adrenomedullin and Pulmonary-Disease--Chronic-Obstructive

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

Plasma proadrenomedullin (ProADM) is a blood biomarker that may aid in multidimensional risk assessment of patients with chronic obstructive pulmonary disease (COPD). Co-secreted 1:1 with adrenomedullin (ADM), ProADM is a less biologically active, more chemically stable surrogate for this pluripotent regulatory peptide, which due to biological and ex vivo physical characteristics is difficult to reliably directly quantify. Upregulated by hypoxia, inflammatory cytokines, bacterial products, and shear stress and expressed widely in pulmonary cells and ubiquitously throughout the body, ADM exerts or mediates vasodilatory, natriuretic, diuretic, antioxidative, anti-inflammatory, antimicrobial, and metabolic effects. Observational data from four separate studies totaling 1366 patients suggest that as a single factor, ProADM is a significant independent, and accurate, long-term all-cause mortality predictor in COPD. This body of work also suggests that combined with different groups of demographic/clinical variables, ProADM provides significant incremental long-term mortality prediction power relative to the groups of variables alone. Additionally, the literature contains indications that ProADM may be a global cardiopulmonary stress marker, potentially supplying prognostic information when cardiopulmonary exercise testing results such as 6-min walk distance are unavailable due to time or other resource constraints or to a patient's advanced disease. Prospective, randomized, controlled interventional studies are needed to demonstrate whether ProADM use in risk-based guidance of site-of-care, monitoring, and treatment decisions improves clinical, quality-of-life, or pharmacoeconomic outcomes in patients with COPD.

Topics: Adrenomedullin; Animals; Biomarkers; Humans; Prognosis; Protein Precursors; Pulmonary Disease, Chronic Obstructive; Risk Assessment

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

Adrenomedullin (AM) is a pluripotent peptide hormone with contradictory effects in human health and disease. In chronic inflammatory lung diseases, such as asthma and COPD, AM has been shown to inhibit inflammation and cell proliferation. In the present study, we aimed to investigate the effect of AM on pro-angiogenic and pro-inflammatory cytokines in asthma and COPD.. Serum levels of pro-AM were measured in patients with asthma, COPD and matched controls. The effect of AM on intracellular signaling proteins and cytokine secretion was assessed in primary cultures of epithelial cells (EC) and airway smooth muscle cells (ASMC) established from endo-bronchial biopsies of patients with asthma, COPD and controls.. Serum pro-AM was higher in patients with asthma and COPD, compared to controls. AM stimulated cAMP in ASMC but not in EC. In EC, AM decreased Erk1/2 MAPK expression and activation but in ASMC, AM activated Erk1/2. This effect was similar in asthma, COPD and controls. AM stimulated the secretion of pro-angiogenic CXCL1 by EC of controls and CXCL5 by EC of asthma patients. AM did not affect the secretion of IL-6 or IL-8 by EC but stimulated the secretion of IL-6 by ASMC. In EC, AM inhibited the stimulatory effect of TGF-β and IL-4 on the secretion of IL-6 and IL-8 but had an additive stimulatory effect with TGF-β in ASMC.. These data suggest that AM mediates the secretion of pro-angiogenic and pro-inflammatory cytokines in a cell-type and/or a disease-specific way, explaining its association with clinical outcomes in COPD.

Topics: Adrenomedullin; Aged; Asthma; Cells, Cultured; Cytokines; Epithelial Cells; Female; Humans; Inflammation; Male; Middle Aged; Myocytes, Smooth Muscle; Neovascularization, Physiologic; Pulmonary Disease, Chronic Obstructive

To assess the value added to the National Early Warning Score (NEWS) by mid-regional pro-adrenomedullin (MR-proADM) blood level in predicting deterioration in mild to moderately ill people.. Prospective observational study.. The Medical Admissions Suite of the Royal Victoria Infirmary, Newcastle.. 300 adults with NEWS between 2 and 5 on admission. Exclusion criteria included receiving palliative care, or admitted for social reasons or self-harming. Patients were enrolled between September and December 2015, and followed up for 30 days after discharge.. The primary outcome measure was the proportion of patients who, within 72 hours, had an. NEWS and MR-proADM together predicted. MR-proADM is potentially a clinically useful biomarker for deterioration in patients admitted to hospital with a mild to moderately severe acute illness, that is, with NEWS between 2 and 5. As a growing number of National Health Service hospitals are routinely recording the NEWS on their clinical information systems, further research should assess the practicality and use of developing a decision aid based on admission NEWS, MR-proADM level, and possibly other clinical data and other biomarkers that could further improve prognostic accuracy.

