The Lancet. Respiratory medicine
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This year is the 50th anniversary of the first description of acute respiratory distress syndrome (ARDS). Since then, much has been learned about the pathogenesis of lung injury in ARDS, with an emphasis on the mechanisms of injury to the lung endothelium and the alveolar epithelium. In terms of treatment, major progress has been made in reducing mortality from ARDS with lung-protective ventilation, using a tidal volume of 6 mL per kg of predicted bodyweight and a plateau airway pressure of less than 30 cm H2O. ⋯ Approaches to reducing heterogeneity in ARDS clinical trials include using physiological, radiographic, and biological criteria to select patients for both phase 2 and 3 trials. Additionally, interest is growing in the design of preventive clinical trials in ARDS and to initiate early treatment of patients with acute lung injury before the need for endotracheal intubation. We also present promising new approaches to treating ARDS, including combination therapies, cell-based therapies, and generic pharmacological compounds with low-risk profiles that are already in routine clinical use for other clinical indications.
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In the 50 years since acute respiratory distress syndrome (ARDS) was first described, substantial progress has been made in identifying the risk factors for and the pathogenic contributors to the syndrome and in characterising the protein expression patterns in plasma and bronchoalveolar lavage fluid from patients with ARDS. Despite this effort, however, pharmacological options for ARDS remain scarce. ⋯ Advances in applied biomolecular technology and bioinformatics have enabled breakthroughs for other complex traits, such as cardiovascular disease or asthma, particularly when a precision medicine paradigm, wherein a biomarker or gene expression pattern indicates a patient's likelihood of responding to a treatment, has been pursued. In this Review, we consider the biological and analytical techniques that could facilitate a precision medicine approach for ARDS.
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Advanced emphysema is a lung disease in which alveolar capillary units are destroyed and supporting tissue is lost. The combined effect of reduced gas exchange and changes in airway dynamics impairs expiratory airflow and leads to progressive air trapping. Pharmacological therapies have limited effects. ⋯ Endobronchial coils might have a role in the treatment of patients with emphysema with severe hyperinflation and less parenchymal destruction. Use of vapour thermal energy or a sclerosant might allow focal treatment but the unpredictability of the inflammatory response limits their current use. In this Review, we aim to summarise clinical trial evidence on lung volume reduction and provide guidance on patient selection for available therapies.