Wisniewski Benjamin L, Shrestha Mahesh, Bojja Dinesh, Shrestha Chandra L, Lee Chris S, Ozuna Hazel, Rayner Rachael E, Bai Shasha, Cormet-Boyaka Estelle, Reynolds Susan D, Kopp Benjamin T
Section of Pediatric Pulmonology & Sleep Medicine, Department of Pediatrics, University of Colorado Anschutz Medical Campus & Children's Hospital Colorado, Aurora, Colorado, United States.
Division of Pulmonology, Asthma, Cystic Fibrosis, and Sleep, Emory University School of Medicine, Atlanta, Georgia, United States.
Am J Physiol Lung Cell Mol Physiol. 2025 Mar 1;328(3):L324-L333. doi: 10.1152/ajplung.00328.2024. Epub 2025 Jan 21.
Secondhand smoke exposure (SHSe) is a public health threat for people with cystic fibrosis (CF) and other lung diseases. Primary smoking reduces CF transmembrane conductance regulator (CFTR) channel function, the causative defect in CF. We reported that SHSe worsens respiratory and nutritional outcomes in CF by disrupting immune responses and metabolic signaling. Recently, electronic cigarette (e-cigs) usage by caregivers and peers has increased rapidly, causing new secondhand e-cig vape exposures. Primary vaping is associated with immunologic deficits in healthy people, but it is unknown whether e-cigs similarly impacts CF immune function or how it differs from SHSe. Human CF and non-CF blood monocyte-derived macrophages (MDMs) and bronchial epithelial cells (HBECs) were exposed to flavored and unflavored e-cigs. The effect of e-cigs on CFTR expression and function, bacterial killing, cytokine signaling, lipid mediators, and metabolism was measured during treatment with CFTR modulators. E-cigs decreased CFTR expression and function in CF and non-CF MDMs and negated CFTR functional restoration by elexacaftor/tezacaftor/ivacaftor (ETI). E-cigs also negated the restoration of anti-inflammatory PGD expression in CF MDMs treated with ETI compared with controls. Flavored but not unflavored e-cigs increased proinflammatory cytokine expression in CF MDMs and e-cigs promoted glycolytic metabolism. E-cigs did not impact bacterial killing. Overall, HBECs were less impacted by e-cigs compared with MDMs. E-cigs reduced macrophage CFTR expression and hindered functional CFTR restoration by CFTR modulators, promoting a glycolytic, proinflammatory state. E-cigs are an emerging public health threat that may limit the efficacy of CFTR modulators in people with CF. New research reveals that e-cigarettes pose a serious health risk for individuals with cystic fibrosis (CF). Exposure to electronic cigarette (e-cig) vapors decreases CF transmembrane conductance regulator (CFTR) function and undermines the effectiveness of CFTR modulators, potentially worsening inflammation and metabolic responses. This highlights an urgent need for awareness around e-cig use, especially among caregivers and peers of those with CF. E-cigarettes may further complicate the management of this chronic lung disease.
接触二手烟（SHSe）对患有囊性纤维化（CF）和其他肺部疾病的人构成公共卫生威胁。主动吸烟会降低CF跨膜传导调节因子（CFTR）通道功能，这是CF的致病缺陷。我们报告称，SHSe会通过破坏免疫反应和代谢信号，恶化CF患者的呼吸和营养状况。最近，护理人员和同龄人使用电子烟的情况迅速增加，导致了新的二手电子烟暴露。主动吸电子烟与健康人的免疫缺陷有关，但尚不清楚电子烟是否同样会影响CF的免疫功能，以及它与SHSe有何不同。将人类CF和非CF血液单核细胞衍生的巨噬细胞（MDM）以及支气管上皮细胞（HBEC）暴露于有香味和无香味的电子烟中。在用CFTR调节剂治疗期间，测量了电子烟对CFTR表达和功能、细菌杀伤、细胞因子信号传导、脂质介质和代谢的影响。电子烟降低了CF和非CF MDM中的CFTR表达和功能，并消除了依列卡福/替扎卡福/依伐卡福（ETI）对CFTR功能的恢复作用。与对照组相比，电子烟还消除了用ETI治疗的CF MDM中抗炎性前列腺素D（PGD）表达的恢复。有香味而非无香味的电子烟增加了CF MDM中促炎细胞因子的表达，并且电子烟促进了糖酵解代谢。电子烟对细菌杀伤没有影响。总体而言，与MDM相比，HBEC受电子烟的影响较小。电子烟降低了巨噬细胞CFTR的表达，并阻碍了CFTR调节剂对CFTR功能的恢复，促进了糖酵解、促炎状态。电子烟是一种新出现的公共卫生威胁，可能会限制CFTR调节剂对CF患者的疗效。新的研究表明，电子烟对囊性纤维化（CF）患者构成严重的健康风险。接触电子烟烟雾会降低CF跨膜传导调节因子（CFTR）的功能，并削弱CFTR调节剂的有效性，可能会加剧炎症和代谢反应。这凸显了迫切需要提高对电子烟使用的认识，尤其是在CF患者的护理人员和同龄人中。电子烟可能会使这种慢性肺病的管理更加复杂。