Topics: Adrenomedullin; Adult; Aged; Aged, 80 and over; Biomarkers; Female; Heart Failure; Hospitalization; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Predictive Value of Tests; Prognosis; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Severity of Illness Index

Elevated levels of midrange proadrenomedullin (MR-proADM) are associated with worse outcome in different diseases, including COPD. The association of stable-state MR-proADM with severe acute exacerbations of COPD (AECOPDs) requiring hospitalization, or with community-acquired pneumonia (CAP) in patients with COPD, has not been studied yet. The aim of this study was to evaluate the association of stable-state MR-proADM with severe AECOPD and CAP in patients with COPD.. This study pooled data of 1,285 patients from the Cohort of Mortality and Inflammation in COPD (COMIC) and PRedicting Outcome using systemic Markers In Severe Exacerbations of Chronic Obstructive Pulmonary Disease (PROMISE-COPD) cohort studies. Time until first severe AECOPD was compared between patients with high (≥ 0.87 nmol/L) or low (< 0.87 nmol/L) levels of plasma MR-proADM in stable state as previously defined. For time until first CAP, only COMIC data (n = 795) were available.. Patients with COPD with high-level stable-state MR-proADM have a significantly higher risk for severe AECOPD compared with those with low-level MR-proADM with a corrected hazard ratio (HR) of 1.30 (95% CI, 1.01-1.68). Patients with high-level stable-state MR-proADM had a significantly higher risk for CAP compared with patients with COPD with low-level MR-proADM in univariate analysis (HR, 1.93; 95% CI, 1.24-3.01), but after correction for age, lung function, and previous AECOPD, the association was no longer significant (corrected HR, 1.10; 95% CI, 0.68-1.80).. Stable-state high-level MR-proADM in patients with COPD is associated with severe AECOPD but not with CAP.

Topics: Adrenomedullin; Aged; Biomarkers; Europe; Female; Follow-Up Studies; Humans; Immunoassay; Male; Prognosis; Prospective Studies; Protein Precursors; Pulmonary Disease, Chronic Obstructive; Radiography, Thoracic; Severity of Illness Index; Survival Rate; Time Factors

Interferon lambdas (IFNLs) have important anti-viral/bacterial and immunomodulatory functions in the respiratory tract. How do IFNLs impact COPD and its exacerbations?. Five hundred twenty eight patients were recruited in a prospective observational multicentre cohort (PROMISE) study. The genetic polymorphisms (rs8099917 and rs12979860) within the IFNL3/4 gene region and circulating levels of IFNL3 in COPD patients were determined and associated with disease activity and outcome during a median follow-up of 24 months.. The GG genotype significantly influenced severe exacerbation rate (42 vs. 23%; p = 0.032) and time to severe exacerbation (HR = 2.260; p = 0.012). Compared to the TT or TG genotypes, the GG genotype was associated with severe dyspnoea (modified medical research council score ≥ median 3; 22 vs 42%, p = 0.030). The CC genotype of the rs12979860 SNP was associated with a poorer prognosis (body mass index, airflow obstruction, dyspnea and exercise capacity index ≥ median 4; 46 vs. 36% TC vs. 20.5% TT; p = 0.031). Patients with stable COPD and at exacerbation had significantly lower circulating IFNL3 compared to healthy controls (p < 0.001 and p < 0.001, respectively). Circulating IFNL3 correlated to post-bronchodilator FEV. IFNL3/4 polymorphisms and circulating IFNL3 may be associated with disease activity and outcomes in COPD.. Clinical Trial registration http://www.isrctn.com/ identifier ISRCTN99586989 on 16 April 2008.

Topics: Adrenomedullin; Aged; Atrial Natriuretic Factor; Case-Control Studies; Cohort Studies; Disease Progression; Dyspnea; Female; Forced Expiratory Volume; Glycopeptides; Humans; Interferons; Interleukins; Male; Middle Aged; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Procalcitonin; Prognosis; Proportional Hazards Models; Prospective Studies; Protein Precursors; Pulmonary Disease, Chronic Obstructive; Severity of Illness Index

