adrenomedullin and Pneumonia

Acute dyspnea is a common chief complaint among patients who visit an emergency room and presents diagnostic challenges for clinicians in both identifying the etiology and determining the clinical severity. The study of biomarkers in the prognostication and risk stratification of these patients has been increasing, including the investigation of the prognostic value for mid-regional pro-adrenomedullin (MR-proADM). Areas covered: In this review, the authors cover what is known about MR-proADM testing in patients presenting with acute dyspnea and the supporting evidence of its prognostic value in common conditions in medical patients with acute dyspnea, including acute heart failure, community acquired pneumonia, acute exacerbation of chronic obstructive pulmonary disease, and acute pulmonary embolism. Expert commentary: Numerous studies have proposed MR-proADM as a more accurate, prognostic tool in the evaluation of acute dyspnea than other biomarkers and consensus risk scores such as Sequential Organ Failure Assessment (SOFA) and quick SOFA (qSOFA). The authors review recent prospective studies, systematic reviews, and meta-analyses that demonstrate its prognostic value and role in risk stratification, including its use in biomarker-based triage algorithms as part of the diagnostic evaluation of the acutely dyspneic patient.

Topics: Adrenomedullin; Biomarkers; Community-Acquired Infections; Dyspnea; Heart Failure; Humans; Pneumonia; Prognosis; Pulmonary Disease, Chronic Obstructive; Pulmonary Embolism

The early identification of patients at risk of dying from community-acquired pneumonia (CAP) is critical for their treatment and for defining hospital resource consumption. Mid-regional pro-adrenomedullin (MR-proADM) has been extensively investigated for its prognostic value in CAP. However, the results are conflicting. The purpose of the present meta-analysis was to explore the diagnostic accuracy of MR-proADM for predicting mortality in patients suffering from CAP, particularly emergency department (ED) patients.. We systematically searched the PubMed, Embase, Web of Knowledge and Cochrane databases. Studies were included if a 2 × 2 contingency table could be constructed based on both the MR-proADM level and the complications or mortality of patients diagnosed with CAP. The prognostic accuracy of MR-proADM in CAP was assessed using the bivariate meta-analysis model. We used the Q-test and I (2) index to evaluate heterogeneity.. MR-proADM displayed moderate diagnostic accuracy for predicting complications in CAP, with an overall area under the SROC curve (AUC) of 0.74 (95 % CI: 0.70-0.78). Eight studies with a total of 4119 patients in the emergency department (ED) were included. An elevated MR-proADM level was associated with increased risk of death from CAP (RR 6.16, 95 % CI 4.71-8.06); the I (2) value was 0.0 %, and a fixed-effects model was used to pool RR. The pooled sensitivity and specificity were 0.74 (95 % CI: 0.67-0.79) and 0.73 (95 % CI: 0.70-0.77), respectively. The positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were 2.8 (95 % CI, 2.3-3.3) and 0.36 (95 % CI, 0.29-0.45), respectively. In addition, the diagnostic odds ratio (DOR) was 8 (95 % CI, 5-11), and the overall area under the SROC curve was 0.76 (95 % CI, 0.72-0.80).. Our study has demonstrated that MR-proADM is predictive of increased complications and higher mortality rates in patients suffering from CAP. Future studies are warranted to determine the prognostic accuracy of MR-proADM in conjunction with severity scores or other biomarkers and to determine an optimal cut-off level.

Topics: Adrenomedullin; Biomarkers; Community-Acquired Infections; Emergency Service, Hospital; Humans; Pneumonia; Prognosis; Sensitivity and Specificity

The initial prognostic assessment of patients with community-acquired pneumonia( CAP) has important clinical implications. We hypothesized that midregional proadrenomedullin(MR-proADM) is a valuable test for the prediction of outcomes in patients with CAP.Methods: We performed a systemic review of the literature and a meta-analysis to evaluate the prognostic value of MR-proADM for short and long-term mortality in patients with CAP.Results: Twelve studies were included in the systematic review. Elevated MR-proADM was associated with an increase in short-term mortality (OR Z 6.8; 95% CI: 4.65-10.13; P value < 0.001) and complications (OR = 5.0; 95% CI: 3.86-6.49; P value < 0.001). The pooled analysis of 4 studies showed an improvement in the discriminant ability by 8% (95% CI: 2%e14%)when MR-proADM was added to CURB-65/CRB-65. Studies that reported long-term prognosis indicated an increased risk of death in patients with elevated MR-proADM.Conclusion: Elevated level of MR-proADM is significantly associated with both short-term mortality and complications in patients with CAP. Studies also indicate that MR-proADM has prognostic value for prediction of long-term mortality in these patients. The addition of MR-proADM improves the discriminant ability of CURB-65/CRB-65.

Topics: Adrenomedullin; Bias; Biomarkers; Community-Acquired Infections; Humans; Pneumonia; Prognosis; Protein Precursors; Risk Assessment; Sensitivity and Specificity

In patients with community-acquired pneumonia (CAP), blood biomarkers can help to substantially improve individual decisions involving initiation, (de-)intensification, and cessation of antibiotics, and initial risk stratification, site-of-care assignment (outpatient versus ward versus ICU), and discharge. To illustrate these processes, this review summarizes recent findings from trials investigating the use of two hormokines, procalcitonin (PCT) or proadrenomedullin (ProADM), in personalized treatment and management decisions in CAP patients.. Many biomarkers from distinct pathophysiological pathways have been evaluated in observational studies. However, only few analytes have been tested for efficacy and safety in numerous, large observational studies or in prospective, randomized, interventional trials. Among the latter, PCT has been demonstrated to be well tolerated and highly effective for monitoring and de-escalating antibiotic therapy. ProADM has shown higher accuracy for short-term and long-term adverse outcome prediction and improves prognostic accuracy when combined with current clinical risk scores, that is, Pneumonia Severity Index, the CURB65 (confusion, uremia, respiratory rate, blood pressure, age at least 65 years) score, and Risk of Early Admission to ICU, compared to applying the respective score alone. ProADM use has - in a pilot interventional study - improved site-of-care decisions and tended to shorten length hospitalization.. Inclusion of biomarker data in clinical algorithms improves individual decision-making in CAP patients. Interventional trials should be conducted to determine these markers' ultimate utility in patient management.

