natriuretic-peptide--brain and Asthma

Can laboratory tests that are routinely used in adult patients also be used in pediatric patients? Does the current literature support the routine use of troponin, brain natriuretic peptide, D-dimer, and lactate in children? Adult problems such as acute coronary syndrome and pulmonary embolism are rare in pediatrics, and there is a paucity of literature on how blood tests commonly used to help diagnose these conditions in adults play a role in the diagnosis and management of children. This article presents the literature about 4 common blood tests and examines the clinical applications of each.

Topics: Asthma; Biomarkers; Child; Fibrin Fibrinogen Degradation Products; Heart Diseases; Humans; Infections; Intussusception; Lactic Acid; Mitochondrial Diseases; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Prognosis; Pulmonary Embolism; Respiratory Distress Syndrome; Sepsis; Troponin; Wounds and Injuries

Brain natriuretic peptide (BNP) modulates several biological processes by activating the natriuretic peptide receptor A (NPR-A). Atria and ventricles secrete BNP. BNP increases natriuresis, diuresis and vasodilatation, thus resulting in a decreased cardiac workload. BNP and NT-proBNP, which is the biologically inactive N-terminal portion of its pro-hormone, are fast and sensitive biomarkers for diagnosing heart failure. The plasma concentrations of both BNP and NT-proBNP also correlate with left ventricular function in patients with acute exacerbation of COPD, even without history of heart failure. Several studies have been conducted in vitro and in vivo, both in animals and in humans, in order to assess the potential role of the NPR-A activation as a novel therapeutic approach for treating obstructive pulmonary disorders. Unfortunately, these studies have yielded conflicting results. Nevertheless, further recent specific studies, performed in ex vivo models of asthma and COPD, have confirmed the bronchorelaxant effect of BNP and its protective role against bronchial hyperresponsiveness in human airways. These studies have also clarified the intimate mechanism of action of BNP, represented by an autocrine loop elicited by the activation of NPR-A, localized on bronchial epithelium, and the relaxant response of the surrounding ASM, which does not expresses NPR-A. This review explores the teleological activities and paradoxical effects of BNP with regard to chronic obstructive respiratory disorders, and provides an excursus on the main scientific findings that explain why BNP should be considered much more than a biomarker.

Topics: Asthma; Biomarkers; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Protective Factors; Pulmonary Disease, Chronic Obstructive

B-type natriuretic peptide (BNP) regulates different physiological processes such as blood pressure, cardiac growth, and neural and skeletal development. Thus, the aim of this study w as to evaluate the effect of BNP in the treatment of acute asthma attacks.. In this randomized clinical trial, patients with acute asthma attacks were enrolled. The patients were divided randomly into two groups. Patients in the interventional group received BNP via intravenous infusion. Two µg/kg of BNP was injected as a bolus in 60 seconds. Then, infusion of BNP immediately began and was given in 0.01, 0.02, and 0.03 µg/kg/min doses every 30 minutes for the first 1.5 hours. The patients in the control group received nebulized salbutamol. Afterwards, peak flow meter findings, hemodynamic parameters, and estimation of the clinical severity of asthma in both groups were checked every 30 minutes.. In total, 40 patients were included in this study. The values of PEFR in the 60th and 90th minutes in the control group were lower than those in the interventional group. In the 60th minute, the mean of PEFR was 377.3 in the BNP group but 335.95 in the control group (P = 0.049). Moreover, this difference remained significant in the 90th minute (P = 0.021). However, forced expiratory volume in one second (FEV1) did not differ between the groups at any time (p > 0.05).. Although a large experimental study is needed to verify our hypothesis, it seems that BNP might be a therapeutic option in asthma exacerbations, particularly in those with b2 agonist receptor polymorphism.

Topics: Administration, Inhalation; Adult; Albuterol; Asthma; Bronchodilator Agents; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Male; Maximal Midexpiratory Flow Rate; Middle Aged; Natriuretic Peptide, Brain; Nebulizers and Vaporizers

Obesity is associated with left ventricular diastolic dysfunction and altered heart rate variability, as well as pulmonary dysfunction. The relationship between asthma and cardiac dysfunction in severely obese subjects is unknown, although it has been hypothesized that cardiac dysfunction may contribute to increase airway hyper-responsiveness (AHR). This study aimed to determine if AHR is associated with left ventricular diastolic dysfunction and heart rate variability in severely obese subjects.. Sixty-one subjects with severe obesity (BMI ≥35 kg/m2 with comorbidities) completed this study. All subjects completed respiratory questionnaires, spirometry, lung volume measurements, methacholine inhalation test, 24hour Holter monitoring and a complete echocardiography evaluation. Blood samples were obtained for measurement of metabolic markers. Subjects with AHR, defined by a provocative concentration of methacholine inducing a 20% fall in FEV1 (PC20) < 8 mg/ml, were compared with those with no AHR (PC20 ≥8 mg/ml).. According to these criteria, 32 subjects had AHR and 29 had no AHR(mean PC201.70 mg/ml and 15.3 mg/ml respectively, p < 0.001). The groups were similar for anthropometric data and comorbidities. Fasting glucose, Hb1Ac, total cholesterol, LDL, triglycerides, Apo-B, C-reactive protein (CRP) and pro-BNP levels were also comparable between groups (p > 0.05). CRP level correlated with PC20 (AHR, r=0.38, p=0.03). Indices of heart rate variability and overall cardiac function were similar in subjects with or without AHR but grade 2 left ventricular diastolic dysfunction was more prevalent in subjects with AHR (p=0.037).. Altered cardiac function, dysglycemia and dyslipidemia do not seem to be significantly associated with AHR in severely obese subjects in contrast to systemic inflammation.

