背景:国际指南推荐添加生物单克隆抗体如贝那利珠单抗(抗IL-5Ra),以减少严重嗜酸性粒细胞性哮喘(SEA)的恶化。然而,很少有研究评估这些疗法对肺功能相关结局的影响.我们的目标是评估贝那利珠单抗对肺功能的有效性,包括肺容量和气道阻力,在葡萄牙的SEA患者中。
方法:这是一个真实的世界,观察,prospective,多中心研究,包括诊断为SEA的成年患者(2023年1月至6月)。在基线(T0)和用贝那利珠单抗治疗六个月后(T6)进行肺活量测定和体积描记术,以评估:总肺活量(TLC),剩余体积(RV),一秒钟用力呼气量(FEV1),强迫肺活量(FVC),平均用力呼气流量在FVC的25%和75%之间(mFEF-25/75),胸内气体量(ITGV),和呼吸道阻力(原始)。描述性统计(分类变量描述为频率,连续值描述为平均值和标准偏差(SD)),并计算配对t检验和Cohen'sd效应大小(在StataCorpv.15.1中进行的分析;StataCorpLLC,TX,美国)。
结果:总体而言,对30例SEA患者进行了评估,主要是女性(n=18,60.0%),特应性(n=22,73.3%),平均年龄58.4岁(SD11.7),并由肺科(n=19,63.3%)或免疫学变态反应学(n=11,36.7%)服务协助。基线时的平均嗜酸性粒细胞为1103.57细胞/mcL(SD604.88;最小-最大460-2400);使用贝那利珠单抗后,计数下降到零。经过6个月的治疗,FVC(15.3%)显著增加(p<0.0001),FEV1(22.6%),从基线观察到mFEF-25/75(17.7%)(Cohen'sd在0.78和1.11之间)。ITGV,RV,RV/TLC,和Raw在研究期间显着下降(p<0.0001)(-17.3%,-29.7%,-8.9%,和-100.6%,分别)(科恩的d在-0.79和-1.06之间)。没有获得TLC差异(p=0.173)。在任何测量中都没有观察到性别之间的差异。嗜酸性粒细胞增多(>900细胞/mcL计数;n=15)的患者在FEV1(p=0.001)和mFEF-25/75(p=0.007)中表现出更好的反应。
结论:在6个月后,添加贝那利珠单抗的嗜酸性粒细胞显著减少导致SEA患者的呼吸功能(静态肺容量和气道阻力)显著改善。贝那利珠单抗对过度充气患者肺的显着放气作用导致呼气流量增强(FEV1和mFEF-25/75增加)和空气滞留(RV/TLC降低),表明这种抗体改善了支气管阻塞,肺过度膨胀,和气道阻力。需要在更大的人群中进行进一步的研究来证实这些发现。
BACKGROUND: Add-on biological monoclonal antibodies such as benralizumab (anti-IL-5Ra) are recommended by international guidelines to reduce exacerbations in severe eosinophilic asthma (SEA). However, few studies have assessed the impact of these therapies on lung function-related outcomes. Our goal was to evaluate the effectiveness of benralizumab on lung function, including lung volumes and airway resistance, in SEA patients in Portugal.
METHODS: This was a real-world, observational, prospective, multicentric study including adult patients diagnosed with SEA (January-June 2023). Spirometry and plethysmography were performed at baseline (T0) and after six months of treatment (T6) with benralizumab to assess: total lung capacity (TLC), residual volume (RV), forced expiratory volume in one second (FEV1), forced vital capacity (FVC), mean forced expiratory flow between 25% and 75% of FVC (mFEF-25/75), intrathoracic gas volume (ITGV), and respiratory airway resistance (Raw). Descriptive statistics (with categorical variables described as frequencies and continuous values as mean and standard deviation (SD)) and paired t-test and Cohen\'s d effect size were calculated (analyses performed in StataCorp v.15.1; StataCorp LLC, TX, USA).
RESULTS: Overall, 30 SEA patients were evaluated, mostly women (n=18, 60.0%), with atopy (n=22, 73.3%), a mean age of 58.4 years (SD 11.7), and assisted by pulmonology (n=19, 63.3%) or immunology-allergology (n=11, 36.7%) services. Mean eosinophilia at baseline was 1103.57 cells/mcL (SD 604.88; minimum-maximum 460-2400); after the use of benralizumab, the count dropped to zero. After six months of treatment, a significant increase (p<0.0001) in FVC (15.3%), FEV1 (22.6%), and mFEF-25/75 (17.7%) were observed from baseline (Cohen\'s d between 0.78 and 1.11). ITGV, RV, RV/TLC, and Raw significantly decreased (p<0.0001) during the study period (-17.3%, -29.7%, -8.9%, and -100.6%, respectively) (Cohen\'s d between -0.79 and -1.06). No differences in TLC were obtained (p=0.173). No differences between sexes were observed for any measure. Patients with more significant eosinophilia (>900 cells/mcL count; n=15) presented better responses in FEV1 (p=0.001) and mFEF-25/75 (p=0.007).
CONCLUSIONS: A notable eosinophil depletion with add-on benralizumab led to significant improvements in SEA patients\' respiratory function (static lung volumes and airway resistance) in real-world settings after six months. The significant deflating effect of benralizumab on patients\' hyperinflated lungs led to enhanced expiratory flow (increased FEV1 and mFEF-25/75) and air trapping (decreased RV/TLC), suggesting this antibody improves bronchial obstruction, lung hyperinflation, and airway resistance. Further studies in a larger population are required to confirm these findings.