Topics: Adrenomedullin; Anti-Bacterial Agents; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Community-Acquired Infections; Humans; Pneumonia; Protein Precursors; Randomized Controlled Trials as Topic; Severity of Illness Index

Community-acquired pneumonia (CAP) is the leading cause of death from infectious diseases worldwide, with an incidence of 0.3 to 0.5% in the adult population. A new diagnostic and prognostic approach relies on evaluation of biomarkers as an expression of the host's inflammatory response against the microorganism. C-reactive protein (CRP), procalcitonin (PCT), and cytokines are the most frequently studied, whereas pro-adrenomedullin (pro-ADM), pro-vasopressin (pro-VNP), and others are currently obtaining promising results. Their usefulness for diagnosis is limited, although PCT has been successfully used to guide prescription of antibiotics in patients with suspected CAP. Nevertheless, the accuracy of PCT in distinguishing between bacterial or viral infection and safely withholding antibiotics in CAP is the subject of debate. Analysis of systemic biomarkers in addition to clinical scores [Pneumonia Severity Index (PSI) or CURB-65 (confusion, urea, respiratory, blood pressure, >65 years)/CRB-65 (confusion, respiratory, blood pressure)] has been shown to improve 30 day mortality prediction and absence of severe complications. Pro-ADM is probably the biomarker that correlates most strongly with mortality prediction. During treatment, ~15% of hospitalized CAP patients develop treatment failure, and almost 6% may manifest rapidly progressive pneumonia. Initially increased and persistent raised levels of biomarkers and cytokines have been shown to identify patients at risk of treatment failure, thereby aiding clinical management. Data from the literature appear to support the use of biomarkers in routine clinical practice to improve the decision making in CAP.

Topics: Adrenomedullin; Anti-Bacterial Agents; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Community-Acquired Infections; Cytokines; Humans; Inflammation; Pneumonia; Prognosis; Protein Precursors; Vasopressins

Biomarkers have been intensively studied in community-acquired pneumonia (CAP) in recent years. In the context of the CAPNETZ study we had the unique opportunity to evaluate old and new biomarkers in a multicentre study with a high number of patients.. In several substudies we found the following results: procalcitonin, CRP and leukocytes show highest values in patients with typical bacterial etiology of CAP, but do not allow individual prediction of etiology. Patients without antibiotic pre-treatment show higher values of biomarkers compared to patients with antibiotic pre-treatment. New cardiovascular biomarkers are good predictors for short- and long-term mortality in CAP, superior to the inflammatory markers procalcitonin, CRP and leukocytes and at least comparable to the clinical CRB-65 score. Pro-Adrenomedullin is among the new biomarkers the one with the best prognostic value.. Biomarkers correlate with the severity of CAP but do not allow individual prediction of etiology. New cardiovascular biomarkers are suitable for the evaluation of short- and long-term prognosis in CAP. The combination of several biomarkers reflecting different pathophysiological pathways has the potential to improve management of CAP in the future.

Topics: Adolescent; Adrenomedullin; Adult; Age Distribution; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Biomarkers; Blood Pressure; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Cardiovascular Diseases; Community-Acquired Infections; Comorbidity; Endothelin-1; Female; Germany; Humans; Inflammation; Leukocyte Count; Male; Middle Aged; Pneumonia; Predictive Value of Tests; Protein Precursors; Respiratory Rate; Survival Analysis; Vasopressins; Young Adult

This review aims to provide physicians with an overview of the potential of biomarkers to complement existing clinical severity scores and in conjunction with clinical parameters to improve the diagnosis, risk-stratification and management of lower respiratory tract infections (LRTIs). The usefulness of biomarkers for diagnosing LRTIs is still unclear. However, the specificity of pneumonia diagnosis is high when high sensitivity C-reactive protein (CRP) and procalcitonin (PCT) are used. PCT, CRP and particularly pro-atrial natriuretic peptide (MR-proANP), pro-vasopressin (CT-proAVP) and proadrenomedullin (proADM) levels can reliably predict LRTIs mortality. These markers do not significantly improve the severity scores predictive values, confirming that biomarkers are meant to complement, rather than supersede, clinician's judgment and validated severity scores. Biomarkers, and particularly PCT, are useful tools as antibiotic treatment duration indicators both in pneumonia and exacerbations of chronic obstructive pulmonary disease (COPD). Even if more data are required to fully appreciate the role of biomarkers in LRTIs management, there is emerging evidence that biomarkers have the potential to improve the daily clinical management of LRTIs.

Topics: Adrenomedullin; Atrial Natriuretic Factor; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Pneumonia; Prognosis; Protein Precursors; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Infections; Vasopressins

Pulmonary arterial hypertension is a progressive, fatal disease. Current treatments including prostanoids, endothelin-1 (ET-1) antagonists, and phosphodiesterase (PDE) inhibitors, have sought to address the pulmonary vascular endothelial dysfunction and vasoconstriction associated with the condition. These treatments may slow the progression of the disease but do not afford a cure. Future treatments must target more directly the structural vascular changes that impair blood flow through the pulmonary circulation. Several novel therapeutic targets have been proposed and are under active investigation, including soluble guanylyl cyclase, phosphodiesterases, tetrahydrobiopterin, 5-HT2B receptors, vasoactive intestinal peptide, receptor tyrosine kinases, adrenomedullin, Rho kinase, elastases, endogenous steroids, endothelial progenitor cells, immune cells, bone morphogenetic protein and its receptors, potassium channels, metabolic pathways, and nuclear factor of activated T cells. Tyrosine kinase inhibitors, statins, 5-HT2B receptor antagonists, EPCs and soluble guanylyl cyclase activators are among the most advanced, having produced encouraging results in animal models, and human trials are underway. This review summarises the current research in this area and speculates on their likely success.

Topics: Adrenomedullin; Animals; Bone Morphogenetic Protein Receptors; Cyclic GMP; Dichloroacetic Acid; Drug Discovery; Endothelial Cells; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension, Pulmonary; NFATC Transcription Factors; Pancreatic Elastase; Pneumonia; Receptor Protein-Tyrosine Kinases; rho-Associated Kinases; Serotonin; Stem Cells; Vasoactive Intestinal Peptide

Community-acquired pneumonia (CAP) in children is one of the most important causes of mortality and morbidity in developing countries. Therefore, it is very important for clinicians to detect the presence and severity of pneumonia. Proadrenomedullin (Pro-ADM) and Interleukin-1β (IL-1β) are thought to have potential for CAP evaluation in children. We sought to investigate the value of Pro-ADM and IL-1β levels for severity assessment and outcome prediction in children with CAP.. A total of 66 hospitalized CAP patients were included in a prospective observational study. Complete blood count, serum C-reactive protein (CRP), Pro-ADM and IL-1β levels were studied in blood samples obtained from the patients upon admission. Respiratory Clinical Score (RCS) was performed to determine the respiratory distress and severity.. The comparison of data with laboratory-severity groups: serum CRP, Pro-ADM and IL-1β levels increased in parallel with the disease severity. Pro-ADM was the best biomarker for severity stratification. Logistic regression analysis revealed that RCS >6 points and Pro-ADM values >1.75 nmol/L combination had the most significant results (OR: 15.38, 95% CI 1.35-166.66,. Serum Pro-ADM and IL-1β levels may offer additional risk/severity stratification in children with CAP. In addition, they may be helpful in predicting the development of complications, requirements for ntensive care unit admission, and intervention procedures.

