Acute Respiratory Distress Syndrome: 30 Years Later?

Abstract

Acute respiratory distress syndrome (ARDS) was first described about 30 years ago. Modern definitions and statements have recently been proposed to describe ARDS accurately, but none is perfect. Diffuse alveolar damage is the basic pathological pattern most commonly observed in ARDS, and the term includes permeability edema. The alveolar epithelium of the alveolar-capillary barrier is clearly a key component requiring repair, given its multipotent functional activity. Lung inflammation and neutrophil accumulation are essential markers of disease in ARDS, and a wide variety of pro- and anti-inflammatory cytokines have been described in the alveolar fluid and blood of patients. These molecules still have to prove their value as diagnostic or prognostic biomarkers of ARDS.Supportive therapy in ARDS improved in the past decade; mechanical ventilation with lung protective strategies and patient positioning are gaining interest, but the indications for corticosteroids for ARDS are still debated. Nitric oxide may have a place in the treatment of one-third of patients. Novel approaches, such as surfactant replacement and liquid ventilation, may further improve supportive therapy. Innovative interventions may be on the horizon in treatments that help to resolve or modulate common pathways of ARDS, such as inflammation (eg, granulocyte-colony stimulating factor) or epithelial repair (eg, keratinocyte growth factor).

Apical, But Not Basolateral, Endotoxin Preincubation Protects Alveolar Epithelial Cells Against Hydrogen Peroxide-Induced Loss of Barrier Function: The Role of Nitric Oxide Synthesis

“…A ctivation of polymorphonuclear leukocytes has long been implicated in the development of acute respiratory distress syndrome (ARDS), 3 characterized by gas exchange abnormalities and pulmonary edema formation due to increased lung endothelial and epithelial permeability (1)(2)(3)(4). Hydrogen peroxide (H 2 O 2 ), a reactive oxygen species, is an established polymorphonuclear leukocyte-derived mediator of epithelial injury.…”

“…In animal models and under cell culture conditions, various clinical features of ARDS may be reproduced by endotoxin (LPS) released from cell walls of Gram-negative bacteria (1)(2)(3). The microcirculatory disturbances with subsequent cellular injury and loss of organ function induced by LPS in intact animals have been attributed to the activation of inflammatory cells and strong inflammatory mediator generation.…”

What Is the Best Mechanical Ventilation Strategy in ARDS?

“…At least in its early stages, ARDS represents the pathologic state of diffuse alveolar damage (DAD). [6][7][8] There is damage to both endothelial and epithelial layers 6,[8][9][10][11] of the alveolar-capillary membrane with resultant edema and alveolar flooding rich in proteins and hemorrhage, leading to hyaline membrane formation and fibrosis. 6,10 These changes can overlap and evolve over hours to days and result in a loss of the barrier and gas exchange functions of the lung (Table 15-2).…”

“…[6][7][8] There is damage to both endothelial and epithelial layers 6,[8][9][10][11] of the alveolar-capillary membrane with resultant edema and alveolar flooding rich in proteins and hemorrhage, leading to hyaline membrane formation and fibrosis. 6,10 These changes can overlap and evolve over hours to days and result in a loss of the barrier and gas exchange functions of the lung (Table 15-2). 6,8,[12][13][14] The clinical consequence is a severe heterogeneous injury to the lung that results in refractory hypoxemia and decreased lung compliance.…”

The Prophylactic and Therapeutic Effects of Cholinolytics on Perfluoroisobutylene Inhalation Induced Acute Lung Injury

“…Furthermore, there is no recognized prophylactic measures for human PFIB exposure although animal studies have indicated that increased pulmonary concentrations of free radical scavengers containing thiol groups may be of value and N-acetylcysteine has been found to be effective 6) . Early administration of corticosteroids, as used for phosgene, seems to be the only clinical recommendation for pharmacological intervention even though proof of their beneficial effects is still lacking in general 7) . When comparisons are made concerning the molecular structure 8,9) , the time course of ALI after the inhalation e x p o s u r e 10, 11) a n d m a n y o t h e r t o x i c o l o g i c a l characteristics [12][13][14] between PFIB and phosgene, it seems clear to us that both primary (direct) injury by the chemical itself and secondary (indirect) injury, possibly mediated by a later signal cascade network, are the two key aspects of PFIB inhalation induced ALI.…”