急性肺损伤/急性呼吸窘迫综合征基因治疗进展

急性肺损伤(acute lung injury,ALI)及其严重阶段急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS)是严重威胁患者生命的常见危重症,其主要的病理生理改变是弥漫性肺毛细血管内皮-肺泡上皮屏障功能的破坏及炎症损害,临床表现为呼吸衰竭.尽管药物治疗和呼吸支持治疗有一定的进步,但ALI的病死率仍高达40％[1],尚缺乏根本而有效的治疗手段.随着对疾病发病机制认识的深入,基因在ALI发病机制中的地位逐渐凸显出来,以病毒及非病毒系统为载体的基因治疗在调控肺内的炎症反应、肺水清除、改善内皮功能及减少肺纤维化、促进肺损伤的修复过程中发挥了显著的作用,为ALI/ARDS的治疗提供了新的途径.     

肺血管内皮细胞分泌功能的改变与急性肺损伤/急性呼吸窘迫综合征

急性肺损伤(acute lung injury,ALI)/急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS)是临床上常见的急危重症,病死率高达25%~45%,治疗上主要限于器官功能与全身支持治疗,尤其是呼吸支持治疗,"等待"肺损伤的缓解。在ARDS发病机制中肺血管内皮细胞(pulmonary vascular endothelial cell,PVEC)既是受损的主要靶细胞,更是活跃的炎症和效应细胞,血管内皮细胞(vascular endothelial cell,VEC)的激活和损伤程度与ARDS预后密切相关。本文将主要阐述ALI/ARDS发病机制中PVEC部分分泌功能的改变。     

炎症反应在急性肺损伤中的作用机制研究进展

正急性肺损伤(acute lung injury,ALI)在美国的发病率为86.2/10万,我国的住院患者发病率约为6.8%,病死率约为41.6%[1]。ALI最常见的病因为重症肺炎,其次为肺挫伤及误吸。尽管对ALI的基础研究及临床治疗都取得了一些进展,重症ALI即ARDS(氧合指数200)的病死率仍高达40%。炎症反应是ARDS发生的关键。ALI发生后,肺毛细血管内皮细胞通透性增加,肿瘤坏死因子、白介     

急性肺损伤中医学发病机制及治疗思路探讨

急性肺损伤(acute lung injury,ALI)是指由心源性以外的各种肺内、外致病因素所致的急性、进行性、缺氧性呼吸衰竭。本病是临床常见病、多发病,其发病机制错综复杂,迄今尚未完全阐明,亦无满意的治疗措施,病死率高达50%[1]。根据其临床表现,ALI当属中医学“肺热证”、“喘证”、     

急性呼吸窘迫综合征4例临床分析

急性呼吸窘迫综合征(acute respiratary distress syndmms ARDS)是危重病急救医学中较为常见的临床综合征，是指心源性以外的各种肺内外致病因素引起肺泡-毛细血管炎症损伤为主的急性呼吸衰竭。属于急性肺损伤(acute lung injury ALI)的严重阶段，常并发多脏器功能衰竭，其病死率很高。现对4例急性呼吸窘迫综合征进行临床分析，目的是提高广大医务工作者的认识。     

气体信号分子与急性肺损伤

急性肺损伤(acute lung injury,ALI)由多种炎性介质及效应细胞共同参与,并呈级联放大的瀑布样炎症继发性损伤与弥漫性肺实质损伤,且可进一步发展为急性呼吸窘迫综合征(ARDS).ALI/ARDS发病机制复杂[1],病死率高,已成为临床危重病学研究的热点和难点,故探寻新的治疗方法显得尤为重要.内源性气体信号分子一氧化氮(NO)、一氧化碳(CO)和硫化氢(H2S)的发现为肺损伤等疾病的研究提供了一个全新的思路.研究发现它们均参与了ALI的发病且对ALI具有调节作用.二氧化硫(SO2)是最近提出的一种新型气体信号分子,在心血管系统中发挥广泛的生物学活性[2].     