In patients with stable COPD, proadrenomedullin (MR-proADM) has been shown to be a good predictor for mortality. This study aims to provide an external validation of earlier observed cut-off values used by Zuur-Telgen et al. and Stolz.et al. in COPD patients in stable state and at hospitalization for an acute exacerbation of COPD (AECOPD). From the COMIC cohort study we included 545 COPD patients with a blood sample obtained in stable state (n = 490) and/or at hospitalization for an AECOPD (n = 101). Time to death was compared between patients with MR-proADM cut-off scores 0.71 and 0.75 nmol/L for stable state or 0.79 and 0.84 nmol/l for AECOPD. The predictive value of MR-proADM for survival was represented by the C statistic. Risk ratios were corrected for sex, age, BMI, presence of heart failure, and GOLD stage. Patients above the cut-off of 0.75 nmol/l had a 2-fold higher risk of dying than patient below this cut-off (95% CI: 1.20-3.41). The cut-off of 0.71 nmol/l showed only a borderline significantly higher risk of 1.67 (95% CI: 0.98-2.85). The corrected odds ratios for one-year mortality were 3.15 (95% CI 1.15-8.64) and 3.70 (95% CI 1.18-11.6) in patients with MR-proADM levels above versus below the cut-off of respectively 0.75 and 0.71 nmol/l measured in stable state. MR-proADM levels in samples at hospitalization for an AECOPD were not predictive for mortality in this validation cohort. MR-proADM in stable state is a powerful predictor for mortality.

Topics: Acute Disease; Adrenomedullin; Aged; Aged, 80 and over; Biomarkers; Cohort Studies; Disease Progression; Female; Hospitalization; Humans; Male; Middle Aged; Odds Ratio; Predictive Value of Tests; Protein Precursors; Pulmonary Disease, Chronic Obstructive; Reference Values; Survival Rate; Symptom Flare Up

Long-term outcome prediction in COPD is challenging. We conducted a prospective 5-7-year follow-up study in patients with COPD to determine the association of exacerbation type, discharge levels of inflammatory biomarkers including procalctionin (PCT), C-reactive protein (CRP), white blood cell count (WBC) and plasma proadrenomedullin (ProADM), alone or combined with demographic/clinical characteristics, with long-term all-cause mortality in the COPD setting. The analyzed cohort comprised 469 patients with index hospitalization for pneumonic (n = 252) or non-pneumonic (n = 217) COPD exacerbation. Five-to-seven-year vital status was ascertained via structured phone interviews with patients or their household members/primary care physicians. We investigated predictive accuracy using univariate and multivariate Cox regression models and area under the receiver operating characteristic curve (AUC). After a median [25th-75th percentile] 6.1 [5.6-6.5] years, mortality was 55% (95%CI 50%-59%). Discharge ProADM concentration was strongly associated with 5-7-year non-survival: adjusted hazard ratio (HR)/10-fold increase (95%CI) 10.4 (6.2-17.7). Weaker associations were found for PCT and no significant associations were found for CRP or WBC. Combining ProADM with demographic/clinical variables including age, smoking status, BMI, New York Heart Association dyspnea class, exacerbation type, and comorbidities significantly improved long-term predictive accuracy over that of the demographic/clinical model alone: AUC (95%CI) 0.745 (0.701-0.789) versus 0.727 (0.681-0.772), (p) = .043. In patients hospitalized for COPD exacerbation, discharge ProADM levels appeared to accurately predict 5-7-year all-cause mortality and to improve long-term prognostic accuracy of multidimensional demographic/clinical mortality risk assessment.

Topics: Adrenomedullin; Age Factors; Aged; Aged, 80 and over; Biomarkers; Body Mass Index; C-Reactive Protein; Calcitonin; Dyspnea; Female; Follow-Up Studies; Humans; Leukocyte Count; Male; Middle Aged; Prognosis; Prospective Studies; Protein Precursors; Pulmonary Disease, Chronic Obstructive; Risk Assessment; Smoking; Switzerland

Current multicomponent scores that predict mortality in COPD patients might underestimate the systemic component of COPD. Therefore, we evaluated the accuracy of circulating levels of proadrenomedullin (MR-proADM) alone or combined with the ADO (Age, Dyspnoea, airflow Obstruction), updated ADO or BOD (Body mass index, airflow Obstruction, Dyspnoea) index to predict all-cause mortality in stable COPD patients.. This study pooled data of 1285 patients from the COMIC and PROMISE-COPD study.. Patients with high MR-proADM levels (≥0.87 nmol/l) had a 2.1 fold higher risk of dying than those with lower levels (p < 0.001). Based on the C-statistic, the ADOA index (ADO plus MR-proADM) (C = 0.72) was the most accurate predictor followed by the BODA (BOD plus MR-proADM) (C = 0.71) and the updated ADOA index (updated ADO plus MR-proADM) (C = 0.70). Adding MR-proADM to ADO and BOD was superior in forecasting 1- and 2-year mortality. The net percentages of persons with events correctly reclassified (NRI+) within respectively 1-year and 2-year was 31% and 20% for ADO, 31% and 20% for updated ADO and 25% and 19% for BOD. The net percentages of persons without events correctly reclassified (NRI-) within respectively 1-year and 2-year was 26% and 27% for ADO, 27% and 28% for updated ADO and 34% and 34% for BOD.. Adding MR-proADM increased the predictive power of BOD, ADO and updated ADO index.

