口服低剂量皮质类固醇与哮喘共患病发病率和死亡率增加相关
2022/02/28
摘要
已知重症哮喘患者长期口服皮质类固醇（OCS）治疗会引起显著的不良反应，但对一般哮喘人群低剂量暴露的影响了解有限。研究目的是在丹麦全国范围内的哮喘人群中探索这一点。纳入1999年至2018年期间，丹麦全国范围内登记的18-45岁的哮喘药物使用者，并在开放队列设计中进行前瞻性跟踪。OCS使用者与非使用者的倾向性得分为1:4。采用Cox回归分析了OCS使用与共患病之间的关系。评估死亡率、死因和计划外住院率。OCS使用者（n=30352）与非使用者（n=121408）相比，所有结果的风险均增加，且从累积剂量开始存在明显的剂量-反应关系≤500毫克（泼尼松龙）。危险比范围从骨折的1.24（95% CI 1.18-1.30）到肾上腺功能不全的8.53（95% CI 3.97-18.33）。抑郁/焦虑的发病率差异最大，为每1000人年4.3例（95% CI 3.6-5.0）。OCS使用者和非使用者的哮喘特异性死亡率通常较低，分别为每1000人年0.15（95% CI 0.11-0.20）和0.04（95% CI 0.02-0.06）。随着OCS的增加，死亡率和计划外就医率增加。对研究结果的解释应考虑到其观察性质。然而，我们发现，即使在累积暴露量较低的情况下，OCS在哮喘治疗中也会增加共患病风险、死亡率和计划外就医。优化哮喘控制和减少OCS使用的有效策略在哮喘管理中至关重要。
Low dose oral corticosteroids in asthma associates with increased morbidity and mortality
Inge Raadal Skov, Hanne Madsen, Daniel Pilsgaard Henriksen, Jacob Harbo Andersen, Anton Pottegård, Jesper Rømhild Davidsen
Abstract
Long-term oral corticosteroid (OCS) treatment for severe asthma is known to cause significant adverse effects, but knowledge on effects of lower exposures in general asthma populations is limited. We aimed to explore this in a nationwide Danish asthma population.Users of asthma medication aged 18-45 were identified in the Danish nationwide registers during 1999-2018 and followed prospectively in an open cohort design. Incident OCS-users were matched 1:4 to non-users by propensity scores with replacement. Associations between OCS use and incident comorbidities were examined by Cox regression. Mortality rates, causes of death, and rates of unscheduled hospital visits were assessed.OCS-users (n 30,352) had, compared to non-users (n 121,408), an increased risk of all outcomes with evident dose-response relationships starting at cumulative doses of ≤500 mg (prednisolone equivalents). Hazard ratios ranged from 1.24 (95% CI 1.18-1.30) for fractures to 8.53 (95% CI 3.97-18.33) for adrenal insufficiency. Depression/anxiety had the highest incidence rate difference at 4.3 (95% CI 3.6-5.0) per 1000 person years. Asthma-specific mortality rates were generally low at 0.15 (95% CI 0.11-0.20) and 0.04 (95% CI 0.02-0.06) per 1000 person years for OCS-users and non-users, respectively. Mortality rates and unscheduled hospital visits increased with increasing OCS exposure.The study findings should be interpreted with their observational nature in mind. However, we found that even at low cumulative exposure, OCS use in asthma management was associated with increased risk of comorbidities, mortality, and unscheduled hospital visits. Effective strategies for optimising asthma control and reducing OCS use are pivotal in asthma management.
已知重症哮喘患者长期口服皮质类固醇（OCS）治疗会引起显著的不良反应，但对一般哮喘人群低剂量暴露的影响了解有限。研究目的是在丹麦全国范围内的哮喘人群中探索这一点。纳入1999年至2018年期间，丹麦全国范围内登记的18-45岁的哮喘药物使用者，并在开放队列设计中进行前瞻性跟踪。OCS使用者与非使用者的倾向性得分为1:4。采用Cox回归分析了OCS使用与共患病之间的关系。评估死亡率、死因和计划外住院率。OCS使用者（n=30352）与非使用者（n=121408）相比，所有结果的风险均增加，且从累积剂量开始存在明显的剂量-反应关系≤500毫克（泼尼松龙）。危险比范围从骨折的1.24（95% CI 1.18-1.30）到肾上腺功能不全的8.53（95% CI 3.97-18.33）。抑郁/焦虑的发病率差异最大，为每1000人年4.3例（95% CI 3.6-5.0）。OCS使用者和非使用者的哮喘特异性死亡率通常较低，分别为每1000人年0.15（95% CI 0.11-0.20）和0.04（95% CI 0.02-0.06）。随着OCS的增加，死亡率和计划外就医率增加。对研究结果的解释应考虑到其观察性质。然而，我们发现，即使在累积暴露量较低的情况下，OCS在哮喘治疗中也会增加共患病风险、死亡率和计划外就医。优化哮喘控制和减少OCS使用的有效策略在哮喘管理中至关重要。
(中日友好医院呼吸与危重症医学科 李红雯 摘译 林江涛 审校)
(Eur Respir J. 2022 Feb 10;2103054. doi: 10.1183/13993003.03054-2021.)
(Eur Respir J. 2022 Feb 10;2103054. doi: 10.1183/13993003.03054-2021.)
Low dose oral corticosteroids in asthma associates with increased morbidity and mortality
Inge Raadal Skov, Hanne Madsen, Daniel Pilsgaard Henriksen, Jacob Harbo Andersen, Anton Pottegård, Jesper Rømhild Davidsen
Abstract
Long-term oral corticosteroid (OCS) treatment for severe asthma is known to cause significant adverse effects, but knowledge on effects of lower exposures in general asthma populations is limited. We aimed to explore this in a nationwide Danish asthma population.Users of asthma medication aged 18-45 were identified in the Danish nationwide registers during 1999-2018 and followed prospectively in an open cohort design. Incident OCS-users were matched 1:4 to non-users by propensity scores with replacement. Associations between OCS use and incident comorbidities were examined by Cox regression. Mortality rates, causes of death, and rates of unscheduled hospital visits were assessed.OCS-users (n 30,352) had, compared to non-users (n 121,408), an increased risk of all outcomes with evident dose-response relationships starting at cumulative doses of ≤500 mg (prednisolone equivalents). Hazard ratios ranged from 1.24 (95% CI 1.18-1.30) for fractures to 8.53 (95% CI 3.97-18.33) for adrenal insufficiency. Depression/anxiety had the highest incidence rate difference at 4.3 (95% CI 3.6-5.0) per 1000 person years. Asthma-specific mortality rates were generally low at 0.15 (95% CI 0.11-0.20) and 0.04 (95% CI 0.02-0.06) per 1000 person years for OCS-users and non-users, respectively. Mortality rates and unscheduled hospital visits increased with increasing OCS exposure.The study findings should be interpreted with their observational nature in mind. However, we found that even at low cumulative exposure, OCS use in asthma management was associated with increased risk of comorbidities, mortality, and unscheduled hospital visits. Effective strategies for optimising asthma control and reducing OCS use are pivotal in asthma management.
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