American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Apr 2019
ReviewObstructive Sleep Apnea, Hypoxia, and Nonalcoholic Fatty Liver Disease.
Recent studies have demonstrated that obstructive sleep apnea (OSA) is associated with the development and evolution of nonalcoholic fatty liver disease (NAFLD), independent of obesity or other shared risk factors. Like OSA, NAFLD is a prevalent disorder associated with major adverse health outcomes: Patients with NAFLD may develop cirrhosis, liver failure, and hepatocellular carcinoma. One major finding that has emerged from these studies is that the OSA-NAFLD association is related to the degree of nocturnal hypoxemia in OSA. ⋯ Intermittent hypoxia leads to tissue hypoxia and can result in oxidative stress, mitochondrial dysfunction, inflammation, and overactivation of the sympathetic nervous system, among many other maladaptive effects. In such models, intermittent hypoxia has been shown to cause insulin resistance, dysfunction of key steps in hepatic lipid metabolism, atherosclerosis, and hepatic steatosis and fibrosis, each of which is pertinent to the development and/or progression of NAFLD. However, many intriguing questions remain unanswered: Principally, how aggressively should the clinician screen for NAFLD in patients with OSA, and vice versa? In this review, we attempt to apply the best evidence from animal and human studies to highlight the relationship between these two disorders and to advocate for further trials aimed at defining these relationships more precisely.
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Am. J. Respir. Crit. Care Med. · Apr 2019
Comparative StudyAge-Specific Associations of Ozone and PM2.5 with Respiratory Emergency Department Visits in the US.
Whereas associations between air pollution and respiratory morbidity for adults 65 years and older are well documented in the United States, the evidence for people under 65 is less extensive. To address this gap, the Centers for Disease Control and Prevention's National Environmental Public Health Tracking Program collected respiratory emergency department (ED) data from 17 states. ⋯ These results address a gap in the evidence used to ensure adequate public health protection under national air pollution policies.
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Am. J. Respir. Crit. Care Med. · Apr 2019
Elastase Exocytosis by Airway Neutrophils Associates with Early Lung Damage in Cystic Fibrosis Children.
Neutrophils are recruited to the airways of individuals with cystic fibrosis (CF). In adolescents and adults with CF, airway neutrophils actively exocytose the primary granule protease elastase (NE), whose extracellular activity correlates with lung damage. During childhood, free extracellular NE activity is measurable only in a subset of patients, and the exocytic function of airway neutrophils is unknown. ⋯ NE exocytosis by airway neutrophils occurs in all children with CF, and its cellular measure correlates with early lung damage. These findings implicate live airway neutrophils in early CF pathogenesis, which should instruct biomarker development and antiinflammatory therapy in children with CF.
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Am. J. Respir. Crit. Care Med. · Apr 2019
Apnea-Hypopnea Event Duration Predicts Mortality in Men and Women in the Sleep Heart Health Study.
Obstructive sleep apnea is a risk factor for mortality, but its diagnostic metric-the apnea-hypopnea index-is a poor risk predictor. The apnea-hypopnea index does not capture the range of physiological variability within and between patients, such as degree of hypoxemia and sleep fragmentation, that reflect differences in pathophysiological contributions of airway collapsibility, chemoreceptive negative feedback loop gain, and arousal threshold. ⋯ Short respiratory event duration, a marker for low arousal threshold, predicts mortality in men and women. Individuals with shorter respiratory events may be predisposed to increased ventilatory instability and/or have augmented autonomic nervous system responses that increase the likelihood of adverse health outcomes, underscoring the importance of assessing physiological variation in obstructive sleep apnea.
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Am. J. Respir. Crit. Care Med. · Apr 2019
Identification of Acute Kidney Injury Sub-phenotypes with Differing Molecular Signatures and Response to Vasopressin Therapy.
Currently, no safe and effective pharmacologic interventions exist for acute kidney injury (AKI). One reason may be that heterogeneity exists within the AKI population, thereby hampering the identification of specific pathophysiologic pathways and therapeutic targets. ⋯ This analysis identified two molecularly distinct AKI subphenotypes with different clinical outcomes and responses to vasopressin therapy. Identification of AKI subphenotypes could improve risk prognostication and may be useful for predictive enrichment in clinical trials.