American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Aug 2016
ReviewNecroptosis: a Novel Cell Death Modality and its Potential Relevance for Critical Care Medicine.
Cell death is intertwined with life in development, homeostasis, pathology, and aging. Until recently, apoptosis was the best known form of programmed cell death, whereas necrosis was for a long time considered accidental owing to physicochemical injury. However, identification of crucial signaling and execution molecules, which are highly regulated, revealed that necrosis encompasses several cell death modalities that can be therapeutically targeted. ⋯ We are only beginning to appreciate the role of necroptosis in different pathological conditions, including critical illnesses. In this review, we discuss the molecular mechanisms of necroptosis and analyze the effect of inhibiting necroptosis in experimental models of critical illnesses. In view of the identification of an increasing number of cell death modalities, we also briefly discuss the simultaneous targeting of multiple cell death modalities because, depending on the cell type and cellular conditions, various types of cell death may contribute to the pathology.
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Am. J. Respir. Crit. Care Med. · Aug 2016
Progression from Asthma to Chronic Obstructive Pulmonary Disease (COPD): Is Air Pollution a Risk Factor?
Individuals with asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS), have more rapid decline in lung function, more frequent exacerbations, and poorer quality of life than those with asthma or COPD alone. Air pollution exposure is a known risk factor for asthma and COPD; however, its role in ACOS is not as well understood. ⋯ Individuals exposed to higher levels of air pollution had nearly threefold greater odds of developing ACOS. Minimizing exposure to high levels of air pollution may decrease the risk of ACOS.
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Am. J. Respir. Crit. Care Med. · Aug 2016
ReviewLung-kidney Crosstalk in the Critically Ill Patient.
Discoveries have emerged highlighting the complex nature of the interorgan cross-talk between the kidney and the lung. Vascular rigidity, neurohormonal activation, tissue hypoxia, and abnormal immune cell signaling have been identified as common pathways leading to the development and progression of chronic kidney disease. However, our understanding of the causal relationships between lung injury and kidney injury is not precise. ⋯ Right ventricular dysfunction and congestive states may contribute to alterations of renal perfusion and oxygenation, leading to diuretic resistance and recurrent hospitalization. In patients with concomitant respiratory failure, noninvasive ventilation represents a promising treatment option for the correction of impaired renal microcirculation and endothelial dysfunction. In patients requiring extracorporeal membrane oxygenation, short- and long-term monitoring of kidney function is warranted, as they are at highest risk of developing acute kidney injury and fluid overload.
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Am. J. Respir. Crit. Care Med. · Aug 2016
Critical Genomic Networks and Vasoreactive Variants in Idiopathic Pulmonary Arterial Hypertension.
Idiopathic pulmonary arterial hypertension (IPAH) is usually without an identified genetic cause, despite clinical and molecular similarity to bone morphogenetic protein receptor type 2 mutation-associated heritable pulmonary arterial hypertension (PAH). There is phenotypic heterogeneity in IPAH, with a minority of patients showing long-term improvement with calcium channel-blocker therapy. ⋯ A pathway-based analysis of WES data in IPAH demonstrated multiple rare GVs that converge on key biological pathways, such as cytoskeletal function and Wnt signaling pathway. Vascular smooth muscle contraction-related genes were enriched in VR-PAH, suggesting a potentially different genetic predisposition for VR-PAH. This pathway-based approach may be applied to next-generation sequencing data in other diseases to uncover the contribution of unexpected or multiple GVs to a phenotype.
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Am. J. Respir. Crit. Care Med. · Aug 2016
Latent Tuberculosis Infection Test Agreement in the National Health and Nutrition Examination Survey.
Latent tuberculosis infection (LTBI) test discordance is poorly understood. ⋯ In the largest population-based sample of concurrently performed TST and QFT tests in a low tuberculosis incidence population, prevalence estimates depended heavily on how LTBI was defined and test agreement was only fair. We identified several predictors of discordance warranting further study.