BackgroundCystic fibrosis (CF) is caused by CF transmembrane conductance regulator (CFTR) gene mutations producing dysfunctional CFTR proteins leading to progressive clinical disease. Elexacaftor‐tezacaftor‐ivacaftor (ETI) remarkably improves lung disease but is associated with substantial weight gain.Study Design and MethodsWe performed a single‐center longitudinal study predicting 6‐month weight gain after ETI initiation. We used linear mixed effects modeling (LME) to determine association of ETI treatment with changing body mass index (BMI). Using linear regression, we examined BMI prediction models with distinct combinations of main effects to identify a model useful for patient counseling. We used up to eight commonly observed clinical characteristics as input variables (age, sex, percent predicted FEV1 [FEV1%], F508del homozygous state, pancreatic sufficiency, HgbA1c, prior modulator use and prior year number of pulmonary exacerbations).ResultsWe evaluated 154 patients (19‐73 years old, 54% female, FEV1% = 19−121, 0−6 prior year pulmonary exacerbations). LME demonstrated an association between ETI use and weight increases. Exhaustive testing suggested a parsimonious linear regression model well‐fitted to data that is potentially useful for counseling. The two variable model shows that on average, BMI decreases by 0.045 (95% Confidence Interval [CI] = −0.069 to −0.021, p < 0.001) for every year of age and increases by 0.322 (CI = 0.142 to 0.502, p = 0.001) for each additional prior year exacerbation at the time of ETI initiation.InterpretationYoung patients with many prior year pulmonary exacerbations likely have the largest 6 month weight gain after starting ETI.

中文翻译：

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使用三重组合调节器预测囊性纤维化患者的体重增加

背景囊性纤维化（CF）是由CF跨膜传导调节因子（CFTR）基因突变引起的，产生功能失调的CFTR蛋白，导致进行性临床疾病。 Elexacaftor-tezacaftor-ivacaftor (ETI) 显着改善肺部疾病，但与体重大幅增加有关。研究设计和方法我们进行了一项单中心纵向研究，预测 ETI 启动后 6 个月的体重增加。我们使用线性混合效应模型 (LME) 来确定 ETI 治疗与体重指数 (BMI) 变化的关联。使用线性回归，我们检查了具有不同主效应组合的 BMI 预测模型，以确定对患者咨询有用的模型。我们使用多达 8 个常见临床特征作为输入变量（年龄、性别、预测 FEV1 百分比 [FEV1%]、F508del 纯合状态、胰腺功能充足、HgbA1c、既往调节剂使用情况和前一年肺部病情恶化次数）。结果我们评估了 154 名患者（19‐73 岁，54% 女性，FEV1% = 19−121, 0−6 前一年肺部恶化）。 LME 证明了 ETI 的使用与体重增加之间存在关联。详尽的测试表明，一种简约的线性回归模型非常适合对咨询可能有用的数据。双变量模型显示，BMI 平均下降 0.045（95% 置信区间 [CI] = -0.069 至 -0.021，p< 0.001) 随着年龄的增长，增加 0.322 (CI = 0.142 至 0.502，p= 0.001) 对于开始 ETI 时每增加一次前一年的恶化。解释 前一年多次肺部恶化的年轻患者可能在开始 ETI 后 6 个月内体重增加最多。