Dataset Information

Disease Burden and Variability in Sarcoidosis.

ABSTRACT: Sarcoidosis is a systemic inflammatory disease with substantial morbidity and increasing mortality. As part of the National Heart, Lung, and Blood Institute's workshop to better understand this disease and improve the outcomes of patients with sarcoidosis, we reviewed the available data on health care burden and outcomes of this disease in the United States. Disparities in outcomes exist by race, ethnicity, sex, and socioeconomic groups, with African Americans having disproportionately more severe disease. Mortality rates are highest in African Americans, but may be increasing in white individuals. The health care burden of sarcoidosis is defined not only by its somatic manifestations, but is also greatly impacted by psychosocial, economic, and comorbid conditions associated with this disease. Fatigue, depression, cognitive dysfunction, treatment side effects, and pain syndromes are highly prevalent in this population and contribute to poor outcomes. The direct and indirect economic costs to patients and society are likely also substantial, although not well defined. We recommend leveraging existing and future technology and infrastructure to more accurately define and monitor the overall total sarcoidosis-attributable health care burden and patient outcomes in the United States.

SUBMITTER: Gerke AK

PROVIDER: S-EPMC5802572 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Disease Burden and Variability in Sarcoidosis.

Gerke Alicia K AK Judson Marc A MA Cozier Yvette C YC Culver Daniel A DA Koth Laura L LL

Annals of the American Thoracic Society 20171201 Supplement_6

Sarcoidosis is a systemic inflammatory disease with substantial morbidity and increasing mortality. As part of the National Heart, Lung, and Blood Institute's workshop to better understand this disease and improve the outcomes of patients with sarcoidosis, we reviewed the available data on health care burden and outcomes of this disease in the United States. Disparities in outcomes exist by race, ethnicity, sex, and socioeconomic groups, with African Americans having disproportionately more seve ...[more]

PMID: 29087725

Similar Datasets

Project description:BackgroundSarcoidosis is a systemic granulomatous disease of unknown etiology that affects the lungs in 90% of patients, but has a wide range of disease manifestations and outcomes including chronic and progressive courses. Noninvasive biomarkers are needed to assess these outcomes and guide decisions for long term monitoring and treatment. Interferon-gamma (IFN-γ)-inducible chemotactic cytokines (chemokines), CXCL9, CXCL10 and CXCL11, show promise in this regard because they have been implicated in the pathogenesis of and reflect the burden of granulomatous inflammation. CXCL11 has been reported to have unique functional properties in modulating adaptive immunity in model systems so our goal was to examine serum levels of CXCL11 in relation to clinical outcomes in a heterogeneous cohort of sarcoidosis subjects.MethodsCXCL19, CXCL10, and CXCL11 serum levels were measured in sarcoidosis and healthy subjects using ELISA assay. We determined relationships between CXCL11 and standard clinical inflammatory markers, expression of IFN-γ-related genes in whole blood, organ involvement, dyspnea scores, and measures of pulmonary function.ResultsIn a cross-sectional analysis of 104 sarcoidosis subjects, serum CXCL11 was significantly elevated compared to 49 healthy controls (p < 0.001). CXCL11 was positively correlated with CXCL9 and CXCL10 (p < 0.001), sedimentation rate (p < 0.01), and mean expression of three IFN-γ-related genes in whole blood (GBP1, STAT1, and STAT2) (p < 0.001). CXCL11 was inversely correlated with FVC %predicted (%pred) and FEV1 %pred and higher levels were associated with higher patient-reported dyspnea scores. We found positive correlations between CXCL11 and number of organs involved. Using survival analyses, we found that CXCL11 levels were predictive of future pulmonary function test (PFT) decline (log rank <0.001 and HR of log10(CXCL11) = 5.1, 95% CI 1.2-21, p = 0.026).ConclusionsThe pattern of expression of serum CXCL11 in sarcoidosis patients suggests that this blood measure could be helpful in identifying patients that need longer-term monitoring for progressive thoracic and extra-thoracic sarcoidosis.

