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莫米松或噻托溴胺治疗痰嗜酸性粒细胞低水平的轻度哮喘
Mometasone or Tiotropium in Mild Asthma with a Low Sputum Eosinophil Level


Stephen C. Lazarus ... 呼吸系统疾病 • 2019.05.23
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• 吸入型类固醇和长效抗毒蕈碱药对于无嗜酸性粒细胞增多的轻度哮喘患者效果如何 • 布地奈德-福莫特罗按需用药治疗轻度哮喘的对照试验 • 我们应如何治疗轻度哮喘患者 • 噻托溴铵治疗早期COPD

摘要


背景

许多轻度持续性哮喘患者的痰嗜酸性粒细胞百分比低于2%(嗜酸性粒细胞低水平)。适合这些患者的治疗方案尚不明确。

 

方法

在这项42周、双盲、交叉试验中,我们将295例年龄至少12岁的轻度持续性哮喘患者随机分组,分别接受莫米松(吸入型糖皮质激素)、噻托溴铵(长效毒蕈碱受体拮抗剂)或安慰剂治疗。我们根据痰嗜酸性粒细胞水平(<2%或≥2%)对患者进行分类。主要结局是在对一种试验药物有预设差异化应答的痰嗜酸性粒细胞低水平患者中,与安慰剂相比对莫米松产生的应答,以及与安慰剂相比对噻托溴铵产生的应答。根据分级复合结局(包括治疗失败、哮喘控制天数和第一秒用力呼气量)确定应答情况;双侧P值小于0.025表示统计学显著。次要结局是痰嗜酸性粒细胞高水平患者和低水平患者的结果比较。

 

结果

共有73%的患者为嗜酸性粒细胞低水平,其中59%对一种试验药物有差异化应答。然而,将与安慰剂相比的莫米松应答结果和与安慰剂相比的噻托溴铵应答结果进行比较,两者无显著差异。在有差异化应答且嗜酸性粒细胞低水平的患者中,57%(95%置信区间[CI],48%~66%)对莫米松的应答较优,43%(95% CI,34%~52%)对安慰剂的应答较优(P=0.14)。相比之下,60%(95% CI,51%~68%)对噻托溴铵的应答较优,而40%(95% CI,32%~49%)对安慰剂的应答较优(P=0.029)。在嗜酸性粒细胞高水平患者中,对莫米松的应答显著优于对安慰剂的应答(74% vs. 26%),但对噻托溴铵的应答并未显著优于对安慰剂的应答(57% vs. 43%)。

 

结论

大部分轻度持续性哮喘患者为痰嗜酸性粒细胞低水平,并且将与安慰剂相比的莫米松应答结果和与安慰剂相比的噻托溴铵应答结果进行比较,两者无显著差异。这些数据表明了临床均势,因此可在嗜酸性粒细胞低水平患者中开展比较吸入型糖皮质激素和其他疗法,并对临床实践具有指导意义的试验(由美国国立心肺血液研究所[National Heart, Lung, and Blood Institute]等资助;SIENA在ClinicalTrials.gov注册号为NCT02066298)。





作者信息

Stephen C. Lazarus, M.D., Jerry A. Krishnan, M.D., Ph.D., Tonya S. King, Ph.D., Jason E. Lang, M.D., Kathryn V. Blake, Pharm.D., Ronina Covar, M.D., Njira Lugogo, M.D., Sally Wenzel, M.D., Vernon M. Chinchilli, Ph.D., David T. Mauger, Ph.D., Anne-Marie Dyer, M.S., Homer A. Boushey, M.D., John V. Fahy, M.D., Prescott G. Woodruff, M.D., Leonard B. Bacharier, M.D., Michael D. Cabana, M.D., Juan C. Cardet, M.D., Mario Castro, M.D., James Chmiel, M.D., Loren Denlinger, M.D., Ph.D., Emily DiMango, M.D., Anne M. Fitzpatrick, Ph.D., Deborah Gentile, M.D., Annette Hastie, Ph.D., Fernando Holguin, M.D., Elliot Israel, M.D., Daniel Jackson, M.D., Monica Kraft, M.D., Craig LaForce, M.D., Robert F. Lemanske, Jr., M.D., Fernando D. Martinez, M.D., Wendy Moore, M.D., Wayne J. Morgan, M.D., James N. Moy, M.D., Ross Myers, M.D., Stephen P. Peters, M.D., Ph.D., Wanda Phipatanakul, M.D., Jacqueline A. Pongracic, M.D., Loretta Que, M.D., Kristie Ross, M.D., Lewis Smith, M.D., Stanley J. Szefler, M.D., Michael E. Wechsler, M.D., and Christine A. Sorkness, Pharm.D. for the National Heart, Lung, and Blood Institute AsthmaNet*
From the Division of Pulmonary and Critical Care Medicine and the Cardiovascular Research Institute (S.C.L., H.A.B., J.V.F., P.G.W.) and the Department of Pediatrics, Epidemiology, and Biostatistics (M.D.C.), University of California, San Francisco, San Francisco; the University of Illinois at Chicago (J.A.K.), the Department of Pediatrics, Rush University Medical Center (J.N.M.), Ann and Robert Lurie Children’s Hospital of Chicago (J.A.P.), and Northwestern University, Feinberg School of Medicine (L.S.) — all in Chicago; the Department of Public Health Sciences, Penn State University, Hershey (T.S.K., V.M.C., D.T.M., A.-M.D.), and the University of Pittsburgh Asthma Institute (S.W., F.H.) and Allegheny General Hospital (D.G.), Pittsburgh — all in Pennsylvania; Nemours Children’s Hospital, University of Central Florida College of Medicine, Orlando (J.E.L., K.V.B.), and Nemours Children’s Health System, Jacksonville (J.E.L., K.V.B.) — both in Florida; the Department of Pediatrics and Medicine, National Jewish Health, Denver (R.C., S.J.S., M.E.W.), and Children’s Hospital Colorado, Aurora (R.C., S.J.S., M.E.W.) — both in Colorado; Duke Allergy, Asthma, and Airway Center, Duke University School of Medicine, Durham (N.L., M.K., L.Q.), Wake Forest University School of Medicine, Winston-Salem (A.H., W.M., S.P.P.), and North Carolina Clinical Research, Raleigh (C.L.) — all in North Carolina; the Departments of Pediatrics and Medicine, Washington University in St. Louis School of Medicine, St. Louis (L.B.B., M.C.); Brigham and Women’s Hospital and Harvard Medical School (J.C.C., E.I.) and Boston Children’s Hospital (W.P.) — all in Boston; Rainbow Babies and Children’s Hospital, Cleveland (J.C., R.M., K.R.); the University of Wisconsin, Madison (L.D., D.J., R.F.L., C.A.S.); Columbia University, New York (E.D.); the Department of Pediatrics, Emory University, Atlanta (A.M.F.); and the Arizona Respiratory Center, University of Arizona, Tucson (F.D.M., W.J.M.). Address reprint requests to Dr. Lazarus at the Division of Pulmonary and Critical Care Medicine and the Cardiovascular Research Institute, University of California, San Francisco, M-1336, 505 Parnassus Ave., San Francisco, CA 94143, or at lazma@ucsf.edu. *A complete list of the investigators in the National Heart, Lung, and Blood Institute AsthmaNet is provided in the Supplementary Appendix, available at NEJM.org.

 

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