Topics: Adolescent; Adrenomedullin; Biomarkers; Child; Child, Preschool; Community-Acquired Infections; Female; Follow-Up Studies; Humans; Interleukin-1beta; Male; Pneumonia; Prognosis; Prospective Studies; Protein Precursors; ROC Curve; Severity of Illness Index

Pro-adrenomedullin (proADM) is helpful for individual risk assessment and outcome prediction in sepsis. A major cause of sepsis is community-acquired pneumonia (CAP). The aim of this study was to investigate the value of proADM levels for severity assessment and outcome prediction in CAP.. Data from 302 patients admitted to the emergency department with CAP were included in a prospective observational study. Procalcitonin, C-reactive protein levels, leukocyte count, clinical variables and the pneumonia severity index (PSI) were measured. ProADM levels were measured with a new sandwich immunoassay for mid regional ProADM (MR-proADM, Brahms AG, Hennigsdorf/Berlin, Germany).. ProADM levels, in contrast to C-reactive protein and leukocyte count, increased with increasing severity of CAP, classified according to the PSI score (ANOVA, p < 0.001). In patients who died during follow-up, proADM levels on admission were significantly higher compared to levels in survivors (2.1 (1.5 to 3.0) versus 1.0 (0.6 to 1.6) nmol/l, p < 0.001). In a receiver operating characteristic (ROC) analysis for survival, the area under the ROC curve (AUC) for proADM was 0.76 (95% confidence interval (CI) 0.71-0.81), which was significantly higher compared to procalcitonin (p = 0.004), C-reactive protein (p < 0.001) and total leukocyte count (p = 0.001) and similar to the AUC of the PSI (0.73, p = 0.54). A clinical model including the PSI and proADM increased the prognostic accuracy to predict failure compared to a model relying on the PSI alone (AUC, 0.77 (0.70 to 0.84), p = 0.03).. ProADM, as a novel biomarker, is a useful tool for the risk stratification of patients with CAP.

Topics: Adrenomedullin; Aged; Aged, 80 and over; Biomarkers; Community-Acquired Infections; Female; Follow-Up Studies; Humans; Male; Middle Aged; Pneumonia; Predictive Value of Tests; Prospective Studies; Protein Precursors; Proteins; Severity of Illness Index; Treatment Outcome

Topics: Adrenomedullin; COVID-19; Critical Illness; Humans; Pneumonia; SARS-CoV-2

Topics: Adrenomedullin; COVID-19; Critical Illness; Humans; Pneumonia; SARS-CoV-2

Plasma proadrenomedullin (proADM) is a promising biomarker to predict disease severity in community-acquired pneumonia (CAP). Urinary biomarkers offer advantages over blood, including ease of collection. We evaluated the association between urinary proADM and disease severity in pediatric CAP.. We performed a prospective cohort study of children 3 months to 18 years with CAP. Urinary proADM/creatinine (Cr) was calculated. Disease severity was defined as: mild (discharged home), mild-moderate (hospitalized but not moderate-severe or severe), moderate-severe (eg, hospitalized with supplemental oxygen and complicated pneumonia) and severe (eg, vasopressors and invasive ventilation). Outcomes were examined using logistic regression within the cohort with suspected CAP and in a subset with radiographic CAP.. Of the 427 children included, higher proADM/Cr was associated with increased odds of severe disease compared with nonsevere disease [suspected CAP, odds ratio (OR) 1.02 (95% confidence interval (CI) 1.003, 1.04); radiographic CAP, OR 1.03 (95% CI 1.01, 1.06)] when adjusted for other covariates. ProADM/Cr had an area under the receiver operating characteristic curve of 0.56 (threshold 0.9 pmol/mg) to differentiate severe from nonsevere disease in suspected CAP and 0.65 in radiographic CAP (threshold 0.82 pmol/mg). Healthy controls had less proADM in their urine (median, 0.61 pmol/mg) compared with suspected (0.87 pmol/mg, P = 0.018) and radiographic (0.73 pmol/mg, P = 0.016) CAP.. Urinary proADM/Cr ratio measured at the time of emergency department visit was statistically associated with the development of severe outcomes in children with CAP, with stronger discriminatory performance in radiographic disease.

Topics: Adolescent; Adrenomedullin; Biomarkers; Child; Child, Preschool; Community-Acquired Infections; Emergency Service, Hospital; Female; Humans; Infant; Logistic Models; Male; Pneumonia; Prognosis; Prospective Studies; Protein Precursors; ROC Curve; Severity of Illness Index

Proadrenomedullin (proADM), a vasodilatory peptide with antimicrobial and anti-inflammatory properties, predicts severe outcomes in adults with community-acquired pneumonia (CAP) to a greater degree than C-reactive protein and procalcitonin. We evaluated the ability of proADM to predict disease severity across a range of clinical outcomes in children with suspected CAP.. We performed a prospective cohort study of children 3 months to 18 years with CAP in the emergency department. Disease severity was defined as mild (discharged home), mild-moderate (hospitalized but not moderate-severe or severe), moderate-severe (eg, hospitalized with supplemental oxygen, broadening of antibiotics, complicated pneumonia), and severe (eg, vasoactive infusions, chest drainage, severe sepsis). Outcomes were examined using proportional odds logistic regression within the cohort with suspected CAP and in a subset with radiographic CAP.. Among 369 children, median proADM increased with disease severity (mild: median [IQR], 0.53 [0.43-0.73]; mild-moderate: 0.56 [0.45-0.71]; moderate-severe: 0.61 [0.47-0.77]; severe: 0.70 [0.55-1.04] nmol/L) (P = .002). ProADM was significantly associated with increased odds of developing severe outcomes (suspected CAP: OR, 1.68; 95% CI, 1.2-2.36; radiographic CAP: OR, 2.11; 95% CI, 1.36-3.38) adjusted for age, fever duration, antibiotic use, and pathogen. ProADM had an AUC of 0.64 (95% CI, .56-.72) in those with suspected CAP and an AUC of 0.77 (95% CI, .68-.87) in radiographic CAP.. ProADM was associated with severe disease and discriminated moderately well children who developed severe disease from those who did not, particularly in radiographic CAP.

Topics: Adrenomedullin; Biomarkers; Child; Community-Acquired Infections; Humans; Pneumonia; Prognosis; Prospective Studies; Protein Precursors; Severity of Illness Index

We assessed the ability of mid-regional proadrenomedullin (MR-proADM) and C-terminal proendothelin-1 (CT-proET-1) to predict 28-day mortality in critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia.. Biomarkers were collected during the first seven days in this prospective observational cohort study. We investigated the relationship between biomarkers and mortality in a multivariable Cox regression model adjusted for age and SOFA score.. In 105 critically ill patients with confirmed SARS-CoV-2 pneumonia 28-day mortality was 28.6%. MR-proADM and CT-proET-1 were significantly higher in 28-day non-survivors at baseline and over time. ROC curves revealed high accuracy to identify non-survivors for baseline MR-proADM and CT-proET-1, AUC 0.84, (95% CI 0.76-0.92), p < 0.001 and 0.79, (95% CI 0.69-0.89), p < 0.001, respectively. The AUC for prediction of 28-day mortality for MR-proADM and CT-proET-1 remained high over time. MR-proADM ≥1.57 nmol/L and CT-proET-1 ≥ 111 pmol/L at baseline were significant predictors for 28-day mortality (HR 6.80, 95% CI 3.12-14.84, p < 0.001 and HR 3.72, 95% CI 1.71-8.08, p 0.01).. Baseline and serial MR-proADM and CT-proET-1 had good ability to predict 28-day mortality in critically ill patients with SARS-CoV-2 pneumonia.. NEDERLANDS TRIAL REGISTER, NL8460.

