吸入糖皮质激素应用与哮喘儿童骨折的关系
2018/01/08
摘要
重要性：日常吸入糖皮质激素在轻度持续性哮喘儿童中是广泛推荐的治疗方法。有人担心，吸入性糖皮质激素与系统应用糖皮质激素一样对骨骼健康有危害。
目的：明确哮喘儿童应用吸入糖皮质激素是否增加骨折风险。
设计，背景和参与者：在这个基于人群的巢式病例对照研究中，我们使用健康管理数据库来确定一组2至18岁，在2003年4月1日至2014年3月31日期间诊断为哮喘，可通过安大略省药物福利计划（加拿大安大略省）获得公共药物的儿童群体。我们根据出生日期（1年内），性别和哮喘诊断年龄（2年内），将诊断为哮喘后的第一次骨折的病例与无骨折对照（比例为1比4）相匹配。我们用了1年的回顾期来确定吸入糖皮质激素的使用史。用多变量条件逻辑回归比较吸入糖皮质激素没有使用与目前、近期和过去使用，获得骨折的比值比（OR）的95％可信区间。
暴露：根据1年的回顾期内吸入糖皮质激素情况，分为目前使用者（到起始日期时少于90天），最近使用者（91-180天），过去使用者（181-365天）或 未使用者。
主要结果和评价标准：哮喘诊断后首次急诊科就诊诊断骨折，判定依据“疾病及相关健康问题国际统计分类”第十次修订版。
结果：这项研究纳入了19420名儿童（61.0％的男性；6-9岁儿童占比最高，为31.5％）。多变量回归分析结果显示，与未使用吸入糖皮质激素者相比，哮喘诊断后第一次骨折与目前使用者（OR，1.07; 95％CI，0.97-1.17）、近期使用者（OR，0.96; 95％CI，0.86-1.07）和过去使用（OR，1.00; 95％CI，0.91-1.11）没有明显相关性，调整社会人口因素和其他药物使用因素后也无明显相关性。然而，在1年的回顾期内使用系统性糖皮质激素会导致更大的骨折风险（OR，1.17; 95％CI，1.04-1.33）。
结论和相关性：全身糖皮质激素使用与儿童哮喘人群中骨折增加显着相关，吸入糖皮质激素与其无相关性。
Association Between Inhaled Corticosteroid Use and Bone Fracture in Children With Asthma.
Gray N, Howard A, Zhu J, Feldman LY, To T.
Abstract
IMPORTANCE:Daily use of inhaled corticosteroids is a widely recommended treatment for mild persistent asthma in children. There is concern that, similar to systemic corticosteroids, inhaled corticosteroids may have adverse effects on bone health.
OBJECTIVE:To determine whether there is an increased risk of bone fracture associated with inhaled corticosteroid use in children with asthma.
DESIGN, SETTING, AND PARTICIPANTS:In this population-based nested case-control study, we used health administrative databases to identify a cohort of children aged 2 to 18 years with a physician diagnosis of asthma between April 1, 2003, and March 31, 2014, who were eligible for public drug coverage through the Ontario Drug Benefit Program (Ontario, Canada). We matched cases of first fracture after asthma diagnosis to fracture-free controls (ratio of 1 to 4) based on date of birth (within 1 year), sex, and age at asthma diagnosis (within 2 years). We used a 1-year lookback period to ascertain history of inhaled corticosteroid use. Multivariable conditional logistic regression was used to obtain an odds ratio (OR) with 95% confidence interval for fracture, comparing no inhaled corticosteroid use vs current, recent, and past use.
EXPOSURES:Inhaled corticosteroid use during the child's 1-year lookback period, measured as current user if the prescription was filled less than 90 days prior to the index date, recent user (91-180 days), past user (181-365 days), or no use.
MAIN OUTCOMES AND MEASURES:First emergency department visit for fracture after asthma diagnosis, identified using International Statistical Classification of Diseases and Related Health Problems, 10th Revision codes.
RESULTS:This study included 19 420 children (61.0% male; largest proportion of children, 31.5%, were aged 6-9 years at their index date). The multivariable regression results did not show a significant association between first fracture after asthma diagnosis and current use (OR, 1.07; 95% CI, 0.97-1.17), recent use (OR, 0.96; 95% CI, 0.86-1.07), or past use (OR, 1.00; 95% CI, 0.91-1.11) of inhaled corticosteroids, compared with no use, while adjusting for sociodemographic factors and other medication use. However, use of systemic corticosteroids in the 1-year lookback period resulted in greater odds of fracture (OR, 1.17; 95% CI, 1.04-1.33).
CONCLUSIONS AND RELEVANCE:Systemic corticosteroids, but not inhaled corticosteroids, were significantly associated with increased odds of fracture in the pediatric asthma population.
