Association of Hyperferritinemia With Distinct Host Response Aberrations in Patients With Community-Acquired Pneumonia.
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ABSTRACT: Background
Strongly elevated ferritin levels have been proposed to reflect systemic hyperinflammation in patients admitted to the intensive care unit. Knowledge of the incidence and pathophysiological implications of hyperferritinemia in patients with acute infection admitted to a non-intensive care setting is limited.Methods
We determined the association between hyperferritinemia, defined by 2 cutoff values (500 and 250 ng/mL), and aberrations in key host response mechanisms among patients with community-acquired pneumonia (CAP) on admission to a general hospital ward (clinicaltrials.gov NCT02928367; trialregister.nl NTR6163).Results
Plasma ferritin levels were higher in patients with CAP (n = 174; median [interquartile ranges], 259.5 [123.1-518.3] ng/mL) than in age- and sex-matched controls without infection (n = 50; 102.8 [53.5-185.7] ng/mL); P < .001); they were ≥500 ng/mL in 46 patients (26%) and ≥250 ng/mL in 90 (52%). Measurements of 26 biomarkers reflective of distinct pathophysiological domains showed that hyperferritinemia was associated with enhanced systemic inflammation, neutrophil activation, cytokine release, endothelial cell activation and dysfunction, and activation of the coagulation system. Results were robust across different cutoff values.Conclusions
Hyperferritinemia identifies patients with CAP with a broad deregulation of various host response mechanisms implicated in the pathogenesis of sepsis. This could inform future therapeutic strategies targeting subgroups within the CAP population.
SUBMITTER: Brands X
PROVIDER: S-EPMC9312861 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundA delay in admission to the intensive care unit (ICU) of patients with community-acquired pneumonia (CAP) has been associated with an increased mortality. Decisions regarding interventions and eligibility for immune modulatory therapy are often made at the time of admission to the ICU. The primary aim of this study was to compare the host immune response measured upon ICU admission in CAP patients admitted immediately from the emergency department (direct ICU admission) with those who were transferred within 72 h after admission to the general ward (delayed ICU admission).MethodsSixteen host response biomarkers providing insight in pathophysiological mechanisms implicated in sepsis and blood leukocyte transcriptomes were analysed in patients with CAP upon ICU admission in two tertiary hospitals in the Netherlands.ResultsOf 530 ICU admissions with CAP, 387 (73.0%) were directly admitted and 143 (27.0%) had a delayed admission. Patients with a delayed ICU admission were more often immunocompromised (35.0 versus 21.2%, P = .002) and had more malignancies (23.1 versus 13.4%, P = .011). Shock was more present in patients who were admitted to the ICU directly (46.6 versus 33.6%, P = .010). Delayed ICU admission was not associated with an increased hospital mortality risk (hazard ratio 1.25, 95% CI 0.89-1.78, P = .20). The plasma levels of biomarkers (n = 297) reflecting systemic inflammation, endothelial cell activation and coagulation activation were largely similar between groups, with exception of C-reactive protein, soluble intercellular adhesion molecule-1 and angiopoietin-1, which were more aberrant in delayed admissions compared to direct ICU admissions. Blood leukocyte transcriptomes (n = 132) of patients with a delayed ICU admission showed blunted innate and adaptive immune response signalling when compared with direct ICU admissions, as well as decreased gene expression associated with tissue repair and extracellular matrix remodelling pathways.ConclusionsBlood leukocytes of CAP patients with delayed ICU admission show evidence of a more immune suppressive phenotype upon ICU admission when compared with blood leukocytes from patients directly transferred to the ICU.Trial registrationMolecular Diagnosis and Risk Stratification of Sepsis (MARS) project, ClinicalTrials.gov identifier NCT01905033.
