轻度哮喘患者乙酰甲胆碱支气管激发试验的变异性及吸入性糖皮质激素的影响
2014/04/15
摘要
背景：乙酰甲胆碱激发试验通过测定导致1秒用力呼气容积下降20% (PC20)的乙酰甲胆碱激发浓度来定量检测气道高反应性。吸入糖皮质激素（ICS）对PC20的影响并非总是剂量效应，患者自身的PC20变异性并不明确。
目的：比较高剂量和低剂量ICS对PC20的影响，并对重复测量PC20的患者检测PC20的个体变异性。
方法：该研究是一项随机、双盲、交叉试验，共64例用药并控制PC20≤8mg/ml的哮喘患者纳入研究，比较使用4周高剂量(1,000 μg/d)或低剂量(250 μg/d)氟替卡松对PC20的影响。此外，对4周前使用相同剂量ICS的患者（n=27）测量2或3次PC20，以评估PC20的变异性。
结果：由于存在显著的周期效应，我们在第一个治疗期比较PC20的剂量变化。高剂量和低剂量ICS组相比，PC20 变化无显著差异(分别增加39% vs 30%, P = 0.87)。患者自身和患者间的log PC20变异值分别为0.84 和0.96。组内相关系数为0.53，且37%的重复测量者的PC20剂量变化超过2倍。
结论：在氟替卡松使用剂量为250-1000ug/ul时，ICS与PC20不呈剂量依赖关系。PC20的个体间差异很大。在解释PC20的任何变化时，应该考虑到准确测量方法的缺少。
（刘国梁 审校）
Ann Allergy Asthma Immunol. 2014 Feb 5. pii: S1081-1206(14)00027-1. doi: 10.1016/j.anai.2014.01.013. [Epub ahead of print]
Variability of methacholinebronchoprovocation and the effect of inhaled corticosteroids in mild asthma.
Sumino K1, Sugar EA2, Irvin CG3, Kaminsky DA3, Shade D4, Wei CY4, Holbrook JT4, Wise RA5, Castro M6; Writing Committee for the American Lung Association Asthma Clinical Research Centers
Abstract
BACKGROUND: The methacholine challenge test quantifies airway hyper-responsiveness, which is measured by the provocative concentration of methacholine causing a 20% decrease in forced expiration volume in 1 second (PC20). The dose-response effect of inhaled corticosteroids (ICS) on PC20 has been inconsistent and within-patient variability of PC20 is not well established.
OBJECTIVES: To determine the effect of high- vs low-dose ICS on PC20 and within-patient variability in those with repeated measurements of PC20.
METHODS: A randomized, double-masked, crossover trial was conducted in patients with asthma on controller medications with PC20 of 8 mg/mL or lower (n = 64) to evaluate the effect of high-dose (1,000 μg/d) vs low-dose (250 μg/d) fluticasone for 4 weeks on PC20. In addition, the variability of PC20 was assessed in participants who underwent 2 or 3 PC20 measurements on the same dose of ICS (n = 27) over a 4-week interval.
RESULTS: Because there was a significant period effect, dose comparison of the change in PC20 was assessed in the first treatment period. There was no significant difference in the change in PC20 for high- vs low-dose ICS (39% vs 30% increase, respectively; P = .87). The within- and between-participant variances for log PC20 were 0.84 and 0.96, respectively, with an intra-class correlation of 0.53, and 37% of participants had more than 2 doubling dose changes in PC20 in those with repeated measurements.
CONCLUSION: The effect of ICS on PC20 is not dose dependent at fluticasone levels of 250 and 1,000 μg/d. Interpersonal variability for PC20 is large. A lack of precise measurements should be taken into account when interpreting any change in PC20.
Ann Allergy Asthma Immunol. 2014 Feb 5. pii: S1081-1206(14)00027-1. doi: 10.1016/j.anai.2014.01.013. [Epub ahead of print]
