莫米松或噻托溴铵与痰低嗜酸性粒细胞水平轻度哮喘治疗
2019/06/13
摘要
背景：在许多轻度持续性哮喘患者中，痰中嗜酸性粒细胞的百分比低于2％（低嗜酸性粒细胞水平）。最适用于这些患者的治疗方法尚不清楚。
方法：在这项为期42周的双盲交叉试验中，295名年龄至少为12岁且患有轻度持续性哮喘的患者被分组分别接受莫米松（一种吸入性糖皮质激素），噻托溴铵（一种长效毒蕈碱拮抗剂），或安慰剂。根据痰嗜酸性粒细胞水平（<2％或≥2％）对患者进行分类。主要结果是，低痰嗜酸性粒细胞水平且对试验药物中任何一种具有预先指定的差异反应的患者中，与安慰剂相比，对莫米松以及噻托溴铵的反应。反应性是综合分层结果来确定的，分层结果包括治疗失败，哮喘控制天数和1秒用力呼气容积，双侧P值小于0.025表示统计显著性。次要结果是痰嗜酸性粒细胞水平高的患者与嗜酸性粒细胞水平低的患者的结果比较。
结果：共有73％的患者嗜酸性粒细胞水平较低；在这些患者中，59％的患者对试验药物有不同的反应。然而，与安慰剂相比，对莫米松或噻托溴铵的反应没有显著差异。在低嗜酸性粒细胞水平且具有差异治疗反应的患者中，57％（95％置信区间[CI]，48-66）对莫米松的反应较好，43％（95％CI，34-52）对安慰剂具有较好的反应（P = 0.14）。相比之下，60％（95％CI，51-68）对噻托溴铵有更好的反应，而40％（95％CI，32-49）对安慰剂的反应更好（P = 0.029）。在高嗜酸性粒细胞水平的患者中，对莫米松的反应显著优于对安慰剂的反应（74％对26％），但对噻托溴铵的反应并不优于对安慰剂的反应（57％对43％）。
结论：大多数轻度持续性哮喘患者的痰嗜酸性粒细胞水平较低，与安慰剂相比，他们对莫米松或噻托溴铵的反应无显著差异。这些数据为比较低嗜酸性粒细胞水平患者应用吸入糖皮质激素或其他治疗方法提供了临床指导。
Lazarus SC, Krishnan JA, King TS, Lang JE, Blake KV, Covar R, Lugogo N, Wenzel S, Chinchilli VM, Mauger DT, Dyer AM, Boushey HA, Fahy JV, Woodruff PG, Bacharier LB, Cabana MD, Cardet JC, Castro M, Chmiel J, Denlinger L, DiMango E, Fitzpatrick AM, Gentile D, Hastie A, Holguin F, Israel E, Jackson D, Kraft M, LaForce C, Lemanske RF Jr, Martinez FD, Moore W, Morgan WJ, Moy JN, Myers R, Peters SP, Phipatanakul W, Pongracic JA, Que L, Ross K, Smith L, Szefler SJ, Wechsler ME, Sorkness CA; National Heart, Lung, and Blood Institute AsthmaNet.
Abstract
BACKGROUND:In many patients with mild, persistent asthma, the percentage of eosinophils in sputum is less than 2% (low eosinophil level). The appropriate treatment for these patients is unknown.
METHODS:In this 42-week, double-blind, crossover trial, we assigned 295 patients who were at least 12 years of age and who had mild, persistent asthma to receive mometasone (an inhaled glucocorticoid), tiotropium (a long-acting muscarinic antagonist), or placebo. The patients were categorized according to the sputum eosinophil level (<2% or ≥2%). The primary outcome was the response to mometasone as compared with placebo and to tiotropium as compared with placebo among patients with a low sputum eosinophil level who had a prespecified differential response to one of the trial agents. The response was determined according to a hierarchical composite outcome that incorporated treatment failure, asthma control days, and the forced expiratory volume in 1 second; a two-sided P value of less than 0.025 denoted statistical significance. A secondary outcome was a comparison of results in patients with a high sputum eosinophil level and those with a low level.
RESULTS:A total of 73% of the patients had a low eosinophil level; of these patients, 59% had a differential response to a trial agent. However, there was no significant difference in the response to mometasone or tiotropium, as compared with placebo. Among the patients with a low eosinophil level who had a differential treatment response, 57% (95% confidence interval [CI], 48 to 66) had a better response to mometasone, and 43% (95% CI, 34 to 52) had a better response to placebo (P = 0.14). In contrast 60% (95% CI, 51 to 68) had a better response to tiotropium, whereas 40% (95% CI, 32 to 49) had a better response to placebo (P = 0.029). Among patients with a high eosinophil level, the response to mometasone was significantly better than the response to placebo (74% vs. 26%) but the response to tiotropium was not (57% vs. 43%).
CONCLUSIONS:The majority of patients with mild, persistent asthma had a low sputum eosinophil level and had no significant difference in their response to either mometasone or tiotropium as compared with placebo. These data provide equipoise for a clinically directive trial to compare an inhaled glucocorticoid with other treatments in patients with a low eosinophil level.
