Tobacco smoke exposure limits the therapeutic benefit of tezacaftor/ivacaftor in pediatric patients with cystic fibrosis.
Tobacco smoke exposure limits the therapeutic benefit of tezacaftor/ivacaftor in pediatric patients with cystic fibrosis.
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DOI：
10.1016/j.jcf.2020.09.011
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发表时间：
2021-07
期刊：
影响因子：
--
通讯作者：
Oates GR
中科院分区：
文献类型：
--
作者：
Baker E;Harris WT;Rowe SM;Rutland SB;Oates GR
烟草烟雾暴露降低体外CFTR功能表达，并导致获得性CFTR功能障碍。我们研究了它是否也抑制了CFTR调节剂的临床获益，重点是2018年2月批准用于CF年龄≥12岁的个体的替扎卡托/依伐卡托。一项对CF基金会患者登记研究（2016-2018）中基于吸烟者的数据进行的回顾性纵向分析，比较了吸烟暴露与未暴露的年龄合格儿科患者在开始替扎卡托/依伐卡托治疗前后肺功能变化（GLI FEV1%预测值）的斜率。根据护理人员的自我报告确定烟草烟雾暴露（曾经/从未）。统计分析采用分层线性混合模型和固定效应回归模型。样本包括6，653人，共105，539人-周期观察。替扎卡托/依伐卡托处方给19%（1，251）的个体，平均年龄17岁，平均基线ppFEV 1 83%，28%吸烟暴露。暴露于烟雾的替扎卡托/依伐卡托使用者基线ppFEV 1较低，肺功能下降更严重。两年内，替扎卡托/依伐卡托使用者之间因吸烟暴露而导致的ppFEV 1差异增加了1.2%（7.6%至8.8%，p<0.001）。在混合效应和固定效应回归模型中，替扎卡托/依伐卡托的使用与未暴露个体的ppFEV 1改善相关（分别为1.2%和1.7%;两者均为p<0.001），但在烟雾暴露者中没有提供任何益处（分别为0.3%，p=0.5和0.6%，p=0.07）。烟草烟雾暴露会抵消替扎卡托/依伐卡托对12-20岁CF患者的治疗益处。为了使CFTR调节剂的治疗机会最大化，必须尽一切努力消除CF中的烟雾暴露。
Tobacco smoke exposure reduces CFTR functional expression in vitro and contributes to acquired CFTR dysfunction. We investigated whether it also inhibits the clinical benefit of CFTR modulators, focusing on tezacaftor/ivacaftor, approved in February 2018 for individuals with CF age ≥12 years. A retrospective longitudinal analysis of encounter-based data from the CF Foundation Patient Registry (2016-2018) compared the slope of change in lung function (GLI FEV1% predicted) before and after tezacaftor/ivacaftor initiation in smoke-exposed vs unexposed age-eligible pediatric patients. Tobacco smoke exposure (Ever/Never) was determined from caregiver self-report. Statistical analyses used hierarchical linear mixed modeling and fixed effects regression modeling. The sample included 6,653 individuals with a total of 105,539 person-period observations. Tezacaftor/ivacaftor was prescribed to 19% (1,251) of individuals, mean age 17 years, mean baseline ppFEV1 83%, 28% smoke-exposed. Tezacaftor/ivacaftor users who were smoke-exposed had a lower baseline ppFEV1 and experienced a greater lung function decline. Over two years, the difference in ppFEV1 by smoke exposure among tezacaftor/ivacaftor users increased by 1.2% (7.6% to 8.8%, p<0.001). In both mixed effects and fixed effects regression models, tezacaftor/ivacaftor use was associated with improved ppFEV1 among unexposed individuals (1.2% and 1.7%, respectively; p<0.001 for both) but provided no benefit among smoke-exposed counterparts (0.3%, p=0.5 and 0.6%, p=0.07, respectively). Tobacco smoke exposure nullifies the therapeutic benefit of tezacaftor/ivacaftor among individuals with CF aged 12-20 years old. To maximize the therapeutic opportunity of CFTR modulators, every effort must be taken to eliminate smoke exposure in CF.
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DOI：
10.1164/rccm.200508-1330oc
发表时间：
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影响因子：
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