adrenomedullin and Respiratory-Tract-Infections

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

Used appropriately, biomarkers improve the assessment of respiratory tract infections and sepsis. Most prominently, circulating procalcitonin levels increase by a factor of several tens of thousands during sepsis. Using a sensitive assay, procalcitonin safely and markedly reduces antibiotic usage in respiratory tract infections and nonbacterial meningitis. Procalcitonin is the protopye of hormokine mediators. The term "hormokine" encompasses the cytokine-like behaviour of hormones during inflammation and infections. The concept is based on a ubiquitous expression of calcitonin peptides during sepsis. Adrenomedullin, another member of the calcitonin peptide superfamily, was shown to complement and improve the current prognostic assessment in lower respiratory tract infections. Other peptides share some features of hormokines, e.g. natriuretic peptide and copeptin. Hormokines are not only biomarkers of infection but are also pivotal inflammatory mediators. Like all mediators, their role during systemic infections is basically beneficial, possibly to combat invading microbes. However, at increased levels they can become harmful for their host. Multiple mechanisms of action were proposed. In several animal models the modulation and neutralisation of hormokines during infection was shown to improve survival, and thus might open new treatment options for severe infections, especially of the respiratory tract.

Topics: Adrenomedullin; Animals; Anti-Bacterial Agents; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Community-Acquired Infections; Critical Pathways; Diagnosis, Differential; Glycopeptides; Humans; Natriuretic Peptides; Pneumonia, Bacterial; Predictive Value of Tests; Prognosis; Protein Precursors; Respiratory Tract Infections; Sepsis

Kinetics of copeptin and mid regional proadrenomedullin (MR-proADM) during febrile pediatric lower respiratory tract infections (LRTI) are unknown. We aimed to analyze kinetic profiles of copeptin and MR-proADM and the impact of clinical and laboratory factors on those biomarkers.. This is a retrospective post-hoc analysis of a randomized controlled trial, evaluating procalcitonin guidance for antibiotic treatment of LRTI (ProPAED-study). In 175 pediatric patients presenting to the emergency department plasma copeptin and MR-proADM concentrations were determined on day 1, 3, and 5. Their association with clinical characteristics and other inflammatory biomarkers were tested by non-linear mixed effect modelling.. Median copeptin and MR-proADM values were elevated on day 1 and decreased during on day 3 and 5 (-26%; -34%, respectively). The initial concentrations of MR-proADM at inclusion were higher in patients receiving antibiotics intravenously compared to oral administration (difference 0.62 pmol/L, 95%CI 0.44;1.42, p<0.001). Intensive care unit (ICU) admission was associated with a daily increase of MR-proADM (increase/day 1.03 pmol/L, 95%CI 0.43;1.50, p<0.001). Positive blood culture in patients with antibiotic treatment and negative results on nasopharyngeal aspirates, or negative blood culture were associated with a decreasing MR-proADM (decrease/day -0.85 pmol/L, 95%CI -0.45;-1.44), p<0.001).. Elevated MR-proADM and increases thereof were associated with ICU admission suggesting the potential as a prognostic factor for severe pediatric LRTI. MR-proADM might only bear limited value for decision making on stopping antibiotics due to its slow decrease. Copeptin had no added value in our setting.

Topics: Adrenomedullin; Anti-Bacterial Agents; Biomarkers; Child; Humans; Kinetics; Prognosis; Protein Precursors; Respiratory Tract Infections; Retrospective Studies

Concerns about inadequate performance and complexity limit routine use of clinical risk scores in lower respiratory tract infections. Our aim was to study feasibility and effects of adding the biomarker proadrenomedullin (proADM) to the confusion, urea>7 mmol·L(-1), respiratory rate≥30 breaths·min(-1), blood pressure<90 mmHg (systolic) or ≤60 mmHg (diastolic), age≥65 years (CURB-65) score on triage decisions and length of stay. In a randomised controlled proof-of-concept intervention trial, triage and discharge decisions were made for adults with lower respiratory tract infection according to interprofessional assessment using medical and nursing risk scores either without (control group) or with (proADM group) knowledge of proADM values, measured on admission, and on days 3 and 6. An adjusted generalised linear model was calculated to investigate the effect of our intervention. On initial presentation the algorithms were overruled in 123 (39.3%) of the cases. Mean length of stay tended to be shorter in the proADM (n=154, 6.3 days) compared with the control group (n=159, 6.8 days; adjusted regression coefficient -0.19, 95% CI -0.41-0.04; p=0.1). This trend was robust in subgroup analyses and for overall length of stay within 90 days (7.2 versus 7.9 days; adjusted regression coefficient -0.18, 95% CI -0.40-0.05; p=0.13). There were no differences in adverse outcomes or readmission. Logistic obstacles and overruling are major challenges to implement biomarker-enhanced algorithms in clinical settings and need to be addressed to shorten length of stay.