Topics: Adult; Aged; Asthma; Blood Glucose; Bronchoconstrictor Agents; C-Reactive Protein; Female; Heart Diseases; Heart Rate; Humans; Inflammation; Lipids; Male; Methacholine Chloride; Middle Aged; Natriuretic Peptide, Brain; Obesity; Respiratory Function Tests

We studied the diagnostic accuracy of bedside lung ultrasound (the presence of a comet-tail sign), N-terminal pro-brain natriuretic peptide (NT-proBNP) and clinical assessment (according to the modified Boston criteria) in differentiating heart failure (HF)-related acute dyspnea from pulmonary (chronic obstructive pulmonary disease (COPD)/asthma)-related acute dyspnea in the prehospital setting.. Our prospective study was performed at the Center for Emergency Medicine, Maribor, Slovenia, between July 2007 and April 2010. Two groups of patients were compared: a HF-related acute dyspnea group (n = 129) and a pulmonary (asthma/COPD)-related acute dyspnea group (n = 89). All patients underwent lung ultrasound examinations, along with basic laboratory testing, rapid NT-proBNP testing and chest X-rays.. The ultrasound comet-tail sign has 100% sensitivity, 95% specificity, 100% negative predictive value (NPV) and 96% positive predictive value (PPV) for the diagnosis of HF. NT-proBNP (cutoff point 1,000 pg/mL) has 92% sensitivity, 89% specificity, 86% NPV and 90% PPV. The Boston modified criteria have 85% sensitivity, 86% specificity, 80% NPV and 90% PPV. In comparing the three methods, we found significant differences between ultrasound sign and (1) NT-proBNP (P < 0.05) and (2) Boston modified criteria (P < 0.05). The combination of ultrasound sign and NT-proBNP has 100% sensitivity, 100% specificity, 100% NPV and 100% PPV. With the use of ultrasound, we can exclude HF in patients with pulmonary-related dyspnea who have positive NT-proBNP (> 1,000 pg/mL) and a history of HF.. An ultrasound comet-tail sign alone or in combination with NT-proBNP has high diagnostic accuracy in differentiating acute HF-related from COPD/asthma-related causes of acute dyspnea in the prehospital emergency setting.. ClinicalTrials.gov NCT01235182.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Asthma; Biomarkers; Diagnosis, Differential; Dyspnea; Emergency Medical Services; Female; Heart Failure; Humans; Lung; Male; Middle Aged; Natriuretic Peptide, Brain; Point-of-Care Systems; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Sensitivity and Specificity; Ultrasonography

To determine the bronchodilator effect of recombinant human B-type natriuretic peptide (BNP; nesiritide) on patients with asthma.. A prospective, open-label study.. Outpatient setting.. Eight adult patients with asthma confirmed by > 12% and > 200 mL increase in FEV1 after bronchodilator inhalation.. An IV nesiritide bolus, 2 microg/kg, followed by continuous infusion for a total of 3 h at escalating doses of 0.01, 0.02, and 0.03 microg/kg/min for 1 h each as tolerated.. Spirometry and forced oscillation technique (FOT) measurements were both obtained at baseline and every 30 min during the infusion. Two doses of albuterol, 90 microg, inhalation via metered-dose inhaler were then administered at the end of nesiritide infusion, followed by repeat spirometry and FOT measurements after 30 min. Primary end points were FEV1 and FVC changes after the nesiritide infusion for 3 h. Wilcoxon signed-ranks tests were used to compare the effects of nesiritide and albuterol.. Baseline measurements (mean +/- SD) were as follows: FEV1, 1.89 +/- 0.87 L; FVC, 3.02 +/- 0.99 L; respiratory resistance at 5 Hz (Rrs5), 10.3 +/- 3.85 cm H2O . s/L; and mean respiratory resistance at 5 to 20 Hz, 7.56 +/- 1.92 cm H2O/L/s. Mean baseline serum BNP level was 27 +/- 27 pg/mL. After 180 min of nesiritide infusion, the following measurements showed significant changes: FEV1 increased to 2.41 +/- 0.78 L (mean increase, 520 mL), p = 0.012; FVC increased to 3.65 +/- 1.05 L (mean increase, 630 mL), p = 0.017; and Rrs5 decreased to 8.24 +/- 4.02 cm H2O/L/s, p = 0.017. After albuterol, there were no further significant changes in these measurements.. IV nesiritide is an effective bronchodilator in patients with asthma.

