哮喘患者增加大剂量吸入皮质类固醇的效果：英国数据库研究
2022/11/22
摘要
背景：目前尚不清楚哮喘患者是否受益于大剂量吸入性皮质类固醇（ICS）。
目的：确定加强高剂量ICS的有效性。
方法：哮喘患者的历史队列研究(≥13岁），从两个大型英国电子病历数据库中识别。将持续使用中剂量ICS的患者与从中剂量升到高剂量的患者进行比较，同时将从低剂量到中剂量的患者与由低剂量到高剂量的患者进行对比。使用多变量Cox比例风险模型比较治疗组之间首次严重恶化的时间（主要结果），并使用负二项回归分析恶化次数和抗生素疗程。治疗权重的反概率用于处理混杂。
结果：持续服用稳定中剂量ICS的患者，首次加重的平均随访时间为2.7（SD 2.7）年，而从中剂量到高剂量ICS患者，平均随访时间则为2.0（SD 2.2）年。对于那些从低到中ICS剂量（2.6（SD 2.5）年）和从低到高剂量ICS（2.3（SD 2.5年）的患者，也发现了类似的模式。与继续使用中剂量ICS的患者（n=51737；危险比[HR]1.17，95%可信区间1.12-1.22）相比，从中剂量ICS升级为高剂量ICS（n=6879）的患者在随访期间发生恶化的风险更高。与低剂量至中剂量（n=12659）ICS（HR 1.10[1.04-1.17]）相比，低剂量至高剂量（n=3232）ICS患者的情况类似。高剂量ICS的增加也与哮喘加重和抗生素疗程的增加有关。不同血嗜酸性粒细胞计数（BEC）患者亚组之间的相关性没有显著差异。
结论：我们发现没有证据表明，增加高剂量ICS对预防未来哮喘加重有效。
Effect of stepping up to high-dose inhaled corticosteroids in patients with asthma: UK Database Study
Ian D Pavord FMedSci, Trung N Tran, Rupert C Jones, Javier Nuevo, Maarten van den Berge, Guy G Brusselle, Andrew N Menzies-Gow, Derek Skinner, Victoria Carter, Janwillem W H Kocks, David B Price
Abstract
Background：It is unclear whether patients with asthma benefit from stepping up to high-dose inhaled corticosteroids (ICS).
Objective: To determine the effectiveness of stepping up to high-dose ICS.
Methods：A historic cohort study of asthma patients (≥13 years old), identified from two large UK electronic medical record databases, was conducted. Patients who remained on medium-dose ICS were compared to those who stepped up from medium- to high-dose ICS, while patients who stepped up from low- to medium-dose were compared to those who stepped up from low- to high-dose ICS. Time to first severe exacerbation (primary outcome) between treatment groups was compared using multivariable Cox proportional hazards models, and number of exacerbations and antibiotics courses were analyzed using negative binomial regression. Inverse probability of treatment weighting was used to handle confounding.
Results：The mean follow-up time to first exacerbation was 2.7 (SD 2.7) years for those who remained on stable medium-dose ICS and 2.0 (SD 2.2) years for those who stepped up from medium-to high-dose ICS. A similar pattern was noted for those who stepped-up from low- to medium-ICS dose (2.6 (SD 2.5) years) and from low- to high-dose ICS (2.3 (SD 2.5) years). Patients who stepped up from medium- to high-dose ICS (n=6,879) had a higher risk of exacerbations during follow-up compared to those who remained on medium-dose ICS (n=51,737; hazard ratio [HR] 1.17, 95% confidence interval 1.12-1.22). This was similar in patients stepping up from low- to high-dose (n=3,232) compared to low- to medium-dose (n=12,659) ICS (HR 1.10 [1.04-1.17]). A step-up to high-dose ICS was also associated with higher number of asthma exacerbations and antibiotics courses. No significant difference in associations was found across subgroups of patients with different blood eosinophil counts (BEC).
Conclusion：We found no evidence that a step-up to high-dose ICS is effective in preventing future asthma exacerbations.
