Robarts Research Institute, Department of Medicine, Western University, London; Department of Medical Biophysics, Department of Medicine, Western University, London.
University of British Columbia Centre for Heart Lung Innovation, St. Paul's Hospital Vancouver, Vancouver, BC, Canada.
Chest. 2022 Sep;162(3):520-533. doi: 10.1016/j.chest.2022.03.003. Epub 2022 Mar 10.
Patients with eosinophilic asthma often report poor symptomatic control and quality of life. Anti-IL-5 therapy, including anti-IL-5Rα (benralizumab), rapidly depletes eosinophils in the blood and airways and also reduces asthma exacerbations and improves quality of life scores. In patients with severe asthma, eosinophilic inflammation-driven airway mucus occlusions have been measured using thoracic x-ray CT imaging. Pulmonary Xe MRI ventilation defect percentage (VDP) also sensitively measures asthma airway dysfunction caused by airway hyperresponsiveness, remodeling, and luminal mucus occlusions. Using Xe MRI and CT imaging together, it is feasible to measure both airway luminal occlusions and airway ventilation in relationship to anti-IL-5 therapy to ascertain the direct impact of therapy-induced eosinophil depletion on airway function.
Does Xe MRI detect airway functional responses to eosinophil depletion after a single benralizumab dose and do airway mucus occlusions mediate this response?
MRI, eosinophil count, spirometry, oscillometry, Asthma Control Questionnaire (ACQ), Asthma Quality of Life Questionnaire (AQLQ), and St. George's Respiratory Questionnaire were completed on day 0 and 28 days after a single 30-mg subcutaneous benralizumab dose. CT scan mucus plugs were scored on day 0, and MRI VDP was quantified on days 0 and 28.
Twenty-nine participants (27 with baseline CT imaging) completed day 0 and day 28 visits. On day 28 after a single benralizumab dose, significantly improved blood eosinophil counts, VDP, ACQ 6 scores, AQLQ scores (all P < .001), and peripheral airway resistance (P = .04) were found in all participants. On day 28, significantly improved VDP and ACQ 6 scores also were found in the subgroup of nine participants with five or more mucus plugs, but not in the subgroup (n = 18) with fewer than five mucus plugs. Based on univariate relationships for change in ACQ 6 score, multivariate models were generated and showed that day 0 VDP (P < .001) and day 0 CT scan mucus score (P < .001) were significant variables for change in ACQ 6 score on day 28 after benralizumab injection.
Xe ventilation significantly improved in participants with uncontrolled asthma and in those with significant mucus plugging after a single dose of benralizumab.
ClinicalTrials.gov; No.: NCT03733535; URL: www.
gov.
嗜酸性粒细胞性哮喘患者常报告症状控制和生活质量较差。抗 IL-5 治疗，包括抗 IL-5Rα（贝那利珠单抗），可迅速耗尽血液和气道中的嗜酸性粒细胞，还可减少哮喘恶化并提高生活质量评分。在严重哮喘患者中，已使用胸部 X 射线 CT 成像测量由嗜酸性粒细胞炎症驱动的气道黏液阻塞。肺部 Xe MRI 通气缺陷百分比（VDP）也可灵敏地测量由气道高反应性、重塑和管腔黏液阻塞引起的哮喘气道功能障碍。使用 Xe MRI 和 CT 成像联合测量，可测量气道管腔阻塞和气道通气与抗 IL-5 治疗的关系，以确定治疗诱导的嗜酸性粒细胞耗竭对气道功能的直接影响。
单次贝那利珠单抗剂量后，Xe MRI 是否可检测到气道对嗜酸性粒细胞耗竭的功能反应，以及气道黏液阻塞是否介导该反应？
在单次皮下给予 30mg 贝那利珠单抗后的第 0 天和 28 天完成 MRI、嗜酸性粒细胞计数、肺活量测定、振荡法、哮喘控制问卷（ACQ）、哮喘生活质量问卷（AQLQ）和圣乔治呼吸问卷。在第 0 天对 CT 扫描黏液栓进行评分，并在第 0 天和第 28 天量化 MRI VDP。
29 名参与者（27 名有基线 CT 成像）完成了第 0 天和第 28 天的访视。在单次贝那利珠单抗剂量后的第 28 天，所有参与者的血液嗜酸性粒细胞计数、VDP、ACQ6 评分和 AQLQ 评分均显著改善（均 P<0.001），外周气道阻力也显著降低（P=0.04）。在第 28 天，9 名黏液栓数≥5 的参与者的 VDP 和 ACQ6 评分也显著改善，但在黏液栓数<5 的 18 名参与者中并未发现这一结果。基于 ACQ6 评分变化的单变量关系，生成了多变量模型，结果表明，贝那利珠单抗注射后第 28 天，ACQ6 评分变化的多变量模型中，第 0 天 VDP（P<0.001）和第 0 天 CT 扫描黏液评分（P<0.001）是重要变量。
在接受单剂量贝那利珠单抗治疗后，哮喘未得到控制的参与者和有显著黏液栓的参与者的 Xe 通气明显改善。
ClinicalTrials.gov；编号：NCT03733535；网址：www.clinicaltrials.gov。
