American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Dec 2015
Multicenter StudyFrailty Phenotypes, Disability, and Outcomes in Adult Candidates for Lung Transplantation.
Frailty is associated with morbidity and mortality in abdominal organ transplantation but has not been examined in lung transplantation. ⋯ Frailty is prevalent among lung transplant candidates and is independently associated with greater disability and an increased risk of delisting or death.
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Am. J. Respir. Crit. Care Med. · Dec 2015
ReviewFuture Research Directions in Asthma: An NHLBI Working Group Report.
Asthma is a common chronic disease without cure. Our understanding of asthma onset, pathobiology, classification, and management has evolved substantially over the past decade; however, significant asthma-related morbidity and excess healthcare use and costs persist. ⋯ The workshop focused on (1) in utero and early-life origins of asthma, (2) the use of phenotypes and endotypes to classify disease, (3) defining disease modification, (4) disease management, and (5) implementation research. This report summarizes the workshop and produces recommendations to guide future research in asthma.
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Am. J. Respir. Crit. Care Med. · Dec 2015
Hepatic Shunting of Eggs and Pulmonary Vascular Remodeling in Bmpr2(+/-) Mice with Schistosomiasis.
Schistosomiasis is a major cause of pulmonary arterial hypertension (PAH). Mutations in the bone morphogenetic protein type-II receptor (BMPR-II) are the commonest genetic cause of PAH. ⋯ This study has shown that levels of BMPR-II expression modify the pulmonary vascular response to chronic schistosomiasis. The likely mechanism involves the increased passage of eggs to the lungs, caused by altered diameter of the hepatic veins and sinusoids in Bmpr2(+/-) mice. Genetically determined differences in the remodeling of hepatic vessels may represent a new risk factor for PAH associated with schistosomiasis.
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Am. J. Respir. Crit. Care Med. · Dec 2015
The Central Role of PCSK9 in Septic Pathogen Lipid Transport and Clearance.
Microbial cell walls contain pathogenic lipids, including LPS in gram-negative bacteria, lipoteichoic acid in gram-positive bacteria, and phospholipomannan in fungi. These pathogen lipids are major ligands for innate immune receptors and figure prominently in triggering the septic inflammatory response. Alternatively, pathogen lipids can be cleared and inactivated, thus limiting the inflammatory response. ⋯ Recent evidence suggests pathogen lipid clearance can be modulated. Importantly, reduced proprotein convertase subtilisin/kexin type 9 activity increases recycling of the LDLR and thereby increases LDLR on the surface of hepatocytes, which increases clearance by the liver of pathogen lipids transported in LDL. Increased pathogen lipid clearance, which can be achieved by inhibiting proprotein convertase subtilisin/kexin type 9, may decrease the systemic inflammatory response to sepsis and improve clinical outcomes.
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Am. J. Respir. Crit. Care Med. · Dec 2015
Endotoxin Exposure: Predictors and Prevalence of Associated Asthma Outcomes in the U.S.
Inhaled endotoxin induces airway inflammation and is an established risk factor for asthma. The 2005-2006 National Health and Nutrition Examination Survey included measures of endotoxin and allergens in homes as well as specific IgE to inhalant allergens. ⋯ In this U.S. nationwide representative sample, higher endotoxin exposure was significantly associated with measures of wheeze, with no observed protective effect regardless of sensitization status.