背景：目前尚不清楚哮喘患者是否受益于大剂量吸入性皮质类固醇（ICS）。
目的：确定加强高剂量ICS的有效性。
方法：哮喘患者的历史队列研究(≥13岁），从两个大型英国电子病历数据库中识别。将持续使用中剂量ICS的患者与从中剂量升到高剂量的患者进行比较，同时将从低剂量到中剂量的患者与由低剂量到高剂量的患者进行对比。使用多变量Cox比例风险模型比较治疗组之间首次严重恶化的时间（主要结果），并使用负二项回归分析恶化次数和抗生素疗程。治疗权重的反概率用于处理混杂。
结果：持续服用稳定中剂量ICS的患者，首次加重的平均随访时间为2.7（SD 2.7）年，而从中剂量到高剂量ICS患者，平均随访时间则为2.0（SD 2.2）年。对于那些从低到中ICS剂量（2.6（SD 2.5）年）和从低到高剂量ICS（2.3（SD 2.5年）的患者，也发现了类似的模式。与继续使用中剂量ICS的患者（n=51737；危险比[HR]1.17，95%可信区间1.12-1.22）相比，从中剂量ICS升级为高剂量ICS（n=6879）的患者在随访期间发生恶化的风险更高。与低剂量至中剂量（n=12659）ICS（HR 1.10[1.04-1.17]）相比，低剂量至高剂量（n=3232）ICS患者的情况类似。高剂量ICS的增加也与哮喘加重和抗生素疗程的增加有关。不同血嗜酸性粒细胞计数（BEC）患者亚组之间的相关性没有显著差异。
结论：我们发现没有证据表明，增加高剂量ICS对预防未来哮喘加重有效。
(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)
(J Allergy Clin Immunol Pract. 2022 Nov 9;S2213-2198(22)01143-6. doi: 10.1016/j.jaip.2022.10.040.)
(J Allergy Clin Immunol Pract. 2022 Nov 9;S2213-2198(22)01143-6. doi: 10.1016/j.jaip.2022.10.040.)
Effect of stepping up to high-dose inhaled corticosteroids in patients with asthma: UK Database Study
Ian D Pavord FMedSci, Trung N Tran, Rupert C Jones, Javier Nuevo, Maarten van den Berge, Guy G Brusselle, Andrew N Menzies-Gow, Derek Skinner, Victoria Carter, Janwillem W H Kocks, David B Price
Abstract
Background：It is unclear whether patients with asthma benefit from stepping up to high-dose inhaled corticosteroids (ICS).
Objective: To determine the effectiveness of stepping up to high-dose ICS.
Methods：A historic cohort study of asthma patients (≥13 years old), identified from two large UK electronic medical record databases, was conducted. Patients who remained on medium-dose ICS were compared to those who stepped up from medium- to high-dose ICS, while patients who stepped up from low- to medium-dose were compared to those who stepped up from low- to high-dose ICS. Time to first severe exacerbation (primary outcome) between treatment groups was compared using multivariable Cox proportional hazards models, and number of exacerbations and antibiotics courses were analyzed using negative binomial regression. Inverse probability of treatment weighting was used to handle confounding.
Results：The mean follow-up time to first exacerbation was 2.7 (SD 2.7) years for those who remained on stable medium-dose ICS and 2.0 (SD 2.2) years for those who stepped up from medium-to high-dose ICS. A similar pattern was noted for those who stepped-up from low- to medium-ICS dose (2.6 (SD 2.5) years) and from low- to high-dose ICS (2.3 (SD 2.5) years). Patients who stepped up from medium- to high-dose ICS (n=6,879) had a higher risk of exacerbations during follow-up compared to those who remained on medium-dose ICS (n=51,737; hazard ratio [HR] 1.17, 95% confidence interval 1.12-1.22). This was similar in patients stepping up from low- to high-dose (n=3,232) compared to low- to medium-dose (n=12,659) ICS (HR 1.10 [1.04-1.17]). A step-up to high-dose ICS was also associated with higher number of asthma exacerbations and antibiotics courses. No significant difference in associations was found across subgroups of patients with different blood eosinophil counts (BEC).
Conclusion：We found no evidence that a step-up to high-dose ICS is effective in preventing future asthma exacerbations.
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