Alamoudi Asma, Petralia Lorenzo, Smith Nicholas M J, Xu Haopeng, Sandhu Dominic, Richmond Graham, Talbot Nick P, Ritchie Grant Ad, Pavord Ian, Robbins Peter A, Petousi Nayia
Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
Department of Respiratory Care, Prince Sultan Military College of Health Sciences, Dhahran, Saudi Arabia.
BMJ Open Respir Res. 2025 Feb 8;12(1):e002721. doi: 10.1136/bmjresp-2024-002721.
INTRODUCTION/AIM: Lung inhomogeneity measures obtained using computed cardiopulmonography (CCP) are sensitive to small-airways disease. Here, we assessed changes in lung inhomogeneity in patients with type-2 high asthma treated with biological therapy and explored the relationship between inhomogeneity measures and conventional asthma disease markers.
This was an observational study of 91 severe type-2 high asthma patients recruited from a tertiary asthma clinic, of whom 67 subsequently started anti-IL5 or anti-IL5R biologics. Patients were evaluated at baseline and, 54 of those commencing biologics, at their fourth injection with either mepolizumab or benralizumab. Assessments included prebronchodilator and postbronchodilator CCP and spirometry, and measurements of blood eosinophil count (BEC), fractional exhaled nitric oxide and Asthma-Symptom Questionnaire (ACQ-5).
Bronchodilation significantly reduced σlnCl, a novel CCP-derived ventilation inhomogeneity index, (ΔσlnCl -0.08, 95% CI (-0.10 to -0.05), p<0.001). Baseline σlnCl, but not forced expiratory volume in 1 s (FEV) % predicted, was significantly associated with BEC (linear mixed-effects (LME) regression coefficient for BEC 0.18, 95% CI (0.04, 0.32), p=0.01). Following biologics, improvements in σlnCl were significantly dependent on BEC (LME regression coefficient +0.19, 95% CI (0.11, 0.27), p<0.001) whereas improvements in FEV % predicted related to both BEC and ACQ-5 responses (LME coefficients: BEC -10.8 % pred, 95% CI (-16.1,-5.5); ACQ-5 -3.5 % pred, 95% CI (-5.1 to -1.9), p<0.001). Following biologics, the change in σlnCl followed a bimodal distribution that dichotomised patients into σlnCl-Responders and σlnCl-Non-Responders. Responders, unlike Non-Responders, experienced significant improvements in symptoms and FEV % predicted (Δ pre-BD FEV15±15% pred, p<0.001) and included a higher proportion of patients in clinical remission at 1 year.
σlnCl is strongly associated with systemic eosinophilic inflammation in severe type-2 high asthma. An early σlnCl response following anti-IL5 biologics identifies patients more likely to experience improvements in symptoms and lung function when systemic eosinophils are depleted. σlnCl may provide a sensitive route for tracking inflammation involving the small airways.
引言/目的：使用计算机心肺成像（CCP）获得的肺不均匀性测量对小气道疾病敏感。在此，我们评估了接受生物治疗的2型重度哮喘患者肺不均匀性的变化，并探讨了不均匀性测量与传统哮喘疾病标志物之间的关系。
这是一项对从三级哮喘诊所招募的91例2型重度哮喘患者的观察性研究，其中67例随后开始使用抗IL5或抗IL5R生物制剂。患者在基线时进行评估，其中54例开始使用生物制剂的患者在第四次注射美泊利单抗或贝那利珠单抗时进行评估。评估包括支气管扩张剂使用前和使用后的CCP和肺量计检查，以及血液嗜酸性粒细胞计数（BEC）、呼出一氧化氮分数和哮喘症状问卷（ACQ-5）的测量。
支气管扩张显著降低了σlnCl，这是一种新的源自CCP的通气不均匀性指数（ΔσlnCl -0.08，95%CI（-0.10至-0.05），p<0.001）。基线σlnCl与BEC显著相关，而不是预测的1秒用力呼气量（FEV）%（BEC的线性混合效应（LME）回归系数为0.18，95%CI（0.04，0.32），p=0.01）。使用生物制剂后，σlnCl的改善显著依赖于BEC（LME回归系数+0.19，95%CI（0.11，0.27），p<0.001），而预测的FEV%的改善与BEC和ACQ-5反应均相关（LME系数：BEC -10.8%pred，95%CI（-16.1，-5.5）；ACQ-5 -3.5%pred，95%CI（-5.1至-1.9），p<0.001）。使用生物制剂后，σlnCl的变化呈双峰分布，将患者分为σlnCl反应者和σlnCl无反应者。与无反应者不同，反应者的症状和预测的FEV%有显著改善（支气管扩张剂使用前ΔFEV15±15%pred，p<0.001），并且在1年时临床缓解的患者比例更高。
在2型重度哮喘中，σlnCl与全身嗜酸性粒细胞炎症密切相关。抗IL5生物制剂治疗后早期的σlnCl反应可识别出在全身嗜酸性粒细胞减少时更有可能症状和肺功能改善的患者。σlnCl可能为追踪涉及小气道的炎症提供一条敏感途径。
