atrial-natriuretic-factor and Pneumonia

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

During the past few years, biomarkers have emerged as an indispensible tool in the diagnosis of pneumonia. To find an ideal diagnostic biomarker for pneumonia is not an easy task. Not only should it allow an early diagnosis of the condition, but it should also allow differential diagnosis from other noninfectious conditions. Ongoing research is being done in this field so as to put an array of biomarkers at the disposal of doctors to improve the diagnosis of pneumonia when patients present to them with cough or nonspecific symptoms which could easily be misinterpreted as symptoms of other conditions. Procalcitonin and soluble triggering receptor expressed on myeloid cells-1 have emerged as reliable diagnostic markers in pneumonia, and are better when compared to other markers, namely, C-reactive protein, leukocyte count, and proinflammatory cytokines. Many other biomarkers are being studied for their probable use in diagnosing pneumonia but have yet to prove their benefit.

Topics: Atrial Natriuretic Factor; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Endotoxins; Glycopeptides; Humans; Hydrocortisone; Membrane Glycoproteins; Pneumonia; Protein Precursors; Receptors, Immunologic; Triggering Receptor Expressed on Myeloid Cells-1

Atrial natriuretic peptide (ANP), the C-terminal peptide comprising residues 99-126 of the pro-ANP hormone, has been studied for 3 decades for its cardiovascular effects. Recent reports suggest that it plays a significant role in modulation of the immune system. Immune cells, including macrophages, dendritic cells, and T lymphocytes, express receptors for ANP. ANP plays a significant role in shaping the early immune response to environmental antigens and may play a critical role in the interaction between cells of the innate and adaptive immune systems; it also appears to be involved in polarizing the immune response to allergens. Thus, ability to alter the magnitude of natriuretic peptide receptor A (NPRA) signaling could be exploited to develop therapeutics for several allergic diseases, including asthma. This report will review and critically evaluate the role of the ANP pathway in asthma and inflammation.

Topics: Animals; Anti-Asthmatic Agents; Anti-Inflammatory Agents, Non-Steroidal; Asthma; Atrial Natriuretic Factor; Humans; Lung; Models, Biological; Pneumonia; Signal Transduction

The use at bedside of C-reactive protein (CRP), procalcitonin (PCT) or mid-regional pro-atrial natriuretic peptide (ANP) has been advocated to help management of patients with community-acquired pneumonia (CAP) in emergency medicine.. To assess the effectiveness of CRP, PCT, and ANP measures in assisting emergency physicians deciding hospital admission for CAP with low risk of complication.. Multicenter, prospective, observational study with blind evaluation.. Emergency departments of 12 French hospitals.. Five hundred forty-nine consecutive, immunocompetent adult patients with mild CAP.. Centralized and blind measure of baseline CRP, PCT, and ANP; sensitivity, specificity, and positive and negative likelihood ratios for determining hospital admission. Gold standard for admission was defined by experts' advice combined with admission requirement or death at 28 days. Optimal threshold values were determined by receiver operating characteristic (ROC) curves, and area under curve (AUC) of the three biomarkers was compared.. According to gold standard, 310 (56%) patients required admission and 239 (44%) needed to be discharged. PCT and ANP levels increased with Pneumonia Severity Index risk categories. ANP (AUC 0.76 [95% CI 0.72-0.80]) more accurately predicted admission requirement than did PCT (AUC 0.65 [95% CI 0.61-0.70]) or CRP (AUC 0.59 [95% CI 0.54-0.64]) (both p values <0.01). We determined that 135 pmol/L was a threshold for ANP level to discriminate admission requirement (positive likelihood ratio 7.45 [95% CI 4.22-8.16]).. In a selected population of CAP with low risk of complication, a single ANP measurement was more accurate than CRP and PCT to predict appropriate admission. These results should be confirmed by additional studies.

