Seminars in respiratory and critical care medicine
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Semin Respir Crit Care Med · Aug 2013
ReviewGenetic heterogeneity and risk of acute respiratory distress syndrome.
Genetic variation explains some of the observed heterogeneity in patients' risk for developing the acute respiratory distress syndrome (ARDS). Although the lack of extant family pedigrees for ARDS precludes an estimate of heritability of the syndrome, ARDS may function as a pattern of response to injury or infection, traits that exhibit strong heritability. ⋯ In addition, novel candidate genes have emerged from agnostic genetic approaches, including genome-wide association studies, orthologous gene expression profiling across animal models of lung injury, and human peripheral blood gene expression data. The genetic risk for ARDS seems to vary both by ancestry and by the subtype of ARDS, suggesting that both factors may be valid considerations in clinical trial design.
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Semin Respir Crit Care Med · Aug 2013
Lung-injured patients do not need a specialized rehabilitation program: ICUAW as a case study.
An episode of critical illness is transformative. Patients suffer important new nerve, brain, and muscle injury. ⋯ In the context of intensive care unit-acquired weakness (ICUAW), each patient who enters the ICU will begin to degrade muscle through upregulation of different proteolytic pathways, and, although the inciting stimulus, or its magnitude, may differ somewhat across patients, the result is the same. This argues for an approach to rehabilitation that is etiologically neutral and based on an understanding of molecular pathophysiology that can be mapped to functional outcome and tailored to individual need.
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Semin Respir Crit Care Med · Aug 2013
Clinical trial design in acute lung injury--issues and controversies.
The evolution of scientific investigation in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) is replete with examples of effective bench-to-bedside transitions, pioneering research methodology, and international collaboration. This article highlights for clinicians a selection of challenges and controversies of clinical trial design in ALI and ARDS. ⋯ The third section discusses the quest for ideal Study Outcomes. The final section presents Interpretation Controversies, such as early stopping of clinical trials.
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Similar to other syndromes, patients are defined as having acute respiratory distress syndrome (ARDS) when they meet prespecified diagnostic criteria. These criteria have evolved over time, having gained and lost complexity, but the core principles have remained remarkably similar over the past 45 years. The specific diagnostic criteria allow clinicians and investigators to reliably identify patients with the syndrome of ARDS. ⋯ Additional physiological derangements include increased venous admixture and physiological dead space along with decreased respiratory system compliance. The corresponding pathological findings are lung edema, inflammation, hyaline membranes, and alveolar hemorrhage (i.e., diffuse alveolar damage). This article discusses the evolution of the definition of ARDS to the new Berlin definition of ARDS proposed in 2012 and its novel iterative refinement.