Project description:BackgroundSarcoidosis is an inflammatory disease characterized by non-caseating granuloma formation in various organs, with several recognized genetic and environmental risk factors. Despite substantial progress, the genetic determinants associated with its prognosis remain largely unknown.ObjectivesThis study aimed to identify the genetic changes involved in sarcoidosis and evaluate their clinical relevance.MethodsWe performed whole-exome sequencing (WES) in 116 sporadic sarcoidosis patients (acute sarcoidosis patients, n=58; chronic sarcoidosis patients, n=58). In addition, 208 healthy controls were selected from 1000 G East Asian population data. To identify genes enriched in sarcoidosis, Fisher exact tests were performed. The identified genes were included for further pathway analysis using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Additionally, we used the STRING database to construct a protein network of rare variants and Cytoscape to identify hub genes of signaling pathways.ResultsWES and Fisher's exact test identified 1,311 variants in 439 protein-coding genes. A total of 135 single nucleotide polymorphisms (SNPs) on 30 protein-coding genes involved in the immunological process based on the GO and KEGG enrichment analysis. Pathway enrichment analysis showed osteoclast differentiation and cytokine-cytokine receptor interactions. Three missense mutations (rs76740888, rs149664918, and rs78251590) in two genes (PRSS3 and CNN2) of immune-related genes showed significantly different mutation frequencies between the disease group and healthy controls. The correlation of genetic abnormalities with clinical outcomes using multivariate analysis of the clinical features and mutation loci showed that the missense variant (rs76740888, Chr9:33796673 G>A) of PRSS3 [p=0.04, odds ratio (OR) = 2.49] was significantly associated with chronic disease prognosis. Additionally, the top two hub genes were CCL4 and CXCR4 based on protein-protein interaction (PPI) network analysis.ConclusionOur study provides new insights into the molecular pathogenesis of sarcoidosis and identifies novel genetic alterations in this disease, especially PRSS3, which may be promising targets for future therapeutic strategies for chronic sarcoidosis.

Project description:BackgroundSeveral studies have investigated the associations between temperature variability (TV) and death counts. However, evidence of TV-attributable years of life lost (YLL) is scarce.ObjectivesTo investigate the associations between TV and YLL rates (/100,000 population), and quantify average life loss per death (LLD) caused by TV in China.MethodsWe calculated daily YLL rates (/100,000 population) of non-accidental causes and cardiorespiratory diseases by using death data from 364 counties of China during 2006-2017, and collected meteorological data during the same period. A distributed lag non-linear model (DLNM) and multivariate meta-analysis were used to estimate the effects of TV at national or regional levels. Then, we calculated the LLD to quantify the mortality burden of TV.ResultsU-shaped curves were observed in the associations of YLL rates with TV in China. The minimum YLL TV (MYTV) was 2.5 °C nationwide. An average of 0.89 LLD was attributable to TV in total, most of which was from high TV (0.86, 95% CI: 0.56, 1.16). However, TV caused more LLD in the young (<65 years old) (1.87, 95% CI: 1.03, 2.71) than 65-74 years old (0.85, 95% CI: 0.40-1.31) and ≥75 years old (0.40, 95% CI: 0.21-0.59), cerebrovascular disease (0.74, 95% CI: 0.36, 1.11) than respiratory disease (0.54, 95% CI: 0.21, 0.87), South (1.23, 95% CI: 0.77, 1.68) than North (0.41, 95% CI: -0.7, 1.52) and Central China (0.40, 95% CI: -0.02, 0.81). TV-attributed LLD was modified by annual mean temperature, annual mean relative humidity, altitude, latitude, longitude, and education attainment.SignificanceOur findings indicate that high and low TVs are both associated with increases in premature death, however the majority of LLD was attributable to high TV. TV-related LLD was modified by county level characteristics. TV should be considered in planning adaptation to climate change or variability.Impact(1) We estimated the associations of TV with YLL rates, and quantified the life loss per death (LLD) caused by TV. (2) An average of 0.89 years of LLD were attributable to TV, most of which were from high TVs. (3) TV caused more LLD in the young, cerebrovascular disease, and southern China. (4) The mortality burdens were modified by county level characteristics.

Dataset Information

Disease Burden and Variability in Sarcoidosis.

Publications

Disease Burden and Variability in Sarcoidosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets