提示: 手机请竖屏浏览!

吸入型糖皮质激素剂量增至5倍用于预防儿童哮喘发作
Quintupling Inhaled Glucocorticoids to Prevent Childhood Asthma Exacerbations


Daniel J. Jackson ... 呼吸系统疾病 妇产科和儿科 • 2018.03.08
相关阅读
• 增加吸入性糖皮质激素以预防哮喘发作

摘要


背景

即使哮喘患者常规使用吸入型糖皮质激素等哮喘控制疗法,仍常出现哮喘发作。在哮喘失控的早期体征出现时,临床医师通常会增加吸入型糖皮质激素的剂量。然而这种策略用于儿童安全性和疗效的数据有限。

 

方法

我们研究了254名5~11岁的儿童,他们患轻至中度持续性哮喘,在过去一年中至少出现过1次使用全身性糖皮质激素治疗的哮喘发作。儿童接受维持剂量的小剂量吸入型糖皮质激素(剂量为44 μg/吸的丙酸氟替卡松,每次2吸,每日2次)治疗48周之后,对他们随机分组,在哮喘失控的早期体征(“黄色区域”)出现时分别继续使用相同剂量(小剂量组)或使用5倍剂量(大剂量组,剂量为220 μg/吸的氟替卡松,每次2吸,每日2次)治疗7日。以双盲方式进行治疗。主要结局是使用全身性糖皮质激素治疗的重度哮喘发作率。

 

结果

使用全身性糖皮质激素治疗的重度哮喘发作率无显著组间差异(大剂量组为0.48次发作/年,小剂量组为0.37次发作/年;相对比例,1.3;95%置信区间[CI],0.8~2.1;P=0.30)。至首次发作时间、治疗失败率、症状评分和黄色区域发作期间沙丁胺醇的使用均无显著组间差异。大剂量组比小剂量组的总糖皮质激素暴露高出16%。大剂量组与小剂量组之间线性生长的差值为-0.23 cm/年(P=0.06)。

 

结论

在患轻至中度持续性哮喘、每日使用吸入型糖皮质激素治疗的儿童中,在哮喘失控的早期体征出现时使用5倍剂量的糖皮质激素治疗,并未降低重度哮喘发作率,也未改善其他的哮喘结局,而且可能与线性生长减少有关联(由美国国立心肺血液研究所 [National Heart, Lung, and Blood Institute]资助;STICS研究在ClinicalTrials.gov注册号为NCT02066129)。





作者信息

Daniel J. Jackson, M.D., Leonard B. Bacharier, M.D., David T. Mauger, Ph.D., Susan Boehmer, M.A., Avraham Beigelman, M.D., James F. Chmiel, M.D., Anne M. Fitzpatrick, Ph.D., Jonathan M. Gaffin, M.D., Wayne J. Morgan, M.D., Stephen P. Peters, M.D., Ph.D., Wanda Phipatanakul, M.D., William J. Sheehan, M.D., Michael D. Cabana, M.D., M.P.H., Fernando Holguin, M.D., Fernando D. Martinez, M.D., Jacqueline A. Pongracic, M.D., Sachin N. Baxi, M.D., Mindy Benson, M.S.N., P.N.P., Kathryn Blake, Pharm.D., Ronina Covar, M.D., Deborah A. Gentile, M.D., Elliot Israel, M.D., Jerry A. Krishnan, M.D., Ph.D., Harsha V. Kumar, M.D., Jason E. Lang, M.D., M.P.H., Stephen C. Lazarus, M.D., John J. Lima, Pharm.D., Dayna Long, M.D., Ngoc Ly, M.D., Jyothi Marbin, M.D., James N. Moy, M.D., Ross E. Myers, M.D., J. Tod Olin, M.D., Hengameh H. Raissy, Pharm.D., Rachel G. Robison, M.D., Kristie Ross, M.D., Christine A. Sorkness, Pharm.D., and Robert F. Lemanske, Jr., M.D. for the National Heart, Lung, and Blood Institute AsthmaNet*
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.). Address reprint requests to Dr. Jackson at the Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, 600 Highland Ave., K4/936 CSC, Madison, WI 53792-9988, or at djj@medicine.wisc.edu. *A complete list of the investigators in the STICS trial is provided in the Supplementary Appendix, available at NEJM.org.

 

参考文献

1. Akinbami LJ, Moorman JE, Bailey C, et al. Trends in asthma prevalence, health care use, and mortality in the United States, 2001-2010. NCHS Data Brief 2012;94:1-8.

2. O’Byrne PM, Pedersen S, Lamm CJ, Tan WC, Busse WW. Severe exacerbations and decline in lung function in asthma. Am J Respir Crit Care Med 2009;179:19-24.