Topics: Adrenomedullin; Adult; Aged; Algorithms; Biomarkers; Blood Pressure; Feasibility Studies; Female; Hospitalization; Humans; Length of Stay; Linear Models; Male; Middle Aged; Protein Precursors; Respiratory Tract Infections; Risk Assessment; Triage

The aim of this study was to determine the prognostic utility of serial measurement of the cardiovascular biomarker midregion proadrenomedullin (MR-proADM) in patients admitted with lower respiratory tract infection. In a previous trial in dyspneic patients (BACH trial) we could show that serial measurement of MR-proADM proves useful for risk assessment and patient monitoring. Models designed to evaluate serial biomarker measurements usually fail to answer two fundamental questions necessary to judge their clinical relevance: whether serial measurements provide additional information on top of the first measurement, and, if yes, at which time point a re-evaluation may be clinically useful.. We apply an adapted time-dependent Cox model to data from the ProHosp trial, a prospective trial, which was observational in regards to application of prognostic biomarkers, where blood draws for biomarker evaluation were collected at day of patient inclusion, days 3, 5 and 7. In this trial, the cardiovascular biomarker MR-proADM was evaluated for its ability to predict survival in comparison to clinical risk scores.. With the adapted time-dependent Cox model, we could demonstrate a significant added value of the follow up measurements on top of that obtained on admission. Despite a high correlation between serial measurements, the gain can be observed as early as 3 days after inclusion. We illustrate the added prognostic value and clinical relevance of re-evaluation via Kaplan-Meier plots.. We could demonstrate that the prognostic biomarker MR-proADM can potentially serve as a outcome monitoring marker in patients admitted with lower respiratory tract infections.

Topics: Adrenomedullin; Aged; Aged, 80 and over; Biomarkers; Cardiovascular Diseases; Female; Follow-Up Studies; Humans; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Protein Precursors; Regression Analysis; Respiratory Tract Infections; Survival Rate; Time Factors

Proadrenomedullin (ProADM) confers additional prognostic information to established clinical risk scores in lower respiratory tract infections (LRTI). We aimed to derive a practical algorithm combining the CURB65 score with ProADM-levels in patients with community-acquired pneumonia (CAP) and non-CAP-LRTI.. We used data of 1359 patients with LRTI enrolled in a multicenter study. We chose two ProADM cut-off values by assessing the association between ProADM levels and the risk of adverse events and mortality. A composite score (CURB65-A) was created combining CURB65 classes with ProADM cut-offs to further risk-stratify patients.. CURB65 and ProADM predicted both adverse events and mortality similarly well in CAP and non-CAP-LRTI. The combined CURB65-A risk score provided better prediction of death and adverse events than the CURB65 score in the entire cohort and in CAP and non-CAP-LRTI patients. Within each CURB65 class, higher ProADM-levels were associated with an increased risk of adverse events and mortality. Overall, risk of adverse events (3.9%) and mortality (0.65%) was low for patients with CURB65 score 0-1 and ProADM ≤0.75 nmol/l (CURB65-A risk class I); intermediate (8.6% and 2.6%, respectively) for patients with CURB65 score of 2 and ProADM ≤1.5 nmol/l or CURB classes 0-1 and ProADM levels between 0.75-1.5 nmol/L (CURB65-A risk class II), and high (21.6% and 9.8%, respectively) for all other patients (CURB65-A risk class III). If outpatient treatment was recommended for CURB65-A risk class I and short hospitalization for CURB65-A risk class II, 17.9% and 40.8% of 1217 hospitalized patients could have received ambulatory treatment or a short hospitalization, respectively.. The new CURB65-A risk score combining CURB65 risk classes with ProADM cut-off values accurately predicts adverse events and mortality in patients with CAP and non-CAP-LRTI. Additional prospective cohort or intervention studies need to validate this score and demonstrate its safety and efficacy for the management of patients with LRTI.. Procalcitonin-guided antibiotic therapy and hospitalisation in patients with lower respiratory tract infections: the prohosp study; isrctn.org Identifier: ISRCTN: ISRCTN95122877.

