背景:CFTR调节疗法可改善营养状况和生活质量。临床试验显示胰腺功能不全转化,主要是用ivacaftor治疗的儿科患者。在老年患者中使用elexacaftor/tezacaftor/ivacaftor(ETI)进行的研究未提示外分泌胰腺功能恢复,但是成年人缺乏高质量的数据。我们的目的是显示成人CF患者的ETI对营养状况和消化功能的影响。我们假设营养参数和胃肠道症状有所改善,减少胰酶替代疗法,但不确定胰腺外分泌功能的改善。
方法:我们前瞻性招募了2021年8月至2022年6月接受ETI治疗的CF成人。我们测量了人体测量参数,实验室营养标记,粪便弹性蛋白酶的变化,胰酶替代疗法的需要,和胃肠道症状。
结果:在29名患者(平均年龄29.1岁)的队列中,82.8%外分泌胰腺功能不全。ETI之后,平均BMI增加1.20kg/m2(p<0.001),平均体重3.51公斤(p<0.001),白蛋白2.81g/L,和前白蛋白下降0.06(均p<0.001)。只有一个病人,最初胰腺不足(4.5%,p<0.001),发展胰腺充足,显示粪便弹性蛋白酶从45µg/g增加到442.1µg/g。脂肪酶替代的平均变化减少了1,969单位/kg/天(p<0.001),粪便频率每天减少了1.18(p<0.001)。
结论:我们的数据表明营养参数增加,较低的胰腺替代要求,并改善了ETI成年CF患者的排便。胰腺外分泌功能的改善可能是突变特异性的,需要进一步研究。
BACKGROUND: Cystic fibrosis transmembrane conductance regulator modulator therapy improves nutritional status and quality of life. Clinical trials have shown pancreatic insufficiency conversion, mostly in pediatric patients treated with ivacaftor. Studies with elexacaftor/tezacaftor/ivacaftor (ETI) in older patients have not suggested restoration of exocrine pancreas function, but quality data in adults are lacking. Our aim was to show the effect of ETI in adults with cystic fibrosis (CF) on nutritional status and digestive function. We hypothesized improvement of nutritional parameters and gastrointestinal symptoms, reduction of pancreatic enzyme replacement therapy, but uncertain improvement in exocrine pancreatic function.
METHODS: We prospectively enrolled adults with CF treated with ETI from August 2021 to June 2022. We measured anthropometric parameters, laboratory nutritional markers, change of fecal elastase, pancreatic enzymes replacement therapy needs, and gastrointestinal symptoms.
RESULTS: In the cohort of 29 patients (mean age 29.1 years), 82.8% suffered exocrine pancreatic insufficiency. After ETI, mean BMI increased by 1.20 kg/m2 (p < 0.001), mean body weight by 3.51 kg (p < 0.001), albumin by 2.81 g/L, and prealbumin by 0.06 (both p < 0.001). Only 1 patient, initially pancreatic insufficient (4.5%, p < 0.001), developed pancreatic sufficiency, indicated by increased fecal elastase from 45 μg/g to 442.1 μg/g. Mean change in lipase substitution decreased by 1,969 units/kg/day (p < 0.001) and stools frequency by 1.18 per day (p < 0.001).
CONCLUSIONS: Our data suggest increased nutritional parameters, lower pancreatic substitution requirements, and improved defecation in adult CF patients on ETI. Improvement in exocrine pancreatic function might be mutation-specific and needs further study.