Respiratory Medicine Unit, University of Ferrara, University Hospital S. Anna, Ferrara, Italy.
Universitätsmedizin Rostock, Zentrum für Innere Medizin, Abteilung für Pneumologie, Rostock, Germany.
J Allergy Clin Immunol. 2021 Jul;148(1):262-265.e2. doi: 10.1016/j.jaci.2021.01.007. Epub 2021 Jan 21.
Previous studies have shown seasonal variation in asthma exacerbations, peaking over the winter months. A single-inhaler triple therapy containing extrafine formulations of the inhaled corticosteroid (ICS) beclomethasone dipropionate (BDP), long-acting β-agonist formoterol fumarate (FF), and long-acting muscarinic antagonist glycopyrronium (G) is in development for asthma.
We sought to evaluate whether calendar season impacted the relative effect of BDP/FF/G versus BDP/FF on moderate and severe asthma exacerbations.
TRIMARAN and TRIGGER were double-blind 52-week studies comparing BDP/FF/G with BDP/FF (TRIMARAN medium-dose ICS; TRIGGER high-dose) in adults with uncontrolled asthma (Asthma Control Questionnaire-7 score ≥1.5), prebronchodilator FEV less than 80% predicted, history of 1 or more asthma exacerbation, who had been receiving ICS/long-acting β-agonist for at least 4 weeks before entry. Moderate and severe asthma exacerbations were captured throughout each study. In these post hoc analyses, the annual moderate and severe exacerbation rate was calculated for each month, with rate ratios determined from events grouped by season.
In patients who received BDP/FF alone, there was a marked seasonal effect on the occurrence of asthma exacerbations, with the rate highest in the winter months. However, the addition of the long-acting muscarinic antagonist component to BDP/FF reduced this seasonal variation, especially during the winter, such that the relative effect of BDP/FF/G versus BDP/FF was greatest in the winter (significant 20.3% reduction [P = .0008]). Reductions in the other seasons ranged between 8.6% and 12.0%.
These post hoc analyses indicate that inhaled triple therapy with extrafine BDP/FF/G reduces seasonal peaks in moderate and severe exacerbations, and confirm the overall utility of adding long-acting muscarinic antagonist to ICS/long-acting β-agonist in the management of asthma.
先前的研究表明哮喘加重存在季节性变化，冬季达到高峰。一种含有精细吸入型糖皮质激素（ICS）倍氯米松二丙酸酯（BDP）、长效β-激动剂富马酸福莫特罗（FF）和长效毒蕈碱拮抗剂格隆溴铵（G）的单一吸入三联疗法正在开发用于哮喘。
我们旨在评估日历季节是否会影响 BDP/FF/G 与 BDP/FF 对中重度哮喘加重的相对疗效。
TRIMARAN 和 TRIGGER 是两项为期 52 周的双盲研究，比较了 BDP/FF/G 与 BDP/FF（TRIMARAN 中剂量 ICS；TRIGGER 高剂量）在未控制的哮喘患者（哮喘控制问卷-7 评分≥1.5）中的疗效，这些患者在接受支气管扩张剂前的 FEV1 预测值低于 80%，有 1 次或多次哮喘加重史，在入组前至少 4 周接受 ICS/长效β-激动剂治疗。在整个研究过程中都记录了中重度哮喘加重事件。在这些事后分析中，为每个月计算了中度和重度哮喘加重的年发生率，通过按季节分组的事件确定了发生率比。
在单独使用 BDP/FF 的患者中，哮喘加重的发生存在明显的季节性，冬季发生率最高。然而，BDP/FF 中加入长效毒蕈碱拮抗剂成分降低了这种季节性变化，特别是在冬季，使得 BDP/FF/G 相对于 BDP/FF 的相对疗效在冬季最大（显著降低 20.3%[P=0.0008]）。其他季节的降幅在 8.6%至 12.0%之间。
这些事后分析表明，精细吸入型 BDP/FF/G 三联疗法可减少中重度哮喘加重的季节性高峰，并证实长效毒蕈碱拮抗剂在 ICS/长效β-激动剂治疗哮喘中的整体作用。
