Gu Runchuan, Bodén Embla, Lindstedt Sandra, Olm Franziska
Department of Clinical Sciences, Lund University, Lund, Sweden.
Wallenberg Centre for Molecular Medicine, Lund University, Lund, Sweden.
Front Transplant. 2025 May 23;4:1516728. doi: 10.3389/frtra.2025.1516728. eCollection 2025.
Long-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 FEV 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.
Lung 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.
At 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.
EBP 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.
与其他实体器官移植相比，肺移植后的长期生存率显著缩短。慢性肺移植功能障碍（CLAD），包括闭塞性细支气管炎综合征（BOS），仍然是生存的主要障碍。CLAD根据国际心脏和肺移植学会（ISHLT）的指南进行诊断：对于1级CLAD，使用肺活量测定法FEV下降20%。鉴于使用肺活量测定法存在混杂因素的困难，正在探索其他精确诊断方法。作为气道颗粒流速（PFR）测量的呼出气颗粒（EBP）已被探索作为在急性呼吸窘迫综合征（ARDS）和原发性移植功能障碍（PGD）的临床前和临床环境中诊断肺损伤的潜在方法。事实上，PFR已被证明在ARDS和PGD环境中均能指示肺损伤的早期迹象。在本研究中，我们探讨了PFR是否可作为BOS的标志物。
纳入不同BOS分级的肺移植患者。所有患者病情稳定，无持续感染，且移植后超过2年。在研究开始时和1年后，总共两个时间点（0年和1年），使用呼出空气中的颗粒（PExA）2.0设备（瑞典哥德堡的PExA）测量PFR（每升颗粒数），该设备包含一个光学颗粒计数器。测量直径范围为0.41 - 4.55 µm的颗粒。
在研究开始时和1年后，0级BOS患者 的PFR均显著高于2 - 3级BOS患者。在研究期间，BOS分级进展的患者随着BOS分级进展，其PFR均降低，而BOS分级保持稳定的患者则没有。不同BOS分级之间的颗粒分布具有相似模式；然而，随着BOS分级严重程度增加，PFR显著降低。
以PFR表示的EBP可用于区分BOS分级的严重程度，并可用于追踪BOS随时间的进展。PFR可作为BOS的一种新的诊断工具，并用于追踪肺功能随时间的发展。
