PDF(Pubmed)
Abstract：
Elexacaftor/tezacaftor/ivacaftor (ETI) therapy has revolutionized the treatment of cystic fibrosis (CF) for most affected individuals but the effects of treatment on sinus microbiota are still unknown. Changes to the airway microbiota in CF are associated with disease state and alterations to the bacterial community after ETI initiation may require changes to clinical management regimens. We collected sinus swab samples from the middle meatus in an observational study of 38 adults with CF and chronic rhinosinusitis (CRS) from 2017 to 2021 and captured the initiation of ETI therapy. We performed 16S and custom amplicon sequencing to characterize the sinus microbiota pre- and post-ETI. Real-time quantitative PCR (RT-qPCR) was performed to estimate total bacterial abundance. Sinus samples from people with CF (pwCF) clustered into three community types, dependent on the dominant bacterial organism: a Pseudomonas-dominant, Staphylococcus-dominant, and mixed dominance cluster. Shannon\'s diversity index was low and not significantly altered post-ETI. Total bacterial load was not significantly lowered post-ETI. Pseudomonas spp. abundance was significantly reduced post-ETI, but eradication was not observed. Staphylococcus spp. became the dominant organism in most individuals post-ETI and we showed the presence of methicillin-resistant Staphylococcus aureus (MRSA) in the sinus both pre- and post-ETI. We also demonstrated that the sinus microbiome is predictive of the presence of Pseudomonas spp., Staphylococcus spp., and Serratia spp. in the sputum. Pseudomonas spp. and Staphylococcus spp., including MRSA, persist in the sinuses of pwCF after ETI therapy, indicating that these pathogens will continue to be important in CF airway disease management in the era of highly effective modulator therapies (HEMT).IMPORTANCEHighly effective modulator therapies (HEMT), such as elexacaftor/tezacaftor/ivacaftor (ETI), for cystic fibrosis (CF) have revolutionized patient care and quality of life for most affected individuals. The effects of these therapies on the microbiota of the airways are still unclear, though work has already been published on changes to microbiota in the sputum. Our study presents evidence for reduced relative abundance of Pseudomonas spp. in the sinuses following ETI therapy. We also show that Staphylococcus spp. becomes the dominant organism in the sinus communities of most individuals in this cohort after ETI therapy. We identified methicillin-resistant Staphylococcus aureus (MRSA) in the sinus microbiota both pre- and post-therapy. These findings demonstrate that pathogen monitoring and treatment will remain a vital part of airway disease management for people with cystic fibrosis (pwCF) in the era of HEMT.
摘要：
Elexacaftor/tezacaftor/ivacaftor（ETI）疗法彻底改变了大多数受影响个体的囊性纤维化（CF）的治疗方法，但对鼻窦微生物群的治疗效果仍然未知。CF中气道微生物群的变化与疾病状态有关，ETI启动后细菌群落的改变可能需要改变临床管理方案。我们在2017年至2021年对38名患有CF和慢性鼻-鼻窦炎（CRS）的成年人的观察性研究中，从中鼻道收集了鼻窦拭子样本，并捕获了ETI治疗的开始。我们进行了16S和定制扩增子测序以表征ETI前后的窦微生物群。进行实时定量PCR(RT-qPCR)以估计总细菌丰度。来自CF（pwCF）人群的鼻窦样本分为三种社区类型，依赖于优势细菌有机体：假单胞菌优势，葡萄球菌为主,和混合优势集群。香农的多样性指数较低，ETI后没有显著变化。ETI后总细菌负荷没有显着降低。假单胞菌属。丰度在ETI后显著降低，但没有观察到根除。葡萄球菌属。在ETI后成为大多数个体的优势生物，我们显示ETI前后窦中都存在耐甲氧西林金黄色葡萄球菌（MRSA）。我们还证明了窦微生物组可以预测假单胞菌的存在。,葡萄球菌属。,和沙雷氏菌。在痰中。假单胞菌属。和葡萄球菌属。,包括MRSA,ETI治疗后坚持pwCF的鼻窦，这表明在高效调节疗法（HEMT）时代，这些病原体将继续在CF气道疾病管理中发挥重要作用。重要高效调质疗法（HEMT），例如elexacaftor/tezacaftor/ivacaftor(ETI)，囊性纤维化（CF）彻底改变了大多数受影响个体的患者护理和生活质量。这些疗法对气道微生物群的影响尚不清楚，尽管已经发表了关于痰中微生物群变化的工作。我们的研究提供了假单胞菌属相对丰度降低的证据。ETI治疗后的鼻窦。我们还表明葡萄球菌属。在ETI治疗后，成为该队列中大多数个体的鼻窦群落中的优势生物。我们在治疗前后的鼻窦微生物群中鉴定了耐甲氧西林金黄色葡萄球菌（MRSA）。这些发现表明，在HEMT时代，病原体监测和治疗仍将是囊性纤维化（pwCF）患者气道疾病管理的重要组成部分。