Topics: Adrenomedullin; Aged; Aged, 80 and over; Algorithms; Cohort Studies; Female; Humans; Male; Middle Aged; Predictive Value of Tests; Prognosis; Protein Precursors; Respiratory Tract Infections

Several studies found mid-regional pro-adrenomedullin (ProADM), the prohormone of the cardiovascular protein adrenomedullin, to be strongly associated with short-term mortality, mostly in the inpatient setting. We evaluated associations of ProADM levels with 10-year mortality in community-dwelling primary care patients with respiratory tract infections.. This is a post-hoc analysis using clinical and biomarker data of 134 primary care patients with respiratory tract infections. ProADM was measured on admission and after 7 days in batch-analysis. 10-year follow-up data was collected by GP, patient and relative tracing through phone interviews. We calculated Cox regression models and area under the receiver operating characteristics curves to assess associations of ProADM with 10-year all-cause mortality.. During the 10-year follow-up 6% of included patients died. Median baseline ProADM blood levels (nmol/l) were significantly higher in non-survivors compared to survivors (0.5, IQR 0.4-1.3; vs. 0.2, IQR 0.1-0.5; p = 0.02) and showed a significant association with 10-year all-cause mortality in an age-adjusted cox regression model (HR: 2.5, 95%-CI: 1.0-6.1, p = 0.04). ProADM levels on day 7 showed similar results.. This posthoc analysis found an association of elevated ProADM blood levels and 10-year all-cause mortality in a primary care cohort with respiratory tract infections. Due to the methodological limitations including incomplete data regarding follow-up information and biomarker measurement, this study warrants validation in future larger studies.. Current Controlled Trials, SRCTN73182671.

Topics: Adrenomedullin; Adult; Aged; Aged, 80 and over; Area Under Curve; Biomarkers; Cause of Death; Female; Humans; Independent Living; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Predictive Value of Tests; Primary Health Care; Prognosis; Proportional Hazards Models; Prospective Studies; Protein Precursors; Randomized Controlled Trials as Topic; Respiratory Tract Infections; Risk Factors; ROC Curve; Switzerland; Time Factors; Up-Regulation

Topics: Adrenomedullin; Biomarkers; Female; Humans; Male; Protein Precursors; Respiratory Tract Infections

Current medical scores have limited efficiency and safety profiles to enable assignment to the most appropriate treatment site in patients with lower respiratory tract infections (LRTIs). We describe our current triage practice and assess the potential of a combination of CURB65 with proadrenomedullin (ProADM) levels for triage decisions.. Consecutive patients with LRTIs presenting to our emergency department were prospectively followed and retrospectively classified according to CURB65 and ProADM levels (CURB65-A). Low medical risk patients were further subgrouped according to biopsychosocial and functional risks. We compared the proportion of patients virtually allocated to triage sites with actual triage decisions and assessed the added impact of ProADM in a subgroup.. Overall, 93% of 146 patients were hospitalised. Among the 138 patients with available CURB65-A, 17.4% had a low medical risk indicating possible treatment in an outpatient or non-acute medical setting; 34.1% had an intermediate medical risk (short-hospitalisation); and 48.6% had a high medical risk (hospitalisation). Fewer patients were in a low CURB65-A class (I) than a low CURB65 class (0,1) (17.4% vs. 46.3%, p <0.001). Mean length of hospitalisation was 9.8 days including 3.6 days after reaching medical stability. In 60.3% of patients, hospitalisation was prolonged after medical stability mainly for medical reasons.. Current rates of hospitalisation are high in patients with LRTI and length of stay frequently extended beyond time of medical stabilization. The lower proportion of patients reclassified as low risk by adding ProADM to the CURB65 score might improve confidence in the triage algorithm.

Topics: Activities of Daily Living; Adrenomedullin; Age Factors; Aged; Ambulatory Care; Biomarkers; Blood Pressure; Confusion; Female; Hospitalization; Humans; Length of Stay; Male; Middle Aged; Patient Transfer; Practice Patterns, Nurses'; Prognosis; Protein Precursors; Respiratory Rate; Respiratory Tract Infections; Severity of Illness Index; Switzerland; Time Factors; Triage; Urea