黑人儿童和成人哮喘控制不佳的升级治疗
2019/10/17
摘要
背景：在黑人患者中，哮喘的发病率比白人患者高得多，但在提供治疗信息的试验中占了很小一部分。数据表明，哮喘控制不佳的患者从增加长效β-激动剂（LABA）而不是糖皮质激素中获益。然而这些数据可能无法为黑人患者提供治疗信息。
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人。 在这两项试验中，这些患者至少有一位祖父母是黑人，且哮喘的低剂量吸入糖皮质激素控制不佳。我们比较了多种治疗方法的组合，其中包括在吸入的糖皮质激素（丙酸氟替卡松）中添加LABA（沙美特罗），将氟替卡松的剂量增加一倍至五倍，或者两者兼而有之。 将治疗与使用评估哮喘发作，哮喘控制天数和肺功能的综合指标进行比较。 根据非洲基因型对数据进行了分层。
结果：当将氟替卡松的剂量增加五倍（250μg，每天两次）与添加沙美特罗（50μg，每天两次）并加倍氟替卡松（100μg，每天两次）进行比较时，两组分别有46％的儿童反应良好（P = 0.99）。 相比之下，更多的青少年和成年人对增加沙美特罗的反应优于氟替卡松的增加（沙美特罗-低剂量氟替卡松与中等剂量氟替卡松，分别为49％和28％[P = 0.003]；沙美特罗-中等剂量氟替卡松与高剂量氟替卡松，分别为49％和31％[P = 0.02]）。无论是非洲血统的程度还是基线生物标志物都不能预测对特定治疗的优越反应。增加吸入糖皮质激素的剂量与8岁以下儿童尿皮质醇与肌酐的比值降低有关。
结论：与黑人青少年和成人相反，哮喘控制不佳的黑人儿童中，有一半对吸入糖皮质激素的剂量增加有较好的反应，有一半对添加LABA有较好的反应。
Step-Up Therapy in Black Children and Adults with Poorly Controlled Asthma.
Wechsler ME, Szefler SJ, Ortega VE, Pongracic JA, Chinchilli V, Lima JJ, Krishnan JA, Kunselman SJ, Mauger D, Bleecker ER, Bacharier LB, Beigelman A, Benson M, Blake KV, Cabana MD, Cardet JC, Castro M, Chmiel JF, Covar R, Denlinger L, DiMango E, Fitzpatrick AM, Gentile D, Grossman N, Holguin F, Jackson DJ, Kumar H, Kraft M, LaForce CF, Lang J, Lazarus SC, Lemanske RF Jr, Long D, Lugogo N, Martinez F, Meyers DA, Moore WC, Moy J, Naureckas E, Olin JT, Peters SP, Phipatanakul W, Que L, Raissy H, Robison RG, Ross K, Sheehan W, Smith LJ, Solway J, Sorkness CA, Sullivan-Vedder L, Wenzel S, White S, Israel E; NHLBI AsthmaNet.
Abstract
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.
背景：在黑人患者中，哮喘的发病率比白人患者高得多，但在提供治疗信息的试验中占了很小一部分。数据表明，哮喘控制不佳的患者从增加长效β-激动剂（LABA）而不是糖皮质激素中获益。然而这些数据可能无法为黑人患者提供治疗信息。
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人。 在这两项试验中，这些患者至少有一位祖父母是黑人，且哮喘的低剂量吸入糖皮质激素控制不佳。我们比较了多种治疗方法的组合，其中包括在吸入的糖皮质激素（丙酸氟替卡松）中添加LABA（沙美特罗），将氟替卡松的剂量增加一倍至五倍，或者两者兼而有之。 将治疗与使用评估哮喘发作，哮喘控制天数和肺功能的综合指标进行比较。 根据非洲基因型对数据进行了分层。
结果：当将氟替卡松的剂量增加五倍（250μg，每天两次）与添加沙美特罗（50μg，每天两次）并加倍氟替卡松（100μg，每天两次）进行比较时，两组分别有46％的儿童反应良好（P = 0.99）。 相比之下，更多的青少年和成年人对增加沙美特罗的反应优于氟替卡松的增加（沙美特罗-低剂量氟替卡松与中等剂量氟替卡松，分别为49％和28％[P = 0.003]；沙美特罗-中等剂量氟替卡松与高剂量氟替卡松，分别为49％和31％[P = 0.02]）。无论是非洲血统的程度还是基线生物标志物都不能预测对特定治疗的优越反应。增加吸入糖皮质激素的剂量与8岁以下儿童尿皮质醇与肌酐的比值降低有关。
结论：与黑人青少年和成人相反，哮喘控制不佳的黑人儿童中，有一半对吸入糖皮质激素的剂量增加有较好的反应，有一半对添加LABA有较好的反应。
(中日友好医院呼吸与危重症医学科 王瑞茵 摘译 林江涛 审校)
(N Engl J Med. 2019 Sep 26;381(13):1227-1239. doi: 10.1056/NEJMoa1905560.)
(N Engl J Med. 2019 Sep 26;381(13):1227-1239. doi: 10.1056/NEJMoa1905560.)
Step-Up Therapy in Black Children and Adults with Poorly Controlled Asthma.
Wechsler ME, Szefler SJ, Ortega VE, Pongracic JA, Chinchilli V, Lima JJ, Krishnan JA, Kunselman SJ, Mauger D, Bleecker ER, Bacharier LB, Beigelman A, Benson M, Blake KV, Cabana MD, Cardet JC, Castro M, Chmiel JF, Covar R, Denlinger L, DiMango E, Fitzpatrick AM, Gentile D, Grossman N, Holguin F, Jackson DJ, Kumar H, Kraft M, LaForce CF, Lang J, Lazarus SC, Lemanske RF Jr, Long D, Lugogo N, Martinez F, Meyers DA, Moore WC, Moy J, Naureckas E, Olin JT, Peters SP, Phipatanakul W, Que L, Raissy H, Robison RG, Ross K, Sheehan W, Smith LJ, Solway J, Sorkness CA, Sullivan-Vedder L, Wenzel S, White S, Israel E; NHLBI AsthmaNet.
Abstract
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.
上一篇：
Transgelin-2在癌症和哮喘中的生化和临床意义
下一篇：
布地奈德-福莫特罗缓解治疗与布地奈德维持加特布他林缓解治疗成人轻中度哮喘：一项52周非盲多中心随机对照试验
