American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Feb 2012
Evidence for a causal relationship between allergic sensitization and rhinovirus wheezing in early life.
Aeroallergen sensitization and virus-induced wheezing are risk factors for asthma development during early childhood, but the temporal developmental sequence between them is incompletely understood. ⋯ Prospective, repeated characterization of a birth cohort demonstrated that allergic sensitization precedes HRV wheezing and that the converse is not true. This sequential relationship and the plausible mechanisms by which allergic sensitization can lead to more severe HRV-induced lower respiratory illnesses support a causal role for allergic sensitization in this developmental pathway. Therefore, therapeutics aimed at preventing allergic sensitization may modify virus-induced wheezing and the development of asthma.
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Am. J. Respir. Crit. Care Med. · Feb 2012
Targeting energetic metabolism: a new frontier in the pathogenesis and treatment of pulmonary hypertension.
This perspective highlights advances in the understanding of the role of cellular metabolism in the pathogenesis of pulmonary hypertension. Insights gained in the past 20 years have revealed several similarities between the cellular processes underlying the pulmonary vascular remodeling in pulmonary hypertension and those seen in cancer processes. ⋯ The glycolytic shift may underlie the resistance to apoptosis and increased vascular cell proliferation, which are hallmarks of pulmonary hypertension. These investigations have led to novel approaches in the diagnosis and therapy of pulmonary hypertension.
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Am. J. Respir. Crit. Care Med. · Feb 2012
Neurogenic changes in the upper airway of patients with obstructive sleep apnea.
Controversy persists regarding the presence and importance of hypoglossal nerve dysfunction in obstructive sleep apnea (OSA). ⋯ These results confirm and quantify the extent and existence of structural neural remodeling in OSA.
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Am. J. Respir. Crit. Care Med. · Feb 2012
DNA methylation in inflammatory genes among children with obstructive sleep apnea.
Pediatric obstructive sleep apnea (OSA) leads to multiple end-organ morbidities that are mediated by the cumulative burden of oxidative stress and inflammation. Because not all children with OSA exhibit increased systemic inflammation, genetic and environmental factors may be affecting patterns of DNA methylation in genes subserving inflammatory functions. ⋯ The FOXP3 gene, which regulates expression of T regulatory lymphocytes, is more likely to display increased methylation among children with OSA who exhibit increased systemic inflammatory responses. Thus, epigenetic modifications may constitute an important determinant of inflammatory phenotype in OSA, and FOXP3 DNA methylation levels may provide a potential biomarker for end-organ vulnerability.
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Am. J. Respir. Crit. Care Med. · Feb 2012
Neonatal cytokine profile in the airway mucosal lining fluid is skewed by maternal atopy.
Heredity from mother or father may impact differently in complex diseases, such as atopy. Maternal atopy is a stronger risk factor than paternal atopy for the development of atopy in the offspring. We hypothesized that mother's and father's atopy would have a differential imprinting on the cytokines and chemokines in the upper airway mucosal lining fluid of healthy neonates. ⋯ Maternal atopy, but not paternal atopy, showed a strong linkage with a suppressed mucosal cytokine and chemokine signature in asymptomatic neonates, suggesting imprinting by the maternal milieu in utero or perinatal life.