Background Ivacaftor (IVA) improves lung function and other extrapulmonary outcomes in people with cystic fibrosis (CF). However, the effect of initiating IVA at earlier versus later ages has not been studied. Methods We conducted an observational cohort study of people in the US CF Foundation Patient Registry aged ≥6 years with ≥1 CF transmembrane conductance regulator–gating mutation to compare the effects of initiating IVA at earlier ages on per cent predicted forced expiratory volume in 1 s (ppFEV1) and pulmonary exacerbation (PEx) outcomes. People with CF were grouped by age at IVA initiation (ages 6–10, 11–15, 16–20 and 21–25 years) to perform three analyses of younger versus older IVA initiation (6–10 vs 11–15, 11–15 vs 16–20 and 16–20 vs 21–25 years). For each analysis, baseline characteristics assessed over 1-year periods at the same age prior to IVA initiation were balanced by standardised mortality/morbidity ratio (SMR) weighting. For each analysis, outcomes were compared over a 5-year outcome assessment period when both groups were in the same age range and receiving IVA. Findings Baseline characteristics were well balanced between younger and older IVA initiator groups after SMR weighting. In the outcome assessment period, younger IVA initiators had significantly higher mean ppFEV1 than older initiators across all comparisons, and those initiating IVA between ages 6–10 and 11–15 years had significantly lower PEx rates. Interpretation Study findings showed the importance of early IVA initiation in people with CF. Data are available upon reasonable request. The data that support the findings of this study are available from the US Cystic Fibrosis Foundation Patient Registry at . The US Cystic Fibrosis Foundation Patient Registry collects and manages its own data and maintains processes for researchers to request summarised data. Restrictions may apply to the availability of these data, which were used under a license agreement for this study.

中文翻译：

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开始使用ivacaftor时的年龄对囊性纤维化患者肺部结局的影响

背景 Ivacaftor (IVA) 可改善囊性纤维化 (CF) 患者的肺功能和其他肺外结局。然而，尚未研究较早开始 IVA 与较晚开始 IVA 的效果。方法 我们对美国 CF 基金会患者登记处年龄≥6 岁且具有≥1 个 CF 跨膜电导调节器门控突变的人群进行了一项观察性队列研究，以比较较早年龄开始 IVA 对 1 秒内预测用力呼气量百分比的影响(ppFEV1) 和肺部病情加重 (PEx) 结果。 CF 患者按开始 IVA 时的年龄（6-10 岁、11-15 岁、16-20 岁和 21-25 岁）进行分组，以对年轻与老年 IVA 开始进行三项分析（6-10 岁 vs 11-15 岁、11-15 岁） 15 岁与 16-20 岁以及 16-20 岁与 21-25 岁）。对于每项分析，在 IVA 开始前一年内评估的相同年龄的基线特征通过标准化死亡率/发病率 (SMR) 权重进行平衡。对于每项分析，都比较了 5 年结果评估期内的结果，当时两组处于相同的年龄范围并接受 IVA。结果 SMR 加权后，年轻和年长 IVA 起始组之间的基线特征得到了很好的平衡。在结果评估期间，在所有比较中，年轻的 IVA 发起者的平均 ppFEV1 均显着高于年长的发起者，而那些在 6-10 岁和 11-15 岁之间开始 IVA 的人的 PEx 率显着较低。研究结果表明早期开始 IVA 对 CF 患者非常重要。数据可根据合理要求提供。支持本研究结果的数据可从美国囊性纤维化基金会患者登记处获取：。美国囊性纤维化基金会患者登记处收集和管理自己的数据，并维护研究人员索取汇总数据的流程。这些数据的可用性可能受到限制，这些数据是根据本研究的许可协议使用的。