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Project description:BackgroundViruses are increasingly recognized as major causes of community-acquired pneumonia (CAP). Few studies have investigated the clinical predictors of viral pneumonia, and the results have been inconsistent. In this study, the clinical predictors of viral pneumonia were investigated in terms of their utility as indicators for viral pneumonia in patients with CAP.MethodsAdult patients (≥ 18 years old) with CAP, tested by polymerase chain reaction (PCR) for respiratory virus, at two teaching hospitals between October 2010 and May 2013, were identified retrospectively. Demographic and clinical data were collected by reviewing the hospital electronic medical records.ResultsDuring the study period, 456 patients with CAP were identified who met the definition, and 327 (72%) patients were tested using the respiratory virus PCR detection test. Viral pneumonia (n = 60) was associated with rhinorrhea, a higher lymphocyte fraction in the white blood cells, lower serum creatinine and ground-glass opacity (GGO) in radiology results, compared to non-viral pneumonia (n = 250) (p < 0.05, each). In a multivariate analysis, rhinorrhea (Odd ratio (OR) 3.52; 95% Confidence interval (CI), 1.58-7.87) and GGO (OR 4.68; 95% CI, 2.48-8.89) were revealed as independent risk factors for viral pneumonia in patients with CAP. The sensitivity, specificity, positive- and negative-predictive values (PPV and NPV) of rhinorrhea were 22, 91, 36 and 83%: the sensitivity, specificity, PPV and NPV of GGO were and 43, 84, 40 and 86%, respectively.ConclusionSymptom of rhinorrhea and GGO predicted viral pneumonia in patients with CAP. The high specificity of rhinorrhea and GGO suggested that these could be useful indicators for empirical antiviral therapy.
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Project description:BACKGROUND:We hypothesized that obstructive sleep apnea (OSA) can predispose individuals to lower airway infections and community-acquired pneumonia (CAP) due to upper airway microaspiration. This study evaluated the association between OSA and CAP. METHODS:We performed a case-control study that included 82 patients with CAP and 41 patients with other infections (control group). The controls were matched according to age, sex and body mass index (BMI). A respiratory polygraph (RP) was performed upon admission for patients in both groups. The severity of pneumonia was assessed according to the Pneumonia Severity Index (PSI). The associations between CAP and the Epworth Sleepiness Scale (ESS), OSA, OSA severity and other sleep-related variables were evaluated using logistic regression models. The associations between OSA, OSA severity with CAP severity were evaluated with linear regression models and non-parametric tests. FINDINGS:No significant differences were found between CAP and control patients regarding anthropometric variables, toxic habits and risk factors for CAP. Patients with OSA, defined as individuals with an Apnea-Hypopnea Index (AHI) ?10, showed an increased risk of CAP (OR = 2·86, 95%CI 1·29-6·44, p = 0·01). Patients with severe OSA (AHI?30) also had a higher risk of CAP (OR = 3·18, 95%CI 1·11-11·56, p = 0·047). In addition, OSA severity, defined according to the AHI quartile, was also significantly associated with CAP (p = 0·007). Furthermore, OSA was significantly associated with CAP severity (p = 0·0002), and OSA severity was also associated with CAP severity (p = 0·0006). CONCLUSIONS:OSA and OSA severity are associated with CAP when compared to patients admitted to the hospital for non-respiratory infections. In addition, OSA and OSA severity are associated with CAP severity. These results support the potential role of OSA in the pathogenesis of CAP and could have clinical implications. This link between OSA and infection risk should be explored to investigate the relationships among gastroesophageal reflux, silent aspiration, laryngeal sensory dysfunction and CAP. TRIAL REGISTRATION:ClinicalTrials.gov NCT01071421.
