van Rensen E L, Straathof K C, Veselic-Charvat M A, Zwinderman A H, Bel E H, Sterk P J
Department of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands.
Thorax. 1999 May;54(5):403-8. doi: 10.1136/thx.54.5.403.
Airway hyperresponsiveness, induced sputum eosinophils, and exhaled nitric oxide (NO) levels have all been proposed as non-invasive markers for monitoring airway inflammation in patients with asthma. The aim of this study was to compare the changes in each of these markers following treatment with inhaled glucocorticosteroids in a single study.
In a randomised, double blind, placebo controlled, parallel study 25 patients with mild asthma (19-34 years, forced expiratory volume in one second (FEV1) >75% predicted, concentration of histamine provoking a fall in FEV1 of 20% or more (PC20) <4 mg/ml) inhaled fluticasone propionate (500 microg twice daily) for four weeks. PC20 to histamine, sputum eosinophil numbers, and exhaled NO levels were determined at weeks 0, 2, and 4, and two weeks after completing treatment. Sputum was induced by inhalation of hypertonic (4.5%) saline and eosinophil counts were expressed as percentage non-squamous cells. Exhaled NO levels (ppb) were measured by chemiluminescence.
In the steroid treated group there was a significant increase in PC20, decrease in sputum eosinophils, and decrease in exhaled NO levels compared with baseline at weeks 2 and 4 of treatment. Subsequently, each of these variables showed significant worsening during the two week washout period compared with week 4. These changes were significantly different from those in the placebo group, except for the changes in sputum eosinophils and exhaled NO levels during the washout period. There were no significant correlations between the changes in the three markers in either group at any time.
Treatment of asthmatic subjects with inhaled steroids for four weeks leads to improvements in airway hyperresponsiveness to histamine, eosinophil counts in induced sputum, and exhaled nitric oxide levels. The results suggest that these markers may provide different information when monitoring anti-inflammatory treatment in asthma.
气道高反应性、诱导痰嗜酸性粒细胞以及呼出一氧化氮（NO）水平均被提议作为监测哮喘患者气道炎症的非侵入性标志物。本研究的目的是在一项单一研究中比较吸入糖皮质激素治疗后这些标志物各自的变化情况。
在一项随机、双盲、安慰剂对照、平行研究中，25例轻度哮喘患者（年龄19 - 34岁，一秒用力呼气容积（FEV1）>预计值的75%，组胺激发使FEV1下降20%或更多时的浓度（PC20）<4 mg/ml）吸入丙酸氟替卡松（每日两次，每次500微克），持续四周。在第0、2、4周以及完成治疗后两周测定对组胺的PC20、痰液嗜酸性粒细胞数量和呼出NO水平。通过吸入高渗（4.5%）盐水诱导痰液，嗜酸性粒细胞计数以非鳞状细胞百分比表示。呼出NO水平（ppb）通过化学发光法测量。
与治疗第2周和第4周的基线相比，类固醇治疗组的PC20显著升高，痰液嗜酸性粒细胞减少，呼出NO水平降低。随后，与第4周相比，在两周的洗脱期内这些变量均显著恶化。除了洗脱期痰液嗜酸性粒细胞和呼出NO水平的变化外，这些变化与安慰剂组的变化有显著差异。两组中这三种标志物在任何时候的变化之间均无显著相关性。
对哮喘患者吸入类固醇治疗四周可改善气道对组胺的高反应性、诱导痰中的嗜酸性粒细胞计数以及呼出一氧化氮水平。结果表明，在监测哮喘抗炎治疗时，这些标志物可能提供不同的信息。
