Table 1_Exhaled breath particles as a diagnostic tool for bronchiolitis obliterans syndrome in lung transplant recipients: a longitudinal study.docx

BackgroundLong-term survival after lung transplantation is significantly shorter compared with other solid organ transplantations. Chronic lung allograft dysfunction (CLAD), including bronchiolitis obliterans syndrome (BOS), remains the major barrier to survival. CLAD is diagnosed according to ISHLT's guidelines: a 20% drop in FEV1 using spirometry for CLAD grade 1. Given the difficulties of confounders using spirometry, other methods for precise diagnostics are being explored. Exhaled breath particles (EBP) measured as particle flow rate (PFR) from the airways have been explored as a potential method to diagnose lung injury in preclinical and clinical settings of acute respiratory distress syndrome (ARDS) and primary graft dysfunction (PGD). In fact, PFR has been shown to indicate early signs of lung injury in both ARDS and PGD settings. In the present study, we explored whether PFR could be used as a marker for BOS.
MethodsLung transplant patients with different BOS grades were included. All patients were in stable condition without ongoing infections and >2 years posttransplantation. PFR (in particles per liter) was measured using a Particles in Exhaled Air (PExA) 2.0 device (PExA, Gothenburg, Sweden), containing an optical particle counter, at the start of the study and then 1 year out, in total two time points (0 and 1 year). Particles in the diameter range of 0.41–4.55 µm were measured.
ResultsAt both the start of the study and 1 year out, patients with BOS grade 0 had significantly higher PFR than patients with BOS grades 2–3. During the study period, patients who progressed in their BOS grade all expressed lower PFR as they progressed in BOS grade, while patients who remained stable in BOS grade did not. The particle distribution between the different BOS grades had a similar pattern; however, it significantly decreased PFR with severity in the BOS grade.
ConclusionsEBP expressed as PFR could be used to distinguish severity in BOS grade and could be used to follow the progression of BOS over time. PFR could be used as a new diagnostic tool for BOS and to follow the development of lung function over time.

背景：与其他实体器官移植相比，肺移植术后患者的长期生存率显著更低。慢性肺移植物功能障碍（Chronic lung allograft dysfunction, CLAD），包括闭塞性细支气管炎综合征（Bronchiolitis obliterans syndrome, BOS），仍是影响患者生存的主要障碍。CLAD的诊断遵循国际心肺移植协会（International Society for Heart and Lung Transplantation, ISHLT）指南：采用肺量测定法检测一秒用力呼气容积（Forced expiratory volume in one second, FEV1）下降≥20%即可诊断为CLAD 1级。鉴于肺量测定法难以排除混杂因素的干扰，目前学界正在探索其他精准诊断方法。呼出气颗粒（Exhaled breath particles, EBP）的颗粒流速（Particle flow rate, PFR）作为一项检测指标，已在急性呼吸窘迫综合征（Acute respiratory distress syndrome, ARDS）和原发性移植物功能障碍（Primary graft dysfunction, PGD）的临床前及临床研究中被探索用于肺损伤的诊断。事实上，已有研究证实PFR可反映ARDS和PGD情境下肺损伤的早期征象。本研究旨在探讨PFR能否作为BOS的检测标志物。
方法：纳入不同BOS分级的肺移植患者。所有患者病情稳定，无活动性感染，且移植术后时长超过2年。本研究采用呼出气颗粒分析仪（Particles in Exhaled Air, PExA）2.0设备（产自瑞典哥德堡的PExA公司，内置光学粒子计数器），分别在研究初始阶段及1年后两个时间点（0年和1年）检测PFR，单位为颗粒数每升。本次检测的颗粒直径范围为0.41~4.55 μm。
结果：在研究初始及1年随访两个时间点，BOS 0级患者的PFR均显著高于BOS 2~3级患者。研究期间，BOS分级出现进展的患者，其PFR随BOS分级升高而持续降低；而BOS分级保持稳定的患者则无此变化。不同BOS分级患者的颗粒分布模式相似，但PFR随BOS分级严重程度升高而显著降低。
结论：以PFR表征的呼出气颗粒可用于区分BOS分级的严重程度，并可用于监测BOS随时间的进展情况。PFR有望成为BOS全新的诊断工具，同时可用于监测肺功能随时间的变化。