Aspirin reduces lipopolysaccharide-induced pulmonary inflammation in human models of ARDS.
Aspirin reduces lipopolysaccharide-induced pulmonary inflammation in human models of ARDS.
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DOI：
10.1136/thoraxjnl-2016-208571
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发表时间：
2017-11
期刊：
影响因子：
10
通讯作者：
O'Kane CM
中科院分区：
文献类型：
--
作者：
Hamid U;Krasnodembskaya A;Fitzgerald M;Shyamsundar M;Kissenpfennig A;Scott C;Lefrancais E;Looney MR;Verghis R;Scott J;Simpson AJ;McNamee J;McAuley DF;O'Kane CM
血小板在急性呼吸窘迫综合征（ARDS）的发病中起着积极的作用。动物和观察性研究表明，阿司匹林的抗血小板和免疫调节作用可能对ARDS有益。在临床相关的人类模型中验证阿司匹林减轻炎症的假设，该模型概括了与ARDS发展有关的病理生理机制。在一项双盲、安慰剂对照、分配隐藏研究中，健康志愿者在吸入脂多糖（LPS）前随机接受安慰剂或阿司匹林75或1200 mg（1：1：1）治疗7天。吸入LPS 50 μg后6 h行支气管肺泡灌洗（BAL）。主要结局指标为BAL IL-8。次要结局指标包括肺泡炎症标志物（BAL中性粒细胞、细胞因子、中性粒细胞蛋白酶）、肺泡上皮细胞损伤、全身炎症（中性粒细胞和血浆C反应蛋白（CRP））和血小板活化（血栓素B2、TXB 2）。将离体灌注和通气（EVLP）的人肺随机分配至安慰剂组或24 mg阿司匹林组，并用LPS损伤。4小时后进行BAL。通过BAL细胞分类计数和组织学变化评估炎症。在健康志愿者（n=33）模型中，合并阿司匹林组的数据。阿司匹林不降低BAL IL-8。然而，阿司匹林降低了肺嗜中性粒细胞和组织损伤性中性粒细胞蛋白酶（基质金属蛋白酶（MMP）-8/-9），降低了肿瘤坏死因子α的BAL浓度，并降低了全身和肺TXB 2。高剂量和低剂量阿司匹林之间没有差异。在EVLP模型中，阿司匹林减少BAL嗜酸性粒细胞和肺泡损伤，如组织学损伤所测量的。这是第一个前瞻性的人类数据，表明阿司匹林在低剂量和高剂量下都能抑制肺部嗜酸性炎症。阿司匹林在预防和治疗ARDS中的作用有待于进一步的临床研究。NCT 01659307结果。
Platelets play an active role in the pathogenesis of acute respiratory distress syndrome (ARDS). Animal and observational studies have shown aspirin’s antiplatelet and immunomodulatory effects may be beneficial in ARDS. To test the hypothesis that aspirin reduces inflammation in clinically relevant human models that recapitulate pathophysiological mechanisms implicated in the development of ARDS. Healthy volunteers were randomised to receive placebo or aspirin 75 or 1200 mg (1:1:1) for seven days prior to lipopolysaccharide (LPS) inhalation, in a double-blind, placebo-controlled, allocation-concealed study. Bronchoalveolar lavage (BAL) was performed 6 hours after inhaling 50 μg of LPS. The primary outcome measure was BAL IL-8. Secondary outcome measures included markers of alveolar inflammation (BAL neutrophils, cytokines, neutrophil proteases), alveolar epithelial cell injury, systemic inflammation (neutrophils and plasma C-reactive protein (CRP)) and platelet activation (thromboxane B2, TXB2). Human lungs, perfused and ventilated ex vivo (EVLP) were randomised to placebo or 24 mg aspirin and injured with LPS. BAL was carried out 4 hours later. Inflammation was assessed by BAL differential cell counts and histological changes. In the healthy volunteer (n=33) model, data for the aspirin groups were combined. Aspirin did not reduce BAL IL-8. However, aspirin reduced pulmonary neutrophilia and tissue damaging neutrophil proteases (Matrix Metalloproteinase (MMP)-8/-9), reduced BAL concentrations of tumour necrosis factor α and reduced systemic and pulmonary TXB2. There was no difference between high-dose and low-dose aspirin. In the EVLP model, aspirin reduced BAL neutrophilia and alveolar injury as measured by histological damage. These are the first prospective human data indicating that aspirin inhibits pulmonary neutrophilic inflammation, at both low and high doses. Further clinical studies are indicated to assess the role of aspirin in the prevention and treatment of ARDS. NCT01659307 Results.
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影响因子：
15.9
作者：
Dunsmore, SE;Saarialho-Kere, UK;Parks, WC
通讯作者：
Parks, WC
DOI：
10.1152/ajplung.00358.2013
发表时间：
2014-05-01
影响因子：
4.9
作者：
McAuley, D. F.;Curley, G. F.;Lee, J. W.
通讯作者：
Lee, J. W.
院前他汀类药物和阿司匹林使用以及严重败血症和急性肺损伤/急性呼吸窘迫综合征的患病率。
影响因子：
8.8
作者：
O'Neal HR Jr;Koyama T;Koehler EA;Siew E;Curtis BR;Fremont RD;May AK;Bernard GR;Ware LB
通讯作者：
Ware LB
DOI：
10.1186/s13054-015-0846-4
发表时间：
2015-03-23
期刊：
Critical care (London, England)
影响因子：
--
作者：
Boyle AJ;Di Gangi S;Hamid UI;Mottram LJ;McNamee L;White G;Cross LJ;McNamee JJ;O'Kane CM;McAuley DF
通讯作者：
McAuley DF
影响因子：
7.4
作者：
Blair P;Flaumenhaft R
通讯作者：
Flaumenhaft R