The prognostic importance of CXCR3 chemokine during organizing pneumonia on the risk of chronic lung allograft dysfunction after lung transplantation.
The prognostic importance of CXCR3 chemokine during organizing pneumonia on the risk of chronic lung allograft dysfunction after lung transplantation.
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DOI：
10.1371/journal.pone.0180281
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Belperio JA
中科院分区：
文献类型：
--
作者：
Shino MY;Weigt SS;Li N;Palchevskiy V;Derhovanessian A;Saggar R;Sayah DM;Huynh RH;Gregson AL;Fishbein MC;Ardehali A;Ross DJ;Lynch JP 3rd;Elashoff RM;Belperio JA
由于慢性肺移植物功能障碍（CLAD）的发病机制仍然不明确，没有已知的有效治疗方法，识别和研究增加CLAD风险的关键事件是改善结局的关键一步。我们假设，在机化性肺炎（OP）期间，支气管肺泡灌洗液（BALF）中CXCR 3配体的浓度会增加，并且OP发作时趋化因子显著升高与CLAD风险显著升高相关。回顾了2000年至2010年期间接受肺移植患者的所有经支气管活检（TBBX）。使用线性混合效应模型比较了OP发作和“健康”活检之间CXCR 3配体（CXCL 9、CXCL 10和CXCL 11）的BALF浓度。使用具有时间依赖性协变量的比例风险模型评估OP期间CXCR 3配体浓度与CLAD风险之间的关联。对441例肺移植受者进行了1894次TBBX支气管镜检查，其中169例（9%）发生OP，907例（49%）发生非OP组织病理学损伤。在常规监测支气管镜检查期间观察到62例（37%）OP发作。838例（44%）TBBX无组织病理学检查，被归类为“健康”活检。与“健康”活检相比，OP期间BALF CXCR 3配体浓度显著升高。在调整其他损伤模式的多变量模型中，当不考虑BAL CXCR 3趋化因子浓度时，OP并没有显著增加CLAD的风险。然而，OP与升高的CXCR 3配体显着增加CLAD的风险，在剂量反应的方式。CXCR 3浓度大于第25、50和75个月的OP发作的CLAD HR分别为1.5（95% CI 1.0-2.3）、1.9（95% CI 1.2-2.8）和2.2（95% CI 1.4-3.4）。本研究鉴定了OP（肺移植后相对不常见的组织病理学发现）作为CLAD发展的主要风险因素，当考虑到干扰素-γ诱导的ELR-CXC趋化因子的同种异体移植物表达增加时。我们首次进一步证明了OP期间BALF CXCR 3配体浓度对随后CLAD风险的预后重要性。
Since the pathogenesis of chronic lung allograft dysfunction (CLAD) remains poorly defined with no known effective therapies, the identification and study of key events which increase CLAD risk is a critical step towards improving outcomes. We hypothesized that bronchoalveolar lavage fluid (BALF) CXCR3 ligand concentrations would be augmented during organizing pneumonia (OP) and that episodes of OP with marked chemokine elevations would be associated with significantly higher CLAD risk. All transbronchial biopsies (TBBX) from patients who received lung transplantation between 2000 to 2010 were reviewed. BALF concentrations of the CXCR3 ligands (CXCL9, CXCL10 and CXCL11) were compared between episodes of OP and “healthy” biopsies using linear mixed-effects models. The association between CXCR3 ligand concentrations during OP and CLAD risk was evaluated using proportional hazards models with time-dependent covariates. There were 1894 bronchoscopies with TBBX evaluated from 441 lung transplant recipients with 169 (9%) episodes of OP and 907 (49%) non-OP histopathologic injuries. 62 (37%) episodes of OP were observed during routine surveillance bronchoscopy. Eight hundred thirty-eight (44%) TBBXs had no histopathology and were classified as “healthy” biopsies. There were marked elevations in BALF CXCR3 ligand concentrations during OP compared with “healthy” biopsies. In multivariable models adjusted for other injury patterns, OP did not significantly increase the risk of CLAD when BAL CXCR3 chemokine concentrations were not taken into account. However, OP with elevated CXCR3 ligands markedly increased CLAD risk in a dose-response manner. An episode of OP with CXCR3 concentrations greater than the 25th, 50th and 75th percentiles had HRs for CLAD of 1.5 (95% CI 1.0–2.3), 1.9 (95% CI 1.2–2.8) and 2.2 (95% CI 1.4–3.4), respectively. This study identifies OP, a relatively uncommon histopathologic finding after lung transplantation, as a major risk factor for CLAD development when considered in the context of increased allograft expression of interferon-γ inducible ELR- CXC chemokines. We further demonstrate for the first time, the prognostic importance of BALF CXCR3 ligand concentrations during OP on subsequent CLAD risk.
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DOI：
10.1164/ajrccm.159.3.9607099
发表时间：
1999-03-01
影响因子：
24.7
作者：
Husain, AN;Siddiqui, MT;Garrity, ER
通讯作者：
Garrity, ER
DOI：
10.1084/jem.184.3.963
发表时间：
1996-09-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Loetscher M;Gerber B;Loetscher P;Jones SA;Piali L;Clark-Lewis I;Baggiolini M;Moser B
通讯作者：
Moser B
DOI：
10.1164/rccm.200706-951oc
发表时间：
2008-05-01
影响因子：
24.7
作者：
Glanville, Allan R.;Aboyoun, Christina L.;Malouf, Monique A.
通讯作者：
Malouf, Monique A.
DOI：
10.1084/jem.187.12.2009
发表时间：
1998-06-15
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Cole KE;Strick CA;Paradis TJ;Ogborne KT;Loetscher M;Gladue RP;Lin W;Boyd JG;Moser B;Wood DE;Sahagan BG;Neote K
通讯作者：
Neote K
DOI：
10.1164/rccm.200302-165oc
发表时间：
2004-11-01
影响因子：
24.7
作者：
Hopkins, PM;Aboyoun, CL;Glanville, AR
通讯作者：
Glanville, AR