Topics: Adrenomedullin; Biomarkers; COVID-19; Critical Illness; Endothelin-1; Endothelium; Humans; Peptide Fragments; Pneumonia; Prognosis; Prospective Studies; Protein Precursors; SARS-CoV-2

Topics: Acute Kidney Injury; Adrenomedullin; Critical Illness; Enkephalins; Humans; Pneumonia; Protein Precursors; Sepsis

To confirm the diagnostic accuracy of candidate biomarkers in stroke-associated pneumonia (SAP), we prospectively enrolled ischemic stroke patients with NIHSS ≥ 10 on admission from March-2016 to August-2017. Blood samples were collected at baseline, 24 and 48 h after stroke onset. Biomarkers (MR-proADM, suPAR, SAA) were determined by immunoassays. Regarding biomarkers, MR-proADM at 24 h (P = 0.04) and both suPAR and SAA at 48 h (P = 0.036 and P = 0.057) were associated with pneumonia. The combination of SAA > 25.15 mg/dL and suPAR> 3.14 ng/mL at 48 h had 80% sensitivity and 95.8% specificity when both biomarkers were above the cut-off. The evaluated biomarkers represent promising tools to be evaluated in future large, prospective studies on SAP. An accurate SAP diagnosis by thorax CT might help to reduce variability in such studies.

Topics: Adrenomedullin; Aged; Aged, 80 and over; Biomarkers; Early Diagnosis; Female; Humans; Male; Peptide Fragments; Pneumonia; Prognosis; Protein Precursors; Receptors, Urokinase Plasminogen Activator; Serum Amyloid A Protein; Stroke

To evaluate the prognostic accuracy of proadrenomedullin (proADM) in comparison with and in addition to the Multidimensional Prognostic Index (MPI), a validated predictive tool for mortality derived from a comprehensive geriatric assessment (CGA) to predict one-month mortality risk in older patients hospitalized with community-acquired pneumonia (CAP).. All patients aged 65 years and older, consecutively admitted to an acute geriatric ward with a diagnosis of CAP from February to July 2012. At admission and at discharge they were submitted to a standard CGA in order to calculate MPI. Moreover, plasma samples were taken at baseline and after one, three and five days of hospitalization for the analysis of pro-ADM.. Fifty patients (mean age 86.2±7.5 years), with 31 at high risk of mortality (MPI-3) were enrolled. ProADM and MPI, both at admission and at discharge, were significant predictor of mortality. As expected, MPI at admission showed lower predictive accuracy than MPI at discharge (survival C-statistic 0.667 vs. 0.851). The addition of proADM to the MPI at admission significantly increased accuracy in predicting one-month mortality (C-statistics from 0.667 to 0.731, P=0.018 at baseline; from 0.667 to 0.733, P=0.008 at 1 day; from 0.633 to 0.724; P=0.019 at 3 days; from 0.667 to 0.828; P=0.003 at 5 days). Conversely, adding pro-ADM to the MPI at discharge did not significantly improve the model's prognostic accuracy.. ProADM may significantly improve the prognostic accuracy of the MPI at admission in hospitalized elderly patients with CAP.

Topics: Adrenomedullin; Aged; Aged, 80 and over; Community-Acquired Infections; Female; Geriatric Assessment; Humans; Male; Patient Admission; Patient Discharge; Pneumonia; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Prospective Studies; Protein Precursors; Risk Factors; Severity of Illness Index

(i) evaluate the performance of MR-pro-ADM in reflecting the outcome and risk for CAP patients in the emergency department, and (ii) compare the prognostic performance of MR-pro-ADM with that of clinical scores PSI and CURB65.. Observational prospective, single-center study in patients with suspected community acquired pneumonia (CAP). Eighty one patients underwent full clinical and laboratory assessment as by protocol, and were followed up a 28 days. Primary endpoints measured were: death, death at 14 days, non-invasive mechanical ventilation (NIMV), endotracheal intubation (EI), ICU admission, overall hospital stay >10 days, emergency department stay >4 days. The discriminative performance of MR-pro-ADM and clinical scores was assessed by AUROC analysis.. The distribution for MR-pro-ADM followed an upward trend, increasing with the increase of both PSI (p<0.001) and CURB65 (p<0.001) classes. However, the difference between MRproADM values and score classes was significant only in the case of CURB65 classes 0 and 1 (p = 0.046), 2 (p = 0.013), and 3 (p = 0.011); and with PSI classes 5, 3 (p = 0.044), and 1 (p = 0.020). As to the differences among variables for the six end-points, MR-pro-ADM values in the two groups selected for each considered end-point differed in a statistically significant manner for all endpoints. Both PSI and CURB65 differed significantly for all end-points, except for stay in the ED longer than 4 days and the hospital stay longer than 10 days and endotracheal intubation (only PSI classes differed with statistical significance). ROC analyses evidenced that MR-pro-ADM values gave the greatest AUC for the prediction of death, endotracheal intubation, hospital stay >10 days and DE stay >4 days, compared to the PSI and CURB (though difference not statistically significant). For each endpoint measured, the best thresholds values for Mr-pro-ADM were: 1.6 (specificity 76.5%; sensitivity 77.8%) for death; 2.5 (specificity 88.9%; sensitivity 80.0%) for death at 14 days; 1.5 (specificity 77.0%; sensitivity 87.5%) for NIMV; 2.4 (specificity 88.7%; sensitivity 83.3%) for endotracheal intubation; 0.9 (specificity 53.5%; sensitivity 70.6%) for DE stay greater than 4 days; 1.9 (specificity 82.1%; sensitivity 55.3%) for hospital stay greater than 10 days. The AUC for the combination of MR-pro-ADM and PSI was 81.29% [63.41%-99.17%], but not in a statistically significant manner compared to the AUCs of the single predictors. Conversely, the AUC for the combination of MR-pro-ADM and CURB65 was 87.58% [75.54%-99.62%], which was significantly greater than the AUC of CURB65 (p = 0.047) or PSI (p = 0.017) alone.. The present study confirms that assessment of MR-pro-ADM levels in CAP patients in addition to CURB scores increases the prognostic accuracy of CURB alone and may help rule out discrepancies arising from flawed clinical severity classification. With particular reference to patients scoring in the upper classes of CURB and PSI, MR-pro-ADM values provided additional information towards a better risk stratification of those patients. In particular, our results pointed towards two MR-pro-ADM threshold values that appear to predict with a good degree of accuracy the patient's need for non-invasive mechanical ventilation, endotracheal intubation, or intensive care. This aspect, however, deserves further investigation.

