哮喘联盟

   摘要
   目的：该项在过敏性哮喘患者中进行的设计良好的对照研究，评价了呼出气一氧化氮(FeNO)浓度与痰液嗜酸性粒细胞对吸入糖皮质激素联合一种长效β2受体激动剂治疗的浓度依赖性。研究者采用FeNO和痰嗜酸粒细胞改变百分比来评价过敏性哮喘患者的气道炎症反应，旨在明确糠酸莫米松/福莫特罗(MF/F)的剂量依赖效应特征。
   方法：在2周开放标签入组期后进入为期2周的双盲治疗期，仅使用短效β2受体激动剂进行按需缓解治疗的93例受试者（≥12岁），随机接受1天2次（BID）的安慰剂，MF/F 100/10 μg、200/10 μg或400/10 μg（压力定量吸入气雾剂[MDI]），以及MF-MDI 200 μg或MF 200 μg（干粉吸入剂[DPI]）治疗。
   结果：治疗组所有观察时间点的FeNO自基线下降的百分比均显著高于安慰剂组（P ≤ 0.034）。治疗终点时，MF/F治疗组的FeNO下降平均值范围为-35.3%～-61.4%。治疗终点时，MF/F 200/10 μg、MF/F 400/10 μg和 MF-DPI 200 μg组痰嗜酸性粒细胞自基线的下降百分比均显著高于安慰剂组（P ≤ 0.023）。所有观察时间点的FeNO（P ≤ 0.001）和痰嗜酸性粒细胞（P ≤ 0.022）水平随MF/F剂量的逐渐递增呈剂量-依赖性的显著降低。所有治疗均耐受良好；并未观察到严重不良事件。
   结论：三个MF/F剂量在降低FeNO水平上都具有显著的临床疗效，并呈剂量依赖性，MF/F 200/10 μg和MF/F 400/10 μg可显著降低痰嗜酸性粒细胞水平。这些结果提示，上述两种炎症标记物均可用来评价哮喘患者对糖皮质激素的治疗反应，并且还可能有助于甄别哮喘亚型。
 

（林江涛 审校）
RespirMed.2013Mar9.pii:S0954-6111(13)00059-0.doi:10.1016/j.rmed.2013.02.01.[Epub ahead of print]

 

Dose-dependent anti-inflammatory effect of inhaled mometasone furoate/formoterol in subjects with asthma.

Nolte H, Pavord I, Backer V, Spector S, Shekar T, Gates D, Nair P, Hargreave F.

Source
Merck Sharp & Dohme Corp., Whitehouse Station, NJ 08889, USA. Electronic address: hendrik.nolte@merck.com.

Abstract
OBJECTIVE:A well-controlled study in patients with allergic asthma was warranted to assess dose-dependency between fractional concentration of exhaled nitric oxide (FeNO) and sputum eosinophils to a combination of an inhaled corticosteroid plus a long-acting β2-agonist. We sought to characterize the dose-dependency of mometasone furoate/formoterol (MF/F) using FeNO and sputum eosinophil percentage as surrogates of airway inflammation in subjects with allergic asthma.
METHODS:Following a 2-week, open-label run-in, 93 subjects (≥12 y) using only short-acting beta agonist reliever medication as needed, were randomized to twice daily (BID) placebo; MF/F 100/10 μg, 200/10 μg, or 400/10 μg (via pressurized metered-dose inhaler [MDI]); MF-MDI 200 μg; or MF 200 μg via dry powder inhaler (DPI) during a 2-week, double-blind treatment period.
RESULTS:All active treatments demonstrated significant percentage reductions from baseline in FeNO compared with placebo at all time points (P ≤ 0.034). At endpoint, mean MF/F treatment group FeNO reductions ranged from -35.3% to -61.4%. Sputum eosinophil percentage reductions from baseline were significant compared with placebo for the MF/F 200/10 μg, MF/F 400/10 μg, and MF-DPI 200 μg groups at endpoint (P ≤ 0.023). Escalating MF/F doses significantly reduced both FeNO (P ≤ 0.001) and sputum eosinophil (P ≤ 0.022) levels in a dose-dependent manner at all time points. All treatments were well tolerated; no serious adverse events were observed.
CONCLUSION:All 3 MF/F doses demonstrated pronounced, clinically meaningful, dose-dependent reductions in FeNO, with reduced sputum eosinophil levels for MF/F 200/10 μg and MF/F 400/10 μg. These findings suggest both inflammatory markers may be useful in assessing corticosteroid responsiveness in asthma patients, and perhaps identifying the same asthma sub phenotype. Clinical Trials.gov: NCT00635882.

RespirMed.2013 Mar 9. pii: S0954-6111(13)00059-0. doi: 10.1016/j.rmed.2013.02.010. [Epub ahead of print]