Topics: Adult; Atrial Natriuretic Factor; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Community-Acquired Infections; Emergency Service, Hospital; Female; Humans; Male; Middle Aged; Patient Admission; Pneumonia; Prognosis; Prospective Studies; Protein Precursors; Radiography; Sensitivity and Specificity; Severity of Illness Index

In patients with pulmonary disease, it is often challenging to distinguish exacerbated pulmonary disease from congestive heart failure (CHF). The impact of B-type natriuretic peptide (BNP) measurements on the management of patients with pulmonary disease and acute dyspnea remains to be defined.. This study evaluated the subgroup of 226 patients with a history of pulmonary disease included in the BASEL Study. Patients were randomly assigned to a diagnostic strategy with (n = 119, BNP group) or without (n = 107, clinical group) the use of BNP levels provided by a rapid bedside assay. Time to discharge and total cost of treatment were recorded as the primary end points.. Baseline characteristics were similar in patients assigned to the BNP and control groups. Comorbidity was extensive, including coronary artery disease and hypertension in half of patients. The primary discharge diagnosis was CHF and exacerbated obstructive pulmonary disease in 39% and 33%, respectively. The use of BNP levels significantly reduced the need for hospital admission (81% vs 91%, P = .034). Median time to discharge was 9.0 days in the BNP group as compared with 12.0 days (P = .001) in the clinical group. Median total cost of treatment was $4841 in the BNP group as compared with $5671 in the clinical group (P = .008). Inhospital mortality was 8% in both groups.. CHF is a major cause of acute dyspnea in patients with a history of pulmonary disease. Used in conjunction with other clinical information, rapid measurement of BNP reduced time to discharge and total treatment cost of these patients.

Topics: Acute Disease; Aged; Asthma; Atrial Natriuretic Factor; Biomarkers; Confidence Intervals; Coronary Artery Disease; Dyspnea; Emergencies; Female; Heart Failure; Humans; Hypertension; Length of Stay; Male; Pneumonia; Pulmonary Disease, Chronic Obstructive; Pulmonary Embolism

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

Microtubule (MT) dynamics is involved in a variety of cell functions, including control of the endothelial cell (EC) barrier. Release of Rho-specific nucleotide exchange factor GEF-H1 from microtubules activates the Rho pathway of EC permeability. In turn, pathologic vascular leak can be prevented by treatment with atrial natriuretic peptide (ANP). This study investigated a novel mechanism of vascular barrier protection by ANP via modulation of GEF-H1 function. In pulmonary ECs, ANP suppressed thrombin-induced disassembly of peripheral MT and attenuated Rho signaling and cell retraction. ANP effects were mediated by the Rac1 GTPase effector PAK1. Activation of Rac1-PAK1 promoted PAK1 interaction with the Rho activator GEF-H1, inducing phosphorylation of total and MT-bound GEF-H1 and leading to attenuation of Rho-dependent actin remodeling. In vivo, ANP attenuated lung injury caused by excessive mechanical ventilation and TRAP peptide (TRAP/HTV), which was further exacerbated in ANP(-/-) mice. The protective effects of ANP against TRAP/HTV-induced lung injury were linked to the increased pool of stabilized MT and inactivation of Rho signaling via ANP-induced, PAK1-dependent inhibitory phosphorylation of GEF-H1. This study demonstrates a novel protective mechanism of ANP against pathologic hyperpermeability and suggests a novel pharmacological intervention for the prevention of increased vascular leak via PAK1-dependent modulation of GEF-H1 activity.

Topics: Actins; Acute Lung Injury; Animals; Atrial Natriuretic Factor; Capillary Permeability; Cytoprotection; Disease Models, Animal; Endothelial Cells; Genes, Dominant; HEK293 Cells; Humans; Lung; Mice; Mice, Inbred C57BL; Microtubules; Models, Biological; Myosin Light Chains; p21-Activated Kinases; Phosphorylation; Pneumonia; Protein Binding; rac1 GTP-Binding Protein; Rho Guanine Nucleotide Exchange Factors; Thrombin

Dysnatremia is a frequent finding in patients with community acquired pneumonia (CAP) and a predictor of mortality. We studied the relation between dysnatremia, comorbidities and CT-pro-AVP and MR-proANP.. We enrolled 2138 patients (60 ± 18 years, 55% male) with CAP from the CAPNETZ database. Pro-atrial natriuretic peptide (proANP), pro-vasopressin (proAVP), serum sodium and CRB-65 score were determined on admission. Patients were followed up for 28 days. Sodium concentration on admission was examined as a function of mortality at 28 days. Hyponatremia (HypoN) was defined as admission serum sodium <136 mmol/L, hypernatremia (HyperN) as admission serum sodium >145 mmol/L.. HypoN was diagnosed in 680 (31.8%) patients, HyperN in 29 (1.4%) patients. Comorbidities were associated with sodium levels, and CT-pro-AVP and MR-proANP were inversely related to sodium levels. Patients with HypoN were older, had a higher CRB-65 score and higher values of CT-proAVP and MR-proANP (all p < 0.05). When examined as a function of sodium values, a U-shaped association was found between sodium levels and 28 day mortality. In multivariate Cox proportional hazards analysis, HypoN and HyperN were independent predictors of 28 day mortality. Sodium levels added to the predictive potential of proAVP and proANP.. HypoN is common at admission among CAP patients and is independently associated with mortality. HyperN is rare at admission among CAP patients but is also independently associated with mortality. The combination of sodium and CT-pro-AVP and MR-proANP levels achieved the highest prediction of mortality.

