Dataset Information

Increased Severity and Mortality of CAP in COPD: Results from the German Competence Network, CAPNETZ.

ABSTRACT: Background:Mortality of community acquired pneumonia (CAP) remains high despite significant research efforts. Knowledge about comorbidities including chronic obstructive pulmonary disease (COPD) might help to improve management and ultimately, survival. The impact of COPD on CAP severity and mortality remains a point of discussion. Objectives:Assess the prevalence and clinical characteristics of COPD in the observational German Competence Network for CAP, CAPNETZ, and to study the impact of COPD on CAP severity and mortality. Methods:1307 consecutive patients with CAP (57.0% males, age 59.0±18.5), classified as CAP-only (n=1043; 78.0%) and CAP-COPD (n=264; 20.2%) were followed up for 180 days. Associations between CAP, COPD and mortality were evaluated by univariate/multivariate and Kaplan-Meier survival analyses. Results:CAP-COPD patients were older, more often males, current/former smokers, with higher confusion-urea-respiratory rate-blood pressure, (CURB) scores. Length of hospital stay, urea, glucose and leucocytes plasma levels, and arterial carbon dioxide tension (PaCO2) were significantly increased in CAP-COPD. Thirty, 90- and 180-day mortality rates were significantly increased in CAP-COPD (p=0.046, odds ratio [OR]=2.48, 95% confidence interval [CI] 1.015-6.037; p=0.003, OR=2.80, 95%CI 1.430-5.468; p=0.001, OR=2.57, 95%CI 1.462-4.498; respectively). Intensive care unit (ICU)-admission and age, but not COPD, were identified as independent predictors of short- and long-term mortality. Conclusion:Severity as well as mortality was significantly higher in COPD patients with CAP. To improve CAP management with the aim to decrease its still-too-high mortality, underlying comorbidities, particularly COPD, need to be assessed.

SUBMITTER: Braeken DCW

PROVIDER: S-EPMC5556967 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Increased Severity and Mortality of CAP in COPD: Results from the German Competence Network, CAPNETZ.

Braeken Dionne C W DCW Franssen Frits M E FME Schütte Hartwig H Pletz Mathias W MW Bals Robert R Martus Peter P Rohde Gernot G U GGU

Chronic obstructive pulmonary diseases (Miami, Fla.) 20150326 2

<b>Background:</b>Mortality of community acquired pneumonia (CAP) remains high despite significant research efforts. Knowledge about comorbidities including chronic obstructive pulmonary disease (COPD) might help to improve management and ultimately, survival. The impact of COPD on CAP severity and mortality remains a point of discussion. <b>Objectives:</b>Assess the prevalence and clinical characteristics of COPD in the observational German Competence Network for CAP, CAPNETZ, and to study the ...[more]

PMID: 28848837

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Project description:Nevirapine exhibits marked interpatient variability in pharmacokinetics. CYP2B6 activity and demographic factors are important, but there are a few data on drug transporters for nevirapine. ABCC10 (MRP7) is an efflux transporter highly expressed in liver, intestine, and peripheral blood cells. We investigated whether nevirapine is a substrate for ABCC10 and whether genetic variants contribute to variability in nevirapine plasma concentrations.Accumulation of nevirapine was assessed in parental and ABCC10-transfected HEK293 cells (HEK293-ABCC10), CD4+ cells, and monocyte-derived macrophages from healthy volunteers (n=8). ABCC10 small interfering RNA studies were also conducted. DNA samples with paired plasma drug concentrations were available from 163 HIV-infected patients receiving nevirapine-containing regimens. Sequenom was used to screen 14 single nucleotide polymorphisms in ABCC10. Linear regression models were used to identify factors independently associated with nevirapine plasma concentration.Nevirapine accumulation was 37% lower in HEK293-ABCC10 cells compared with parental HEK293 cells (P=0.02), and this was reversed by cepharanthine (an ABCC10 inhibitor). After small interfering RNA knockdown of ABCC10, there was an increase in accumulation of nevirapine in CD4 cells (32%; P=0.03) and monocyte-derived macrophages (38%; P=0.04). Marked differences in the haplotype structure of ABCC10 was observed between White and Black patients in the cohort. In Whites, an exonic single nucleotide polymorphism (rs2125739) was significantly associated with nevirapine plasma concentration (P=0.02). Multivariate regression analysis identified carriage of a composite genotype of ABCC10 rs2125739 and CYP2B6 516G>T (P=0.001), time post dose (P=0.01) and BMI (P=0.07) to be independently associated with nevirapine plasma concentrations.Nevirapine is a substrate for ABCC10 and genetic variants influence its plasma concentrations. ABCC10 in lymphocytes and macrophages may also contribute to variability in intracellular permeation of nevirapine. Further studies are required to determine the clinical implications of these findings.

Dataset Information

Increased Severity and Mortality of CAP in COPD: Results from the German Competence Network, CAPNETZ.

Publications

Increased Severity and Mortality of CAP in COPD: Results from the German Competence Network, CAPNETZ.

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