Topics: Adrenomedullin; Aged; Biomarkers; Body Mass Index; Cohort Studies; Female; Humans; Male; Middle Aged; Netherlands; Observational Studies as Topic; Prognosis; Prospective Studies; Protein Precursors; Pulmonary Disease, Chronic Obstructive; Severity of Illness Index

The BODE (body mass index, airflow obstruction, dyspnoea, exercise capacity) index is well-validated for mortality prediction in chronic obstructive pulmonary disease (COPD). Concentrations of plasma pro-adrenomedullin, a surrogate for mature adrenomedullin, independently predicted 2-year mortality among inpatients with COPD exacerbation. We compared accuracy of initial pro-adrenomedullin level, BODE and BODE components, alone or combined, in predicting 1-year or 2-year all-cause mortality in a multicentre, multinational observational cohort with stable, moderate to very severe COPD. Pro-adrenomedullin was significantly associated (p<0.001) with 1-year mortality (4.7%) and 2-year mortality (7.8%) and comparably predictive to BODE regarding both (C statistics 0.691 versus 0.745 and 0.635 versus 0.679, respectively). Relative to using BODE alone, adding pro-adrenomedullin significantly improved 1-year and 2-year mortality prognostication (C statistics 0.750 and 0.818, respectively; both p<0.001). Pro-adrenomedullin plus BOD was more predictive than the original BODE including 6-min walk distance. In multivariable analysis, pro-adrenomedullin (likelihood ratio Chi-squared 13.0, p<0.001), body mass index (8.5, p=0.004) and 6-min walk distance (7.5, p=0.006) independently foretold 2-year survival, but modified Medical Research Council dyspnoea score (2.2, p=0.14) and forced expiratory volume in 1 s % predicted (0.3, p=0.60) did not. Pro-adrenomedullin plus BODE better predicts mortality in COPD patients than does BODE alone; pro-adrenomedullin may substitute for 6-min walk distance in BODE when 6-min walk testing is unavailable.

Topics: Adrenomedullin; Aged; Airway Obstruction; Biomarkers; Body Mass Index; Dyspnea; Exercise Tolerance; Female; Follow-Up Studies; Forced Expiratory Volume; Humans; Longitudinal Studies; Male; Middle Aged; Prospective Studies; Protein Precursors; Pulmonary Disease, Chronic Obstructive; Reproducibility of Results; Severity of Illness Index; Time Factors; Treatment Outcome

Topics: Adrenomedullin; Female; Humans; Male; Protein Precursors; Pulmonary Disease, Chronic Obstructive; Severity of Illness Index

The prevalence of exertional hypoxemia in unselected patients with COPD is unknown. Intermittent hypoxia leads to adrenomedullin (ADM) upregulation through the hypoxia-inducible factor-1 pathway. We aimed to assess the prevalence and the annual probability to develop exertional hypoxemia in stable COPD. We also hypothesized that increased ADM might be associated with exertional hypoxemia and envisioned that adding ADM to clinical variables might improve its prediction in COPD.. A total of 1,233 6-min walk tests and circulating proadrenomedullin (proADM) levels from 574 patients with clinically stable, moderate to very severe COPD enrolled in a multinational cohort study and followed up for 2 years were concomitantly analyzed.. The prevalence of exertional hypoxemia was 29.1%. In a matrix derived from a fitted-multistate model, the annual probability to develop exertional hypoxemia was 21.6%. Exertional hypoxemia was associated with greater deterioration of specific domains of health-related quality of life, higher severe exacerbation, and death annual rates. In the logistic linear and conditional Cox regression multivariable analyses, both FEV1% predicted and proADM proved independent predictors of exertional hypoxemia (P < .001 for both). Adjustment for comorbidities, including cardiovascular disorders, and exacerbation rate did not influence results. Relative to using FEV1% predicted alone, adding proADM resulted in a significant improvement of the predictive properties (P = .018). Based on the suggested nonlinear nomogram, patients with moderate COPD (FEV1% predicted = 50%) but high proADM levels (> 2 nmol/L) presented increased risk (> 30%) for exertional desaturation.. Exertional desaturation is common and associated with poorer clinical outcomes in COPD. ADM improves prediction of exertional desaturation as compared with the use of FEV1% predicted alone.. ISRCTN Register; No.: ISRCTN99586989; URL: www.controlled-trials.com.