Topics: Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Biomarkers; Community-Acquired Infections; Comorbidity; Databases, Factual; Female; Germany; Humans; Hypernatremia; Hyponatremia; Male; Middle Aged; Pneumonia; Predictive Value of Tests; Prognosis; Sodium; Vasopressins

A positive association between air pollution exposure and increased human risk of chronic heart disease progression is well established. In the current study, we test two hypotheses: (1) the cardiac compensatory changes in response to air pollution are dependent on its composition and (2) specific cardiac adaptations are regulated by atrial natriuretic peptide (ANP). We address these hypotheses by initially examining the exposure effects of ozone (O(3)) and/or particulate matter (PM) on cardiac function in C57Bl/6J (B6) mice. Subsequently, the results are compared with cardiac functional changes to the same exposures in Nppa (the precursor gene for ANP) knockout (KO) mice. Separate groups of mice underwent 3 consecutive days of the same exposure sequence for 3h each consisting of the following: (1) 6h of filtered air (FAFA), (2) O(3) then FA (O(3)FA), (3) FA then carbon black (FACB), or (4) O(3) then CB. Cardiac function was assessed using a conductance catheter to generate cardiac pressure-volume loops 8-10h following each exposure sequence. As compared with FAFA, each sequence led to a substantial drop (as much as 33%) in stroke volume and cardiac output. However, these losses of cardiac function occurred by different compensatory mechanisms dependent on the pollutant composition. For example, O(3)FA exposure led to reductions in both end-systolic and end-diastolic left ventricular (LV) volumes, whereas FACB exposure led an increase in end-diastolic LV volume. These same cardiac compensatory changes were largely abolished in Nppa KO mice following O(3)FA or FACB exposure. These results suggest that cardiac functional changes in response to air pollution exposure are strongly dependent on the pollutant constituents, especially related to O(3) and/or PM. Furthermore, ANP regulation appears to be crucial to these cardiac compensatory mechanisms induced by air pollution.

Topics: Air Pollutants; Animals; Atrial Natriuretic Factor; Body Weight; Bronchoalveolar Lavage Fluid; Gene Expression; Gene-Environment Interaction; Heart Function Tests; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Myocardium; Natriuretic Peptide, C-Type; Organ Size; Ozone; Particulate Matter; Pneumonia; Protein Precursors; Ventricular Function, Left; Ventricular Function, Right

Previous research found precursor levels of the atrial natriuretic peptide (MR-proANP) to be promising prognostic markers. This study aims to validate these findings and describe patterns of MR-proANP in a large cohort of patients with lower respiratory tract infections.. We conducted a multicenter prospective cohort study, and measured MR-proANP in patients with lower respiratory tract infections on admission, and days 3, 5 and 7. The prognostic value of MR-proANP for predicting 30-day and 180-day mortalities was evaluated. We stratified MR-proANP levels a priori into quartiles, and compared it with severity of illness using the pneumonia severity index.. A total of 1359 patients, including 925 with community-acquired pneumonia, were enrolled. The mortality risk at days 30 and 180 significantly increased with increasing MR-proANP quartiles (<84 pmol/L, 84-158 pmol/L, >158-311 pmol/L, and >311 pmol/L). This was true for low-risk, as well as high-risk subjects (pneumonia severity index classes I-III and IV-V). In Kaplan-Meier survival curves, MR-proANP quartiles significantly separated survivors from non-survivors in the overall cohort (p log-rank<0.001), and in low-risk (p log-rank<0.03) and high-risk (p log-rank=0.007) pneumonia severity index patients at day 30. In multivariate logistic regression analysis, MR-proANP was an independent risk factor for 30-day and 180-day mortalities (odds ratio per unit increase of log transformation MR-proANP level: 5.58, 95%CI 1.97-15.82 and 5.08, 95%CI 2.44-10.60).. This study confirms the high prognostic performance of MR-proANP for short- and long-term mortality, particularly its high negative predictive value, in lower respiratory tract infections and community-acquired pneumonia, thereby complementing clinical risk assessment with the pneumonia severity index.