Topics: Adrenomedullin; Aged; Biomarkers; Community-Acquired Infections; Cross Infection; Emergency Service, Hospital; Female; Hospitals; Humans; Intensive Care Units; Male; Middle Aged; Mortality; Peptide Fragments; Pneumonia; Prognosis; Protein Precursors

Topics: Adrenomedullin; Community-Acquired Infections; Female; Humans; Male; Pneumonia; Protein Precursors

The evaluation of the role of novel biomarkers in the management of cardiac and pulmonary conditions has received particular attention in recent years. A further particular perspective is the use of biomarker panels in the evaluation of patients presenting with acute dyspnea.. We prospectively evaluated three biomarkers (MR-proANP, PCT, and MR-proADM) in consecutive patients presenting with acute dyspnea in a medical emergency unit during a 4-week period. Patients received a final diagnosis. Biomarkers were tested for their potential to predict diagnoses and survival. No intervention was done.. Overall, n = 172 patients were included. Of these, 32.6 % had acute heart failure, 16.9 % pneumonia, and 5.8 % died. MR-proANP was the highest in patients with acute heart failure and lung embolism. Dyspnea scores and levels of MR-pro-ANP correlated positively. MR-proANP achieved an AUC of 0.83 for the diagnosis of acute heart failure. Using a cut-off of 120 pmol/l, sensitivity was 91.1 % and specificity 50 %. PPV was 46.8 % and NPV 92.1 %. In patients with MR-proANP >300 pmol/l, PPV raised to 67.3 %. MR-proADM had an AUC of 0.84 for the prediction of death. PPV was 16 % and NPV 98.4 %. The AUC of PCT was 0.74 for the diagnosis of pneumonia. Using a cut-off of 0.25 ng/ml, PCT had a sensitivity of 44.8 % and a specificity of 85.3 %. PPV was 38.2 and NPV 88.4 %. Using a lower cut-off of <0.1 ng/ml, NPV reached 92.9 %.. A panel of three biomarkers (MR-proANP, PCT, and MR-proADM) in patients presenting to the emergency unit with acute dyspnea provides information about the probability of acute heart failure, nonsurvival, and pneumonia. These biomarkers achieve low to moderate positive predictive values (PPV) and high negative predictive values (NPV).

Topics: Acute Disease; Adrenomedullin; Aged; Aged, 80 and over; Area Under Curve; Atrial Natriuretic Factor; Biomarkers; Calcitonin; Dyspnea; Emergency Service, Hospital; Female; Heart Failure; Humans; Male; Middle Aged; Pneumonia; Predictive Value of Tests; Prognosis; Prospective Studies; Protein Precursors; Reproducibility of Results; Risk Factors; ROC Curve; Time Factors

We sought to evaluate the usefulness of biomarkers-procalcitonin (PCT), C-reactive protein (CRP) and proadrenomedullin (pro-ADM)-combined with prognostic scales (PSI, CURB-65 and SCAP score) for identifying adverse outcomes in patients with community-acquired pneumonia (CAP) attending at an Emergency Department (ED).. Prospective observational study in a teaching hospital among patients with CAP. In addition to collecting data for the prognostic scales, samples were taken at the ED for assessing PCT, CRP and pro-ADM levels. We compared the prognostic accuracy of these biomarkers with severity scores to predict pneumonia related complications, using the area under the receiver operating characteristics curves (AUC), which evaluates how well the model discriminate between patients who had a pneumonia related complication or not.. A total of 491 patients with CAP were enrolled, 256 being admitted to the hospital and 235 treated as outpatients. Admitted patients had higher biomarker levels than outpatients (p < 0.001). The SCAP score and pro-ADM level had the best AUCs for predicting pneumonia related complications (0.83 and 0.84, respectively). Considering SCAP score plus pro-ADM level, the AUC increased significantly to 0.88. SCAP score class 0 or 1 with a pro-ADM level <0.5 ng/mL was the best indicator for selecting patients for outpatient care.. A new risk score combining SCAP score with pro-ADM level is useful to classify severity risk in CAP patients and hence supporting decision-making on hospital admission.

Topics: Adrenomedullin; Adult; Aged; Aged, 80 and over; Ambulatory Care; Area Under Curve; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Community-Acquired Infections; Emergency Service, Hospital; Female; Hospitalization; Humans; Male; Middle Aged; Pneumonia; Predictive Value of Tests; Prognosis; Prospective Studies; Protein Precursors; ROC Curve; Severity of Illness Index

Topics: Adrenomedullin; Community-Acquired Infections; Female; Humans; Male; Pneumonia; Protein Precursors

midregional proadrenomedullin (MR-proADM) is a prognostic biomarker in patients with community-acquired pneumonia (CAP). We sought to confirm whether MR-proADM added to Pneumonia Severity Index (PSI) improves the potential prognostic value of PSI alone, and tested to what extent this combination could be useful in predicting poor outcome of patients with CAP in an Emergency Department (ED).. Consecutive patients diagnosed with CAP were enrolled in this prospective, single-centre, observational study. We analyzed the ability of MR-proADM added to PSI to predict poor outcome using receiver operating characteristic (ROC) curves, logistic regression and risk reclassification and comparing it with the ability of PSI alone. The primary outcome was "poor outcome", defined as the incidence of an adverse event (ICU admission, hospital readmission, or mortality at 30 days after CAP diagnosis).. 226 patients were included; 33 patients (14.6%) reached primary outcome. To predict primary outcome the highest area under curve (AUC) was found for PSI (0.74 [0.64-0.85]), which was not significantly higher than for MR-proADM (AUC 0.72 [0.63-0.81, p > 0.05]). The combination of PSI and MR-proADM failed to improve the predictive potential of PSI alone (AUC 0.75 [0.65-0.85, p=0.56]). Ten patients were appropriately reclassified when the combined PSI and MR-proADM model was used as compared with the model of PSI alone. Net reclassification improvement (NRI) index was statistically significant (7.69%, p = 0.03) with an improvement percentage of 3.03% (p = 0.32) for adverse event, and 4.66% (P = 0.02) for no adverse event.. MR-proADM in combination with PSI may be helpful in individual risk stratification for short-term poor outcome of CAP patients, allowing a better reclassification of patients compared with PSI alone.

