lung disease

Details about this human disease

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Definitions (2)

Updating out dated CUI and removing lung abscess as a synonym., A lower respiratory tract disease in which the function of the lungs is adversely affected by narrowing or blockage of the airways resulting in poor air flow, a loss of elasticity in the lungs that produces a decrease in the total volume of air that the lungs are able to hold, and clotting, scarring, or inflammation of the blood vessels that affect the ability of the lungs to take up oxygen and to release carbon dioxide.


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CapSys - Systems Medicine of Community Acquired Pneumonia

CAPSyS is an interdisciplinary research network that investigates the causes and course of severe pneumonia. The network works in five subprojects at seven locations throughout Germany. CAPSyS is funded by the Federal Ministry of Education and Research (BMBF) with 3.8 million euros.

Programme: This Project is not associated with a Programme

Public web page: https://www.capsys.imise.uni-leipzig.de

Start date: 1st Jan 2014

End date: 1st Jan 2019

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Sequential organ failure assessment score is an excellent operationalization of disease severity of adult patients with hospitalized community acquired pneumonia - results from the prospective observational PROGRESS study.
Genetical Statistics and Systems Biology

Abstract (Expand)

BACKGROUND: CAP (Community acquired pneumonia) is frequent, with a high mortality rate and a high burden on health care systems. Development of predictive biomarkers, new therapeutic concepts, and … epidemiologic research require a valid, reproducible, and quantitative measure describing CAP severity. METHODS: Using time series data of 1532 patients enrolled in the PROGRESS study, we compared putative measures of CAP severity for their utility as an operationalization. Comparison was based on ability to correctly identify patients with an objectively severe state of disease (death or need for intensive care with at least one of the following: substantial respiratory support, treatment with catecholamines, or dialysis). We considered IDSA/ATS minor criteria, CRB-65, CURB-65, Halm criteria, qSOFA, PSI, SCAP, SIRS-Score, SMART-COP, and SOFA. RESULTS: SOFA significantly outperformed other scores in correctly identifying a severe state of disease at the day of enrollment (AUC = 0.948), mainly caused by higher discriminative power at higher score values. Runners-up were the sum of IDSA/ATS minor criteria (AUC = 0.916) and SCAP (AUC = 0.868). SOFA performed similarly well on subsequent study days (all AUC > 0.9) and across age groups. In univariate and multivariate analysis, age, sex, and pack-years significantly contributed to higher SOFA values whereas antibiosis before hospitalization predicted lower SOFA. CONCLUSIONS: SOFA score can serve as an excellent operationalization of CAP severity and is proposed as endpoint for biomarker and therapeutic studies. TRIAL REGISTRATION: clinicaltrials.gov NCT02782013 , May 25, 2016, retrospectively registered.

Authors: P. Ahnert, P. Creutz, K. Horn, F. Schwarzenberger, M. Kiehntopf, H. Hossain, M. Bauer, F. M. Brunkhorst, K. Reinhart, U. Volker, T. Chakraborty, M. Witzenrath, M. Loffler, N. Suttorp, M. Scholz

Date Published: 4th Apr 2019

Publication Type: Journal article

Human Diseases: pneumonia

Footprints of Sepsis Framed Within Community Acquired Pneumonia in the Blood Transcriptome.
CAPSys - Footprints of Sepsis Framed Within Community Acquired Pneumonia in the Blood Transcriptome, oBIG - omics Bioinformatics for Health

Abstract (Expand)

We analyzed the blood transcriptome of sepsis framed within community-acquired pneumonia (CAP) and characterized its molecular and cellular heterogeneity in terms of functional modules of co-regulated … genes with impact for the underlying pathophysiological mechanisms. Our results showed that CAP severity is associated with immune suppression owing to T-cell exhaustion and HLA and chemokine receptor deactivation, endotoxin tolerance, macrophage polarization, and metabolic conversion from oxidative phosphorylation to glycolysis. We also found footprints of host's response to viruses and bacteria, altered levels of mRNA from erythrocytes and platelets indicating coagulopathy that parallel severity of sepsis and survival. Finally, our data demonstrated chromatin re-modeling associated with extensive transcriptional deregulation of chromatin modifying enzymes, which suggests the extensive changes of DNA methylation with potential impact for marker selection and functional characterization. Based on the molecular footprints identified, we propose a novel stratification of CAP cases into six groups differing in the transcriptomic scores of CAP severity, interferon response, and erythrocyte mRNA expression with impact for prognosis. Our analysis increases the resolution of transcriptomic footprints of CAP and reveals opportunities for selecting sets of transcriptomic markers with impact for translation of omics research in terms of patient stratification schemes and sets of signature genes.

Authors: L. Hopp, H. Loeffler-Wirth, L. Nersisyan, A. Arakelyan, H. Binder

Date Published: 2nd Aug 2018

Publication Type: Not specified

Human Diseases: disease by infectious agent, pneumonia

Cartography of Pathway Signal Perturbations Identifies Distinct Molecular Pathomechanisms in Malignant and Chronic Lung Diseases.
LHA - Leipzig Health Atlas

Abstract (Expand)

Lung diseases are described by a wide variety of developmental mechanisms and clinical manifestations. Accurate classification and diagnosis of lung diseases are the bases for development of effective … treatments. While extensive studies are conducted toward characterization of various lung diseases at molecular level, no systematic approach has been developed so far. Here we have applied a methodology for pathway-centered mining of high throughput gene expression data to describe a wide range of lung diseases in the light of shared and specific pathway activity profiles. We have applied an algorithm combining a Pathway Signal Flow (PSF) algorithm for estimation of pathway activity deregulation states in lung diseases and malignancies, and a Self Organizing Maps algorithm for classification and clustering of the pathway activity profiles. The analysis results allowed clearly distinguish between cancer and non-cancer lung diseases. Lung cancers were characterized by pathways implicated in cell proliferation, metabolism, while non-malignant lung diseases were characterized by deregulations in pathways involved in immune/inflammatory response and fibrotic tissue remodeling. In contrast to lung malignancies, chronic lung diseases had relatively heterogeneous pathway deregulation profiles. We identified three groups of interstitial lung diseases and showed that the development of characteristic pathological processes, such as fibrosis, can be initiated by deregulations in different signaling pathways. In conclusion, this paper describes the pathobiology of lung diseases from systems viewpoint using pathway centered high-dimensional data mining approach. Our results contribute largely to current understanding of pathological events in lung cancers and non-malignant lung diseases. Moreover, this paper provides new insight into molecular mechanisms of a number of interstitial lung diseases that have been studied to a lesser extent.

Authors: A. Arakelyan, L. Nersisyan, M. Petrek, H. Loffler-Wirth, H. Binder

Date Published: 21st May 2016

Publication Type: Not specified

Human Diseases: lung disease

Common genomic variation in the FER gene: useful to stratify patients with sepsis due to pneumonia?
LIFE - Leipzig Research Center for Civilization Diseases

Abstract

Not specified

Authors: F. Schoneweck, E. Kuhnt, M. Scholz, F. M. Brunkhorst, A. Scherag

Date Published: 30th Apr 2015

Publication Type: Not specified

Human Diseases: bacterial infectious disease, pneumonia

Methylation associated pathway activity deregulation in lung adenocarcinoma
CapSys - Systems Medicine of Community Acquired Pneumonia

Abstract (Expand)

Methylation impairments are tightly associated with gene expression and molecular pathway deregulation in cancer development. However, other regulatory mechanisms exist, making it important to distinguish … those from methylation driven changes. Here we specifically assessed molecular pathway states associated with gene methylation in lung adenocarcinoma. Paired gene expression and methylation data (id:GSE32867) were obtained from Gene Expression Omnibus. Self organizing maps (Wirth, H. et al.BMC Bioinformatics 2011;12:306 ) and in-house pathway signal flow algorithms were applied to describe expression (PSF) and methylation (mPSF) states in KEGG pathways. 35 and 24 KEGG pathways had at least one branch deregulated at significance levels p<0.05 and 0.05<p < 0.1, respectively. Because many pathways are multibranch, our analysis totalled in 54 up- (PSF>1) and 73 down-regulated (PSF<1) branches. From these branches, 19 were positively (mPSF<0) or negatively (mPSF>0) correlated with methylation states (see table).

Authors: L. Nersisyan, Henry Löffler-Wirth, A. Gevorgyan, Hans Binder, A. Arakelyan

Date Published: 2014

Publication Type: Not specified

Human Diseases: lung disease

Mining common pathway deregulation profiles in lung diseases
CapSys - Systems Medicine of Community Acquired Pneumonia

Abstract (Expand)

This study is aimed at investigating lung diseases described by common pathomechanisms based on evaluation of gene expression profiles in molecular pathways. 16 datasets containing 428 samples for 22 … health conditions were taken from Gene Expression Omnibus. Self organizing maps (Wirth, H. et al.BMC Bioinformatics 2011;12:306) and cluster analysis with dynamic tree cut were used for gene expression based disease clustering. In-house pathway signal flow algorithm and phylogenetic analysis were applied to find common pathway deregulation patterns in clusters. Analysis resulted in grouping the 22 conditions into 5 clusters (fig.1). PSF and phylogenetic analysis identified unique pathway deregulation patterns for each cluster (fig.2).

Authors: A. Arakelyan, L. Nersisyan, Henry Löffler-Wirth, Hans Binder

Date Published: 2014

Publication Type: Not specified

Human Diseases: lung disease

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CAP Severity Scores
Genetical Statistics and Systems Biology

This Shiny-App implements the calculation of several CAP (Community-Aquired-Pneumonia) severity scores for one or multiple patients based on user-updated data.

Creators: Markus Scholz, Maciej Rosolowski, Carl Beuchel

Submitter: Carl Beuchel

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