增敏治疗在黑人儿童和成年哮喘控制不佳患者中的应用。
Step-Up Therapy in Black Children and Adults with Poorly Controlled Asthma.
机构信息
From National Jewish Health (M.E.W., R.C., J.T.O.), Denver, and University of Colorado School of Medicine (M.E.W., S.J.S., R.C., F.H., J.T.O.) and Children's Hospital Colorado (S.J.S.), Aurora - all in Colorado; Wake Forest School of Medicine (V.E.O., W.C.M., S.P.P.), Winston-Salem, North Carolina Clinical Research (C.F.L.), Raleigh, and Duke University Medical Center (N.L., L.Q.), Durham - all in North Carolina; 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.K.), Rush University Medical Center (J.M.), University of Chicago (E.N., J.S., S. White), and Northwestern University Feinberg School of Medicine (L.J.S.) - all in Chicago; Penn State University (V.C., S.J.K., D.M.), Hershey, and Allegheny General Hospital (D.G.) and University of Pittsburgh Medical Center (S. Wenzel), Pittsburgh - all in Pennsylvania; Nemours Children's Health System, Jacksonville (J.J.L., K.V.B., J.L.), and University of South Florida Morsani College of Medicine, Tampa (J.-C.C.) - both in Florida; University of Arizona Health Sciences, Tucson (E.R.B., M.K., F.M., D.A.M.); Washington University School of Medicine, St. Louis (L.B.B., A.B., M.C.); University of California, San Francisco (UCSF), San Francisco (M.B., M.D.C., S.C.L., D.L.) and UCSF Benioff Children's Hospital, Oakland (M.B., D.L.) - both in California; Brigham and Women's Hospital and Harvard Medical School (J.-C.C., N.G., E.I.) and Boston Children's Hospital (W.P., W.S.) - all in Boston; University Hospitals Rainbow Babies and Children's Hospital, Case Western Reserve University School of Medicine, Cleveland (J.F.C., K.R.); University of Wisconsin-Madison, Madison (L.D., D.J.J., R.F.L., C.A.S.) and Aurora Sinai Medical Center, Milwaukee (L.S.-V.) - both in Wisconsin; Columbia University Irving Medical Center, New York, (E.D.); Emory University, Atlanta (A.M.F.); and University of New Mexico, Albuquerque (H.R.).
出版信息
N Engl J Med. 2019 Sep 26;381(13):1227-1239. doi: 10.1056/NEJMoa1905560.
BACKGROUND
Morbidity from asthma is disproportionately higher among black patients than among white patients, and black patients constitute the minority of participants in trials informing treatment. Data indicate that patients with inadequately controlled asthma benefit more from addition of a long-acting beta-agonist (LABA) than from increased glucocorticoids; however, these data may not be informative for treatment in black patients.
METHODS
We conducted two prospective, randomized, double-blind trials: one involving children and the other involving adolescents and adults. In both trials, the patients had at least one grandparent who identified as black and had asthma that was inadequately controlled with low-dose inhaled glucocorticoids. We compared combinations of therapy, which included the addition of a LABA (salmeterol) to an inhaled glucocorticoid (fluticasone propionate), a step-up to double to quintuple the dose of fluticasone, or both. The treatments were compared with the use of a composite measure that evaluated asthma exacerbations, asthma-control days, and lung function; data were stratified according to genotypic African ancestry.
RESULTS
When quintupling the dose of fluticasone (to 250 μg twice a day) was compared with adding salmeterol (50 μg twice a day) and doubling the fluticasone (to 100 μg twice a day), a superior response occurred in 46% of the children with quintupling the fluticasone and in 46% of the children with doubling the fluticasone and adding salmeterol (P = 0.99). In contrast, more adolescents and adults had a superior response to added salmeterol than to an increase in fluticasone (salmeterol-low-dose fluticasone vs. medium-dose fluticasone, 49% vs. 28% [P = 0.003]; salmeterol-medium-dose fluticasone vs. high-dose fluticasone, 49% vs. 31% [P = 0.02]). Neither the degree of African ancestry nor baseline biomarkers predicted a superior response to specific treatments. The increased dose of inhaled glucocorticoids was associated with a decrease in the ratio of urinary cortisol to creatinine in children younger than 8 years of age.
CONCLUSIONS
In contrast to black adolescents and adults, almost half the black children with poorly controlled asthma had a superior response to an increase in the dose of an inhaled glucocorticoid and almost half had a superior response to the addition of a LABA. (Funded by the National Heart, Lung, and Blood Institute; BARD ClinicalTrials.gov number, NCT01967173.).
背景
哮喘的发病率在黑人群体中明显高于白人群体，而参与指导治疗的试验参与者中，黑人群体构成少数。数据表明，与增加糖皮质激素相比，接受长效β激动剂（LABA）治疗的哮喘控制不佳的患者获益更多；然而，这些数据对于黑人群体的治疗可能没有参考意义。
方法
我们进行了两项前瞻性、随机、双盲试验：一项涉及儿童，另一项涉及青少年和成年人。在两项试验中，患者至少有一位祖先是黑人，并且有哮喘，低剂量吸入糖皮质激素治疗控制不佳。我们比较了两种治疗方案，一种是在吸入糖皮质激素（丙酸氟替卡松）中添加 LABA（沙美特罗），另一种是将剂量增加一倍至五倍，或两者兼用。使用综合评估哮喘加重、哮喘控制天数和肺功能的指标来比较治疗效果；根据基因型非洲血统对数据进行分层。
结果
与添加沙美特罗（50μg，每日两次）相比，将丙酸氟替卡松（250μg，每日两次）剂量增加五倍，在接受丙酸氟替卡松剂量增加五倍的儿童中，46%有更好的反应，在接受丙酸氟替卡松剂量增加一倍和添加沙美特罗的儿童中，46%有更好的反应（P=0.99）。相比之下，更多的青少年和成年人对添加沙美特罗的反应优于增加丙酸氟替卡松（沙美特罗-低剂量丙酸氟替卡松与中剂量丙酸氟替卡松相比，49%对 28%[P=0.003]；沙美特罗-中剂量丙酸氟替卡松与高剂量丙酸氟替卡松相比，49%对 31%[P=0.02]）。非洲血统的程度或基线生物标志物都不能预测对特定治疗的更好反应。吸入糖皮质激素剂量的增加与 8 岁以下儿童尿皮质醇与肌酐比值的降低有关。
结论
与黑人和成年人相比，几乎一半哮喘控制不佳的黑人儿童对吸入糖皮质激素剂量的增加有更好的反应，几乎一半对添加 LABA 有更好的反应。（由美国国立心肺血液研究所资助；BARD ClinicalTrials.gov 编号，NCT01967173。）
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