Topics: Adrenomedullin; Aged; Aged, 80 and over; Biomarkers; Community-Acquired Infections; Female; Humans; Male; Middle Aged; Pneumonia; Prognosis; Prospective Studies; Protein Precursors; Severity of Illness Index

Proadrenomedullin (proADM), a cardiovascular biomarker, has shown high prognostic power for community-acquired pneumonia (CAP) outcomes. Red-blood-cell distribution width (RDW), linked to cardiovascular disorders, has been associated with short-term and medium-term mortality after CAP. Our objective was to assess the accuracy of both biomarkers for CAP long-term mortality (>90 days). Adults hospitalized with CAP underwent blood proADM, RDW, C-reactive protein (CRP) and procalcitonin (PCT) measurements at admission, and were evaluated after 30, 90, and 180 days, and 1, 2, and 3 years, until either death or 5 years of follow-up. A group of 265 patients were recruited, with an average follow-up 1018 ± 539 days. Of these, 217 were followed for 1 year, and 187 for 3 years. Levels of both proADM and RDW were higher in those who died in the short term (p = 0.017 and p < 0.0001, respectively), medium term (p = 0.004 and p < 0.0001, respectively) and long term (p < 0.0001 and p < 0.0001, respectively). RDW showed lower accuracy (30-day AUC, 0.673) than proADM (AUC, 0.816), PSI (AUC, 0.846), and CURB65 (AUC, 0.817) scores for short-term and medium-term mortality prediction. However, accuracy was similar (3-year AUC, 0.692, 0.698, 0.743, and 0.704, respectively) for long-term mortality, and RDW > 14% (RDW > 14) increased the prediction power of both PSI (AUC, 0.743 vs 0.779; p < 0.0001) and CURB65 (AUC, 0.704 vs 0.747; p < 0.0001) scores, as did proADM. RDW > 14 + PSI and RDW > 14 + CURB65 associations had a sensitivity for long-term mortality of 80.8%-90% and 74%-90%, and a specificity of 56.7%-61.5% and 59.3%-64.2%, respectively. Both proADM and RDW > 14 (HR, 4.116) were independent risk factors for long-term mortality and were associated with poorer survival. Our findings agree with the suggested association between cardiovascular disease and long-term CAP mortality. RDW, routinely provided as part of the whole blood count, and especially associated with clinical scores, can provide useful information about long-term CAP outcomes.

Topics: Adrenomedullin; Adult; Aged; Aged, 80 and over; Biomarkers; Community-Acquired Infections; Erythrocyte Indices; Female; Follow-Up Studies; Hospitalization; Humans; Male; Middle Aged; Pneumonia; Prognosis; Protein Precursors; Sensitivity and Specificity; Severity of Illness Index; Spain

To evaluate the prognostic and stratified value of adrenomedullin (AM) in community acquired pneumonia (CAP) patients in the emergency department (ED).. A prospective observational study was conducted. Adult patients who fulfilled the CAP criteria admitted to the ED of Beijing Chaoyang Hospital from August 2011 to November 2012 were enrolled. Serum AM was detected, pneumonia severity index (PSI) score and CURB-65 score were calculated at enrollment. AM level, PSI and CURB-65 scores were compared between patients with severe CAP (SCAP) and non-SCAP (NSCAP), survivors and non-survivors. The prognostic and stratified value of AM, PSI score and CURB-65 score was assessed by logistic regression analysis and receiver operating characteristic (ROC) curve.. 511 CAP patients, including 127 of SCAP, were enrolled. The 28-day mortality of the study was 34.2% (175/511). AM, PSI score and CURB-65 score in SCAP patients were much higher than those in NSCAP patients, and were higher in non-survivors than those in survivors. Using logistic regression analysis, AM and CURB-65 score were independent predictors of SCAP [AM: odds ratio (OR)=1.127, 95% confidence interval (95%CI): 1.096-1.158, P=0.000; CURB-65 score: OR=1.421, 95%CI: 1.072-1.882, P=0.014]. Combination of AM and CURB-65 score [area under ROC curve (AUC): 0.822, 95%CI: 0.781-0.863, P=0.000] improved the accuracy of both AM (AUC: 0.808, 95%CI: 0.766-0.850, P=0.000) and CURB-65 score (AUC: 0.644, 95%CI: 0.590-0.698, P=0.000) in predicting SCAP (sensitivity: 81.1% vs. 75.6%, 70.9%; specificity: 70.1% vs. 72.9%, 52.3%; positive predictive value: 46.6% vs. 48.0%, 33.0%; negative predictive value: 91.7% vs. 90.0%, 84.5%). AM and PSI score were independent predictors of 28-day mortality (AM: OR=1.084, 95%CI: 1.060-1.108, P=0.000; PSI score: OR=1.019, 95%CI: 1.011-1.027, P=0.000). The accuracy of AM (AUC: 0.724, 95%CI: 0.678-0.770, P=0.000) and PSI score (AUC: 0.731, 95%CI: 0.686-0.776, P=0.000) in predicting the risk of 28-day mortality was improved with the combination of AM and PSI score (AUC: 0.803, 95%CI: 0.763-0.843, P=0.000; sensitivity: 78.3% vs. 69.1%, 77.7%; specificity: 70.5% vs. 65.5%, 58.9%; positive predictive value: 56.6% vs. 51.1%, 49.6%; negative predictive value: 85.9% vs. 80.3%, 83.5%).. AM is valuable for prognosis and stratification of CAP patients in ED. Combination of AM and CURB-65 score is useful for the diagnosis of SCAP. Combination of AM and PSI score improves the prognostic performance in predicting 28-day mortality.

Topics: Adrenomedullin; Aged; Community-Acquired Infections; Female; Health Status Indicators; Humans; Male; Middle Aged; Pneumonia; Prognosis; Prospective Studies

A high genomic load of Pneumococcus from blood or cerebrospinal fluid has been associated with increased mortality. We aimed to analyse whether nasopharyngeal colonisation density in HIV-infected patients with community-acquired pneumonia (CAP) is associated with markers of disease severity or poor outcome.. Quantitative lytA real-time PCR was performed on nasopharyngeal swabs in HIV-infected South African adults hospitalised for acute CAP at Chris Hani Baragwanath Hospital, Soweto, South Africa. Pneumonia aetiology was considered pneumococcal if any sputum culture or Gram stain, urinary pneumococcal C-polysaccharide-based antigen, blood culture or whole blood lytA real-time PCR revealed pneumococci.. There was a moderate correlation between the mean nasopharyngeal colonisation densities and increasing CURB65 scores among all-cause patients with pneumonia (Spearman correlation coefficient r=0.15, p=0.06) or with the Pitt bacteraemia score among patients with pneumococcal bacteraemia (p=0.63). In patients with pneumococcal pneumonia, nasopharyngeal pneumococcal colonisation density was higher among non-survivors than survivors (7.7 vs 6.1 log10 copies/mL, respectively, p=0.02) and among those who had pneumococci identified from blood cultures and/or by whole blood lytA real-time PCR than those with non-bacteraemic pneumococcal pneumonia (6.6 vs 5.6 log10 copies/mL, p=0.03). Nasopharyngeal colonisation density correlated positively with the biomarkers procalcitonin (Spearman correlation coefficient r=0.37, p<0.0001), proadrenomedullin (r=0.39, p=0.008) and copeptin (r=0.30, p=0.01).. In addition to its previously reported role as a diagnostic tool for pneumococcal pneumonia, quantitative nasopharyngeal colonisation density also correlates with mortality and prognostic biomarkers. It may also be useful as a severity marker for pneumococcal pneumonia in HIV-infected adults.

