Müller Catharina, Andersson-Sjöland Annika, Schultz Hans Henrik, Eriksson Leif T, Andersen Claus B, Iversen Martin, Westergren-Thorsson Gunilla
Lung Biology Unit, Department of Experimental Medical Science, Lund University, Lund, Sweden.
Section for Lung Transplantation, Department of Cardiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
BMJ Open Respir Res. 2017 Apr 12;4(1):e000177. doi: 10.1136/bmjresp-2016-000177. eCollection 2017.
Chronic lung allograft dysfunction in the form of bronchiolitis obliterans syndrome (BOS) is the main cause of death beyond 1-year post-lung transplantation. The disease-initiating triggers as well as the molecular changes leading to fibrotic alterations in the transplanted lung are largely unknown. The aim of this study was to identify potential early changes in the extracellular matrix (ECM) in different compartments of the transplanted lung prior to the development of BOS.
Transbronchial biopsies from a cohort of 58 lung transplantation patients at the Copenhagen University hospital between 2005 and 2006, with or without development of BOS in a 5-year follow-up, were obtained 3 and 12 months after transplantation. Biopsies were assessed for total collagen, collagen type IV and biglycan in the alveolar and small airway compartments using Masson's Trichrome staining and immunohistochemistry.
A time-specific and compartment-specific pattern of ECM changes was detected. Alveolar total collagen (p=0.0190) and small airway biglycan (p=0.0199) increased between 3 and 12 months after transplantation in patients developing BOS, while collagen type IV (p=0.0124) increased in patients without BOS. Patients with early-onset BOS mirrored this increase. Patients developing grade 3 BOS showed distinct ECM changes already at 3 months. Patients with BOS with treated acute rejections displayed reduced alveolar total collagen (p=0.0501) and small airway biglycan (p=0.0485) at 3 months.
Patients with future BOS displayed distinct ECM changes compared with patients without BOS. Our data indicate an involvement of alveolar and small airway compartments in post-transplantation changes in the development of BOS.
闭塞性细支气管炎综合征（BOS）形式的慢性肺移植功能障碍是肺移植术后1年以上患者死亡的主要原因。引发该疾病的触发因素以及导致移植肺纤维化改变的分子变化在很大程度上尚不清楚。本研究的目的是在BOS发生之前，确定移植肺不同区域细胞外基质（ECM）的潜在早期变化。
获取了2005年至2006年间在哥本哈根大学医院接受肺移植的58例患者的经支气管活检样本，这些患者在5年随访期内有或没有发生BOS，样本在移植后3个月和12个月获取。使用Masson三色染色和免疫组织化学法评估活检样本中肺泡和小气道区域的总胶原蛋白、IV型胶原蛋白和双糖链蛋白聚糖。
检测到了ECM变化的时间特异性和区域特异性模式。发生BOS的患者在移植后3至12个月期间，肺泡总胶原蛋白（p = 0.0190）和小气道双糖链蛋白聚糖（p = 0.0199）增加，而未发生BOS的患者IV型胶原蛋白（p = 0.0124）增加。早发性BOS患者呈现出类似的增加。发生3级BOS的患者在3个月时就已出现明显的ECM变化。接受过急性排斥反应治疗的BOS患者在3个月时肺泡总胶原蛋白（p = 0.0501）和小气道双糖链蛋白聚糖（p = 0.0485）减少。
与未发生BOS的患者相比，未来发生BOS的患者表现出明显的ECM变化。我们的数据表明，肺泡和小气道区域参与了移植后BOS发生过程中的变化。