Topics: Aged; Aged, 80 and over; Atrial Natriuretic Factor; Community-Acquired Infections; Female; Follow-Up Studies; Humans; Male; Pneumonia; Predictive Value of Tests; Prospective Studies; Randomized Controlled Trials as Topic; Respiratory Tract Infections; Time Factors; Treatment Outcome

Early and accurate risk stratification for patients with community-acquired pneumonia (CAP) is an unmet clinical need.. We enrolled 341 unselected patients presenting to the ED with CAP in whom blinded measurements of N-terminal pro-B-type natriuretic peptide (NT-proBNP), midregional pro-atrial natriuretic peptide (MR-proANP), and B-type natriuretic peptide (BNP) were performed. The potential of these natriuretic peptides to predict short- (30-day) and long-term mortality was compared with the pneumonia severity index (PSI) and CURB-65 (confusion, urea plasma level, respiratory rate, BP, age over 65 years). The median follow-up was 942 days.. NT-proBNP, MR-proANP, and BNP levels at presentation were higher in short-term (median 4,882 pg/mL vs 1,133 pg/mL; 426 pmol/L vs 178 pmol/L; 436 pg/mL vs 155 pg/mL, all P < .001) and long-term nonsurvivors (3,515 pg/mL vs 548 pg/mL; 283 pmol/L vs 136 pmol/L; 318 pg/mL vs 103 pg/mL, all P < .001) as compared with survivors. Receiver operating characteristics analysis to quantify the prognostic accuracy showed comparable areas under the curve for the three natriuretic peptides to PSI for short-term (PSI 0.76, 95% CI, 0.71-0.81; NT-proBNP 0.73, 95% CI, 0.67-0.77; MR-proANP 0.72, 95% CI, 0.67-0.77; BNP 0.68, 95% CI, 0.63-0.73) and long-term (PSI 0.72, 95% CI, 0.66-0.77; NT-proBNP 0.75, 95% CI, 0.70-0.80; MR-proANP 0.73, 95% CI, 0.67-0.77, BNP 0.70, 95% CI, 0.65-0.75) mortality. In multivariable Cox-regression analysis, NT-proBNP remained an independent mortality predictor (hazard ratio 1.004, 95% CI, 1.00-1.01, P = .02 for short-term; hazard ratio 1.004, 95% CI, 1.00-1.01, P = .001 for long-term, increase of 300 pg/mL). A categorical approach combining PSI point values and NT-pro-BNP levels adequately identified patients at low, medium, and high short- and long-term mortality risk.. Natriuretic peptides are simple and powerful predictors of short- and long-term mortality for patients with CAP. Their prognostic accuracy is comparable to PSI.

Topics: Aged; Aged, 80 and over; Atrial Natriuretic Factor; Biomarkers; Community-Acquired Infections; Female; Follow-Up Studies; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pneumonia; Prognosis; Regression Analysis; Severity of Illness Index

Topics: Atrial Natriuretic Factor; Community-Acquired Infections; Female; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Pneumonia

A recent approach for the management of chronic obstructive pulmonary disease (COPD) is the measurement of systemic biomarkers. The aim of this study was to evaluate the usefulness of mid regional pro-atrial natriuretic peptide (MR-proANP) to predict short and long term prognosis.. We included 318 COPD patients: 46 in a stable phase, 217 undergoing an exacerbation and 55 with pneumonia. Serum samples were collected at admission. For 20 exacerbated patients, we also collected a second sample one month later. MR-proANP was measured by an inmunofluorescent assay.. Statistically higher levels of MR-proANP were found in patients with pneumonia when comparing to patients in the stable state (p=0.031). For those patients with paired samples, MR-proANP decreased statistically one month later (p=0.027). MR-proANP showed significant lower levels in exacerbations with isolation of pathogenic bacteria (p=0.011). MR-proANP levels were higher in patients that died within one month, decreasing as long as the moment of death occurred later on (p=0.163).. The identification of exacerbation etiology by means of MR-proANP is not clinically reliable. Levels of MR-proANP vary depending on the clinical status, being higher during pneumonia in comparison to the stable state. MR-proANP levels were higher in patients that died within one month after the exacerbation episode.