Topics: Adolescent; Adrenomedullin; Adult; Bacteremia; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Community-Acquired Infections; HIV Infections; Hospitalization; Humans; Nasopharynx; Pneumonia; Pneumonia, Pneumococcal; Protein Precursors; Real-Time Polymerase Chain Reaction; Severity of Illness Index; South Africa; Streptococcus pneumoniae

The aim of the present study was, first, to evaluate the prognostic value of mid-regional proadrenomedullin (proADM) in emergency department (ED) patients with a diagnosis of community acquired pneumonia (CAP) and, second, to analyze the added value of proADM as a risk stratification tool in comparison with other biomarkers and clinical severity scores. We evaluated proADM, C-reactive protein and procalcitonin, along with the Pneumonia Severity Index (PSI) score in consecutive CAP patients. Ability to predict 30-day mortality was assessed using receiver operating characteristic curve analysis, logistic regression, and reclassification metrics for all patients and for patients with high PSI scores. Primary outcome was death within 30 days after ED admission. One hundred nine patients were included (median age [interquartile range] 71 [27] years). Nine patients died within 30 days. A significant correlation between proADM and PSI was found (ρ = 0.584, P < .001). PSI and proADM levels were significantly predictive of risk of death. In patients with PSI class IV and V (score >90), proADM levels significantly predicted risk of death (OR [95% CI], 4.681 (1.661-20.221), P = .012) whereas PSI score did not (P = .122). ROC(AUC) (area under the receiver operating characteristic curve) was higher for proADM than for PSI score (ROC(AUC) [95% CI], 0.810 [0.654-0.965] and 0.669 [0.445-0.893] respectively). Reclassification analysis revealed that combination of PSI and proADM allows a better risk assessment than PSI alone (P = .001). MR-proADM may be helpful in individual risk stratification of CAP patients with a high PSI score in the ED, allowing to a better identification of patients at risk of death.

Topics: Adrenomedullin; Aged; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Community-Acquired Infections; Emergency Service, Hospital; Female; Humans; Logistic Models; Male; Pneumonia; Predictive Value of Tests; Prognosis; Prospective Studies; Protein Precursors; Risk Assessment; ROC Curve; Severity of Illness Index; Statistics, Nonparametric

In adult population with community acquired pneumonia high levels of pro-adrenomedullin (pro-ADM) have been shown to be predictors of worse prognosis. The role of this biomarker in pediatric patients had not been analyzed to date. The objective of this study is to know the levels of pro-ADM in children with community acquired pneumonia (CAP) and analyze the relation between these levels and the patients' prognosis.. Prospective observational study including patients attended in the emergency service (January to October 2009) admitted to hospital with CAP and no complications at admission. The values for pro-ADM were analyzed in relation to: need for oxygen therapy, duration of oxygen therapy, fever and antibiotic therapy, complications, admission to the intensive care unit, and length of hospital stay. Fifty patients were included. Ten presented complications (7 pleural effusion). The median level of pro-ADM was 1.0065 nmol/L (range 0.3715 to 7.2840 nmol/L). The patients presenting complications had higher levels of pro-ADM (2.3190 vs. 1.1758 nmol/L, p = 0.013). Specifically, the presence of pleural effusion was associated with higher levels of pro-ADM (2.9440 vs. 1.1373 nmol/L, p < 0.001).. In our sample of patients admitted to hospital with CAP, pro-ADM levels are related to the development of complications during hospitalization.

Topics: Adolescent; Adrenomedullin; Anti-Bacterial Agents; Biomarkers; Chi-Square Distribution; Child; Child, Preschool; Community-Acquired Infections; Emergency Service, Hospital; Female; Fever; Humans; Infant; Intensive Care Units; Length of Stay; Male; Oxygen Inhalation Therapy; Patient Admission; Pleural Effusion; Pneumonia; Predictive Value of Tests; Prognosis; Prospective Studies; Protein Precursors; Risk Assessment; Risk Factors; Spain; Up-Regulation

Long-term outcomes in patients surviving community-acquired pneumonia (CAP) are still incompletely understood. This study investigates the association of clinical parameters and blood markers with long-term mortality. We prospectively followed 877 CAP patients from a previous multicentre trial for 18 months follow-up and investigated all-cause mortality following hospital discharge. Overall mortality was 17.3% (95% CI 14.8-19.8%) with a 12.8% (95% CI 10.9-15.0%) mortality incidence rate per year. Initial risk assignment using the Pneumonia Severity Index was accurate during the 18 month follow-up. Multivariable regression models (hazard ratio, 95% CI) designated the following as independent risk factors for long-term mortality: male sex (1.7, 1.2-2.5); chronic obstructive pulmonary disease (1.5, 1.1-2.1); neoplastic disease (2.5, 1.7-3.7); and highest quartile of peak pro-adrenomedullin level (3.3, 1.7-6.2). Initial presentation with temperature>38.7°C (0.4, 0.2-0.6), chills (0.6, 0.4-0.99) and highest quartile of the inflammatory marker C-reactive-protein (0.3, 0.2-0.5) were independent protective factors. A weighted risk score based on these variables showed good discrimination (area under receiver operating characteristic curve 0.78, 95% CI 0.74-0.82). Pronounced clinical and laboratory signs of systemic inflammatory host response upon initial hospital stay were associated with favourable long-term prognosis. Further studies should address whether closer monitoring of high-risk CAP patients after hospital discharge favourably impacts long-term mortality.

Topics: Adrenomedullin; Aged; Aged, 80 and over; C-Reactive Protein; Chills; Community-Acquired Infections; Female; Fever; Humans; Inflammation; Male; Middle Aged; Neoplasms; Pneumonia; Prognosis; Prospective Studies; Protein Precursors; Pulmonary Disease, Chronic Obstructive; Risk; Severity of Illness Index; Sex Factors; Treatment Outcome

Adrenomedullin (AM), a 52-amino acid ringed-structure peptide with C-terminal amidation, was originally isolated from human pheochromocytoma. AM are widely distributed in various tissues and acts as a local vasoactive hormone in various conditions.. In the present study, we investigated the efficacy of AM on the animal model of bleomycin (BLM)-induced lung injury. Mice were subjected to intratracheal administration of BLM and were assigned to receive AM daily by an intraperitoneal injection of 200 ngr/kg.. Myeloperoxidase activity, lung histology, immunohistochemical analyses for cytokines and adhesion molecules expression, inducible nitric oxide synthase (iNOS), nitrotyrosine, and poly (ADP-ribose) polymerase (PARP) were performed one week after fibrosis induction. Lung histology and transforming growth factor beta (TGF-β) were performed 14 and 21 days after treatments. After bleomycin administration, AM-treated mice exhibited a reduced degree of lung damage and inflammation compared with BLM-treated mice, as shown by the reduction of (1) myeloperoxidase activity (MPO), (2) cytokines and adhesion molecules expression, (3) nitric oxide synthase expression, (4) the nitration of tyrosine residues, (5) poly (ADP-ribose) (PAR) formation, a product of the nuclear enzyme poly (ADP-ribose) polymerase (PARP) (6) transforming growth factor beta (TGF-β) (7)and the degree of lung injury.. Our results indicate that AM administration is able to prevent bleomycin induced lung injury through the down regulation of proinflammatory factors.

