β2-agonists and acute respiratory distress syndrome.
β2-agonists and acute respiratory distress syndrome.
复制标题
β2-激动剂和急性呼吸窘迫综合征。
DOI：
10.1164/rccm.201401-0170ed
复制
发表时间：
2014
影响因子：
24.7
通讯作者：
Mutlu,GökhanM
中科院分区：
文献类型：
--
作者：
Budinger,GRScott;Mutlu,GökhanM
在急性呼吸窘迫综合征(ARDS)患者的支持性护理方面的最新进展使死亡率显著降低(1-4)。然而，针对ARDS的药物治疗仍然难以捉摸，死亡率仍然高得令人无法接受(4，5)。ARDS的解决需要清除多余的肺水肿液和急性炎症细胞，同时修复受损的肺泡上皮(5，6)。过量肺泡液的吸收是一个主动的、依赖于三磷酸腺苷的过程，它涉及到钠离子通过顶端钠通道和氯离子通道以及肺泡上皮细胞底侧Na-K-ATPase从肺泡空间向外转运的过程(6-8)。Ware和Matthay证实了大量临床前数据表明水肿液的清除具有重要作用，他们发现大多数ARDS患者的肺泡液清除受到损害，保持正常清除与更好的预后相关(9)。在动物模型和人类细胞中，b2肾上腺素能受体(B2ARs)的刺激增加了钠在肺泡上皮细胞中的矢量运输，以改善水肿物的清除(6-8，10-13)。长效b2激动剂沙美特罗的临床试验证实了b2激动剂在人类肺水肿清除方面的有效性，该试验降低了高危旅行者中高原肺水肿的发生率(14)。这些有希望的发现为b2激动剂治疗ARDS的临床试验奠定了基础。小型II期试验--b-Agonist肺损伤(BALTI)-1试验(15)的令人鼓舞的结果促使两个大规模随机对照试验(16，17)。不幸的是，由于徒劳和安全考虑，这两项试验都被终止了。在沙丁胺醇治疗急性肺损伤(ALTA)研究中，ARDS患者被随机分为每4小时雾化吸入沙丁胺醇或安慰剂(16例)。无呼吸机天数的主要结果或出院前死亡或中毒的次要结果没有显著差异。第二项大型随机对照研究Balti-2解决了通过吸入给药的沙丁胺醇可能没有被输送到肺水肿最严重的区域的担忧，在这项研究中，ARDS患者被随机分配接受最大剂量的持续静脉输注沙丁胺醇，该剂量不会导致危重患者心律失常的增加(17)。中期分析显示，与安慰剂相比，接受沙丁胺醇治疗的患者28天死亡率增加(34%比23%)后，这项研究终止。
Recent advances in the supportive care of patients with acute respiratory distress syndrome (ARDS) have resulted in significant reductions in mortality (1–4). However, pharmacologic therapies specific for ARDS have remained elusive, and mortality remains unacceptably high (4, 5). The resolution of ARDS requires the removal of excess lung edema fluid and acute inflammatory cells accompanied by repair of the injured alveolar epithelium (5, 6). The absorption of excess alveolar fluid is an active, ATP-dependent process that involves the vectorial transport of sodium ions out of alveolar air spaces via the apical sodium and chloride channels and basolateral Na-K-ATPases in the alveolar epithelium (6–8). Confirming a wealth of preclinical data suggesting an important role for the removal of edema fluid, Ware and Matthay found that alveolar fluid clearance is impaired in the majority of patients with ARDS and that preservation of normal clearance is associated with better outcomes (9).In animal models and human cells, the stimulation of b2-adrenergic receptors (b2ARs) increases the vectorial transport of sodium across the alveolar epithelium to improve edema clearance (6–8, 10–13). The efficacy of b2-agonist therapy in lung edema clearance in humans was confirmed in a clinical trial where the administration of the long-acting b2-agonist salmeterol reduced the incidence of high-altitude pulmonary edema in a high-risk group of travelers (14). These promising findings were the basis for clinical trials of b2-agonists for the treatment of ARDS. Encouraging results from a small phase II trial, the b-Agonist Lung Injury (BALTI)-1 trial (15), prompted two large-scale randomized control trials (16, 17). Unfortunately, both trials were terminated due to futility and safety concerns. In the Albuterol to Treat Acute Lung Injury (ALTA) study, patients with ARDS were randomized to receive either nebulized albuterol or placebo every 4 hours (16). There was no significant difference in the primary outcome of ventilator-free days or in the secondary outcomes of death before hospital discharge or toxicity. The concern that albuterol administered via inhalation may not have been delivered to the regions of the lung with the most severe edema was addressed in the second large, randomized control study, BALTI-2, in which patients with ARDS were randomized to receive a continuous intravenous infusion of salbutamol at the maximal dose that did not result in an increase in arrhythmias in critically ill patients (17). This study was terminated after an interim analysis showed an increase in 28-day mortality in the patients treated with salbutamol compared with placebo (34% vs. 23%).
登录
查看更多内容
白介素4对人类巨噬细胞形成的抑制4。
影响因子：
15.3
作者：
JANSEN, JH;WIENTJENS, GJHM;FIBBE, WE;WILLEMZE, R;KLUINNELEMANS, HC
通讯作者：
KLUINNELEMANS, HC
检测干扰脱氧核糖核苷 5-三磷酸酶测定的活性。
DOI：
10.1016/s0021-9258(18)43617-4
发表时间：
1980
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
T. North;R. Bestwick;C. Mathews
通讯作者：
C. Mathews
纯化的 GM-CSF 直接刺激多能细胞和红系前体细胞的增殖。
影响因子：
20.3
作者：
D. Metcalf;G. Johnson;A. Burgess
通讯作者：
A. Burgess
人类肺泡巨噬细胞起源于骨髓的直接证据。
影响因子：
56.9
作者：
Thomas Ed;Ramberg Re;G. Sale;RS Sparkes;D. Golde
通讯作者：
D. Golde
人单核吞噬细胞内细胞内病原体的存活。
影响因子：
3.6
作者：
Murray,HW
通讯作者：
Murray,HW