Pharmacotherapy of acute lung injury and the acute respiratory distress syndrome.

Cardiovascular Research Institute, University of California San Francisco, CA 94143-0130, USA.
Journal of Intensive Care Medicine 05/2006; 21(3):119-43. DOI: 10.1177/0885066606287045
Source: PubMed

ABSTRACT Acute lung injury and the acute respiratory distress syndrome are common syndromes with a high mortality rate that affect both medical and surgical patients. Better understanding of the pathophysiology of acute lung injury and the acute respiratory distress syndrome and advances in supportive care and mechanical ventilation have led to improved clinical outcomes since the syndrome was first described in 1967. Although several promising pharmacological therapies, including surfactant, nitric oxide, glucocorticoids and lysofylline, have been studied in patients with acute lung injury and the acute respiratory distress syndrome, none of these pharmacological treatments reduced mortality. This article provides an overview of pharmacological therapies of acute lung injury and the acute respiratory distress syndrome tested in clinical trials and current recommendations for their use as well as a discussion of potential future pharmacological therapies including beta(2)-adrenergic agonist therapy, keratinocyte growth factor, and activated protein C.

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    ABSTRACT: Introduction: Acute respiratory distress syndromes (ARDS) are devastating disorders of overwhelming pulmonary inflammation and hypoxemia, resulting in high morbidity and mortality. Areas covered: The main pharmacological treatment strategies have focused on the attempted inhibition of excessive inflammation or the manipulation of the resulting physiological derangement causing respiratory failure. Additionally, such interventions may allow reduced occurence mechanical ventilation injury. Despite promising preclinical and small clinical studies, almost all therapies have been shown to be unsuccessful in large-scale randomized controlled trials. The evidence for pharmacological treatment for ARDS is reviewed. Potential future treatments are also presented. Expert opinion: We suggest for future clinical trials addressing prevention and early intervention to attenuate lung injury and progression to respiratory failure.
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    ABSTRACT: Inhalation injury, which is among the causes of acute lung injury and acute respiratory distress syndrome (ARDS), continues to represent a significant source of mortality in burned patients. Inhalation injury often requires mechanical ventilation, but the ideal tidal volume strategy is not clearly defined in burned pediatric patients. The aim of this study was to determine the effects of low and high tidal volume on the number of ventilator days, ventilation pressures, and incidence of atelectasis, pneumonia, and ARDS in pediatric burned patients with inhalation injury within 1 year post burn injury. From 1986 to 2014, inhalation injury was diagnosed by bronchoscopy in pediatric burned patients (n = 932). Patients were divided into 3 groups: unventilated (n = 241), high tidal volume (HTV, 15 ± 3 mL/kg, n = 190), and low tidal volume (LTV, 9 ± 3 mL/kg, n = 501). High tidal volume was associated with significantly decreased ventilator days (p < 0.005) and maximum positive end expiratory pressure (p < 0.0001) and significantly increased maximum peak inspiratory pressure (p < 0.02) and plateau pressure (p < 0.02) compared with those in patients with LTV. The incidence of atelectasis (p < 0.0001) and ARDS (p < 0.02) was significantly decreased with HTV compared with LTV. However, the incidence of pneumothorax was significantly increased in the HTV group compared with the LTV group (p < 0.03). High tidal volume significantly decreases ventilator days and the incidence of both atelectasis and ARDS compared with low tidal volume in pediatric burned patients with inhalation injury. Therefore, the use of HTV may interrupt sequences leading to lung injury in our patient population. Copyright © 2015 American College of Surgeons. Published by Elsevier Inc. All rights reserved.
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    ABSTRACT: Background. Paraquat (PQ) poisoning is a lethal toxicological challenge that served as a disease model of acute lung injury and pulmonary fibrosis, but the mechanism is undetermined and no effective treatment has been discovered. Methods and Findings. We demonstrated that PQ injures mitochondria and leads to mtDNA release. The mtDNA mediated PBMC recruitment and stimulated the alveolar epithelial cell production of TGF-β1 in vitro. The levels of mtDNA in circulation and bronchial alveolar lavage fluid (BALF) were elevated in a mouse of PQ-induced lung injury. DNaseI could protect PQ-induced lung injury and significantly improved survival. Acute lung injury markers, such as TNFα, IL-1β, and IL-6, and marker of fibrosis, collagen I, were downregulated in parallel with the elimination of mtDNA by DNaseI. These data indicate a possible mechanism for PQ-induced, mtDNA-mediated lung injury, which may be shared by other causes of lung injury, as suggested by the same protective effect of DNaseI in bleomycin-induced lung injury model. Interestingly, increased mtDNA in the BALF of patients with amyopathic dermatomyositis-interstitial lung disease can be appreciated. Conclusions. DNaseI targeting mtDNA may be a promising approach for the treatment of PQ-induced acute lung injury and pulmonary fibrosis that merits fast tracking through clinical trials.
    BioMed Research International 02/2015; 2015:386952. DOI:10.1155/2015/386952 · 2.71 Impact Factor


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