重要性：日常吸入糖皮质激素在轻度持续性哮喘儿童中是广泛推荐的治疗方法。有人担心，吸入性糖皮质激素与系统应用糖皮质激素一样对骨骼健康有危害。
目的：明确哮喘儿童应用吸入糖皮质激素是否增加骨折风险。
设计，背景和参与者：在这个基于人群的巢式病例对照研究中，我们使用健康管理数据库来确定一组2至18岁，在2003年4月1日至2014年3月31日期间诊断为哮喘，可通过安大略省药物福利计划（加拿大安大略省）获得公共药物的儿童群体。我们根据出生日期（1年内），性别和哮喘诊断年龄（2年内），将诊断为哮喘后的第一次骨折的病例与无骨折对照（比例为1比4）相匹配。我们用了1年的回顾期来确定吸入糖皮质激素的使用史。用多变量条件逻辑回归比较吸入糖皮质激素没有使用与目前、近期和过去使用，获得骨折的比值比（OR）的95％可信区间。
暴露：根据1年的回顾期内吸入糖皮质激素情况，分为目前使用者（到起始日期时少于90天），最近使用者（91-180天），过去使用者（181-365天）或 未使用者。
主要结果和评价标准：哮喘诊断后首次急诊科就诊诊断骨折，判定依据“疾病及相关健康问题国际统计分类”第十次修订版。
结果：这项研究纳入了19420名儿童（61.0％的男性；6-9岁儿童占比最高，为31.5％）。多变量回归分析结果显示，与未使用吸入糖皮质激素者相比，哮喘诊断后第一次骨折与目前使用者（OR，1.07; 95％CI，0.97-1.17）、近期使用者（OR，0.96; 95％CI，0.86-1.07）和过去使用（OR，1.00; 95％CI，0.91-1.11）没有明显相关性，调整社会人口因素和其他药物使用因素后也无明显相关性。然而，在1年的回顾期内使用系统性糖皮质激素会导致更大的骨折风险（OR，1.17; 95％CI，1.04-1.33）。
结论和相关性：全身糖皮质激素使用与儿童哮喘人群中骨折增加显着相关，吸入糖皮质激素与其无相关性。
(中日友好医院呼吸与危重症医学科 顾宪民 摘译 林江涛 审校)
(JAMA Pediatr. 2017 Nov 13.)
(JAMA Pediatr. 2017 Nov 13.)
Association Between Inhaled Corticosteroid Use and Bone Fracture in Children With Asthma.
Gray N, Howard A, Zhu J, Feldman LY, To T.
Abstract
IMPORTANCE:Daily use of inhaled corticosteroids is a widely recommended treatment for mild persistent asthma in children. There is concern that, similar to systemic corticosteroids, inhaled corticosteroids may have adverse effects on bone health.
OBJECTIVE:To determine whether there is an increased risk of bone fracture associated with inhaled corticosteroid use in children with asthma.
DESIGN, SETTING, AND PARTICIPANTS:In this population-based nested case-control study, we used health administrative databases to identify a cohort of children aged 2 to 18 years with a physician diagnosis of asthma between April 1, 2003, and March 31, 2014, who were eligible for public drug coverage through the Ontario Drug Benefit Program (Ontario, Canada). We matched cases of first fracture after asthma diagnosis to fracture-free controls (ratio of 1 to 4) based on date of birth (within 1 year), sex, and age at asthma diagnosis (within 2 years). We used a 1-year lookback period to ascertain history of inhaled corticosteroid use. Multivariable conditional logistic regression was used to obtain an odds ratio (OR) with 95% confidence interval for fracture, comparing no inhaled corticosteroid use vs current, recent, and past use.
EXPOSURES:Inhaled corticosteroid use during the child's 1-year lookback period, measured as current user if the prescription was filled less than 90 days prior to the index date, recent user (91-180 days), past user (181-365 days), or no use.
MAIN OUTCOMES AND MEASURES:First emergency department visit for fracture after asthma diagnosis, identified using International Statistical Classification of Diseases and Related Health Problems, 10th Revision codes.
RESULTS:This study included 19 420 children (61.0% male; largest proportion of children, 31.5%, were aged 6-9 years at their index date). The multivariable regression results did not show a significant association between first fracture after asthma diagnosis and current use (OR, 1.07; 95% CI, 0.97-1.17), recent use (OR, 0.96; 95% CI, 0.86-1.07), or past use (OR, 1.00; 95% CI, 0.91-1.11) of inhaled corticosteroids, compared with no use, while adjusting for sociodemographic factors and other medication use. However, use of systemic corticosteroids in the 1-year lookback period resulted in greater odds of fracture (OR, 1.17; 95% CI, 1.04-1.33).
CONCLUSIONS AND RELEVANCE:Systemic corticosteroids, but not inhaled corticosteroids, were significantly associated with increased odds of fracture in the pediatric asthma population.