Topics: Adrenomedullin; Aged; Biomarkers; Disease Progression; Europe; Female; Follow-Up Studies; Forced Expiratory Volume; Humans; Hypoxia; Male; Physical Exertion; Prevalence; Prognosis; Prospective Studies; Protein Precursors; Pulmonary Disease, Chronic Obstructive; Risk Factors; Time Factors

Adrenomedullin (ADM) is a regulatory peptide with many biological actions, but little is known about its role in patients with COPD exacerbation. The purpose of this study was to evaluate the diagnostic and prognostic value of plasma ADM levels on hospital admission in patients with COPD exacerbation.. Consecutive subjects admitted to the hospital for COPD exacerbation were included and were followed up for 1 y; in addition, subjects with stable COPD from an out-patient clinic and healthy volunteers were recruited as controls.. Compared with healthy subjects (145 pg/mL [interquartile range {IQR} 103-290 pg/mL]), plasma ADM levels were significantly higher in subjects with COPD exacerbation (270 pg/mL [IQR 170-510 pg/mL], P = .001) and in subjects with stable COPD (400 pg/mL [IQR 210-525 pg/mL], P < .001). In subjects with COPD exacerbation, ADM levels were significantly elevated during exacerbation (560 pg/mL [IQR 495-630 pg/mL]) compared with the recovery phase (470 pg/mL [IQR 393-553 pg/mL], P = .01) and the stable phase (200 pg/mL [IQR 143-308 pg/mL], P < .001). In receiver operating characteristic analysis, in subjects with COPD exacerbation, ADM had high diagnostic accuracy in differentiating between exacerbation and the stable phase (area under the curve 0.97, 95% CI 0.93-1.02, P < .001). In Cox regression analysis, plasma ADM was not independently associated with 1-y survival (P = .97), but it could accurately predicted the need for ICU care (hazard ratio 1.37, 95% CI 1.09-1.72, P = .008).. Plasma ADM is a valuable biomarker to confirm COPD exacerbation; furthermore, plasma ADM independently predicts the need of ICU care, although it is not associated with long-term mortality in patients with COPD exacerbation.

Topics: Adrenomedullin; Aged; Biomarkers; Case-Control Studies; China; Female; Humans; Intensive Care Units; Male; Middle Aged; Patient Admission; Predictive Value of Tests; Prognosis; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests

Chronic obstructive pulmonary disease (COPD) is a complex disease with various phenotypes. The simultaneous determination of multiple biomarkers reflecting different pathobiological pathways could be useful in identifying individuals with an increased risk of death. We derived and validated a combination of three biomarkers (adrenomedullin, arginine vasopressin and atrial natriuretic peptide), assessed in plasma samples of 385 patients, to estimate mortality risk in stable COPD. Biomarkers were analysed in combination and defined as high or low. In the derivation cohort (n = 142), there were 73 deaths during the 5-year follow-up. Crude hazard ratios for mortality were 3.0 (95% CI 1.8-5.1) for one high biomarker, 4.8 (95% CI 2.4-9.5) for two biomarkers and 9.6 (95% CI 3.3-28.3) for three high biomarkers compared with no elevated biomarkers. In the validation cohort (n = 243), 87 individuals died. Corresponding hazard ratios were 1.9 (95% CI 1.1-3.3), 3.1 (95% CI 1.8-5.4) and 5.4 (95% CI 2.5-11.4). Multivariable adjustment for clinical variables as well as the BODE (body mass index, airflow obstruction, dyspnoea, exercise capacity) index and stratification by the Global Initiative for Chronic Obstructive Lung Disease stages provided consistent results. The addition of the panel of three biomarkers to the BODE index generated a net reclassification improvement of 57.9% (95% CI 21.7-92.4%) and 45.9% (95% CI 13.9-75.7%) at 3 and 5 years, respectively. Simultaneously elevated levels of adrenomedullin, arginine vasopressin and atrial natriuretic peptide are associated with increased risk of death in patients with stable COPD.

