将吸入性糖皮质激素剂量增加至五倍以预防儿童哮喘发作
Quintupling Inhaled Glucocorticoids to Prevent Childhood Asthma Exacerbations.
作者信息
Jackson Daniel J, Bacharier Leonard B, Mauger David T, Boehmer Susan, Beigelman Avraham, Chmiel James F, Fitzpatrick Anne M, Gaffin Jonathan M, Morgan Wayne J, Peters Stephen P, Phipatanakul Wanda, Sheehan William J, Cabana Michael D, Holguin Fernando, Martinez Fernando D, Pongracic Jacqueline A, Baxi Sachin N, Benson Mindy, Blake Kathryn, Covar Ronina, Gentile Deborah A, Israel Elliot, Krishnan Jerry A, Kumar Harsha V, Lang Jason E, Lazarus Stephen C, Lima John J, Long Dayna, Ly Ngoc, Marbin Jyothi, Moy James N, Myers Ross E, Olin J Tod, Raissy Hengameh H, Robison Rachel G, Ross Kristie, Sorkness Christine A, Lemanske Robert F
机构信息
From the Department of Pediatrics, University of Wisconsin School of Medicine and Public Health (D.J.J., R.F.L.J.), and the University of Wisconsin-Madison (C.A.S.) - both in Madison; the Department of Pediatrics, Washington University in St. Louis School of Medicine and St. Louis Children's Hospital, St. Louis (L.B.B., A.B.); the Department of Public Health Sciences, Penn State University, Hershey (D.T.M., S.B.), and the University of Pittsburgh Asthma Institute at University of Pittsburgh Medical Center-University of Pittsburgh School of Medicine (F.H.) and the Department of Pediatrics, Allegheny General Hospital (D.A.G.), Pittsburgh - all in Pennsylvania; the Department of Pediatrics, Case Western Reserve University School of Medicine, Rainbow Babies and Children's Hospital, Cleveland (J.F.C., R.E.M., K.R.); the Department of Pediatrics, Emory University, Atlanta (A.M.F.); the Divisions of Respiratory Diseases (J.M.G.) and Allergy-Immunology, Boston Children's Hospital (W.P., W.J.S., S.N.B.), Harvard Medical School, and Brigham and Women's Hospital, Harvard Medical School (E.I.) - all in Boston; the Arizona Respiratory Center, University of Arizona, Tucson (W.J.M., F.D.M.); Wake Forest University School of Medicine, Winston-Salem, NC (S.P.P.); the Departments of Pediatrics (M.D.C., N.L.), Epidemiology (M.D.C.), Biostatistics (M.D.C.), and Medicine (S.C.L.), University of California, San Francisco (UCSF), and UCSF Benioff Children's Hospital (M.D.C.) - both in San Francisco; Ann and Robert H. Lurie Children's Hospital of Chicago (J.A.P., R.G.R.), University of Illinois at Chicago (J.A.K., H.V.K.), and the Department of Pediatrics, Stroger Hospital of Cook County, Rush University Medical Center (J.N.M.) - all in Chicago; UCSF Benioff Children's Hospital Oakland, Oakland (M.B., D.L., J.M.); Nemours Children's Health System, Jacksonville (K.B., J.J.L.), and Nemours Children's Hospital, University of Central Florida College of Medicine, Orlando (J.E.L.) - both in Florida; the Department of Pediatrics, National Jewish Health, Denver (R.C., J.T.O.); and the Department of Pediatrics, University of New Mexico, Albuquerque (H.H.R.).
出版信息
N Engl J Med. 2018 Mar 8;378(10):891-901. doi: 10.1056/NEJMoa1710988. Epub 2018 Mar 3.
BACKGROUND
Asthma exacerbations occur frequently despite the regular use of asthma-controller therapies, such as inhaled glucocorticoids. Clinicians commonly increase the doses of inhaled glucocorticoids at early signs of loss of asthma control. However, data on the safety and efficacy of this strategy in children are limited.
METHODS
We studied 254 children, 5 to 11 years of age, who had mild-to-moderate persistent asthma and had had at least one asthma exacerbation treated with systemic glucocorticoids in the previous year. Children were treated for 48 weeks with maintenance low-dose inhaled glucocorticoids (fluticasone propionate at a dose of 44 μg per inhalation, two inhalations twice daily) and were randomly assigned to either continue the same dose (low-dose group) or use a quintupled dose (high-dose group; fluticasone at a dose of 220 μg per inhalation, two inhalations twice daily) for 7 days at the early signs of loss of asthma control ("yellow zone"). Treatment was provided in a double-blind fashion. The primary outcome was the rate of severe asthma exacerbations treated with systemic glucocorticoids.
RESULTS
The rate of severe asthma exacerbations treated with systemic glucocorticoids did not differ significantly between groups (0.48 exacerbations per year in the high-dose group and 0.37 exacerbations per year in the low-dose group; relative rate, 1.3; 95% confidence interval, 0.8 to 2.1; P=0.30). The time to the first exacerbation, the rate of treatment failure, symptom scores, and albuterol use during yellow-zone episodes did not differ significantly between groups. The total glucocorticoid exposure was 16% higher in the high-dose group than in the low-dose group. The difference in linear growth between the high-dose group and the low-dose group was -0.23 cm per year (P=0.06).
CONCLUSIONS
In children with mild-to-moderate persistent asthma treated with daily inhaled glucocorticoids, quintupling the dose at the early signs of loss of asthma control did not reduce the rate of severe asthma exacerbations or improve other asthma outcomes and may be associated with diminished linear growth. (Funded by the National Heart, Lung, and Blood Institute; STICS ClinicalTrials.gov number, NCT02066129 .).
背景
尽管经常使用哮喘控制疗法，如吸入糖皮质激素，但哮喘急性发作仍频繁发生。临床医生通常在哮喘控制丧失的早期迹象出现时增加吸入糖皮质激素的剂量。然而，关于该策略在儿童中的安全性和有效性的数据有限。
方法
我们研究了254名5至11岁的儿童，他们患有轻度至中度持续性哮喘，且在前一年至少有一次哮喘急性发作接受过全身糖皮质激素治疗。儿童接受维持低剂量吸入糖皮质激素治疗48周（丙酸氟替卡松，每次吸入剂量44μg，每日两次，每次两吸），并在哮喘控制丧失的早期迹象（“黄色区域”）出现时随机分配继续使用相同剂量（低剂量组）或使用五倍剂量（高剂量组；每次吸入剂量220μg，每日两次，每次两吸），为期7天。治疗采用双盲方式。主要结局是接受全身糖皮质激素治疗的严重哮喘急性发作率。
结果
两组间接受全身糖皮质激素治疗的严重哮喘急性发作率无显著差异（高剂量组每年0.48次急性发作，低剂量组每年0.37次急性发作；相对发生率为1.3；95%置信区间为0.8至2.1；P = 0.30）。首次急性发作时间、治疗失败率、症状评分以及黄色区域发作期间沙丁胺醇的使用情况在两组间无显著差异。高剂量组的总糖皮质激素暴露量比低剂量组高16%。高剂量组与低剂量组的线性生长差异为每年-0.23cm（P = 0.06）。
结论
在接受每日吸入糖皮质激素治疗的轻度至中度持续性哮喘儿童中，在哮喘控制丧失的早期迹象出现时将剂量增加至五倍并不能降低严重哮喘急性发作率或改善其他哮喘结局，且可能与线性生长减缓有关。（由美国国立心肺血液研究所资助；STICS临床试验注册号，NCT02066129。）
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