Supplementary Material for: ICS Use May Modify FEV1 Decline in α1-Antitrypsin Deficiency Patients with Relatively High Blood Eosinophils

Background: α1-Antitrypsin deficiency (AATD) predisposes to chronic obstructive pulmonary disease (COPD). In COPD unrelated to AATD, the role of a higher blood eosinophil count in disease and subsequent personalization of therapy has recently received much attention. We sought to investigate this concept in patients with AATD-associated COPD. Objectives: The study aims to evaluate eosinophilia status against outcomes including mortality and FEV1 decline in patients with AATD. Methods: All patients with PiSZ and PiZZ genotypes were identified from the UK AATD registry. The participants were substratified according to inhaled corticosteroid (ICS) use. Blood eosinophil counts were assessed from baseline and annually during follow-up (range 1–18 years). Eosinophilia was defined as a level >0.2 × 109/L, and classified by the frequency of such counts into “always,” “intermittent,” or “never present.” Univariate and multivariate analyses were conducted. Results: In total, 646 participants were included, 53.9% of whom demonstrated intermittent and 7.4% persistent eosinophilia. Survival did not differ according to eosinophilic group (p > 0.05). Those with persistent eosinophilia showed a slower FEV1 decline (p p = 0.002) and having a lower FEV1 (p p 1 decline were stratified for baseline ICS use, the association of persistent eosinophilia with slower decline persisted in those on ICS. Conclusions: Blood eosinophil levels persistently >0.2 × 109/L may be an indication for ICS use in PiZZ AATD in order to reduce FEV1 decline.研究背景：α1-抗胰蛋白酶缺乏症（α1-Antitrypsin deficiency, AATD）易诱发慢性阻塞性肺疾病（chronic obstructive pulmonary disease, COPD）。在与AATD无关的COPD患者中，血液嗜酸性粒细胞计数升高在疾病进程及后续治疗个体化中的作用近来受到广泛关注。本研究旨在探究AATD相关COPD患者中的这一临床概念。 研究目的：本研究旨在评估嗜酸性粒细胞增多症状态与AATD患者的死亡率及第一秒用力呼气容积（FEV1）下降速率等转归的相关性。 研究方法：研究从英国AATD登记库中筛选出所有携带PiSZ与PiZZ基因型的患者。根据吸入性糖皮质激素（inhaled corticosteroid, ICS）使用情况对受试者进行亚组分层。在基线及随访周期（1~18年）内每年检测血液嗜酸性粒细胞计数。将嗜酸性粒细胞增多症定义为计数>0.2×10^9/L，并依据该异常计数的发生频率分为“持续存在”“间断出现”及“从未出现”三类。随后开展单因素及多因素统计分析。 研究结果：本研究共纳入646名受试者，其中53.9%存在间断性嗜酸性粒细胞增多，7.4%存在持续性嗜酸性粒细胞增多。不同嗜酸性粒细胞分组患者的生存率无显著差异（p>0.05）。持续性嗜酸性粒细胞增多患者的FEV1下降速率更慢（p=0.002），且基线FEV1水平更低。在按基线ICS使用情况进行分层分析后，持续性嗜酸性粒细胞增多与FEV1下降速率减缓的相关性在使用ICS的患者亚组中依然存在。 研究结论：血液嗜酸性粒细胞计数持续>0.2×10^9/L或可作为PiZZ基因型AATD患者使用ICS的临床指征，以减缓FEV1的下降速率。