1,721,076 research outputs found
Editorial: Crosstalk between lung and brain, heart, kidney and vascular system in critical illness
No full textAn update on the pharmacological management of acute respiratory distress syndrome
No full textIntroduction: Acute respiratory distress syndrome (ARDS) is characterized by acute inflammatory injury to the lungs, alterations in vascular permeability, loss of aerated tissue, bilateral infiltrates, and refractory hypoxemia. ARDS is considered a heterogeneous syndrome, which complicates the search for effective therapies. The goal of this review is to provide an update on the pharmacological management of ARDS. Areas covered: The difficulties in finding effective pharmacological therapies are mainly due to the challenges in designing clinical trials for this unique, varied population of critically ill patients. Recently, some trials have been retrospectively analyzed by dividing patients into hyper-inflammatory and hypo-inflammatory sub-phenotypes. This approach has led to significant outcome improvements with some pharmacological treatments that previously failed to demonstrate efficacy, which suggests that a more precise selection of ARDS patients for clinical trials could be the key to identifying effective pharmacotherapies. This review is provided after searching the main studies on this topics on the PubMed and clinicaltrials.gov databases. Expert opinion: The future of ARDS therapy lies in precision medicine, innovative approaches to drug delivery, immunomodulation, cell-based therapies, and robust clinical trial designs. These should lead to more effective and personalized treatments for patients with ARDS
Lung parenchyma remodeling in acute respiratory distress syndrome
No full textAcute respiratory distress syndrome (ARDS), the most severe manifestation of acute lung injury (ALI), is described as a stereotyped response to lung injury with a transition from alveolar capillary damage to a fibroproliferative phase. Most ARDS patients survive the acute initial phase of lung injury and progress to either reparation of the lesion or evolution of the syndrome. Despite advances in the management of ARDS, mortality remains high (40%) and autopsies show extended pulmonary fibrosis in 55% of patients, suggesting the importance of deregulated repair in the morbidity and mortality of these patients. Factors influencing progression to fibroproliferative ARDS versus resolution and reconstitution of the normal pulmonary parenchymal architecture are poorly understood. Abnormal repair and remodeling may be profoundly affected by both environmental and genetic factors. In this line, mechanical ventilation may affect the macromolecules that constitute the extracellular matrix (collagen, elastin, fibronectin, laminin, proteoglycan and glycosaminoglycans), suffer changes and impact the biomechanical behavior of lung parenchyma. Furthermore, evidence suggests that acute inflammation and fibrosis may be partially independent and/or interacting processes that are autonomously regulated, and thus amenable to individual and specific therapies. In this review, we explore recent advances in the field of fibroproliferative ARDS/ALI, with special emphasis on 1) the physiological properties of the extracellular matrix, 2) the mechanisms of remodeling, 3) the impact of mechanical ventilation on lung fibrotic response, and (4) therapeutic interventions in the remodeling process
Response to letter to the editor: catastrophic antiphospholipid antibody syndrome and multiple organ dysfunctions in critically ill patients with COVID-19: Multiple organ dysfunction syndrome in SARS-CoV-2 infection: are antiphospholipid antibodies the killer?
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New insights in mechanical ventilation and adjunctive therapies in ARDS
No full textPatients with acute respiratory distress syndrome (ARDS) often require mechanical ventilation (MV) and may experience high morbidity and mortality. The ventilatory management of ARDS patients has changed over the years to mitigate the risk of ventilator-induced lung injury (VILI) and improve outcomes. Current recommended MV strategies include the use of low tidal volume (VT) at 4–6 mL/kg of predicted body weight (PBW) and plateau pressure (PP LAT) below 27 cmH2O. Some patients achieve better outcomes with low VT than others, and several strategies have been proposed to individualize VT, including standardization for end-expiratory lung volume or inspiratory capacity. To date, no strategy for individualizing positive-end expiratory pressure (PEEP) based on oxygenation, recruitment, respiratory mechanics, or hemodynamics has proven superior for improving survival. Driving pressure, transpulmonary pressure, and mechanical power have been proposed as markers to quantify risk of VILI and optimize ventilator settings. Several rescue therapies, including neuromuscular blockade, prone positioning, recruitment maneuvers (RMs), vasodilators, and extracorporeal membrane oxygenation (ECMO), may be considered in severe ARDS. New ventilator strategies such as airway pressure release ventilation (APRV) and time-controlled adaptive ventilation (TCAV) have demonstrated potential benefits to reduce VILI, but further studies are required to evaluate their clinical relevance. This review aims to discuss the cornerstones of MV and new insights in ARDS ventilatory management, as well as their rationales, to guide the physician in an individually tailored rather than a fixed, sub-physiological approach. We recommend that MV be individualized based on physiological targets to achieve optimal ventilatory settings for each patient
Personalized pharmacological therapy for ARDS: a light at the end of the tunnel
No full textIntroduction: Pharmacotherapy for the acute respiratory distress syndrome (ARDS) has been tested in preclinical and clinical studies. However, to date, no pharmacological interventions have proven effective. This may be attributed to lack of proper identification of different ARDS phenotypes. Areas covered: We designed inclusive search strings and searched four bibliographic databases (Cochrane Database of Systematic Reviews, PubMed, Web of Science, and clinicaltrials.gov) to identify relevant research. Search results were mainly restricted to papers published from 2009 through 2019. ARDS is a heterogeneous syndrome, and its different phenotypes–defined according to clinical, radiological, and biological parameters–may affect response to therapy. The most promising pharmacological approaches to date have been based on ARDS pathophysiology. They focus on reducing inflammation and pulmonary edema, promoting selective vasodilation, and repairing alveolar epithelial and endothelial cells. Expert opinion: Pharmacotherapeutic approaches targeting ARDS pathophysiology have failed to exert beneficial effects. Personalized medicine targeting the different ARDS phenotypes has emerged as an option to improve survival. Identification of specific ARDS patient phenotypes that respond to specific therapies seems to be the most important challenge for the next decade. Additional research is warranted before personalized medicine approaches can be applied at bedside for ARDS patients
Effects of mechanical ventilation on the extracellular matrix
No full textThe extracellular matrix (ECM) plays an important role in the biomechanical behaviour of the lung parenchyma. The ECM is composed of a three-dimensional fibre mesh filled with different macromolecules, including the glycosaminoglycans and the proteoglycans, which have important functions in many lung pathophysiological processes: (1) regulating the hydration and water homeostasis, (2) maintaining the structure and function, (3) modulating the inflammatory response, and (4) influencing tissue repair and remodelling. Ventilator-induced lung injury is the result of a complex interplay among various mechanical forces acting on lung structures such as the epithelial and endothelial cells, the extracellular matrix, and the peripheral airways during mechanical ventilation. Although excellent reviews have synthesized our current knowledge of the role of repeated cyclic stretch and high tidal volume ventilation on alveolar and endothelial cells, few have addressed the effects of mechanical ventilation on the ECM. The present review focused on the organization of the ECM, mechanotransduction and ECM interactions, and the effects of mechanical ventilation on the ECM. The study of the ECM may be useful to improve our understanding of the pathophysiology of lung damage induced by mechanical ventilation
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