Topics: Adrenomedullin; Aged; Aged, 80 and over; Arginine Vasopressin; Atrial Natriuretic Factor; Biomarkers; Cohort Studies; Female; Humans; Male; Middle Aged; Multivariate Analysis; Prognosis; Proportional Hazards Models; Pulmonary Disease, Chronic Obstructive; Reproducibility of Results; Risk Assessment

Topics: Adrenomedullin; Arginine Vasopressin; Atrial Natriuretic Factor; Female; Humans; Male; Pulmonary Disease, Chronic Obstructive

Midrange-proadrenomedullin (MR-proADM) has been shown to be elevated in patients hospitalized for an acute exacerbation of COPD (AECOPD) and in patients with community-acquired pneumonia. When measured during AECOPDs, MR-proADM has also been shown to be a predictor of mortality. We hypothesized that MR-proADM levels measured in a stable state could also predict mortality.. We included 181 patients in whom we had paired plasma samples for MR-proADM determinations during a stable state and at hospitalization for an AECOPD when they also produced sputum. Time to death or censoring was compared between patients with MR-proADM above or below the median of 0.71 nmol/L. The predictive value of MR-proADM for survival was determined by calculating the C statistic.. Patients with COPD and MR-proADM levels > 0.71 nmol/L in the stable state had a threefold-higher risk of dying than did patients with MR-proADM levels < 0.71 nmol/L (hazard ratio, 2.98 [95% CI, 1.51-5.90]; C statistic, 0.76). The corrected OR for 1-year mortality was 8.90 (95% CI, 1.94-44.6) in patients with high MR-proADM levels measured in the stable state, compared with patients with low levels measured in the stable state.. MR-proADM measured in the stable state appeared to be a strong predictor of mortality in patients with COPD. MR-proADM is far easier to measure than other predictors of mortality in COPD, such as BMI, airflow obstruction, dyspnea, and exercise capacity score.

Topics: Adrenomedullin; Aged; Female; Humans; Male; Middle Aged; Mortality; Netherlands; Patient Acuity; Peptide Fragments; Predictive Value of Tests; Prognosis; Protein Precursors; Pulmonary Disease, Chronic Obstructive; Reproducibility of Results; Sputum

Topics: Adrenomedullin; Atrial Natriuretic Factor; Female; Humans; Male; Protein Precursors; Pulmonary Disease, Chronic Obstructive; Walking

The prevalence of cardiovascular mortality is high in Chronic Obstructive Pulmonary Disease (COPD) and the identification of clinical parameters to improve risk stratification is of great interest.. This study aims to assess the predictive strength of daily walking activity on expression of cardiac biomarkers in patients with COPD.. One hundred and five patients with COPD (66.1 ± 8.7 years of age) were prospectively analyzed. Daily walking activity was measured by means of accelerometry. Stepwise multivariate regression analyses were employed with either midregional proatrial natriuretic peptide (MRproANP) or plasma proadrenomedullin (MRproADM) as dependent variables, and age, age-adjusted Charlson score, Modified Medical Research Council Dyspnea Scale (MMRC), Saint Georges Respiratory Questionnaire total score and either total walk, steps per day or fast walk as covariates.. Independent predictors of MRproANP included age (p = 0.015) and either total walk or steps per day (both p < 0.0001). Total walk or steps per day were the only independent predictors of MRproADM (p < 0.0001). There was a significant negative correlation between fast walk and MMRC (R = -0.70; p < 0.001) and fast walk was only independently predictive of MRproANP but not MRproADM once MMRC was excluded from the list of covariates (p = 0.023 and p = 0.057, respectively).. Daily walking activity independently predicts levels of circulating MRproANP and MRproADM in stable COPD patients, two prognostic biomarkers of cardiac distress associated with long-term survival upon exacerbation of COPD. Employing activity monitors in the stable state might simplify risk stratification in daily living.

Topics: Accelerometry; Adrenomedullin; Aged; Atrial Natriuretic Factor; Biomarkers; Female; Humans; Male; Middle Aged; Prospective Studies; Protein Precursors; Pulmonary Disease, Chronic Obstructive; Regression Analysis; Risk Assessment; Walking

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

Plasma endothelin and adrenomedullin are increased in patients with pulmonary arterial hypertension, hypoxia, and pulmonary infections, conditions that predict survival in patients with COPD. We investigated whether plasma pro-endothelin-1 (proET-1) and/or pro-adrenomedullin (proADM) on admission to the hospital for acute exacerbation predict survival in patients with COPD.. We examined 167 patients who had been admitted to the hospital for acute exacerbation, and we followed them up for 2 years. We measured plasma C-terminal (CT) proET-1 and mid-regional (MR) proADM on hospital admission, after 14 to 18 days, and after 6 months. In addition to plasma CT proET-1 and MR proADM, we assessed with Cox regression univariate and multivariate analyses the predictive value of clinical, functional, and laboratory parameters on 2-year survival. We analyzed the time to death by Kaplan-Meier curves.. Compared to recovery and stable state, CT-proET-1 and MR-proADM were significantly increased on hospital admission (p < 0.001 and p = 0.002, respectively). MR-proADM, but not CT-proET-1, was associated with increased in-hospital mortality (p = 0.049) and independently predicted 2-year survival (p = 0.017). ProADM plasma levels > 0.84 nmol/L on hospital admission increased the mortality risk within 2 years from 13 to 32% (p = 0.004). By contrast, age (p = 0.779), Charlson comorbidity score (p = 0.971), body mass index (p = 0.802), FEV(1) percent predicted (p = 0.741), PAo(2) (p = 0.744), PAco(2) (p = 0.284), leukocyte counts (p = 0.333), C-reactive protein (p = 0.772), procalcitonin (p = 0.069), pulmonary arterial hypertension (p = 0.971), and CT-proET-1 (p = 0.223) were not independently associated with 2-year survival.. This study shows that plasma proADM but not plasma proET-1 on admission to the hospital for acute exacerbation independently predicts survival, thus suggesting that this biomarker could be used to predict prognosis in patients with COPD.