RAGE及其配体钙粒蛋白S100A12在急性肺损伤中研究进展

正脓毒症是临床较为常见的一种危重症,它除可引起剧烈的全身炎症反应外,还常导致肺、肝、肾、肠道、脑等多个器官的功能失常。尤其是脓毒症所致的肺损伤,其发生早,病情较重,表现为急性肺损伤(acute lung injury,ALI)或急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS),常是患者死亡的直接原因。尽管目前监护技术及机械通气设备的进展为脓毒症所致的ALI/ARDS救治提供很大帮助,但其病死率仍高达38%~50%[1]。生理状态下,晚期糖基化终末产物受体     

急性肺损伤/急性呼吸窘迫综合征患者机械通气管理策略

急性肺损伤(acute lung injury,ALI)/急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS)是临床常见的肺部综合征[1],临床以进行性呼吸困难、低氧血症、肺顺应性下降为特征,病死率为40%~50%。机械通气作为支持呼吸的重要手段,能够缓解呼吸窘迫、改善肺压力-容量关系,为ALI/ARDS患者的病因治疗争取时间、创造条件。本文将重点讨论ALI/ARDS患者的机械通气管理策略。保护性机械通气策略ALI/ARDS患者的临床监护往往面临努力确保足够氧合与减小氧中毒潜在危险两方面的困难选择[2]。20世纪70年代,ALI/ARDS患者机械通气…     

脂联素在急性肺损伤中的研究进展

急性肺损伤(acute lung injury,ALI)是指在严重感染、休克、烧创伤等多种非心源性致病因素作用下导致的肺泡-毛细血管通透性增加,造成弥漫性肺间质与肺实质水肿,临床表现为进行性低氧血症,严重时表现为急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS),甚至可进展为致命性呼吸衰竭[1-3]。流行病学调查显示,目前ALI的发病率及病死率仍较高,在美国的发病率为86.2/10万,中国的住院患者发病率约为6.8%,病死率约为40%[4]。近些年来,ALI的基础研究和临床研究都取得了一些进展,但其病死率仍然居高不下[5-7]。如能进一步阐明其发病机制,在早期阶段对病情进行及时的评估和干预,有望进一步降低病死率和改善预后[2]。脂联素是脂肪组织分泌的一种特征性蛋白质,其血清水平在脂肪量增多时反而下降,在慢性炎症性疾病的发生发展过程中发挥重要作用[8]。ALI作为一种以炎症损伤为主要发病机制的疾病,近年来有大量文献报道了其与脂联素之间的关系,并提示脂联素在ALI的发生发展中发挥重要作用[9]。因此,本文就脂联素在ALI中的作用机制及应用作一简要综述。     

急性肺损伤的治疗进展

急性肺损伤(ALI)/急性呼吸窘迫综合征(ARDS)是ICU最常见的急危重症,是一种以失控炎症反应为根本发病原因,以肺泡上皮和肺毛细血管内皮细胞的损伤为主要病理生理改变,以急性非心源性肺水肿和顽固性低氧血症为主要临床表现的综合征[1].由于机械通气等支持治疗技术的进步,尤其是近十年来肺保护性通气策略的推广,ALI的病死率已显著下降,但仍高达30％～40％[ 2].规范化的机械通气策略、创新性的药物治疗以及细胞疗法应当是进一步改善ALI患者预后的希望所在,也是目前ALI基础和临床研究的重点.     

Anti-interleukin-8 autoantibody:interleukin-8 immune complexes in acute lung injury/acute respiratory distress syndrome

ALI/ARDS (acute lung injury/acute respiratory distress syndrome) is a severe inflammatory lung disease associated with very high mortality. Importantly, no effective therapy has been developed to date for ALI/ARDS. Neutrophils have been implicated in the pathogenesis of ALI/ARDS, and IL-8 (interleukin-8) has been identified as the main chemotactic factor for neutrophils in lung fluids of patients with ALI/ARDS. Significantly, studies from our laboratory have revealed the presence of anti-IL-8 autoantibody:IL-8 immune complexes in lung fluids from patients with ALI/ARDS. Autoantibodies to several cytokines, including IL-8, have been found in human plasma and other tissues. The function of anticytokine autoantibodies is far from clear; however, in some instances, it has been suggested that such autoantibodies may contribute to the pathogenesis of variety of human diseases. In addition, many of these autoantibodies can form immune complexes with target cytokines. Furthermore, immune complexes consisting of anti-IL-8 autoantibodies and IL-8 are very stable due to the high affinity of autoantibodies against IL-8. These complexes are present in various human tissues, including the lung, as they have been detected in lung fluids from patients with ALI/ARDS. In this review, the significance of the latter findings are explored, and the possible involvement of anti-IL-8 autoantibody:IL-8 immune complexes in pathogenesis of ALI/ARDS is discussed.     

Surfactant therapy for acute lung injury and acute respiratory distress syndrome

This article examines exogenous lung surfactant replacement therapy and its usefulness in mitigating clinical acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS). Surfactant therapy is beneficial in term infants with pneumonia and meconium aspiration lung injury, and in children up to age 21 years with direct pulmonary forms of ALI/ARDS. However, extension of exogenous surfactant therapy to adults with respiratory failure and clinical ALI/ARDS remains a challenge. This article reviews clinical studies of surfactant therapy in pediatric and adult patients with ALI/ARDS, focusing on its potential advantages in patients with direct pulmonary forms of these syndromes.     