Topics: Aged; Atrial Natriuretic Factor; Female; Follow-Up Studies; Humans; Male; Pneumonia; Prognosis; Pulmonary Disease, Chronic Obstructive

Community-acquired pneumonia (CAP) is the most important clinical infection with a high long-term mortality rate. The aim of this study was to evaluate the value of biomarkers for the prediction of short-term and long-term mortality in CAP.. A total of 1740 patients of mean + or - SD age 60 + or - 18 years (45% female) with proven CAP were enrolled in the study. Mid-regional pro-atrial natriuretic peptide (MR-proANP), C-terminal pro-atrial vasopressin (CT-proAVP), procalcitonin, C-reactive protein, leucocyte count (WBC) and CRB-65 score were determined on admission. Patients were followed up for 180 days.. MR-proANP and CT-proAVP levels increased with increasing severity of CAP, classified according to CRB-65 score. In patients who died within 28 and 180 days, median MR-proANP (313.9 vs 80.0 and 277.8 vs 76.0 pmol/l, each p<0.0001) and CT-proAVP (42.6 vs 11.2 and 33.2 vs 10.7 pmol/l, each p<0.0001) levels were significantly higher than the levels in survivors. In receiver operating characteristics analysis for survival at 28 and 180 days, the areas under the curves (AUCs) for CT-proAVP (0.84, 95% CI 0.82 to 0.86 and 0.78, 95% CI 0.76 to 0.80) and MR-proANP (0.81, 95% CI 0.79 to 0.83 and 0.81, 95% CI 0.79 to 0.83) were superior to the AUC of CRB-65 (0.74, 95% CI 0.71 to 0.76 and 0.71, 95% CI 0.69 to 0.74, p<0.05), procalcitonin, C-reactive protein and WBC. In multivariable Cox proportional hazards regression analyses adjusted for comorbidity and pneumonia severity, MR-proANP and CT-proAVP were independent and the strongest predictors of short-term and long-term mortality.. MR-proANP and CT-proAVP are powerful tools for the prediction of short-term and long-term risk stratification of patients with CAP.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Biomarkers; Community-Acquired Infections; Epidemiologic Methods; Female; Germany; Humans; Male; Middle Aged; Pneumonia; Prognosis; Vasopressins; Young Adult

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

Atrial natriuretic peptide (ANP) and its receptor, NPRA, have been extensively studied in terms of cardiovascular effects. We have found that the ANP-NPRA signaling pathway is also involved in airway allergic inflammation and asthma. ANP, a C-terminal peptide (amino acid 99-126) of pro-atrial natriuretic factor (proANF) and a recombinant peptide, NP73-102 (amino acid 73-102 of proANF) have been reported to induce bronchoprotective effects in a mouse model of allergic asthma. In this report, we evaluated the effects of vessel dilator (VD), another N-terminal natriuretic peptide covering amino acids 31-67 of proANF, on acute lung inflammation in a mouse model of allergic asthma.. A549 cells were transfected with pVD or the pVAX1 control plasmid and cells were collected 24 hrs after transfection to analyze the effect of VD on inactivation of the extracellular-signal regulated receptor kinase (ERK1/2) through western blot. Luciferase assay, western blot and RT-PCR were also performed to analyze the effect of VD on NPRA expression. For determination of VD's attenuation of lung inflammation, BALB/c mice were sensitized and challenged with ovalbumin and then treated intranasally with chitosan nanoparticles containing pVD. Parameters of airway inflammation, such as airway hyperreactivity, proinflammatory cytokine levels, eosinophil recruitment and lung histopathology were compared with control mice receiving nanoparticles containing pVAX1 control plasmid.. pVD nanoparticles inactivated ERK1/2 and downregulated NPRA expression in vitro, and intranasal treatment with pVD nanoparticles protected mice from airway inflammation.. VD's modulation of airway inflammation may result from its inactivation of ERK1/2 and downregulation of NPRA expression. Chitosan nanoparticles containing pVD may be therapeutically effective in preventing allergic airway inflammation.

