Smith Andrew D, Cowan Jan O, Brassett Karen P, Herbison G Peter, Taylor D Robin
Respiratory Research Unit, Department of Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
N Engl J Med. 2005 May 26;352(21):2163-73. doi: 10.1056/NEJMoa043596. Epub 2005 May 24.
International guidelines for the treatment of asthma recommend adjusting the dose of inhaled corticosteroids on the basis of symptoms, bronchodilator requirements, and the results of pulmonary-function tests. Measurements of the fraction of exhaled nitric oxide (FE(NO)) constitute a noninvasive marker that may be a useful alternative for the adjustment of inhaled-corticosteroid treatment.
In a single-blind, placebo-controlled trial, we randomly assigned 97 patients with asthma who had been regularly receiving treatment with inhaled corticosteroids to have their corticosteroid dose adjusted, in a stepwise fashion, on the basis of either FE(NO) measurements or an algorithm based on conventional guidelines. After the optimal dose was determined (phase 1), patients were followed up for 12 months (phase 2). The primary outcome was the frequency of exacerbations of asthma; the secondary outcome was the mean daily dose of inhaled corticosteroid.
Forty-six patients in the FE(NO) group and 48 in the group whose asthma was treated according to conventional guidelines (the control group) completed the study. The final mean daily doses of fluticasone, the inhaled corticosteroid that was used, were 370 microg per day for the FE(NO) group (95 percent confidence interval, 263 to 477) and 641 microg per day for the control group (95 percent confidence interval, 526 to 756; P=0.003), a difference of 270 microg per day (95 percent confidence interval, 112 to 430). The rates of exacerbation were 0.49 episode per patient per year in the FE(NO) group (95 percent confidence interval, 0.20 to 0.78) and 0.90 in the control group (95 percent confidence interval, 0.31 to 1.49), representing a nonsignificant reduction of 45.6 percent (95 percent confidence interval for mean difference, -78.6 percent to 54.5 percent) in the FE(NO) group. There were no significant differences in other markers of asthma control, use of oral prednisone, pulmonary function, or levels of airway inflammation (sputum eosinophils).
With the use of FE(NO) measurements, maintenance doses of inhaled corticosteroids may be significantly reduced without compromising asthma control.
哮喘治疗的国际指南建议根据症状、支气管扩张剂使用需求以及肺功能测试结果来调整吸入性糖皮质激素的剂量。呼出一氧化氮分数（FE(NO)）测量是一种非侵入性标志物，可能是调整吸入性糖皮质激素治疗的有用替代方法。
在一项单盲、安慰剂对照试验中，我们将97例一直接受吸入性糖皮质激素常规治疗的哮喘患者随机分组，根据FE(NO)测量结果或基于传统指南的算法逐步调整其糖皮质激素剂量。确定最佳剂量后（第1阶段），对患者进行12个月的随访（第2阶段）。主要结局是哮喘加重的频率；次要结局是吸入性糖皮质激素的平均每日剂量。
FE(NO)组46例患者和按照传统指南治疗哮喘的组（对照组）48例患者完成了研究。所使用的吸入性糖皮质激素氟替卡松的最终平均每日剂量，FE(NO)组为每日370微克（95%置信区间为263至477），对照组为每日641微克（95%置信区间为526至756；P = 0.003），相差每日270微克（95%置信区间为112至430）。FE(NO)组的加重率为每名患者每年0.49次发作（95%置信区间为0.20至0.78），对照组为0.90次（95%置信区间为0.31至1.49），FE(NO)组减少了45.6%（平均差异的95%置信区间为 -78.6%至54.5%），差异无统计学意义。在哮喘控制的其他指标、口服泼尼松的使用、肺功能或气道炎症水平（痰液嗜酸性粒细胞）方面，两组无显著差异。
使用FE(NO)测量，吸入性糖皮质激素的维持剂量可显著降低，且不影响哮喘控制。
