University of Wisconsin School of Medicine and Public Health, Madison, USA.
N Engl J Med. 2010 Mar 18;362(11):975-85. doi: 10.1056/NEJMoa1001278. Epub 2010 Mar 2.
For children who have uncontrolled asthma despite the use of low-dose inhaled corticosteroids (ICS), evidence to guide step-up therapy is lacking.
We randomly assigned 182 children (6 to 17 years of age), who had uncontrolled asthma while receiving 100 microg of fluticasone twice daily, to receive each of three blinded step-up therapies in random order for 16 weeks: 250 microg of fluticasone twice daily (ICS step-up), 100 microg of fluticasone plus 50 microg of a long-acting beta-agonist twice daily (LABA step-up), or 100 microg of fluticasone twice daily plus 5 or 10 mg of a leukotriene-receptor antagonist daily (LTRA step-up). We used a triple-crossover design and a composite of three outcomes (exacerbations, asthma-control days, and the forced expiratory volume in 1 second) to determine whether the frequency of a differential response to the step-up regimens was more than 25%.
A differential response occurred in 161 of 165 patients who were evaluated (P<0.001). The response to LABA step-up therapy was most likely to be the best response, as compared with responses to LTRA step-up (relative probability, 1.6; 95% confidence interval [CI], 1.1 to 2.3; P=0.004) and ICS step-up (relative probability, 1.7; 95% CI, 1.2 to 2.4; P=0.002). Higher scores on the Asthma Control Test before randomization (indicating better control at baseline) predicted a better response to LABA step-up (P=0.009). White race predicted a better response to LABA step-up, whereas black patients were least likely to have a best response to LTRA step-up (P=0.005).
Nearly all the children had a differential response to each step-up therapy. LABA step-up was significantly more likely to provide the best response than either ICS or LTRA step-up. However, many children had a best response to ICS or LTRA step-up therapy, highlighting the need to regularly monitor and appropriately adjust each child's asthma therapy. (ClinicalTrials.gov number, NCT00395304.)
对于尽管使用低剂量吸入皮质激素(ICS)但哮喘仍未得到控制的儿童,缺乏指导升级治疗的证据。
我们随机分配了 182 名年龄在 6 至 17 岁之间的儿童(每天两次接受 100 微克氟替卡松),他们在接受每天两次 100 微克氟替卡松治疗的同时接受了三种盲法升级治疗,顺序随机进行,为期 16 周:每天两次 250 微克氟替卡松(ICS 升级)、每天两次 100 微克氟替卡松加 50 微克长效β-激动剂(LABA 升级)或每天两次 100 微克氟替卡松加 5 或 10 毫克白三烯受体拮抗剂(LTRA 升级)。我们使用三交叉设计和三个结果(加重、哮喘控制天数和 1 秒用力呼气量)的组合来确定对升级方案的差异反应频率是否超过 25%。
在 165 名接受评估的患者中,有 161 名(P<0.001)出现了差异反应。与 LTRA 升级(相对概率,1.6;95%置信区间[CI],1.1 至 2.3;P=0.004)和 ICS 升级(相对概率,1.7;95%CI,1.2 至 2.4;P=0.002)相比,LABA 升级治疗的反应最有可能是最佳反应。在随机分组前的哮喘控制测试中获得较高的分数(表明在基线时控制较好)预示着对 LABA 升级治疗的反应更好(P=0.009)。白种人预测对 LABA 升级的反应更好,而黑人患者对 LTRA 升级的反应最差(P=0.005)。
几乎所有儿童对每种升级治疗都有差异反应。与 ICS 或 LTRA 升级相比,LABA 升级更有可能提供最佳反应。然而,许多儿童对 ICS 或 LTRA 升级治疗有最佳反应,这突出表明需要定期监测并适当调整每个儿童的哮喘治疗。(临床试验.gov 编号,NCT00395304。)