elexacaftor/tezacaftor/ivacaftor (ETI) 的三重组合显着改善了至少具有一种 F508del 突变的囊性纤维化 (pwCF) 患者的治疗结果。然而，罕见囊性纤维化跨膜电导调节因子 (CFTR) 变异的携带者不适合这种创新治疗。在这项观察性研究中，我们报告了 10 名罕见突变 pwCF 携带者在治疗 2 个月后同情使用 ETI 的结果。从四名受试者中获得直肠类器官和通过直肠抽吸活检和鼻刷获得的鼻上皮短期培养物。经过 2 个月的 ETI，所有患者（4 名男性，平均年龄 30.1±13.3 岁）均显示 FEV1% 显着增加预测值 [ 8.0 (3.5-12.7) %, p < 0.010]，体重指数 [ 0.85 (0-1.22) kg/m2, p < 0.020] 和囊性纤维化问卷修订版 [ 19.5 (6.3-29.2) 点，p < 0.009]。还记录了汗液氯化物浓度显着降低[-11.2（-1.7至-34.0）mmol/L，p < 0.020]和恶化[-1.5（-2至-1），p< 0.008]。总体而言，十分之七的参与者被认为是完全响应者。所有患者均报告咳嗽消失（n = 3）或减轻（n = 7）。三分之二的患者停止了长期吸氧，其中一名患者也停止了无创通气，并从肺移植等待名单中删除。尽管病例数量有限，但我们的结果支持在患有罕见 CFTR 变异的患者中使用 CFTR 调节剂目前尚未在欧洲获得 ETI 批准。© 2024 Wiley periodicals LLC。

The triple combination of elexacaftor/tezacaftor/ivacaftor (ETI) has dramatically improved the outcome of people with Cystic Fibrosis (pwCF) with at least one F508del mutation. However, carriers of rare cystic fibrosis transmembrane conductance regulator (CFTR) variants are not candidates for this innovative treatment.In this observational study, we report the results of the compassionate use of ETI in 10 pwCF carriers of rare mutations after 2 months of treatment. Rectal organoids and short-term cultures of nasal epithelium obtained from rectal suction biopsies and nasal brushing were obtained from four subjects.After 2 months of ETI, all patients (4 males, mean age 30.1 ± 13.3 years) showed a significant increase of FEV1% predicted values [+8.0 (3.5-12.7) %, p < 0.010], body mass index [+0.85 (0-1.22) kg/m2, p < 0.020] and cystic fibrosis questionnaire-revised [+19.5 (6.3-29.2) points, p < 0.009]. A significant decrease of sweat chloride concentration [-11.2 (-1.7 to -34.0) mmol/L, p < 0.020] and exacerbations [-1.5 (-2 to -1), p < 0.008] was also recorded. Overall, 7 out of 10 participants were considered full responders. All patients reported cough disappearance (n = 3) or reduction (n = 7). Long-term oxygen was discontinued in two out of three patients and one also stopped noninvasive ventilation and was removed from the lung transplantation waiting list.Despite the limited number of cases, our results support the use of CFTR modulators in patients with rare CFTR variants that are not currently approved for ETI in Europe.© 2024 Wiley Periodicals LLC.