Toronto Lung Transplant Program, University Health Network, Toronto, Canada.
Biostatistics Research Unit, University Health Network, Toronto, Canada.
Respir Res. 2022 Aug 26;23(1):219. doi: 10.1186/s12931-022-02131-5.
Bronchoalveolar lavage (BAL) is a key tool in respiratory medicine for sampling the distal airways. BAL bile acids are putative biomarkers of pulmonary microaspiration, which is associated with poor outcomes after lung transplantation. Compared to BAL, large airway bronchial wash (LABW) samples the tracheobronchial space where bile acids may be measurable at more clinically relevant levels. We assessed whether LABW bile acids, compared to BAL bile acids, are more strongly associated with poor clinical outcomes in lung transplant recipients.
Concurrently obtained BAL and LABW at 3 months post-transplant from a retrospective cohort of 61 lung transplant recipients were analyzed for taurocholic acid (TCA), glycocholic acid (GCA), and cholic acid by mass spectrometry and 10 inflammatory proteins by multiplex immunoassay. Associations between bile acids with inflammatory proteins and acute lung allograft dysfunction were assessed using Spearman correlation and logistic regression, respectively. Time to chronic lung allograft dysfunction and death were evaluated using multivariable Cox proportional hazards and Kaplan-Meier methods.
Most bile acids and inflammatory proteins were higher in LABW than in BAL. LABW bile acids correlated with inflammatory proteins within and between sample type. LABW TCA and GCA were associated with acute lung allograft dysfunction (OR = 1.368; 95%CI = 1.036-1.806; P = 0.027, OR = 1.064; 95%CI = 1.009-1.122; P = 0.022, respectively). No bile acids were associated with chronic lung allograft dysfunction. Adjusted for risk factors, LABW TCA and GCA predicted death (HR = 1.513; 95%CI = 1.014-2.256; P = 0.042, HR = 1.597; 95%CI = 1.078-2.366; P = 0.020, respectively). Patients with LABW TCA in the highest tertile had worse survival compared to all others.
LABW bile acids are more strongly associated than BAL bile acids with inflammation, acute lung allograft dysfunction, and death in lung transplant recipients. Collection of LABW may be useful in the evaluation of microaspiration in lung transplantation and other respiratory diseases.
支气管肺泡灌洗（BAL）是呼吸医学中用于采样远端气道的重要工具。BAL 胆汁酸是肺微吸入的潜在生物标志物，与肺移植后不良结局相关。与 BAL 相比，大气道支气管冲洗（LABW）可采集到更具临床相关性的气管支气管空间中的胆汁酸。我们评估了与 BAL 胆汁酸相比，LABW 胆汁酸是否与肺移植受者的不良临床结局更密切相关。
通过对 61 例肺移植受者的回顾性队列研究，同时在移植后 3 个月时采集 BAL 和 LABW 样本，采用质谱法检测牛磺胆酸（TCA）、甘氨胆酸（GCA）和胆酸，并采用多重免疫分析法检测 10 种炎症蛋白。采用 Spearman 相关分析和 logistic 回归分析分别评估胆汁酸与炎症蛋白和急性肺移植物功能障碍之间的相关性。采用多变量 Cox 比例风险和 Kaplan-Meier 方法评估慢性肺移植物功能障碍和死亡的时间。
LABW 中的大多数胆汁酸和炎症蛋白均高于 BAL。LABW 胆汁酸与同一样本类型和不同样本类型中的炎症蛋白相关。LABW TCA 和 GCA 与急性肺移植物功能障碍相关（OR=1.368；95%CI=1.036-1.806；P=0.027，OR=1.064；95%CI=1.009-1.122；P=0.022）。无胆汁酸与慢性肺移植物功能障碍相关。在调整了危险因素后，LABW TCA 和 GCA 预测死亡（HR=1.513；95%CI=1.014-2.256；P=0.042，HR=1.597；95%CI=1.078-2.366；P=0.020）。LABW TCA 水平最高的 tertile 患者的生存率低于其他患者。
与 BAL 胆汁酸相比，LABW 胆汁酸与肺移植受者的炎症、急性肺移植物功能障碍和死亡更密切相关。采集 LABW 可能有助于评估肺移植和其他呼吸系统疾病中的微吸入。
