Frailty in Chronic Obstructive Pulmonary Disease and Risk of Exacerbations and Hospitalizations

Background: Frailty is a complex clinical syndrome associated with vulnerability to adverse health outcomes. While frailty is thought to be common in chronic obstructive pulmonary disease (COPD), the relationship between frailty and COPD-related outcomes such as risk of acute exacerbations of COPD (AE-COPD) and hospitalizations is unclear.Purpose: To examine the association between physical frailty and risk of acute exacerbations, hospitalizations, and mortality in patients with COPD.Methods: A longitudinal analysis of data from a cohort of 280 participants was performed. Baseline frailty measures included exhaustion, weakness, low activity, slowness, and undernutrition. Outcome measures included AE-COPD, hospitalizations, and mortality over 2 years. Negative binomial regression and Cox proportional hazard modeling were used.Results: Sixty-two percent of the study population met criteria for pre-frail and 23% were frail. In adjusted analyses, the frailty syndrome was not associated with COPD exacerbations. However, among the individual components of the frailty syndrome, weakness measured by handgrip strength was associated with increased risk of COPD exacerbations (IRR 1.46, 95% CI 1.09– 1.97). The frailty phenotype was not associated with all-cause hospitalizations but was associated with increased risk of non-COPD-related hospitalizations.Conclusion: This longitudinal cohort study shows that a high proportion of patients with COPD are pre-frail or frail. The frailty phenotype was associated with an increased risk of non-COPD hospitalizations but not with all-cause hospitalizations or COPD exacerbations. Among the individual frailty components, low handgrip strength was associated with increased risk of COPD exacerbations over a 2-year period. Measuring handgrip strength may identify COPD patients who could benefit from programs to reduce COPD exacerbations

Design of the Subpopulations and Intermediate Outcome Measures in COPD (SPIROMICS) AIR Study.

IntroductionPopulation-based epidemiological evidence suggests that exposure to ambient air pollutants increases hospitalisations and mortality from chronic obstructive pulmonary disease (COPD), but less is known about the impact of exposure to air pollutants on patient-reported outcomes, morbidity and progression of COPD.Methods and analysisThe Subpopulations and Intermediate Outcome Measures in COPD (SPIROMICS) Air Pollution Study (SPIROMICS AIR) was initiated in 2013 to investigate the relation between individual-level estimates of short-term and long-term air pollution exposures, day-to-day symptom variability and disease progression in individuals with COPD. SPIROMICS AIR builds on a multicentre study of smokers with COPD, supplementing it with state-of-the-art air pollution exposure assessments of fine particulate matter, oxides of nitrogen, ozone, sulfur dioxide and black carbon. In the parent study, approximately 3000 smokers with and without airflow obstruction are being followed for up to 3 years for the identification of intermediate biomarkers which predict disease progression. Subcohorts undergo daily symptom monitoring using comprehensive daily diaries. The air monitoring and modelling methods employed in SPIROMICS AIR will provide estimates of individual exposure that incorporate residence-specific infiltration characteristics and participant-specific time-activity patterns. The overarching study aim is to understand the health effects of short-term and long-term exposures to air pollution on COPD morbidity, including exacerbation risk, patient-reported outcomes and disease progression.Ethics and disseminationThe institutional review boards of all the participating institutions approved the study protocols. The results of the trial will be presented at national and international meetings and published in peer-reviewed journals

WashU Epigenome Browser update 2022

WashU Epigenome Browser (https://epigenomegateway.wustl.edu/browser/) is a web-based genomic data exploration tool that provides visualization, integration, and analysis of epigenomic datasets. The newly renovated user interface and functions have enabled researchers to engage with the browser and genomic data more efficiently and effectively since 2018. Here, we introduce a new integrated panel design in the browser that allows users to interact with 1D (genomic features), 2D (such as Hi-C), 3D (genome structure), and 4D (time series) data in a single web page. The browser can display three-dimensional chromatin structures with the 3D viewer module. The 4D tracks, called \u27Dynamic\u27 tracks, animatedly display time-series data, allowing for a more striking visual impact to identify the gene or genomic region candidates as a function of time. Genomic data, such as annotation features, numerical values, and chromatin interaction data can all be viewed in the dynamic track mode. Imaging data from microscopy experiments can also be displayed in the browser. In addition to software development, we continue to service and expand the data hubs we host for large consortia including 4DN, Roadmap Epigenomics, TaRGET and ENCODE, among others. Our growing user/developer community developed additional track types as plugins, such as qBed and dynseq tracks, which extend the utility of the browser. The browser serves as a foundation for additional genomics platforms including the WashU Virus Genome Browser (for COVID-19 research) and the Comparative Genome Browser. The WashU Epigenome Browser can also be accessed freely through Amazon Web Services at https://epigenomegateway.org/

Dnmt3a regulates emotional behavior and spine plasticity in the nucleus accumbens.

Despite abundant expression of DNA methyltransferases (Dnmts) in brain, the regulation and behavioral role of DNA methylation remain poorly understood. We found that Dnmt3a expression was regulated in mouse nucleus accumbens (NAc) by chronic cocaine use and chronic social defeat stress. Moreover, NAc-specific manipulations that block DNA methylation potentiated cocaine reward and exerted antidepressant-like effects, whereas NAc-specific Dnmt3a overexpression attenuated cocaine reward and was pro-depressant. On a cellular level, we found that chronic cocaine use selectively increased thin dendritic spines on NAc neurons and that DNA methylation was both necessary and sufficient to mediate these effects. These data establish the importance of Dnmt3a in the NAc in regulating cellular and behavioral plasticity to emotional stimuli