Annals of the American Thoracic Society
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Autophagy is a highly conserved process by which cells can recycle organelles and proteins by degrading them in the lysosomes. Although autophagy is considered a dynamic system responsible for cellular renovation and homeostasis under physiological conditions, it is increasingly clear that autophagy is directly relevant to clinical disease. During disease progression, autophagy not only serves as a cellular protective mechanism but also can represent a harmful event under certain conditions. ⋯ In this article, we outline the most recent studies implicating autophagy and selective autophagy in human lung diseases, including chronic obstructive pulmonary disease, pulmonary hypertension, idiopathic pulmonary fibrosis, and sepsis. We also discuss the relationship between autophagy and other molecular mechanisms related to disease progression, including programmed necrosis (necroptosis) and the inflammasome, an inflammatory signaling platform that regulates the secretion of IL-1β and IL-18. Finally, we examine the dual nature of autophagy and selective autophagy in the lung, which have both protective and injurious effects for human lung disease.
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Successful treatment of life-threatening community-acquired pneumonia requires appropriate empiric antibiotic coverage. But using conventional diagnostic techniques, a microbiological diagnosis is often not achieved. The diagnostic usefulness of tracheal aspirate at the time of intubation in patients with severe pneumonia has not been well studied. ⋯ Tracheal aspirate cultures obtained as part of routine care identified a plausible pneumonia pathogen in more than one-half of emergency department adult patients with severe pneumonia requiring intubation. Tracheal aspirate culture offers important additive diagnostic value to other routine tests.
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Ready access to physiologic measures, including respiratory mechanics, lung volumes, and ventilation/perfusion inhomogeneity, could optimize the clinical management of the critically ill pediatric or neonatal patient and minimize lung injury. There are many techniques for measuring respiratory function in infants and children but very limited information on the technical ease and applicability of these tests in the pediatric and neonatal intensive care unit (PICU, NICU) environments. This report summarizes the proceedings of a 2011 American Thoracic Society Workshop critically reviewing techniques available for ventilated and spontaneously breathing infants and children in the ICU. ⋯ Most techniques now have commercially available equipment for the PICU and NICU, and many can generate continuous data points to help with ventilator weaning and other interventions. Technical and validation studies in the PICU and NICU are published for the majority of techniques; some have been used as outcome measures in clinical trials, but few have been assessed specifically for their ability to improve clinical outcomes. Although they show considerable promise, these techniques still require further study in the PICU and NICU together with increased availability of commercial equipment before wider incorporation into daily clinical practice.
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Immunocompromised patients are at high risk for developing severe sepsis. Currently, there are no validated strategies for identifying this group of patients in large administrative databases. ⋯ Patients who are immunosuppressed are a large subgroup of those with severe sepsis. Following its validation as a search strategy using other large databases, and its adaptation for International Classification of Diseases, 10th revision, this novel method may allow researchers to account for a patient's immune state when examining outcomes.