BackgroundMechanisms underlying the development of virus-induced asthma exacerbations remain unclear. To investigate if epigenetic mechanisms could be involved in virus-induced asthma exacerbations, we undertook DNA methylation profiling in asthmatic and healthy nasal epithelial cells (NECs) during Human Rhinovirus (HRV) infection in vitro.MethodsGlobal and loci-specific methylation profiles were determined via Alu element and Infinium Human Methylation 450 K microarray, respectively. Principal components analysis identified the genomic loci influenced the most by disease-status and infection. Real-time PCR and pyrosequencing were used to confirm gene expression and DNA methylation, respectively.ResultsHRV infection significantly increased global DNA methylation in cells from asthmatic subjects only (43.6% to 44.1%, p = 0.04). Microarray analysis revealed 389 differentially methylated loci either based on disease status, or caused by virus infection. There were disease-associated DNA methylation patterns that were not affected by HRV infection as well as HRV-induced DNA methylation changes that were unique to each group. A common methylation locus stood out in response to HRV infection in both groups, where the small nucleolar RNA, H/ACA box 12 (SNORA12) is located. Further analysis indicated that a relationship existed between SNORA12 DNA methylation and gene expression in response to HRV infection.ConclusionsWe describe for the first time that Human rhinovirus infection causes DNA methylation changes in airway epithelial cells that differ between asthmatic and healthy subjects. These epigenetic differences may possibly explain the mechanism by which respiratory viruses cause asthma exacerbations.

The practice of anesthesia includes multiple competing practice models, including services delivered by anesthesiologists, independent practice by certified registered nurse anesthetists (CRNAs), and team-based approaches incorporating anesthesiologist supervision or direction of CRNAs. Despite data demonstrating very low risk of death and complications associated with anesthesia, debate among professional societies and policymakers persists over the superiority or equivalence among these models. The American Society of Anesthesiologists uses published findings as evidence for claims that anesthesia is safer when anesthesiologists lead in providing care. The American Association of Nurse Anesthetists cites its own research on safety and cost-efficiency outcomes to defend against these claims. We review and critique studies of the safety outcomes and cost-effectiveness of anesthesia delivery that have been cited in the Federal Trade Commission comment letters related to competition in health care, where each profession has laid out their case for how they ought to be recognized in the market for anesthesia services. The Federal Trade Commission has a role in protecting consumers from anticompetitive conduct that has the potential to impact quality and cost in health care. Thus, it is important to evaluate the evidence used to make claims about these topics. We argue that while research in this area is imperfect, the strong safety record of anesthesia in general and CRNAs in particular suggest that politics and professional interests are the main drivers of supervision policy in anesthesia delivery.

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