长期应用全身糖皮质激素对重症哮喘的影响：英国回顾性队列分析
2017/12/20
摘要
目的：全身应用糖皮质激素（SGCs）是重症哮喘的治疗方式，但其应用与不良事件（AES）的发展有关。关于应用SGC及其剂量和重症哮喘发生AE风险之间的关系程度的证据是有限的。
方法：重症哮喘患者（全球哮喘倡议的4或5级），根据英国的临床实践研究数据链数据库（2004-2012）确定的重症哮喘患者，在<6-12月没有应用全身糖皮质激素。对在8年观察期内患者是否应用SGC和SGC相关AE事件（白内障、糖尿病、心肌梗死[MI]、骨质疏松症、消化性溃疡或中风）进行评价。使用AE特定Cox比例风险模型确定SGC相关的AE与SGC的剂量相关的风险。
结果：总体而言，在8年随访时间里60418名确诊为重度哮喘的患者中有75%人接受了SGC 治疗，大多数剂量为平均0-2.5毫克/天。与没有应用SGC的患者相比，在应用低剂量SGC（0-2.5 SGC毫克/天)时，糖尿病（危险比：1.20）[ 95%置信度]间期（CI）：1.11，1.30 ]，MI（HR：1.25 [ 95% CI：1.09，1.43 ]）和骨质疏松症的发病风险（HR为1.64 [ 95%可信区间：1.51，1.78 ]）都是增加的，随着SGC剂量增加到> 2.5毫克/天，其发病风险也随之增加。与没有应用SGC的患者相比，应用SGC增加消化性溃疡的风险，但与应用SGC的剂量无关。是否应用SGC对于中风的风险是不变的。
结论：大多数应用SGC的重症哮喘患者其SGC相关的AE风险是增加的。这表明哮喘治疗指南应减少对应用SGC的推荐程度。
The impact of long-term systemic glucocorticoid use in severe asthma: A UK retrospective cohort analysis.
Daugherty J(1)(2), Lin X(3), Baxter R(4), Suruki R(5)(6), Bradford E(7).
Absract
OBJECTIVE:Systemic glucocorticoids (SGCs) are a treatment option for severeasthma but are associated with the development of adverse events (AEs). Evidenceon the extent of SGC use and the relationship between SGC dose and AE risk in
severe asthma is limited.
METHODS: Patients with severe asthma (Global Initiative for Asthma step 4/5),with no SGC use during the <6-12 months before severe asthma determination (indexdate) were identified in the UK-based Clinical Practice Research Datalink
database (2004-2012). Patients were assessed for SGC exposure and an incidentdiagnosis of an SGC-related AE (cataracts, diabetes, myocardial infarction [MI],osteoporosis, peptic ulcer or stroke) during the 8-year observation phase. Thedose-related risk of an SGC-related AE was determined using AE-specific Coxproportional hazards models.
RESULTS: Overall, 75% of 60,418 patients identified with severe asthma receivedSGC during the 8-year follow-up, with the majority receiving an average of>0-≤2.5 mg/day. The risk of diabetes (hazard ratio [HR]:1.20 [95% confidenceinterval (CI): 1.11, 1.30]), MI (HR: 1.25 [95% CI: 1.09, 1.43]) and osteoporosis(HR: 1.64 [95% CI: 1.51, 1.78]) was increased at low SGC doses (0-2.5 mg/day),
with further risk increases at doses >2.5 mg/day versus no SGC use. Compared withno SGC use, SGC increased the risk of peptic ulcer in a non-dose-dependentmanner, but the risk of stroke was unchanged.
CONCLUSIONS: Most patients with severe asthma are exposed to SGC, which increases SGC-related AE risk. This suggests that SGC exposure should be minimized as recommended by asthma treatment guidelines.
目的：全身应用糖皮质激素（SGCs）是重症哮喘的治疗方式，但其应用与不良事件（AES）的发展有关。关于应用SGC及其剂量和重症哮喘发生AE风险之间的关系程度的证据是有限的。
方法：重症哮喘患者（全球哮喘倡议的4或5级），根据英国的临床实践研究数据链数据库（2004-2012）确定的重症哮喘患者，在<6-12月没有应用全身糖皮质激素。对在8年观察期内患者是否应用SGC和SGC相关AE事件（白内障、糖尿病、心肌梗死[MI]、骨质疏松症、消化性溃疡或中风）进行评价。使用AE特定Cox比例风险模型确定SGC相关的AE与SGC的剂量相关的风险。
结果：总体而言，在8年随访时间里60418名确诊为重度哮喘的患者中有75%人接受了SGC 治疗，大多数剂量为平均0-2.5毫克/天。与没有应用SGC的患者相比，在应用低剂量SGC（0-2.5 SGC毫克/天)时，糖尿病（危险比：1.20）[ 95%置信度]间期（CI）：1.11，1.30 ]，MI（HR：1.25 [ 95% CI：1.09，1.43 ]）和骨质疏松症的发病风险（HR为1.64 [ 95%可信区间：1.51，1.78 ]）都是增加的，随着SGC剂量增加到> 2.5毫克/天，其发病风险也随之增加。与没有应用SGC的患者相比，应用SGC增加消化性溃疡的风险，但与应用SGC的剂量无关。是否应用SGC对于中风的风险是不变的。
结论：大多数应用SGC的重症哮喘患者其SGC相关的AE风险是增加的。这表明哮喘治疗指南应减少对应用SGC的推荐程度。
（中日友好医院呼吸与危重症医学科 禹汶伯 摘译 林江涛 审校）
（J Asthma. 2017 Sep 19:1-8. doi: 10.1080/02770903.2017.1353612. [Epub ahead of print]）
The impact of long-term systemic glucocorticoid use in severe asthma: A UK retrospective cohort analysis.
Daugherty J(1)(2), Lin X(3), Baxter R(4), Suruki R(5)(6), Bradford E(7).
Absract
OBJECTIVE:Systemic glucocorticoids (SGCs) are a treatment option for severeasthma but are associated with the development of adverse events (AEs). Evidenceon the extent of SGC use and the relationship between SGC dose and AE risk in
severe asthma is limited.
METHODS: Patients with severe asthma (Global Initiative for Asthma step 4/5),with no SGC use during the <6-12 months before severe asthma determination (indexdate) were identified in the UK-based Clinical Practice Research Datalink
database (2004-2012). Patients were assessed for SGC exposure and an incidentdiagnosis of an SGC-related AE (cataracts, diabetes, myocardial infarction [MI],osteoporosis, peptic ulcer or stroke) during the 8-year observation phase. Thedose-related risk of an SGC-related AE was determined using AE-specific Coxproportional hazards models.
RESULTS: Overall, 75% of 60,418 patients identified with severe asthma receivedSGC during the 8-year follow-up, with the majority receiving an average of>0-≤2.5 mg/day. The risk of diabetes (hazard ratio [HR]:1.20 [95% confidenceinterval (CI): 1.11, 1.30]), MI (HR: 1.25 [95% CI: 1.09, 1.43]) and osteoporosis(HR: 1.64 [95% CI: 1.51, 1.78]) was increased at low SGC doses (0-2.5 mg/day),
with further risk increases at doses >2.5 mg/day versus no SGC use. Compared withno SGC use, SGC increased the risk of peptic ulcer in a non-dose-dependentmanner, but the risk of stroke was unchanged.
CONCLUSIONS: Most patients with severe asthma are exposed to SGC, which increases SGC-related AE risk. This suggests that SGC exposure should be minimized as recommended by asthma treatment guidelines.
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哮喘表型：咳嗽和喘息是否预示持续性哮喘的加重？
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