Chao Bonnie T, Sage Andrew T, Yeung Jonathan C, Bai Xiaohui, Ma Jin, Martinu Tereza, Liu Mingyao, Cypel Marcelo, Van Raemdonck Dirk, Ceulemans Laurens J, Neyrinck Arne, Verleden Stijn, Keshavjee Shaf
Toronto Lung Transplant Program and Latner Thoracic Research Laboratories, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada; Institute of Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada.
Toronto Lung Transplant Program and Latner Thoracic Research Laboratories, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada; Ajmera Transplant Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada; Department of Surgery, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Institute of Medical Science, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
J Thorac Cardiovasc Surg. 2023 Dec;166(6):1520-1528.e3. doi: 10.1016/j.jtcvs.2023.07.013. Epub 2023 Jul 21.
Diagnosing lung injury is a challenge in lung transplantation. It has been unclear if a single biopsy specimen is truly representative of the entire organ. Our objective was to investigate lung inflammatory biomarkers using human lung tissue biopsies and ex vivo lung perfusion perfusate.
Eight human donor lungs declined for transplantation were air inflated, flash frozen, and partitioned from apex to base. Biopsies were then sampled throughout the lung. Perfusate was sampled from 4 lung lobes in 8 additional donor lungs subjected to ex vivo lung perfusion. The levels of interleukin-6, interleukin-8, interleukin-10, and interleukin-1β were measured using quantitative reverse transcription polymerase chain reaction from lung biopsies and enzyme-linked immunosorbent assay from ex vivo lung perfusion perfusate.
The median intra-biopsy equal-variance P value was .50 for messenger RNA biomarkers in tissue biopsies. The median intra-biopsy coefficient of variance was 18%. In donors with no apparent focal injuries, the biopsies in each donor showed no difference in various lung slices, with a coefficient of variance of 20%. The exception was biopsies from the lingula and injured focal areas that demonstrated larger differences. Cytokines in ex vivo lung perfusion perfusate showed minimal variation among different lobes (coefficient of variance = 4.9%).
Cytokine gene expression in lung biopsies was consistent, and the biopsy analysis reflects the whole lung, except when specimens were collected from the lingula or an area of focal injury. Ex vivo lung perfusion perfusate also provides a representative measurement of lung inflammation from the draining lobe. These results will reassure clinicians that a lung biopsy or an ex vivo lung perfusion perfusate sample can be used to inform donor lung selection.
诊断肺损伤是肺移植中的一项挑战。单个活检标本是否能真正代表整个器官尚不清楚。我们的目的是使用人肺组织活检和体外肺灌注灌流液来研究肺炎症生物标志物。
8个被拒绝用于移植的人供体肺经充气、速冻后，从肺尖到肺底进行分割。然后在整个肺中采集活检标本。在另外8个接受体外肺灌注的供体肺中，从4个肺叶采集灌流液。使用定量逆转录聚合酶链反应检测肺活检标本中白细胞介素-6、白细胞介素-8、白细胞介素-10和白细胞介素-1β的水平，并使用酶联免疫吸附测定法检测体外肺灌注灌流液中的这些指标。
组织活检中信使核糖核酸生物标志物的活检内等方差P值中位数为0.50。活检内变异系数中位数为18%。在没有明显局灶性损伤的供体中，每个供体的活检标本在不同肺切片中无差异，变异系数为20%。例外的是来自舌叶和损伤局灶区域的活检标本，其差异较大。体外肺灌注灌流液中的细胞因子在不同肺叶间的变化极小（变异系数 = 4.9%）。
肺活检中的细胞因子基因表达是一致的，活检分析反映了整个肺，除非标本是从舌叶或局灶性损伤区域采集的。体外肺灌注灌流液也能对引流肺叶的肺炎症提供具有代表性的测量。这些结果将使临床医生放心，肺活检或体外肺灌注灌流液样本可用于指导供体肺的选择。