背景：在许多轻度持续性哮喘患者中，痰中嗜酸性粒细胞的百分比低于2％（低嗜酸性粒细胞水平）。最适用于这些患者的治疗方法尚不清楚。
方法：在这项为期42周的双盲交叉试验中，295名年龄至少为12岁且患有轻度持续性哮喘的患者被分组分别接受莫米松（一种吸入性糖皮质激素），噻托溴铵（一种长效毒蕈碱拮抗剂），或安慰剂。根据痰嗜酸性粒细胞水平（<2％或≥2％）对患者进行分类。主要结果是，低痰嗜酸性粒细胞水平且对试验药物中任何一种具有预先指定的差异反应的患者中，与安慰剂相比，对莫米松以及噻托溴铵的反应。反应性是综合分层结果来确定的，分层结果包括治疗失败，哮喘控制天数和1秒用力呼气容积，双侧P值小于0.025表示统计显著性。次要结果是痰嗜酸性粒细胞水平高的患者与嗜酸性粒细胞水平低的患者的结果比较。
结果：共有73％的患者嗜酸性粒细胞水平较低；在这些患者中，59％的患者对试验药物有不同的反应。然而，与安慰剂相比，对莫米松或噻托溴铵的反应没有显著差异。在低嗜酸性粒细胞水平且具有差异治疗反应的患者中，57％（95％置信区间[CI]，48-66）对莫米松的反应较好，43％（95％CI，34-52）对安慰剂具有较好的反应（P = 0.14）。相比之下，60％（95％CI，51-68）对噻托溴铵有更好的反应，而40％（95％CI，32-49）对安慰剂的反应更好（P = 0.029）。在高嗜酸性粒细胞水平的患者中，对莫米松的反应显著优于对安慰剂的反应（74％对26％），但对噻托溴铵的反应并不优于对安慰剂的反应（57％对43％）。
结论：大多数轻度持续性哮喘患者的痰嗜酸性粒细胞水平较低，与安慰剂相比，他们对莫米松或噻托溴铵的反应无显著差异。这些数据为比较低嗜酸性粒细胞水平患者应用吸入糖皮质激素或其他治疗方法提供了临床指导。
(中日友好医院呼吸与危重症医学科 顾宪民 摘译 林江涛 审校)
(N Engl J Med. 2019 May 23;380(21):2009-2019. doi: 10.1056/NEJMoa1814917.)
Mometasone or Tiotropium in Mild Asthma with a Low Sputum Eosinophil Level.(N Engl J Med. 2019 May 23;380(21):2009-2019. doi: 10.1056/NEJMoa1814917.)
Lazarus SC, Krishnan JA, King TS, Lang JE, Blake KV, Covar R, Lugogo N, Wenzel S, Chinchilli VM, Mauger DT, Dyer AM, Boushey HA, Fahy JV, Woodruff PG, Bacharier LB, Cabana MD, Cardet JC, Castro M, Chmiel J, Denlinger L, DiMango E, Fitzpatrick AM, Gentile D, Hastie A, Holguin F, Israel E, Jackson D, Kraft M, LaForce C, Lemanske RF Jr, Martinez FD, Moore W, Morgan WJ, Moy JN, Myers R, Peters SP, Phipatanakul W, Pongracic JA, Que L, Ross K, Smith L, Szefler SJ, Wechsler ME, Sorkness CA; National Heart, Lung, and Blood Institute AsthmaNet.
Abstract
BACKGROUND:In many patients with mild, persistent asthma, the percentage of eosinophils in sputum is less than 2% (low eosinophil level). The appropriate treatment for these patients is unknown.
METHODS:In this 42-week, double-blind, crossover trial, we assigned 295 patients who were at least 12 years of age and who had mild, persistent asthma to receive mometasone (an inhaled glucocorticoid), tiotropium (a long-acting muscarinic antagonist), or placebo. The patients were categorized according to the sputum eosinophil level (<2% or ≥2%). The primary outcome was the response to mometasone as compared with placebo and to tiotropium as compared with placebo among patients with a low sputum eosinophil level who had a prespecified differential response to one of the trial agents. The response was determined according to a hierarchical composite outcome that incorporated treatment failure, asthma control days, and the forced expiratory volume in 1 second; a two-sided P value of less than 0.025 denoted statistical significance. A secondary outcome was a comparison of results in patients with a high sputum eosinophil level and those with a low level.
RESULTS:A total of 73% of the patients had a low eosinophil level; of these patients, 59% had a differential response to a trial agent. However, there was no significant difference in the response to mometasone or tiotropium, as compared with placebo. Among the patients with a low eosinophil level who had a differential treatment response, 57% (95% confidence interval [CI], 48 to 66) had a better response to mometasone, and 43% (95% CI, 34 to 52) had a better response to placebo (P = 0.14). In contrast 60% (95% CI, 51 to 68) had a better response to tiotropium, whereas 40% (95% CI, 32 to 49) had a better response to placebo (P = 0.029). Among patients with a high eosinophil level, the response to mometasone was significantly better than the response to placebo (74% vs. 26%) but the response to tiotropium was not (57% vs. 43%).
CONCLUSIONS:The majority of patients with mild, persistent asthma had a low sputum eosinophil level and had no significant difference in their response to either mometasone or tiotropium as compared with placebo. These data provide equipoise for a clinically directive trial to compare an inhaled glucocorticoid with other treatments in patients with a low eosinophil level.
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