Articles: function.
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Observational Study
Application of heart rate variability in patients undergoing weaning from mechanical ventilation.
The process of weaning may impose cardiopulmonary stress on ventilated patients. Heart-rate variability (HRV), a noninvasive tool to characterize autonomic function and cardiorespiratory interaction, may be a promising modality to assess patient capability during the weaning process. We aimed to evaluate the association between HRV change and weaning outcomes in critically ill patients. ⋯ HRV responses differ between patients with different weaning outcomes. Measuring HRV change during the weaning process may help clinicians to predict weaning results and, in the end, to improve patient care and outcome.
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Editorial Comment
Detrimental role of humoral signalling in cardio-renal cross-talk.
In critically ill patients, any acute organ injury is associated with a sudden change of circulating factors that may play a role in distant organ dysfunction through a complex cross-talk. In this issue, Virzì and colleagues discuss the relevance of humoral signalling between heart and kidney, focusing on type 1 and type 3 cardio-renal syndrome. We herein review the mechanisms of heart-kidney cross-talk, discussing the role of circulating detrimental mediators in the pathogenetic mechanisms of cardio-renal syndrome.
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Am. J. Respir. Crit. Care Med. · Jan 2014
Gene Correction of Human Induced Pluripotent Stem Cells Repairs the Cellular Phenotype in Pulmonary Alveolar Proteinosis.
Hereditary pulmonary alveolar proteinosis (hPAP) caused by granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor α-chain (CSF2RA) deficiency is a rare, life-threatening lung disease characterized by accumulation of proteins and phospholipids in the alveolar spaces. The disease is caused by a functional insufficiency of alveolar macrophages, which require GM-CSF signaling for terminal differentiation and effective degradation of alveolar proteins and phospholipids. Therapeutic options are extremely limited, and the pathophysiology underlying the defective protein degradation in hPAP alveolar macrophages remains poorly understood. ⋯ These data establish PAP-iPSC-derived monocytes and macrophages as a valid in vitro disease model of CSF2RA-deficient PAP, and introduce gene-corrected iPSC-derived monocytes and macrophages as a potential autologous cell source for innovative therapeutic strategies. Transplantation of such cells to patients with hPAP could serve as a paradigmatic proof for the potential of iPSC-derived cells in clinical gene therapy.
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Am. J. Respir. Crit. Care Med. · Jan 2014
Use of Induced Pluripotent Stem Cells To Recapitulate Pulmonary Alveolar Proteinosis Pathogenesis.
In patients with pulmonary alveolar proteinosis (PAP) syndrome, disruption of granulocyte/macrophage colony-stimulating factor (GM-CSF) signaling is associated with pathogenic surfactant accumulation from impaired clearance in alveolar macrophages. ⋯ We used patient-specific iPS cells to accurately reproduce the molecular and cellular defects of alveolar macrophages that drive the pathogenesis of PAP in more than 90% of patients. These results demonstrate the critical role of GM-CSF signaling in surfactant homeostasis and PAP pathogenesis in humans and have therapeutic implications for hPAP.
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Am. J. Respir. Crit. Care Med. · Jan 2014
Multicenter Study Comparative StudyClinical and Epidemiologic Phenotypes of Childhood Asthma.
Clinical and epidemiologic approaches have identified two distinct sets of classifications for asthma and wheeze phenotypes. ⋯ Clinical phenotypes were well supported by LCA analysis. The hypothesis-free LCA phenotypes were a useful reference for comparing clinical phenotypes. Thereby, we identified children with clinically conspicuous but undiagnosed disease. Because of their high area under the curve values, clinical phenotypes such as (recurrent) unremitting wheeze emerged as promising alternative asthma definitions for epidemiologic studies.