Topics: Administration, Intranasal; Animals; Asthma; Atrial Natriuretic Factor; Bronchoconstrictor Agents; Cell Line; Chitosan; Cytokines; Down-Regulation; Extracellular Signal-Regulated MAP Kinases; Humans; Luciferases; Methacholine Chloride; Mice; Mice, Inbred BALB C; Nanoparticles; Ovalbumin; Peptide Fragments; Pneumonia; Receptors, Atrial Natriuretic Factor; Respiratory Hypersensitivity; Reverse Transcriptase Polymerase Chain Reaction; Th2 Cells; Transfection

To evaluate the usefulness of midregional pro-atrial natriuretic peptide (MR-proANP) measurement in the stratification of severity in community-acquired pneumonia.. The population studied was three hundred patients admitted to Emergency Department of a tertiary university hospital presenting clinical signs of lower respiratory tract infection, a new infiltrate on the chest radiograph and a confirmed pneumonia by clinical evolution. Patients were stratified by the Pneumonia Severity Index (PSI), by CURB-65 score and by the development of complications. Serum samples were obtained at the moment of admission and prior to antibiotic therapy, and stored until analysis. MR-proANP was measured by B.R.A.H.M.S MR-proANP KRYPTOR.. Serum levels of MR-proANP increased with the severity of pneumonia, according to PSI score and CURB-65 score. Median MR-proANP levels were significantly higher (p<0.0001) in patients with high PSI risk class (IV-V) than in those with low PSI risk class (I-III). MR-proANP levels were also significantly higher (p=0.029) in those patients that developed complications or died. There was no association between MR-proANP and etiology of pneumonia and the radiographic extent.. We can conclude that MR-proANP measurement was helpful for individual risk assessment in patients with pneumonia admitted to the emergency department.

Topics: Aged; Atrial Natriuretic Factor; Community-Acquired Infections; Female; Humans; Lung; Male; Pneumonia; Prognosis; Radiography; Severity of Illness Index

To analyse the mid region of plasma N-terminal pro-atrial natriuretic peptide (MR-proANP) levels in patients with lower respiratory tract infections to evaluate its prognostic use for the severity of disease and outcome.. Prospective observational study. Setting. Emergency department of a university hospital.. A total of 545 consecutive patients with lower respiratory tract infections and 50 healthy controls. Interventions. MR-proANP was measured in serum from all patients using a new sandwich immunoassay.. MR-proANP levels (median [IQR], in pmol L(-1)) were significantly higher in patients with lower respiratory tract infections when compared with controls (138.0 [74.1-279.0] vs. 72.7 [62.5-89.5], P < 0.001), with highest levels in patients with community-acquired pneumonia (CAP). MR-proANP, but not C-reactive protein (CRP) levels, gradually increased with increasing severity of CAP, classified according to the pneumonia severity index (PSI) score (P < 0.001). On admission, MR-proANP levels were significantly higher in nonsurvivors when compared with survivors (293.0 [154.0-633.0] vs. 129.0 [71.4-255.0], P < 0.001). In a receiver operating characteristic (ROC) analysis for the prediction of survival of patients with CAP the area under the ROC curve (AUC) for MR-proANP was 0.69, similar when compared with the PSI (AUC 0.74, P = 0.31), and better when compared with other biomarkers, i.e. procalcitonin (AUC 0.57, P = 0.08), CRP (AUC 0.52, P = 0.02), and leucocyte count (AUC 0.56, P = 0.07).. MR-proANP levels are increased in lower respiratory tract infections, especially in CAP. Together with other clinical, radiographic and laboratory findings, MR-proANP levels might be helpful for the risk stratification in CAP.

Topics: Acute Disease; Aged; Atrial Natriuretic Factor; Biomarkers; Bronchitis; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Chronic Disease; Community-Acquired Infections; Female; Humans; Leukocyte Count; Male; Pneumonia; Prognosis; Prospective Studies; Protein Precursors; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Infections; ROC Curve; Severity of Illness Index

