Jatakanon A, Kharitonov S, Lim S, Barnes P J
Department of Thoracic Medicine, Imperial College School of Medicine at National Heart and Lung Institute, London, UK.
Thorax. 1999 Feb;54(2):108-14. doi: 10.1136/thx.54.2.108.
It is desirable to prescribe the minimal effective dose of inhaled steroids to control asthma. To ensure that inflammation is suppressed whilst using the lowest possible dose, a sensitive and specific method for assessing airway inflammation is needed.
The usefulness of exhaled nitric oxide (NO), sputum eosinophils, and methacholine airway responsiveness (PC20) for monitoring airway inflammatory changes following four weeks of treatment with an inhaled corticosteroid (budesonide via Turbohaler) were compared. Mild stable steroid naive asthmatic subjects were randomised into two double blind, placebo controlled studies. The first was a parallel group study involving three groups receiving either 100 micrograms/day budesonide (n = 8), 400 micrograms/day budesonide (n = 7), or a matched placebo (n = 6). The second was a crossover study involving 10 subjects randomised to receive 1600 micrograms budesonide or placebo. The groups were matched with respect to age, PC20, baseline FEV1 (% predicted), exhaled NO, and sputum eosinophilia.
There were significant improvements in FEV1 following 400 micrograms and 1600 micrograms budesonide (11.3% and 6.5%, respectively, p < 0.05). This was accompanied by significant reductions in eosinophil numbers in induced sputum (0.7 and 0.9 fold, p < 0.05). However, levels of exhaled NO were reduced following each budesonide dose while PC20 was improved only with 1600 micrograms budesonide. These results suggest that exhaled NO and PC20 may not reflect the control of airway inflammation as accurately as the number of eosinophils in sputum. There were dose dependent changes in exhaled NO, sputum eosinophils, and PC20 to inhaled budesonide but a plateau response of exhaled NO was found at a dose of 400 micrograms daily.
Monitoring the number of eosinophils in induced sputum may be the most accurate guide to establish the minimum dose of inhaled steroids needed to control inflammation. This, however, requires further studies involving a larger number of patients.
理想的做法是开具吸入性类固醇的最小有效剂量以控制哮喘。为确保在使用尽可能低的剂量时炎症得到抑制，需要一种灵敏且特异的评估气道炎症的方法。
比较了呼出一氧化氮（NO）、痰液嗜酸性粒细胞以及乙酰甲胆碱气道反应性（PC20）在吸入性皮质类固醇（通过都保使用布地奈德）治疗四周后监测气道炎症变化的效用。轻度稳定、未使用过类固醇的哮喘患者被随机分为两项双盲、安慰剂对照研究。第一项是平行组研究，涉及三组，分别接受100微克/天布地奈德（n = 8）、400微克/天布地奈德（n = 7）或匹配的安慰剂（n = 6）。第二项是交叉研究，涉及10名受试者，随机接受1600微克布地奈德或安慰剂。各组在年龄、PC20、基线第一秒用力呼气容积（预计值百分比）、呼出NO以及痰液嗜酸性粒细胞增多方面相匹配。
400微克和1600微克布地奈德治疗后第一秒用力呼气容积有显著改善（分别为11.3%和6.5%，p < 0.05）。这伴随着诱导痰液中嗜酸性粒细胞数量显著减少（分别减少0.7倍和0.9倍，p < 0.05）。然而，每个布地奈德剂量后呼出NO水平均降低，而PC20仅在使用1600微克布地奈德时得到改善。这些结果表明，呼出NO和PC20可能不如痰液中嗜酸性粒细胞数量那样准确地反映气道炎症的控制情况。呼出NO、痰液嗜酸性粒细胞以及PC20对吸入布地奈德有剂量依赖性变化，但发现每日剂量为400微克时呼出NO出现平台反应。
监测诱导痰液中嗜酸性粒细胞数量可能是确定控制炎症所需吸入性类固醇最小剂量的最准确指导。然而，这需要涉及更多患者的进一步研究。
