Mackintosh John A, Yerkovich Stephanie T, Tan Maxine E, Samson Luke, Hopkins Peter Ma, Chambers Daniel C
Queensland Lung Transplant Service, Department of Thoracic Medicine, The Prince Charles Hospital, Brisbane, QLD, Australia.
Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia.
Front Immunol. 2021 Apr 16;12:658062. doi: 10.3389/fimmu.2021.658062. eCollection 2021.
Chronic lung allograft dysfunction (CLAD) represents the major impediment to long term survival following lung transplantation. Donor and recipient telomere length have been shown to associate with lung transplant outcomes, including CLAD. In this study we aimed to measure the telomere lengths of bronchial and bronchiolar airway cells in lung allografts early after transplantation and to investigate associations with CLAD and all-cause mortality.
This prospective, longitudinal study was performed at The Prince Charles Hospital, Australia. Airway cells were collected bronchial and bronchiolar airway brushings at post-transplant bronchoscopies. The relative telomere length in airway cells was determined by quantitative PCR based on the T/S ratio. All patients were censored for CLAD and all-cause mortality in August 2020.
In total 231 bronchoscopies incorporating transbronchial brush and bronchial brush were performed in 120 patients. At the time of censoring, 43% and 35% of patients, respectively, had developed CLAD and had died. Airway bronchiolar and bronchial telomere lengths were strongly correlated (r=0.78, p<0.001), confirming conservation of telomere length with airway branch generation. Both the bronchiolar (r = -0.34, p<0.001) and bronchial (r = -0.31, p<0.001) telomere length decreased with age. Shorter airway telomere length was associated with older donor age and higher donor pack-year smoking history. Neither the bronchiolar nor the bronchial airway telomere length were associated with the development of CLAD (HR 0.39 (0.06-2.3), p=0.30; HR 0.66 (0.2-1.7), p=0.39, respectively) or all-cause mortality (HR 0.92 (0.2-4.5), p=0.92; HR 0.47 (0.1-1.9), p=0.28, respectively).
In this cohort, airway telomere length was associated with donor age and smoking history but was not associated with the future development of CLAD or all-cause mortality.
慢性肺移植功能障碍（CLAD）是肺移植后长期生存的主要障碍。供体和受体的端粒长度已被证明与肺移植结果相关，包括CLAD。在本研究中，我们旨在测量移植后早期肺移植中支气管和细支气管气道细胞的端粒长度，并研究其与CLAD和全因死亡率的关系。
这项前瞻性纵向研究在澳大利亚查尔斯王子医院进行。在移植后的支气管镜检查中，通过支气管和细支气管气道刷检收集气道细胞。基于T/S比值，通过定量PCR测定气道细胞中的相对端粒长度。所有患者在2020年8月被审查是否发生CLAD和全因死亡率。
共对120例患者进行了231次包括经支气管刷检和支气管刷检的支气管镜检查。在审查时，分别有43%和35%的患者发生了CLAD并死亡。气道细支气管和支气管的端粒长度高度相关（r = 0.78，p < 0.001），证实了随着气道分支的产生端粒长度的保守性。细支气管（r = -0.34，p < 0.001）和支气管（r = -0.31，p < 0.001）的端粒长度均随年龄增长而缩短。较短的气道端粒长度与供体年龄较大和供体吸烟史较长有关。细支气管和支气管气道的端粒长度均与CLAD的发生（HR 0.39（0.06 - 2.3），p = 0.30；HR 0.66（0.2 - 1.7），p = 0.39）或全因死亡率（HR 0.92（0.2 - 4.5），p = 0.92；HR 0.47（0.1 - 1.9），p = 0.28）无关。
在该队列中，气道端粒长度与供体年龄和吸烟史相关，但与CLAD的未来发生或全因死亡率无关。