3. O’Brian AL, Lemanske RF Jr, Evans MD, Gangnon RE, Gern JE, Jackson DJ. Recurrent severe exacerbations in early life and reduced lung function at school age. J Allergy Clin Immunol 2012;129:1162-1164.

4. Sorkness CA, Lemanske RF Jr, Mauger DT, et al. Long-term comparison of 3 controller regimens for mild-moderate persistent childhood asthma: the Pediatric Asthma Controller Trial. J Allergy Clin Immunol 2007;119:64-72.

5. Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention. 2017 (http://www.ginasthma.org/).

6. Guidelines for the diagnosis and management of asthma: National Asthma Education and Prevention Program expert panel report 3. Bethesda, MD: National Heart, Lung, and Blood Institute, October 2007.

7. Thomas A, Lemanske RF Jr, Jackson DJ. Approaches to stepping up and stepping down care in asthmatic patients. J Allergy Clin Immunol 2011;128:915-926.

8. Dinakar C, Oppenheimer J, Portnoy J, et al. Management of acute loss of asthma control in the yellow zone: a practice parameter. Ann Allergy Asthma Immunol 2014;113:143-159.

9. Kew KM, Quinn M, Quon BS, Ducharme FM. Increased versus stable doses of inhaled corticosteroids for exacerbations of chronic asthma in adults and children. Cochrane Database Syst Rev 2016;6:CD007524-CD007524.

10. Oborne J, Mortimer K, Hubbard RB, Tattersfield AE, Harrison TW. Quadrupling the dose of inhaled corticosteroid to prevent asthma exacerbations: a randomized, double-blind, placebo-controlled, parallel-group clinical trial. Am J Respir Crit Care Med 2009;180:598-602.

11. Voorend-van Bergen S, Vaessen-Verberne AA, Landstra AM, et al. Monitoring childhood asthma: web-based diaries and the asthma control test. J Allergy Clin Immunol 2014;133(6):1599-605.e2.

12. Busse WW, Morgan WJ, Gergen PJ, et al. Randomized trial of omalizumab (anti-IgE) for asthma in inner-city children. N Engl J Med 2011;364:1005-1015.

13. Bacharier LB, Phillips BR, Zeiger RS, et al. Episodic use of an inhaled corticosteroid or leukotriene receptor antagonist in preschool children with moderate-to-severe intermittent wheezing. J Allergy Clin Immunol 2008;122(6):1127-1135.e8.

14. Miller MR, Hankinson J, Brusasco V, et al. Standardisation of spirometry. Eur Respir J 2005;26:319-338.

15. Wilson NM, Silverman M. Treatment of acute, episodic asthma in preschool children using intermittent high dose inhaled steroids at home. Arch Dis Child 1990;65:407-410.

16. Connett G, Lenney W. Prevention of viral induced asthma attacks using inhaled budesonide. Arch Dis Child 1993;68:85-87.

17. Volovitz B, Nussinovitch M, Finkelstein Y, Harel L, Varsano I. Effectiveness of inhaled corticosteroids in controlling acute asthma exacerbations in children at home. Clin Pediatr (Phila) 2001;40:79-86.

18. Harrison TW, Oborne J, Newton S, Tattersfield AE. Doubling the dose of inhaled corticosteroid to prevent asthma exacerbations: randomised controlled trial. Lancet 2004;363:271-275.

19. Zeiger RS, Mauger D, Bacharier LB, et al. Daily or intermittent budesonide in preschool children with recurrent wheezing. N Engl J Med 2011;365:1990-2001.

20. Ducharme FM, Lemire C, Noya FJD, et al. Preemptive use of high-dose fluticasone for virus-induced wheezing in young children. N Engl J Med 2009;360:339-353.

21. Boushey HA, Sorkness CA, King TS, et al. Daily versus as-needed corticosteroids for mild persistent asthma. N Engl J Med 2005;352:1519-1528.

22. Martinez FD, Chinchilli VM, Morgan WJ, et al. Use of beclomethasone dipropionate as rescue treatment for children with mild persistent asthma (TREXA): a randomised, double-blind, placebo-controlled trial. Lancet 2011;377:650-657.

23. Garrett J, Williams S, Wong C, Holdaway D. Treatment of acute asthmatic exacerbations with an increased dose of inhaled steroid. Arch Dis Child 1998;79:12-17.

24. Bisgaard H, Le Roux P, Bjåmer D, Dymek A, Vermeulen JH, Hultquist C. Budesonide/formoterol maintenance plus reliever therapy: a new strategy in pediatric asthma. Chest 2006;130:1733-1743.

服务条款 | 隐私政策 | 联系我们