Topics: Adrenomedullin; Animals; Anti-Inflammatory Agents; Bleomycin; Cell Adhesion Molecules; Cytokines; Disease Models, Animal; Inflammation Mediators; Injections, Intraperitoneal; Lung; Male; Mice; Mice, Inbred ICR; Nitric Oxide Synthase Type II; Peroxidase; Pneumonia; Poly(ADP-ribose) Polymerases; Pulmonary Fibrosis; Severity of Illness Index; Time Factors; Transforming Growth Factor beta; Tyrosine

Several new biomarkers are related to mortality in community-acquired pneumonia (CAP).. Aim of this study was to compare new biomarkers for the prediction of short- and long-term all-cause mortality in CAP.. We enrolled 728 patients (59.0 ± 18.2 yr) with CAP. Midregional proadrenomedullin (MR-proADM), midregional proatrial natriuretic peptide (MR-proANP), proarginin-vasopressin (copeptin), proendothelin-1 (CT-proET-1), procalcitonin (PCT), C-reactive protein, white blood cell (WBC) count, and clinical confusion, respiratory rate, blood pressure, and age over 65 years (CRB-65) score were determined on admission. Patients were followed up for 180 days.. In patients who died of any cause within 28 and 180 days (2.5 and 5.1%, respectively), MR-proADM, MR-proANP, copeptin, CT-proET-1 and PCT as well as CRB-65 were significantly higher compared with survivors. MR-proADM had the best performance for 28 days (HR 3.67) and 180 days (HR 2.84) survival. The C index of MR-proADM for 28-day survival (0.85) was superior to MR-proANP (0.81), copeptin (0.78), CT-proET-1 (0.79), and CRB-65 (0.72) for the prediction of mortality. For prediction of mortality at 180 days, the C index of MR-proADM (0.78) was higher than that for MR-proANP (0.74), copeptin (0.73), CT-proET-1 (0.76), PCT, C-reactive protein, and white blood cells. MR-proADM was independent of CRB-65, and added prognostic information for short- and long-term mortality. MR-proADM was an independent and strong predictor of short- and long-term mortality.. All new biomarkers were good predictors of short- and long-term all-cause mortality, superior to inflammatory markers, and at least comparable to CRB-65 score. MR-proADM showed the best performance. A combination of CRB-65 with MR-proADM might be the best predictor for mortality.

Topics: Adolescent; Adrenomedullin; Adult; Age Distribution; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Biomarkers; Blood Pressure; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Cardiovascular Diseases; Community-Acquired Infections; Comorbidity; Endothelin-1; Female; Germany; Humans; Inflammation; Leukocyte Count; Male; Middle Aged; Pneumonia; Predictive Value of Tests; Protein Precursors; Respiratory Rate; Survival Analysis; Vasopressins; Young Adult

Midregional proadrenomedullin (MR-proADM) is a potential prognostic biomarker in patients with community-acquired pneumonia (CAP). Previous work has been hampered by sample size and illness spectrum limits. We sought to describe the pattern of MR-proADM in a broad CAP cohort, confirm its prognostic role, and compare its performance to procalcitonin, a novel biomarker of infection.. We conducted a multicenter prospective cohort study in 28 community and teaching EDs. Patients with a clinical and radiographic diagnosis of CAP were enrolled. We stratified MR-proADM levels a priori into quartiles and quantified severity of illness using the pneumonia severity index (PSI); and confusion (abbreviated mental test score of or= 7 mmol/L, respiratory rate >or= 30 breaths/min, BP < 90 mm Hg systolic or < 60 mm Hg diastolic, age >or= 65 years (CURB-65). The primary outcome was 30-day mortality.. A total of 1,653 patients formed the study cohort. MR-proADM levels consistently rose with PSI class and 30-day mortality (p < 0.001). MR-proADM had a higher area under the curve for 30-day mortality than procalcitonin (0.76 vs 0.65, respectively; p < 0.001), but adding MR-proADM to the PSI in all subjects minimally improved performance. Among low-risk subjects (PSI classes I to III), mortality was low and did not differ by MR-proADM quartile. However, among high-risk subjects (PSI class IV/V; n = 546), subjects in the highest MR-proADM quartile (n = 232; 42%) had higher 30-day mortality than those in MR-proADM quartiles 1 to 3 (23% vs 9%, respectively; p < 0.0001). Similar results were seen with CURB-65. MR-proADM and procalcitonin levels were generally concordant; only 6% of PSI class IV/V subjects in the highest MR-proADM quartile had very low procalcitonin levels (< 0.1 ng/mL).. In our multicenter CAP cohort, MR-proADM levels correlate with increasing severity of illness and death. High MR-proADM levels offer additional risk stratification in high-risk CAP patients, but otherwise MR-proADM levels do not alter PSI-based risk assessment in most CAP patients.

Topics: Adrenomedullin; Aged; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Community-Acquired Infections; Female; Humans; Male; Pneumonia; Prognosis; Prospective Studies; Protein Precursors; ROC Curve; Severity of Illness Index; Statistics, Nonparametric; United States

Adrenomedullin (AM), an endogenous peptide, has been shown to have a variety of protective effects on the cardiovascular system. However, the effect of AM on acute lung injury remains unknown. Accordingly, we investigated whether AM infusion ameliorates lipopolysaccharide (LPS)-induced acute lung injury in rats. Rats were randomized to receive continuous intravenous infusion of AM (0.1 microg x kg(-1) x min(-1)) or vehicle through a microosmotic pump. The animals were intratracheally injected with either LPS (1 mg/kg) or saline. At 6 and 18 h after intratracheal instillation, we performed histological examination and bronchoalveolar lavage and assessed the lung wet/dry weight ratio as an index of acute lung injury. Then we measured the numbers of total cells and neutrophils and the levels of tumor necrosis factor (TNF)-alpha and cytokine-induced neutrophil chemoattractant (CINC) in bronchoalveolar lavage fluid (BALF). In addition, we evaluated BALF total protein and albumin levels as indexes of lung permeability. LPS instillation caused severe acute lung injury, as indicated by the histological findings and the lung wet/dry weight ratio. However, AM infusion attenuated these LPS-induced abnormalities. AM decreased the numbers of total cells and neutrophils and the levels of TNF-alpha and CINC in BALF. AM also reduced BALF total protein and albumin levels. In addition, AM significantly suppressed apoptosis of alveolar wall cells as indicated by cleaved caspase-3 staining. In conclusion, continuous infusion of AM ameliorated LPS-induced acute lung injury in rats. This beneficial effect of AM on acute lung injury may be mediated by inhibition of inflammation, hyperpermeability, and alveolar wall cell apoptosis.

Topics: Adrenomedullin; Animals; Apoptosis; Bronchoalveolar Lavage Fluid; Bronchodilator Agents; Extravascular Lung Water; Lipopolysaccharides; Male; Pneumonia; Pulmonary Alveoli; Rats; Rats, Sprague-Dawley; Respiratory Distress Syndrome; Trachea