分离。
在 Feno 升高的哮喘患者中，ICS 对日间 Feno 有显著的剂量反应，这可转化为控制良好的哮喘。需要进一步使用家庭 Feno 进行这一特定表型的干预性研究。
ClinicalTrials.gov；编号：NCT00995657；网址：clinicaltrials.gov。
