Ibrahim Hisham, O'Mahony Alexander T, Deasy Kevin F, Waldron Michael, McCarthy Mairead, Dorgan James, Fleming Claire, Howlett Ciara, O'Riordan Edel, McCarthy Yvonne, Twohig Sarah, Mansfield Janice, Vagg Tamara, Murphy Desmond M, O'Regan Paul, Kirwan Laura, Eustace Joseph A, O'Connor Owen J, Maher Michael M, Plant Barry J
Cork Centre for Cystic Fibrosis (3CF), Cork University Hospital, University College Cork, Wilton, Ireland.
The HRB-funded Clinical Research Facility, University College Cork, Cork, Ireland.
ERJ Open Res. 2025 Jun 2;11(3). doi: 10.1183/23120541.00897-2024. eCollection 2025 May.
Clinical trials with elexacaftor/tezacaftor/ivacaftor (ETI) in people with cystic fibrosis were associated with significant improvements in % predicted forced expiratory volume in 1 s (FEV % pred), sweat chloride, weight and quality of life in the respiratory domain from the cystic fibrosis questionnaire revised (CFQ-R). Limited data exist on its effect on structural lung disease and inflammatory cytokines.
In a real-world setting with 61 people with cystic fibrosis, we prospectively recorded FEV, sweat chloride, body mass index (BMI) and CFQ-R at baseline, 3 and 6 months after commencement of ETI. In addition, changes in ultra-low-dose (ULD) computed tomography (CT) Bhalla score, peripheral-blood and sputum inflammatory cytokines and patient-reported outcome measures (PROMs), including sino-nasal outcomes test-22 (SNOT-22) and fatigue scale (FACIT-Fatigue).
Significant improvements in FEV % pred (p=0.0001), sweat chloride (p<0.0001) and BMI (p=0.0147) after ETI treatment were noted. ULD-CT scores demonstrated reductions in peri-bronchial thickening, mucus plugging and total Bhalla score (p<0.001), and improvements in emphysema extent (p<0.0027). Improvements in systemic inflammatory status were seen with a reduction in interleukin (IL)-1β (p=0.0049), IL-6 and IL-8 (p<0.0001), and increasing IL-10 (p=0.004). Sputum cytokine analysis was not performed as only four of 61 patients spontaneously expectorated sputum after ETI. PROMs improved significantly for the SNOT-22 (p<0.0001), FACIT-Fatigue score (p=0.0001) and CFQ-R domains, including respiratory (p<0.0001), physical (p=0.007), vitality (p=0.0004), treatment burden (p=0.0028), health (p=0.0007), social (p=0.0073), weight (p=0.0068) and role/school domain (p=0.0018).
ETI responders, demonstrate significant improvements in CT imaging, circulating cytokines and PROMs, which may be of further use evaluating cystic fibrosis transmembrane conductance regulator modulation treatment response.
针对囊性纤维化患者使用依列卡福/替扎卡福/依伐卡托（ETI）进行的临床试验显示，1秒用力呼气容积预测值百分比（FEV%pred）、汗液氯化物水平、体重以及经修订的囊性纤维化问卷（CFQ-R）呼吸领域的生活质量均有显著改善。关于其对肺部结构疾病和炎性细胞因子影响的数据有限。
在一个针对61名囊性纤维化患者的真实世界研究中，我们前瞻性地记录了ETI开始治疗前、治疗3个月和6个月时的FEV、汗液氯化物、体重指数（BMI）和CFQ-R。此外，还记录了超低剂量（ULD）计算机断层扫描（CT）的巴拉评分变化、外周血和痰液中的炎性细胞因子以及患者报告的结局指标（PROMs），包括鼻窦结局测试-22（SNOT-22）和疲劳量表（FACIT-疲劳）。
ETI治疗后，FEV%pred（p=0.0001）、汗液氯化物（p<0.0001）和BMI（p=0.0147）有显著改善。ULD-CT评分显示支气管周围增厚、黏液阻塞和总巴拉评分降低（p<0.001），肺气肿程度改善（p<0.0027）。全身炎症状态改善，白细胞介素（IL）-1β降低（p=0.0049），IL-6和IL-8降低（p<0.0001），IL-10升高（p=0.004）。由于61名患者中只有4名在ETI治疗后能自主咳出痰液，因此未进行痰液细胞因子分析。SNOT-22（p<0.0001）、FACIT-疲劳评分（p=0.0001）和CFQ-R各领域的PROMs均有显著改善，包括呼吸领域（p<0.0001）、身体领域（p=0.007）、活力领域（p=0.0004）、治疗负担领域（p=0.0028）、健康领域（p=0.0007）、社交领域（p=0.0073）、体重领域（p=0.0068）和角色/学校领域（p=0.0018）。
ETI治疗有效的患者在CT成像、循环细胞因子和PROMs方面有显著改善，这可能有助于进一步评估囊性纤维化跨膜传导调节因子调节剂的治疗反应。
