The alveolar space is the site of intense inflammatory and profibrotic reactions in the early phase of acute respiratory distress syndrome
The alveolar space is the site of intense inflammatory and profibrotic reactions in the early phase of acute respiratory distress syndrome
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DOI：
10.1097/00003246-199902000-00036
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发表时间：
1999-02-01
影响因子：
8.8
通讯作者：
Matthay, MA
中科院分区：
文献类型：
--
作者：
Pugin, J;Verghese, G;Matthay, MA
目的：确定早期急性呼吸窘迫综合征（ARDS）患者和对照组流体静力性肺水肿患者未稀释肺水肿液和血浆中促炎介质、胶原酶和III型前胶原肽的浓度;并评估这些炎症和促纤维化标志物之间的关系。设计：一项测量肺水肿液和配对血浆样本中炎症标志物的前瞻性临床研究。本研究前瞻性入组了患有肺渗透性（n = 23）和流体静力性（n = 8）肺水肿的插管患者。使用简化急性生理评分（SAPS）II和肺损伤评分（LIS）评估插管时疾病的严重程度，干预：在插管时获得血浆和未稀释的水肿液，肺水肿需要机械通气;在一些患者中，几小时后采集第二份水肿液样本，测量和主要结果：与充血性心力衰竭患者的血浆或对照液相比，ARDS液中的促炎活性（依赖于生物活性促炎细胞因子、白细胞介素（IL）8和中性粒细胞基质金属蛋白酶（MMP）-9的存在）显著增加。相比之下，与血浆相比，源自吞噬细胞以外的肺细胞的MMP-2在ARDS水肿液中略有增加，但与静水性水肿液中发现的水平相似，在ARDS患者的血浆中检测不到促炎活性。与流体静力性水肿液或血浆相比，渗透性水肿液中的前胶原肽III（胶原合成的标志物）水平增加，证实了肺泡胶原合成很早就开始，并且与ARDS中的急性炎症平行。与ARDS患者相比，流体静力性水肿的对照患者具有相似的SAPS II和LIS评分。这些结果有力地支持了以下结论：在ARDS的早期阶段，肺是强烈的炎症过程的部位，具有细胞因子、趋化因子和蛋白酶分泌的顺序激活，以及伴随的胶原蛋白合成。炎症主要局限于肺，体循环中的炎症介质水平较低。与临床评分系统（SAPS II和LIS）不同，炎症标志物可区分渗透性和流体静力性肺水肿患者。
Objectives: To determine the concentrations of proinflammatory mediators, collagenases, and procollagen type III peptides in undiluted pulmonary edema fluids and in plasma obtained in patients with early acute respiratory distress syndrome (ARDS) and in control patients with hydrostatic lung edema; and to assess the relationship between these inflammatory and profibrotic markers.Design: A prospective, clinical study with measurements of inflammatory markers in pulmonary edema fluids and in paired plasma samples.Setting: A medical intensive care unit.Patients: Patients intubated with lung permeability (n = 23) and hydrostatic (n = 8) pulmonary edema were prospectively enrolled in the study. The severity of the disease at the time of intubation was assessed, using the Simplified Acute Physiological Score (SAPS) II and the Lung Injury Score (LIS),Interventions: Plasma and undiluted edema fluids were obtained at the time of intubation with pulmonary edema requiring mechanical ventilation; and in some patients, a second edema fluid sample was collected a few hours later,Measurements and Main Results: Proinflammatory activity, dependent on the presence of bioactive proinflammatory cytokines, interleukin (IL) 8, and neutrophil matrix metalloproteinase (MMP)-9 were significantly increased in ARDS fluids compared with plasma or control fluids from patients with congestive heart failure. In contrast, MMP-2, originating from lung cells other than phagocytes, was slightly increased in ARDS edema fluids compared with plasma, but similar to levels found in hydrostatic edema fluids, Proinflammatory activity was undetectable in plasma from ARDS patients. Levels of procollagen peptide III, a marker of collagen synthesis, were increased in permeability edema fluids compared with hydrostatic edema fluids or plasma, confirming that alveolar collagen synthesis begins very early and in parallel with acute inflammation in ARDS, Control patients with hydrostatic edema had similar SAPS II and LIS scores compared with ARDS patients.Conclusions: These results strongly support the conclusion that during the early phase of ARDS, the lung is the site of an intense inflammatory process with sequential activation of cytokines, chemokines, and secretion of proteases, as well as concomitant collagen synthesis. The inflammation is mostly limited to the lung, with low levels of inflammatory mediators in the systemic circulation, Unlike clinical scoring systems (SAPS II and LIS), inflammatory markers differentiate patients with permeability and hydrostatic pulmonary edema.