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Project description:ImportancePatients with alcohol use disorder (AUD) are at elevated risk of developing pneumonia, but few studies have assessed the outcomes of pneumonia in patients with AUD.ObjectivesTo compare the causes, treatment, and outcomes of pneumonia in patients with and without AUD and to understand the associations of comorbid illnesses, alcohol withdrawal, and any residual effects due to alcohol itself with patient outcomes.Design, setting, and participantsA retrospective cohort study was conducted of 137 496 patients 18 years or older with pneumonia who were admitted to 177 US hospitals participating in the Premier Healthcare Database from July 1, 2010, to June 30, 2015. Statistical analysis was conducted from October 27, 2017, to August 20, 2018.ExposureAlcohol use disorders identified from International Classification of Diseases, Ninth Revision, Clinical Modification codes.Main outcomes and measuresPneumonia cause, antibiotic treatment, inpatient mortality, clinical deterioration, length of stay, and cost. Associations of AUD with these variables were studied using generalized linear mixed models.ResultsOf 137 496 patients with community-acquired pneumonia (70 358 women and 67 138 men; mean [SD] age, 69.5 [16.2] years), 3.5% had an AUD. Patients with an AUD were younger than those without an AUD (median age, 58.0 vs 73.0 years; P < .001), more often male (77.3% vs 47.8%; P < .001), and more often had principal diagnoses of aspiration pneumonia (10.9% vs 9.8%; P < .001), sepsis (38.6% vs 30.7%; P < .001), or respiratory failure (9.3% vs 5.5%; P < .001). Their cultures more often grew Streptococcus pneumoniae (43.7% vs 25.5%; P < .001) and less frequently grew organisms resistant to guideline-recommended antibiotics (25.0% vs 43.7%; P < .001). Patients with an AUD were treated more often with piperacillin-tazobactam (26.2% vs 22.5%; P < .001) but equally as often with anti-methicillin-resistant Staphylococcus aureus agents (32.9% vs 31.8%; P = .11) compared with patients without AUDs. When adjusted for demographic characteristics and insurance, AUD was associated with higher mortality (odds ratio, 1.40; 95% CI, 1.25-1.56), length of stay (risk-adjusted geometric mean ratio, 1.24; 95% CI, 1.20-1.27), and costs (risk-adjusted geometric mean ratio, 1.33; 95% CI, 1.28-1.38). After additional adjustment for differences in comorbidities and risk factors for resistant organisms, AUD was no longer associated with mortality but remained associated with late mechanical ventilation (odds ratio, 1.28; 95% CI, 1.12-1.46), length of stay (risk-adjusted geometric mean ratio, 1.04; 95% CI, 1.01-1.06), and costs (risk-adjusted geometric mean ratio, 1.06; 95% CI, 1.03-1.09). Models segregating patients undergoing alcohol withdrawal showed that poorer outcomes among patients with AUD were confined to the subgroup undergoing alcohol withdrawal.Conclusions and relevanceThis study suggests that, compared with hospitalized patients with community-acquired pneumonia but without AUD, those with AUD less often harbor resistant organisms. The higher age-adjusted risk of death among patients with AUD appears to be largely attributable to differences in comorbidities, whereas greater use of health care resources may be attributable to alcohol withdrawal.
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Project description:INTRODUCTION: Diagnosis of severe influenza pneumonia remains challenging because of a lack of correlation between the presence of influenza virus and clinical status. We conducted gene-expression profiling in the whole blood of critically ill patients to identify a gene signature that would allow clinicians to distinguish influenza infection from other causes of severe respiratory failure, such as bacterial pneumonia, and noninfective systemic inflammatory response syndrome. METHODS: Whole-blood samples were collected from critically ill individuals and assayed on Illumina HT-12 gene-expression beadarrays. Differentially expressed genes were determined by linear mixed-model analysis and overrepresented biological pathways determined by using GeneGo MetaCore. RESULTS: The gene-expression profile of H1N1 influenza A pneumonia was distinctly different from those of bacterial pneumonia and systemic inflammatory response syndrome. The influenza gene-expression profile is characterized by upregulation of genes from cell-cycle regulation, apoptosis, and DNA-damage-response pathways. In contrast, no distinctive gene-expression signature was found in patients with bacterial pneumonia or systemic inflammatory response syndrome. The gene-expression profile of influenza infection persisted through 5 days of follow-up. Furthermore, in patients with primary H1N1 influenza A infection in whom bacterial co-infection subsequently developed, the influenza gene-expression signature remained unaltered, despite the presence of a superimposed bacterial infection. CONCLUSIONS: The whole-blood expression-profiling data indicate that the host response to influenza pneumonia is distinctly different from that caused by bacterial pathogens. This information may speed the identification of the cause of infection in patients presenting with severe respiratory failure, allowing appropriate patient care to be undertaken more rapidly.
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