Topics: Adrenomedullin; Adult; Aged; Aged, 80 and over; Endothelin-1; Female; Follow-Up Studies; Hospital Mortality; Humans; Kaplan-Meier Estimate; Length of Stay; Male; Middle Aged; Patient Admission; Predictive Value of Tests; Protein Precursors; Pulmonary Disease, Chronic Obstructive

To study adrenomedullin (AM) plasma levels in patients with severe lung disease and to analyze the relationship between AM and heart changes, hemodynamics and blood gases.. Case control study of 56 patients (36 men, 20 women) with severe lung disease and 9 control subjects (7 men, 2 women). Patients with end-stage pulmonary disease, including chronic obstructive pulmonary disease (COPD, n=11), cystic fibrosis (CF, 26), idiopatic pulmonary fibrosis (ILD, n=9), and idiopatic pulmonary arterial hypertension (PAH, n=10), who were evaluated for lung trasplantation between January 1997 and September 2000, and nine patients who underwent lung surgery for a solitary benign nodule. AM plasma levels in pulmonary artery (mixed venous blood, vein) and aorta or femoral artery (arterial, art), art and vein blood gases, pulmonary hemodynamics, systemic hemodynamics, two-dimensional transthoracic echocardiography and echo-Doppler study.. Plasma AM (art and ven) levels were higher among patients' group compared to the controls (AMart p<0.02 and AMven p<0.04) for CF, ILD, PAH (AMart, pg ml(-1) Controls 13.7+/-3.6, COPD 22.8+/-6.2, CF 28.1+/-11.4, ILD 34.1+/-14.3, PAH 35.1+/-18.9; AMven, pg ml(-1) Controls 14.2+/-4.8, COPD 28.1+/-12.6, CF 31.7+/-14.1, ILD 38.7+/-16.5, PAH 40.1+/-4.4). We found with a trend towards higher concentration in ILD and PAH patients compared to COPD and CF but no statistical significant differences. Mixed-venous AM was higher than arterial AM in all groups resulting in AM uptake (AMPulmUp pg min(-1) Controls 4.8+/-22.6, COPD 21.1+/-44.9, CF 20.6+/-45.1, ILD 23.7+/-38.5, PAH 29.9+/-49.7). The univariate analysis showed a weak but significant correlation between AMart and mean systemic arterial pressure, heart rate, mean pulmonary arterial pressure and systemic vascular resistance. In the multivariate analysis, four variables emerged as independent factors of AMart including mean pulmonary arterial pressure, heart rate, mean systemic arterial pressure and left ventricular diastolic diameter (F=8.6, p<0.00001, r=0.60, r2=0.32). A similar weak correlation was apparent between AMven, systemic vascular resistance, and mean pulmonary arterial pressure. The results of multivariate analysis identify right atrial enlargement, mean right atrial pressure, heart rate and left ventricular dimensions as the only independent variables related to AMven (F=4.3, p<0.0004 r=0.56, r2=0.26). AM pulmonary uptake was significantly correlated with AMven (r=0.65), but not with hemodynamic, blood gas and echocardiographic variables.. AM plasma levels are elevated in patients with severe lung disease in face of a preserved pulmonary uptake. These results suggest that the high AM plasma levels in patients with severe lung disease are not caused by a reduced pulmonary clearance, instead suggesting a systemic production.