Approaches to refractory hypoxemia in acute respiratory distress syndrome: current understanding, evidence, and debate

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) cause substantial morbidity and mortality despite our improved understanding of lung injury, advancements in the application of lung-protective ventilation, and strategies to prevent ventilator-induced lung injury. Severe refractory hypoxemia may develop in a subset of patients with severe ARDS. We review several approaches referred to as "rescue" therapies for severe hypoxemia, including lung-recruitment maneuvers, ventilation modes, prone positioning, inhaled vasodilator therapy, and the use of extracorporeal membrane oxygenation. Each shows evidence for improving oxygenation, though each has associated risks, and no single therapy has proven superior in the management of severe hypoxemia. Importantly, increased survival with these strategies has not been clearly established.     

The impact of clinical risk factors in the conversion from acute lung injury to acute respiratory distress syndrome in severe multiple trauma patients

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are different stages of the same disease, the aggravated stage of ALI leading to ARDS. Patients with ARDS have higher hospital mortality rates and reduced long-term pulmonary function and quality of life. It is, therefore, important to prevent ALI converting to ARDS. This study evaluated 17 risk factors potentially associated with the conversion from ALI to ARDS in severe multiple trauma. The results indicate that the impact of pulmonary contusion, APACHE II score, gastrointestinal haemorrhage and disseminated intravascular coagulation may help to predict conversion from ALI to ARDS in the early phase after multiple-trauma injury. Trauma duration, in particular, strongly impacted the short- and long-term development of ALI. Being elderly (aged > or = 65 years) and undergoing multiple blood transfusions in the early phase were independent risk factors correlated with secondary sepsis, deterioration of pulmonary function and transfusion-related acute lung injury due to early multiple fluid resuscitation.     

Airway pressure release ventilation in acute respiratory distress syndrome

Airway pressure release ventilation (APRV) is an alternative mode of ventilation that is increasingly used in patients with acute respiratory failure, acute lung injury (ALI), and acute respiratory distress syndrome (ARDS). Animal and clinical studies have demonstrated that, compared with conventional ventilation, APRV has beneficial effects on lung recruitment, oxygenation, end-organ blood flow, pulmonary vasoconstriction, and sedation requirements. Further studies, however, are required to directly compare APRV to ARDSnet protocol ventilation, specifically in patients with ALI/ARDS, and to determine whether managing ALI/ARDS with APRV will also achieve mortality reduction.     

Pulmonary coagulopathy as a new target in therapeutic studies of acute lung injury or pneumonia--a review

OBJECTIVES: To review the involvement of coagulation and fibrinolysis in the pathogenesis of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), pulmonary infection, and ventilator-induced lung injury (VILI). DATA SOURCE: Published articles on experimental and clinical studies of coagulation and fibrinolysis in ALI/ARDS, pneumonia, and mechanical ventilation. CONCLUSIONS: Alveolar fibrin deposition is an important feature of ALI/ARDS and pulmonary infection. The mechanisms that contribute to disturbed alveolar fibrin turnover are localized tissue factor-mediated thrombin generation and depression of bronchoalveolar urokinase plasminogen activator-mediated fibrinolysis, caused by the increase of plasminogen activator inhibitors. These effects on pulmonary coagulation and fibrinolysis are regulated by various proinflammatory cytokines and are similar to those found in the intravascular spaces during severe systemic inflammation. Some studies also suggest that pulmonary coagulopathy is a feature of VILI. Recent studies have demonstrated the beneficial effect of anticoagulant therapy in sepsis. Theoretical considerations suggest that this anticoagulant therapy will benefit patients with primary lung pathology including VILI, but clinical studies are needed to examine this hypothesis before such therapy is to be advocated as a standard of care in critically ill patients.     

间充质干细胞在急性肺损伤治疗中的研究进展

急性肺损伤(acute lung injure, ALI)是在ICU中常见的危重症,通常是由多种直接或者间接损伤因素所导致的,具有较高的死亡率,而急性呼吸窘迫综合征(acute respiratory distress syndrome, ARDS)通常认为是ALI的严重阶段。目前临床上对于ALI/ARDS的治疗主要是通过呼吸末正压通气的方式,但是这种方式仍然需要通过不断优化来提高存活率。间充质干细胞(mesenchymal stem cells, MSCs)治疗作为一种非侵入式的、新型的治疗方法,在动物实验中已经取得了很好的疗效,并且已经开始研究MSCs在临床实际治疗时的细节。因此,本文将对阐述MSCs在ALI治疗机制等方面的研究,以期为临床治疗奠定基础。     

