短效β2受体激动剂应用与重度哮喘发作：欧洲和北美的SABINA研究结果
2022/04/19
摘要
背景：国家/全球哮喘管理专家建议提出了一个问题，即短效β2受体激动剂（SABA）在不同时使用吸入性皮质类固醇（ICS）的情况下是否存在安全阈值。
目的：研究SABA和维持疗法与北美和欧洲重度哮喘发作的关系。
方法：对SABA在哮喘中应用（SABINA）研究中的来自加拿大、法国、荷兰、波兰、西班牙、英国和美国的1033564名患者(≥12年）的数据进行观察性分析。负二项式模型（发病率 [95%置信区间]）根据预先指定的协变量进行调整）评估了SABA与急性发作之间的相关性。
结果：在所有严重程度中，40.2%的患者被处方/持有≥3罐SABA/年。根据GINA-2018定义，3‒5级患者中被处方/持有≥3罐SABA的与1‒2罐的相比有更重的哮喘发作（美国医保介于1.08[1.04‒1.13]之间；波兰介于2.11[1.96‒2.27]之间）。在所有1-2级治疗的患者中未观察到这种关联（荷兰1.25[0.91-1.71]；美国商保0.92[0.91-0.93]；美国医保0.74[0.71-0.76]）。我们假设，在美国数据集中，SABA与重度发作之间的这种反向关联可归因于拥有<3 SABA且没有维持治疗的，以及在没有面对面医疗服务提供者的情况下接受口服皮质类固醇治疗的大量患者群体。在美国，SABA单一疗法治疗的患者，≥3 SABA与更多急诊/门诊就诊和住院相关（1.31[1.29-1.34]）。研究中大多数接受GINA 2‒5级治疗的患者（60.6%）最多有50%的时间没有接受维持治疗；然而去除掉这些患者后≥3 SABA与重度哮喘发作的相关性仍然存在1.32[1.18‒1.49]），当英国的包括ICS的药物年覆盖率高达100%的患者的SABA数据被作为连续变量分析时，这一独立效应被进一步证实。
结论：增加SABA应用与重度发作风险相关，与维持治疗无关。正如GINA所述，根据对哮喘严重程度的研究，与单用SABA相比，按需的速效支气管扩张剂联合ICS可减少重度发作，我们的研究结果强调了避免SABA单药急救/缓解治疗的重要性。
Short-acting β 2-agonist exposure and severe asthma exacerbations: SABINA findings from Europe and North America
Jennifer K Quint, Sofie Arnetorp, Janwillem W H Kocks, Maciej Kupczyk, Javier Nuevo, Vicente Plaza, Claudia Cabrera, Chantal Raherison-Semjen, Brandie Walker, Erika Penz, Ileen Gilbert, Njira Lucia Lugogo, Ralf J P van der Valk, SABINA North American and European Study contributors
Abstract
Background：Expert national/global asthma management recommendations raise the issue whether a safe threshold of short-acting β2-agonist (SABA) use without concomitant inhaled corticosteroids (ICS) exists.
Objective：To examine SABA and maintenance therapy associations with severe asthma exacerbations across North America and Europe.
Methods：Observational analyses of 10 SABa use IN Asthma (SABINA) datasets involving 1,033,564 patients (≥12 years) from Canada, France, the Netherlands, Poland, Spain, United Kingdom (UK), and United States (US). Negative binomial models (incidence rate-ratio [95% confidence interval]) adjusted for prespecified-covariates]) evaluated associations between SABA and exacerbations.
Results：Across severities, 40.2% of patients were prescribed/possessed ≥3 SABA canisters/year. Per GINA-2018 definitions, step 3‒5-treated patients prescribed/possessing ≥3 vs. 1‒2 SABA experienced more severe exacerbations (between 1.08 [1.04‒1.13], US-Medicare; 2.11 [1.96‒2.27], Poland). This association was not observed in all step 1‒2-treated patients (the Netherlands 1.25 [0.91‒1.71]; US-commercial 0.92 [0.91‒0.93]; US-Medicare 0.74 [0.71‒0.76]). We hypothesize that this inverse association between SABA and severe exacerbations in the US datasets was attributable to the large patient population possessing <3 SABA and no maintenance therapy and receiving oral corticosteroid bursts without face-to-face healthcare provider encounters. In US SABA monotherapy-treated patients, ≥3 SABA was associated with more emergency/outpatient visits and hospitalizations (1.31 [1.29‒1.34]). Most GINA 2‒5-treated study patients (60.6%) did not have maintenance therapy for up to 50% of the time; however, the association of ≥3 SABA and severe exacerbations persisted (1.32 [1.18‒1.49]) after excluding these patients and the independent effect was further confirmed when UK SABA data was analyzed as a continuous variable in patients with up to 100% annual coverage for ICS-containing medications.
Conclusions：Increasing SABA exposure is associated with severe exacerbation risk, independent of maintenance therapy. As addressed by GINA, based on studies across asthma severities where as-needed fast-acting bronchodilators with concomitant ICS decrease severe exacerbations compared with SABA, our findings highlight the importance of avoiding a rescue/reliever paradigm utilizing SABA monotherapy.
