Association between use of ß2-adrenergic receptor agonists and incidence of Parkinson's disease: Retrospective cohort analysis.
Association between use of ß2-adrenergic receptor agonists and incidence of Parkinson's disease: Retrospective cohort analysis.
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DOI：
10.1371/journal.pone.0276368
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发表时间：
2022
期刊：
影响因子：
3.7
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中科院分区：
文献类型：
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先前评估β-2激动剂/拮抗剂使用对帕金森病风险的观察性研究得出了相互矛盾的结果。我们评估了β-2激动剂的使用与慢性肺病患者帕金森病发病率的关系。我们对从美国传统(按服务收费)的医疗保险计划中抽取的20%的随机样本进行了回溯性队列分析。纳入标准是指在2007-2010年期间参加处方药(独立D部分)计划并活到2014年的65岁以上被诊断患有哮喘、慢性阻塞性肺病和/或支气管扩张的个人。主要结果衡量标准是2011-2014年间帕金森氏症的诊断结果，以及2007-2010年间30天当量药物申报的数量。对236,201名医疗保险受益人进行了Logistic回归分析。截至2010年，样本中68%为女性，80%为白人，平均年龄为77岁。与非使用者相比，β2激动剂使用者更有可能是年轻(76.3岁对78.0岁)、吸烟者(40.4%对31.1%)和哮喘(62.4%对28.3%)。在调整了人口统计学、吸烟史、呼吸恶化、合并症和其他药物使用后，β2激动剂声称发生帕金森病的优势比为0.986(95%可信区间0.977-0.995)。男性的风险降低幅度大于女性(0.974比0.994，P=0.032)，慢性阻塞性肺病患者的风险降低幅度大于哮喘患者(0.968比0.998，P=0.049)。通过COX分析解决了反向因果关系，该分析允许β-2激动剂的使用从用药开始到疾病开始不同。在随访期结束时，β-2激动剂的使用被证明与对帕金森病发作的真正保护作用有关。β-2激动剂的使用与帕金森病发病率的降低相关。有必要进行进一步的研究，可能包括临床试验，以加强支持临床决策者寻求改变药物用途以防止神经退行性疾病发病的证据基础。
Previous observational studies assessing β2-agonist/-antagonist use on PD risk have yielded conflicting results. We evaluated the relationship between β2-agonist use and the incidence of Parkinson’s disease in patients with chronic lung disease. We performed a retrospective cohort analysis on a 20% random sample abstracted from a traditional (fee-for-service) Medicare program in the United States. Inclusion criteria were individuals over 65 years old diagnosed with asthma, COPD, and/or bronchiectasis who were enrolled in a prescription drug (standalone Part D) plan over 2007–2010 and alive through 2014. The main outcome measure was a diagnosis of Parkinson’s disease over the period 2011–2014, in relation to the number of 30-day-equivalent drug claims over 2007–2010. Logistic regression analysis was performed on a sample including 236,201 Medicare beneficiaries. The sample was 68% female, 80% white, and on average 77 years old as of 2010. Compared to non-users, β2-agonist users were more likely to be younger (76.3y versus 78.0y), smokers (40.4% versus 31.1%) and asthmatic (62.4% versus 28.3%). The odds ratio for a β2-agonist claim on PD development was 0.986 (95% CI 0.977–0.995) after adjusting for demographics, smoking history, respiratory exacerbations, comorbidities, and other drug use. Risk reductions were larger for males than females (0.974 versus 0.994, P = 0.032), and for individuals with COPD compared to those with asthma (0.968 versus 0.998, P = 0.049). Reverse causality was addressed with a Cox analysis that allowed β2-agonist use to vary from medication initiation to disease onset. By the end of the follow-up period, β2-agonist use was shown to be associated with a true protective effect against PD onset. β2-agonist use is associated with decreased risk of PD incidence. Further investigation, possibly including clinical trials, is warranted to strengthen the evidence base supporting clinical decision-makers looking to repurpose pharmaceuticals to prevent neurodegenerative disease onset.