American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · May 2015
Non-invasive Analysis of the Sputum Transcriptome Discriminates Clinical Phenotypes of Asthma.
The airway transcriptome includes genes that contribute to the pathophysiologic heterogeneity seen in individuals with asthma. ⋯ There are common patterns of gene expression in the sputum and blood of children and adults that are associated with near-fatal, severe, and milder asthma.
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Am. J. Respir. Crit. Care Med. · May 2015
Risk Assessment of Tuberculosis in Contacts by Interferon-γ Release Assays (IGRAs). A TBNET Study.
Latent infection with Mycobacterium tuberculosis is defined by a positive IFN-γ release assay (IGRA) result in the absence of active tuberculosis. Only few, mostly monocentric studies have evaluated the role of IGRAs to predict the development of tuberculosis in recent contacts in low-incidence countries of tuberculosis. ⋯ Tuberculosis rarely developed among contacts, and preventive chemotherapy effectively reduced the tuberculosis risk among IGRA-positive contacts. Although the negative predictive value of IGRAs is high, the risk for the development of tuberculosis is poorly predicted by these assays.
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Am. J. Respir. Crit. Care Med. · May 2015
The DosR Regulon Modulates Adaptive Immunity and is Essential for M. tuberculosis Persistence.
Hypoxia promotes dormancy by causing physiologic changes to actively replicating Mycobacterium tuberculosis. DosR controls the response of M. tuberculosis to hypoxia. ⋯ Delayed adaptive responses, a hallmark of M. tuberculosis infection, not only lead to persistence but also interfere with the development of effective antituberculosis vaccines. The DosR regulon therefore modulates both the magnitude and the timing of adaptive immune responses in response to hypoxia in vivo, resulting in persistent infection. Hence, DosR regulates key aspects of the M. tuberculosis life cycle and limits lung pathology.
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Am. J. Respir. Crit. Care Med. · May 2015
Diaphragm Muscle Fiber Weakness and Ubiquitin-Proteasome Activation in Critically Ill Patients.
The clinical significance of diaphragm weakness in critically ill patients is evident: it prolongs ventilator dependency, and increases morbidity and duration of hospital stay. To date, the nature of diaphragm weakness and its underlying pathophysiologic mechanisms are poorly understood. ⋯ These findings show that diaphragm muscle fibers of critically ill patients display atrophy and severe contractile weakness, and in the diaphragm of critically ill patients the ubiquitin-proteasome pathway is activated. This study provides rationale for the development of treatment strategies that target the contractility of diaphragm fibers to facilitate weaning.