Atrial natriuretic peptide (ANP) has known natriuretic, diuretic, and vasodilatatory effects. It is synthesized and stored in the atrial cells. Stretching of the atrial muscle fibers during an increase in venous return sets a response of ANP release into the blood stream. High levels of ANP were measured in a number of lung diseases. Pneumonia in children is frequently accompanied by the hyponatremia of the syndrome of inappropriate antidiuretic hormone (ADH) secretion (SIADH). High levels of ANP were found among patients with SIADH. Our objective was to determine if ANP plasma levels are altered in children with pneumonia, and to evaluate a possible correlation between severity of pneumonia and ANP levels. Blood samples from 28 children diagnosed with pneumonia were collected. Plasma ANP levels were determined by radioimmunoassay and compared to levels in 25 children without pneumonia. ANP levels in the pneumonia group (mean +/- SD, 16.02 +/- 11.69 pg/ml) increased significantly (P < 0.01) compared to levels in the control group (mean +/- SD, 7.44 +/- 9.29 pg/ml). Children in the pneumonia group also exhibited low levels of plasma sodium (mean +/- SD, 134.88 +/- 2.5 mmol/l) compared to levels in children without pneumonia (mean +/- SD, 139.77 +/- 4.15 mmol/l) (P < 0.01). There was no correlation between ANP plasma levels and severity of pneumonia. In conclusion, ANP levels in children with pneumonia, as in other lung diseases, are increased. High ANP levels may play a role in maintaining water and electrolyte equilibrium during a state of inappropriate ADH secretion accompanying pneumonia.

Topics: Atrial Natriuretic Factor; Child; Child, Preschool; Humans; Inappropriate ADH Syndrome; Pneumonia; Radioimmunoassay

To clarify which endocrine modifications can be observed in acute hypoxaemic respiratory failure, 15 severely ill male patients [PAT; median age: 61 (range: 48 years); median height: 173 (range: 12) cm; median mass: 73 (range 31) kg] were investigated immediately upon admission to an intensive care unit (ICU) for this clinical disorder. Before starting treatment, the blood gases were measured and a number of selected hormones with special relevance for an ICU setting were determined. These are known to be modified by acute hypoxaemia in healthy subjects and to possess glucoregulatory properties, or an influence upon cardiocirculation or the vascular volume regulation: insulin, cortisol, adrenaline, noradrenaline, atrial natriuretic peptide, renin, aldosterone, angiotensin converting enzyme, and endothelin-I (ET). To elucidate whether potential endocrine changes resulted from acute hypoxaemia alone, the underlying disease, or unspecific influences connected with the ICU setting, all measurements were compared to those of a completely healthy reference group (REF) with comparable acute experimental hypoxaemia. The latter state was achieved by having the REF breathe a gas mixture with the oxygen content reduced to 14% (H). In the REF, neither the medians nor the distribution of endocrinologic measurements were modified significantly by acute hypoxaemia. In the PAT, the medians were increased considerably, yet with a slight diminution of ET. The distribution of individual values was considerably broader than in the REF with H. In conclusion, considerable increases in the means of the above hormones, with the exception of ET, can be registered in severely ill patients admitted to ICUs with acute hypoxaemic failure. However, such modifications cannot be considered attributable exclusively to acute arterial hypoxaemia. The underlying clinical disorders, such as septicaemia or an unspecific endocrine epiphenomenon, including severe and not only hypoxaemic stress, seem to be predominant.

Topics: Acute Disease; Adult; Aged; Aldosterone; Atrial Natriuretic Factor; C-Peptide; Critical Care; Endocrine Glands; Endothelins; Epinephrine; Humans; Hydrocortisone; Hypoxia; Insulin; Male; Middle Aged; Norepinephrine; Peptidyl-Dipeptidase A; Pneumonia; Renin; Respiratory Insufficiency

Plasma atrial natriuretic peptide (ANP) Levels were measured by radioimmunoassay both in 38 infants with pneumonia and 20 infants with pneumonia associated with congestive heart failure (CHF). 10 of the 20 infants with CHF were examined with echocardiography during CHF and recovery period. The plasma ANP Levels in the pneumonia group was 424.3 +/- 214.4 pg/ml (mean +/- SD). Which was significantly higher than that of the control group (P less than 0.01). The plasma ANP levels in pneumonia with CHF group was 684.4 +/- 366.9 pg/ml, which was significantly higher than that in the group of pneumonia without CHF (P less than 0.01). Positive linear correlation was found between the mean pulmonary artery pressure and plasma ANP content (r = 0.717, P less than 0.05). The results of this study suggest that plasma ANP concentration may give useful information on the indication of using vasodilators in infant with pneumonia. It may also be taken as a practical diagnostic indicator in pneumonia associated with CHF.

Topics: Atrial Natriuretic Factor; Child, Preschool; Echocardiography, Doppler; Female; Heart Failure; Humans; Infant; Male; Middle Aged; Pneumonia; Radioimmunoassay