Project

The Pneumonia Project in Buskerud, Norway

Goal: Explore etiology, pathogenesis and pathophyiology in community-acquired pneumoni. Determine diagnostic and prognostic biomarkers.

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Project log

Jan C Holter
added 14 research items
Identification of confounders in the association between vitamin D status (25-hydroxyvitamin D 30–49 nmol/L or <30 nmol/L versus ≥50 nmol/L [reference category]) and long-term all-cause mortality after hospitalization for CAP. (DOCX)
The inclusion process for the study population. (DOCX)
Lars Heggelund
added a research item
Background: Biomarkers may facilitate clinical decisions in order to guide antimicrobial treatment and prediction of prognosis in community-acquired pneumonia (CAP). We measured serum C-reactive protein, procalcitonin (PCT) and calprotectin levels, and plasma pentraxin 3 (PTX3) and presepsin levels, along with whole-blood white cell counts, at three time-points, and examined their association with microbial aetiology and adverse clinical outcomes in CAP. Methods: Blood samples were obtained at hospital admission, clinical stabilisation and 6-week follow-up from 267 hospitalised adults with CAP. Adverse short-term outcome was defined as intensive care unit admission and 30-day mortality. Long-term outcome was evaluated as 5-year all-cause mortality. Results: Peak levels of all biomarkers were seen at hospital admission. Increased admission levels of Creactive protein, PCT and calprotectin were associated with bacterial aetiology of CAP, while increased admission levels of PCT, PTX3 and presepsin were associated with adverse short-term outcome. In univariate and multivariate regression models, white blood cells and calprotectin at 6-week follow-up were predictors of 5-year all-cause mortality. Conclusions: Calprotectin emerges as both a potential early marker of bacterial aetiology and a predictor for 5-year all-cause mortality in CAP, whereas PCT, PTX3 and presepsin may predict short-term outcome.
Lars Heggelund
added a research item
Background Disease severity and outcome in community-acquired pneumonia (CAP) depend on the host and on the challenge of the causal microorganism(s). We measured levels of immunoglobulins (Igs) and complement in 257 hospitalized adults with CAP and examined the association of low levels of Igs or complement to microbial etiology, disease severity and short-term and long-term outcome. Methods Serum Igs were analyzed in blood samples obtained at admission and at 6-weeks post-discharge if low admission levels. Serum complement deficiencies were screened with a total complement activity enzyme-linked immunosorbent assay, with further analyzes performed if justified. Disease severity was assessed by the CURB-65 severity score. Short-term outcome was defined as a composite endpoint of intensive care unit admission and 30-day mortality, long-term outcome as 5-year all-cause mortality. Results At admission, 87 (34%) patients had low levels of at least one Ig, with low IgG2 as the most prevalent finding (55/21%). IgG levels were lower in bacterial than viral CAP (8.48 versus 9.97 g/L, p=0.023), but low Igs were not associated with microbial etiology. Fifty-five (21%) patients had low lectin pathway activity, of which 33 (13%) were mannose-binding lectin (MBL) deficient. Low admission levels of any Ig or MBL were not associated with disease severity, short-term or long-term outcome. Excluding patients defined as immunocompromised from analysis did not substantially affect these results. Conclusion In hospitalized adults with CAP, low admission levels of Igs or complement were in general not associated with microbial etiology, disease severity, short-term or long-term outcome.
Lars Heggelund
added 6 research items
Background Low vitamin D status has been associated with short-term (30-day) mortality in hospitalized adults with community-acquired pneumonia (CAP). Data on its prevalence in these patients are scarce, and impact on long-term prognosis is unknown. We examined the prevalence of vitamin D deficiency and inadequacy and their effect on long-term mortality in hospitalized adults with CAP. Methods Secondary follow-up analysis of data from a prospectively recruited (January 2008–January 2011) well-defined cohort of 241 hospital survivors of CAP (Norway, latitude 60°N). Serum 25-hydroxyvitamin D levels, demographic, clinical, and laboratory data were measured within 48 hours of admission. The etiology of CAP was established in 63% of patients through extensive microbiological investigations. Mortality data were obtained from the national Cause of Death Registry. Explanatory strategy and Cox regression models were used to explore the association between vitamin D status and all-cause mortality. Results Median age was 66 years. Eighty-seven (36%) patients were vitamin D deficient (<30 nmol/L), 81 (34%) were inadequate (30–49 nmol/L), and 73 (30%) were sufficient (≥50 nmol/L). Seventy-two patients died over a median of 1839 days (range 1–2520 days), corresponding to cumulative 5-year survival rates of 66.2% (95% CI 56.2–76.2%), 77.0% (67.6–86.4%), and 77.8% (67.8–87.8%) for vitamin D deficient, inadequate, and sufficient patients, respectively. After adjusting for confounders (age, chronic obstructive pulmonary disease, immunocompromization and season), vitamin D deficiency, but not inadequacy, was significantly associated with higher mortality compared to patients with sufficiency (HR 1.91, 95% CI 1.06–3.45; P = .031). Conclusions There is a high prevalence of vitamin D deficiency and inadequacy among hospitalized adults with CAP. The results of this study also suggest that vitamin D deficiency is associated with an increased risk of mortality way beyond the short-term in these patients.
Background: The inflammatory response in community-acquired pneumonia (CAP) is orchestrated through activation of cytokine networks and the complement system. We examined the association of multiple cytokines and the terminal complement complex (TCC) with microbial etiology, disease severity and short-term outcome. Materials and methods: Plasma levels of 27 cytokines and TCC were analyzed in blood samples obtained at hospital admission, clinical stabilization and 6-weeks follow up from 247 hospitalized adults with CAP. Fourteen mediators were included in final analyses. Adverse short-term outcome was defined as intensive care unit (ICU) admission and 30-day mortality. Results: Cytokine and TCC levels were dynamic in the clinical course of CAP, with highest levels seen at admission for most mediators. Admission levels of cytokines and TCC did not differ between groups of microbial etiology. High admission levels of IL-6 (odds ratio (OR) 1.47, 95% confidence interval (CI) 1.18 - 1.84, p=0.001), IL-8 (OR 1.79, 95% CI 1.26 - 2.55, p=0.001) and MIP-1β (OR 2.28, 95% CI 1.36 - 3.81, p=0.002) were associated with a CURB-65 severity score of ≥3, while IL-6 (OR 1.37, 95% CI 1.07 - 1.74, p=0.011) and MIP-1β (OR 1.86, 95% CI 1.03 - 3.36, p=0.040) were associated with a high risk of an adverse short-term outcome. Conclusions: In this CAP cohort, admission levels of IL-6, IL-8 and MIP-1β were associated with disease severity and/or adverse short-term outcome. Still, for most mediators, only non-significant variations in inflammatory responses were observed for groups of microbial etiology, disease severity and short-term outcome. This article is protected by copyright. All rights reserved.
Lars Heggelund
added a project goal
Explore etiology, pathogenesis and pathophyiology in community-acquired pneumoni. Determine diagnostic and prognostic biomarkers.