Background

Increased (abnormal) ventilation inhomogeneity in individuals with mild Cystic Fibrosis (CF) lung disease may become a treatable trait for small-molecule therapeutics improving Cystic Fibrosis Transmembrane Regulator (CFTR) function. The relationship between CFTR function and ventilation inhomogeneity is unknown. We aimed to identify and quantify increased ventilation inhomogeneity in relation to CFTR function.

Methods

This was an international, multi-center, cross-sectional study. We collated data from individuals aged 3–25 years with minimal (CFTR-MF) or residual (CFTR-RF) function of a variety of CFTR genotypes and FEV₁ ≥ 70% predicted. We measured lung function using nitrogen multiple-breath washout and spirometry. We compared lung clearance index (LCI) and FEV₁ between individuals with CFTR-MF vs CFTR-RF using a mixed effects multi-variable linear regression model to account for study differences and a logistic model based on propensity-score matching to adjust for possible confounding.

Results

We included 141 with CFTR-MF and 35 with CFTR-RF. LCI (> 1.96 z-score) was elevated in 71.6% individuals with CFTR-MF and in 40.0% with CFTR-RF. FEV₁ (< -1.96 z-score) was reduced in 11.3% individuals with CFTR-MF and in 5.7% with CFTR-RF. The mean difference (95% CI) of LCI and FEV₁ between CFTR-MF and CFTR-RF was 3.71 (1.63 to 5.79) and -0.40 (-0.83 to 0.02) z-score. The LCI differences were similar after adjustment for confounders and in individuals with normal FEV₁.

Conclusion

Increased ventilation inhomogeneity is associated with less CFTR function. In individuals with mild CF lung disease, LCI can identify and quantify increased ventilation inhomogeneity, a candidate treatable trait.

中文翻译：

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囊性纤维化个体的 CFTR 功能和通气不均匀性

背景

患有轻度囊性纤维化（CF）肺病的个体增加（异常）通气不均匀性可能成为改善囊性纤维化跨膜调节剂（CFTR）功能的小分子疗法的可治疗特征。CFTR 功能与通气不均匀性之间的关系尚不清楚。我们旨在识别和量化与 CFTR 功能相关的增加的通气不均匀性。

方法

这是一项国际、多中心、横断面研究。我们整理了来自 3-25 岁个体的数据，这些个体具有各种 CFTR 基因型的最小 (CFTR-MF) 或残余 (CFTR-RF) 功能和 FEV ₁ ≥ 70% 的预测值。我们使用氮气多次呼吸冲洗和肺活量测定法测量肺功能。我们使用混合效应多变量线性回归模型来解释研究差异和基于倾向得分匹配的逻辑模型来调整可能的 CFTR-MF 与 CFTR-RF 个体之间的肺清除指数 (LCI) 和 FEV ₁令人困惑。

结果

我们包括 141 个 CFTR-MF 和 35 个 CFTR-RF。LCI（> 1.96 z 分数）在 71.6% 的 CFTR-MF 个体和 40.0% 的 CFTR-RF 个体中升高。11.3% 的 CFTR-MF 个体和 5.7% 的 CFTR-RF 个体的FEV _{1 (< -1.96 z-score) 降低。}CFTR-MF 和 CFTR-RF 之间LCI 和 FEV ₁的平均差异 (95% CI)为 3.71（1.63 至 5.79）和 -0.40（-0.83 至 0.02）z 分数。_{在调整混杂因素和 FEV 1}正常的个体中，LCI 差异相似。

结论

通气不均匀性增加与 CFTR 功能减少有关。在患有轻度 CF 肺病的个体中，LCI 可以识别和量化增加的通气不均匀性，这是一种候选的可治疗特征。