Topics: Adrenomedullin; Adult; Cystic Fibrosis; Echocardiography; Female; Humans; Lung Diseases; Male; Middle Aged; Peptides; Pulmonary Disease, Chronic Obstructive; Pulmonary Fibrosis

To investigate the relationship between the plasma adrenomedullin (ADM) levels and the extent of chronic cor-pulmonale and its underlying diseases, and explore the role of ADM in these diseases.. Totally 26 patients with chronic bronchitis, chronic bronchitis accompanied with obstructive pneumonectasia or chronic cor-pulmonale were included respectively as clinical test group T1, T2 and T3; 26 normal people and 14 patients with pneumonia were chosen as control groups (group C1 and C2). Plasma concentration of ADM in every selected individual had been measured with specific radioimmunoassay.. Levels of plasma ADM in T3 were significantly higher than those in T2, and T2 than T1, C1 and C2 (P < 0.05), but there were no obvious difference between T1 and C1, between T1 and C2 (P > 0.05).. Plasma ADM levels can reflect the severity of the above series of diseases.

Topics: Adrenomedullin; Aged; Bronchitis, Chronic; Female; Humans; Male; Middle Aged; Peptides; Pulmonary Disease, Chronic Obstructive; Pulmonary Heart Disease; Severity of Illness Index

To investigate the expression and role of adrenomedullin (ADM) and adrenomedullin receptor (ADMR) in patients with chronic obstructive pulmonary disease (COPD).. Small pulmonary artery remodeling was observed using morphometric analysis. The expression of ADM and ADMR mRNA in lung tissue was calculated by in situ hybridization in 9 COPD cases. Cardiac catheterization was performed in 22 COPD cases to monitor changes of hemodynamic parameters and patients were divided into two groups based on mean pulmonary artery pressure (mPAP). The cases without pulmonary hypertension (PH) were placed in Group A (n = 12) and those with PH were placed in Group B (n = 10). The levels of pulmonary arterial plasma ADM were measured by radioimmunoassay. Blood gas analysis was also conducted.. The ratio of vascular wall thickness to external diameter (MT%) and the ratio of vascular wall area to total area (MA%) were higher in patients with COPD (P < 0.01). In situ hybridization showed that ADM mRNA and ADMR mRNA were expressed in the pulmonary artery walls of control subjects. The expression levels were significantly higher in those of COPD sufferers (P < 0.01). Statistically positive relationships were visible between ADM and ADMR, and the plasma ADM level of Group B was significantly higher than that of Group A (P < 0.05). The plasma ADM level had a significantly positive correlation to mPAP and pulmonary vascular resistance (PVR), while being negatively correlated to levels of PaO(2).. ADM may play an extremely protective role as a local autocrine/paracrine factor in COPD.

Topics: Adrenomedullin; Adult; Aged; Aged, 80 and over; Female; Hemodynamics; Humans; Male; Middle Aged; Oxygen; Peptides; Pulmonary Disease, Chronic Obstructive; Receptors, Adrenomedullin; Receptors, Peptide; RNA, Messenger

To investigate the expression and role of adrenomedullin (ADM) and adrenomedullin receptor (ADMR) in patients with chronic obstructive pulmonary disease (COPD).. The first study included 9 COPD patients (group I) and 7 control patients (group II) who had underwent pulmonary lobe resection. Small pulmonary artery remodeling was observed with morphometric analysis. The expressions of ADM and ADMR mRNA in lung tissue were examined by hybridization in situ. The second study recruited 22 patients with COPD. Cardiac catheterization was performed to monitor the changes of hemodynamic parameters and the subjects were divided into two groups according to the mean pulmonary artery pressure (mPAP): patients without pulmonary hypertension (PH, group A, n = 10) and patients with PH (group B, n = 12). The levels of pulmonary arterial plasma ADM were measured by radioimmunoassay. Arterial blood gas was also measured.. (1) In patients underwent pulmonary lobe resection: (1) Morphometry studies showed that the ratio of vascular wall thickness to external diameter (MT%) and ratio of vascular wall area to total area (MA%) increased in group I (P < 0.01); (2) Hybridization in situ showed that ADM/ADMR mRNA expressions were significantly higher in pulmonary artery walls of group I as compared with group II (P < 0.01). (2) In COPD patients without pulmonary lobe resection, the plasma ADM level of group B was significantly higher than that of group A (P < 0.05), and the plasma ADM level had a significantly positive correlation with mPAP and pulmonary vascular resistance (PVR), but a negative correlation with PaO(2).. ADM may play an important protective role as a local autocrine/paracrine factor in the development of COPD and PH.

Topics: Adrenomedullin; Adult; Aged; Case-Control Studies; Female; Gene Expression; Humans; Hypertension, Pulmonary; In Situ Hybridization; Lung; Male; Middle Aged; Peptides; Pneumonectomy; Pulmonary Artery; Pulmonary Disease, Chronic Obstructive; Receptors, Adrenomedullin; Receptors, Peptide; RNA, Messenger