背景：国家/全球哮喘管理专家建议提出了一个问题，即短效β2受体激动剂（SABA）在不同时使用吸入性皮质类固醇（ICS）的情况下是否存在安全阈值。
目的：研究SABA和维持疗法与北美和欧洲重度哮喘发作的关系。
方法：对SABA在哮喘中应用（SABINA）研究中的来自加拿大、法国、荷兰、波兰、西班牙、英国和美国的1033564名患者(≥12年）的数据进行观察性分析。负二项式模型（发病率 [95%置信区间]）根据预先指定的协变量进行调整）评估了SABA与急性发作之间的相关性。
结果：在所有严重程度中，40.2%的患者被处方/持有≥3罐SABA/年。根据GINA-2018定义，3‒5级患者中被处方/持有≥3罐SABA的与1‒2罐的相比有更重的哮喘发作（美国医保介于1.08[1.04‒1.13]之间；波兰介于2.11[1.96‒2.27]之间）。在所有1-2级治疗的患者中未观察到这种关联（荷兰1.25[0.91-1.71]；美国商保0.92[0.91-0.93]；美国医保0.74[0.71-0.76]）。我们假设，在美国数据集中，SABA与重度发作之间的这种反向关联可归因于拥有<3 SABA且没有维持治疗的，以及在没有面对面医疗服务提供者的情况下接受口服皮质类固醇治疗的大量患者群体。在美国，SABA单一疗法治疗的患者，≥3 SABA与更多急诊/门诊就诊和住院相关（1.31[1.29-1.34]）。研究中大多数接受GINA 2‒5级治疗的患者（60.6%）最多有50%的时间没有接受维持治疗；然而去除掉这些患者后≥3 SABA与重度哮喘发作的相关性仍然存在1.32[1.18‒1.49]），当英国的包括ICS的药物年覆盖率高达100%的患者的SABA数据被作为连续变量分析时，这一独立效应被进一步证实。
结论：增加SABA应用与重度发作风险相关，与维持治疗无关。正如GINA所述，根据对哮喘严重程度的研究，与单用SABA相比，按需的速效支气管扩张剂联合ICS可减少重度发作，我们的研究结果强调了避免SABA单药急救/缓解治疗的重要性。
(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)
(J Allergy Clin Immunol Pract. 2022 Mar 29;S2213-2198(22)00285-9. doi: 10.1016/j.jaip.2022.02.047.)
(J Allergy Clin Immunol Pract. 2022 Mar 29;S2213-2198(22)00285-9. doi: 10.1016/j.jaip.2022.02.047.)
Short-acting β 2-agonist exposure and severe asthma exacerbations: SABINA findings from Europe and North America
Jennifer K Quint, Sofie Arnetorp, Janwillem W H Kocks, Maciej Kupczyk, Javier Nuevo, Vicente Plaza, Claudia Cabrera, Chantal Raherison-Semjen, Brandie Walker, Erika Penz, Ileen Gilbert, Njira Lucia Lugogo, Ralf J P van der Valk, SABINA North American and European Study contributors
Abstract
Background：Expert national/global asthma management recommendations raise the issue whether a safe threshold of short-acting β2-agonist (SABA) use without concomitant inhaled corticosteroids (ICS) exists.
Objective：To examine SABA and maintenance therapy associations with severe asthma exacerbations across North America and Europe.
Methods：Observational analyses of 10 SABa use IN Asthma (SABINA) datasets involving 1,033,564 patients (≥12 years) from Canada, France, the Netherlands, Poland, Spain, United Kingdom (UK), and United States (US). Negative binomial models (incidence rate-ratio [95% confidence interval]) adjusted for prespecified-covariates]) evaluated associations between SABA and exacerbations.
Results：Across severities, 40.2% of patients were prescribed/possessed ≥3 SABA canisters/year. Per GINA-2018 definitions, step 3‒5-treated patients prescribed/possessing ≥3 vs. 1‒2 SABA experienced more severe exacerbations (between 1.08 [1.04‒1.13], US-Medicare; 2.11 [1.96‒2.27], Poland). This association was not observed in all step 1‒2-treated patients (the Netherlands 1.25 [0.91‒1.71]; US-commercial 0.92 [0.91‒0.93]; US-Medicare 0.74 [0.71‒0.76]). We hypothesize that this inverse association between SABA and severe exacerbations in the US datasets was attributable to the large patient population possessing <3 SABA and no maintenance therapy and receiving oral corticosteroid bursts without face-to-face healthcare provider encounters. In US SABA monotherapy-treated patients, ≥3 SABA was associated with more emergency/outpatient visits and hospitalizations (1.31 [1.29‒1.34]). Most GINA 2‒5-treated study patients (60.6%) did not have maintenance therapy for up to 50% of the time; however, the association of ≥3 SABA and severe exacerbations persisted (1.32 [1.18‒1.49]) after excluding these patients and the independent effect was further confirmed when UK SABA data was analyzed as a continuous variable in patients with up to 100% annual coverage for ICS-containing medications.
Conclusions：Increasing SABA exposure is associated with severe exacerbation risk, independent of maintenance therapy. As addressed by GINA, based on studies across asthma severities where as-needed fast-acting bronchodilators with concomitant ICS decrease severe exacerbations compared with SABA, our findings highlight the importance of avoiding a rescue/reliever paradigm utilizing SABA monotherapy.
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