Advances in mechanisms of repair and remodelling in acute lung injury

Background Acute respiratory distress syndrome (ARDS) is the most severe manifestation of acute lung injury (ALI). In patients who survive the acute injury the process of repair and remodelling may be an independent risk factor determining morbidity and mortality. This review explores recent advances in the field of fibroproliferative ARDS/ALI, with a special emphasis on (a) the primary contributing factors with a focus on cellular and soluble factors, and (b) mechanisms involved in repair and remodelling as they pertain to the importance of cell death, re-population, and matrix deposition. Discussion Factors influencing progression to fibroproliferative ARDS vs. resolution and reconstitution of the normal pulmonary parenchymal architecture are poorly understood. Determinants of persistent injury and abnormal repair and remodelling may be profoundly affected by both environmental and genetic factors. Moreover, cumulative evidence suggests that acute inflammation and fibrosis may be in part independent and interactive processes that are autonomously regulated and thus amenable to individual and specific therapy. Conclusions Although our current understanding of these processes is limited by the inability to accurately replicate the complex human physiology in laboratory settings, it has recently become apparent that the process of repair and remodelling begins early in the course of ARDS/ALI and may be determined by the type of pulmonary injury. Understanding the mechanisms leading to and regulating fibroproliferative changes may contribute to the development of novel early therapeutic interventions in ARDS/ALI patients. This article is discussed in the editorial available at: .     

Angiotensin-converting enzyme inhibitor captopril prevents oleic acid-induced severe acute lung injury in rats

Lack of specific and efficient therapy leads to the high mortality rate of acute lung injury (ALI) and acute respiratory distress (ARDS). Recent evidence implies that angiotensin-converting enzyme (ACE) plays an important role in the pathogenesis of ALI. Pharmaceutical inhibitors of ACE have been used clinically for hypertension but not for ALI/ARDS yet. The objective was to study the effects of ACE inhibition with captopril on severe lung injury induced by oleic acid (OA) in rats. Oleic acid was intravenously injected into Sprague Dawley rats, followed by i.p. administration of captopril or saline control. Lung injury, endothelium damage and related molecules, and disturbance of coagulation were examined in comparison between the treated and the nontreated groups. An OA-induced ALI was featured with thickening of the alveolar septa, alveolar hemorrhage, and infiltration of inflammatory cells. Comparing with the nontreated OA group, the administration of captopril prevented the rats from OA-induced severe lungs injury, with a significantly lower lung injury score, less albumin content and infiltrated cells in the alveoli, decreased wet/dry weight ratio of the lung tissues, and improved lung function (PaO2 per fraction of inspired oxygen). Captopril also dramatically reduced the expression of intercellular adhesion molecule-1 in the lung tissue and in the circulating endothelial cells in the blood, indicating a protective effect on endothelial cells activation/damage. Moreover, captopril treatment led to a blockage of nuclear factor kappaB activation in lung tissues and to the recovery of the fibrinolytic disturbance. Thus, our data suggest that the inhibition of ACE with its clinically used inhibitor offers protective effects on ALI/ARDS, implying the potential for therapeutic option.     

Acute respiratory distress syndrome and lung injury: Pathogenetic mechanism and therapeutic implication

To review possible mechanisms and therapeutics for acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). ALI/ARDS causes high mortality. The risk factors include head injury, intracranial disorders, sepsis, infections and others. Investigations have indicated the detrimental role of nitric oxide (NO) through the inducible NO synthase (iNOS). The possible therapeutic regimen includes extracorporeal membrane oxygenation, prone position, fluid and hemodynamic management and permissive hypercapnic acidosis etc. Other pharmacological treatments are anti-inflammatory and/or antimicrobial agents, inhalation of NO, glucocorticoids, surfactant therapy and agents facilitating lung water resolution and ion transports. β-adrenergic agonists are able to accelerate lung fluid and ion removal and to stimulate surfactant secretion. In conscious rats, regular exercise training alleviates the endotoxin-induced ALI. Propofol and N-acetylcysteine exert protective effect on the ALI induced by endotoxin. Insulin possesses anti-inflammatory effect. Pentobarbital is capable of reducing the endotoxin-induced ALI. In addition, nicotinamide or niacinamide abrogates the ALI caused by ischemia/reperfusion or endotoxemia. This review includes historical retrospective of ALI/ARDS, the neurogenic pulmonary edema due to head injury, the detrimental role of NO, the risk factors, and the possible pathogenetic mechanisms as well as therapeutic regimen for ALI/ARDS.