Topics: Administration, Inhalation; Adult; Albuterol; Asthma; Bronchodilator Agents; Female; Forced Expiratory Volume; Humans; Infusions, Intravenous; Male; Middle Aged; Natriuretic Agents; Natriuretic Peptide, Brain; Prospective Studies; Severity of Illness Index; Spirometry

This research is aimed at analyzing the safety profile and nursing highlights of continuous renal replacement therapy (CRRT) for hypertension (HT) complicated by refractory heart failure (RHF).. Sixty-six HT + RHF patients admitted between March 2018 and December 2021 were enrolled and assigned to two groups: a CRRT group with 33 cases treated with CRRT and a control group with 33 cases intervened by routine treatment. The therapeutic effect and alterations of cardiac function (CF) indexes were observed in both cohorts. Besides, statistics were made in terms of serum B-type natriuretic peptide (BNP), C-reactive protein (CRP) and mean arterial pressure (MAP) concentrations, time of asthma relief, heart rate recovery (HRR), edema resolution, and hospitalization, as well as incidence of adverse reactions (ARs). Finally, pre- and posttreatment psychological quality and pain of both cohorts of subjects were assessed using the self-rating anxiety and depression scale (SAS and SDS) and visual analogue scale (VAS), respectively.. CRRT group exhibited higher overall response rate and better CF than control group (. CRRT can effectively improve the therapeutic effect and CF of patients with HT complicated by RHF, to protect the health and safety of patients.

Topics: Acute Kidney Injury; Asthma; C-Reactive Protein; Continuous Renal Replacement Therapy; Heart Failure; Humans; Hypertension; Natriuretic Peptide, Brain; Renal Replacement Therapy

Although women account for up to half of patients hospitalized for coronavirus disease 2019 (COVID-19), no specific data have been reported in this population.. To assess the burden and impact of cardiovascular comorbidities in women with COVID-19.. All consecutive patients hospitalized for COVID-19 across 24 hospitals from 26 February to 20 April 2020 were included. The primary composite outcome was transfer to an intensive care unit or in-hospital death.. Among 2878 patients, 1212 (42.1%) were women. Women were older (68.3±18.0 vs. 65.4±16.0 years; P<0.001), but had less prevalent cardiovascular comorbidities than men. Among women, 276 (22.8%) experienced the primary outcome, including 161 (13.3%) transfers to an intensive care unit and 115 (9.5%) deaths without transfer to intensive care unit. The rate of in-hospital death or transfer to an intensive care unit was lower in women versus men (crude hazard ratio [HR]: 0.62, 95% confidence interval [CI]: 0.53-0.72). Age (adjusted HR: 1.05 per 5-year increase, 95% CI: 1.01-1.10), body mass index (adjusted HR: 1.06 per 2-unit increase, 95% CI: 1.02-1.10), chronic kidney disease (adjusted HR: 1.57, 95% CI: 1.11-2.22) and heart failure (adjusted HR: 1.52, 95% CI: 1.04-2.22) were independently associated with the primary outcome in women. Elevated B-type natriuretic peptide/N-terminal prohormone of B-type natriuretic peptide (adjusted HR: 2.41, 95% CI: 1.70-3.44) and troponin (adjusted HR: 2.00, 95% CI: 1.39-2.88) concentrations at admission were also associated with the primary outcome, even in women free of previous coronary artery disease or heart failure.. Although female sex was associated with a lower risk of transfer to an intensive care unit or in-hospital death, COVID-19 remained associated with considerable morbimortality in women, especially in those with cardiovascular diseases.

Topics: Aged; Asthma; Biomarkers; Cardiovascular Diseases; Comorbidity; COVID-19; Diabetes Mellitus; Female; France; Hospital Mortality; Humans; Intensive Care Units; Length of Stay; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Proportional Hazards Models; Retrospective Studies; Risk Assessment; Risk Factors; Sex Distribution; Smoking; Troponin

To describe the clinical profiles and risk factors for critical illness in hospitalized children and adolescents with coronavirus disease 2019 (COVID-19).. Children 1 month to 21 years of age with COVID-19 from a single tertiary care children's hospital between March 15 and April 13, 2020 were included. Demographic and clinical data were collected.. In total, 67 children tested positive for COVID-19; 21 (31.3%) were managed as outpatients. Of 46 admitted patients, 33 (72%) were admitted to the general pediatric medical unit and 13 (28%) to the pediatric intensive care unit (PICU). Obesity and asthma were highly prevalent but not significantly associated with PICU admission (P = .99). Admission to the PICU was significantly associated with higher C-reactive protein, procalcitonin, and pro-B type natriuretic peptide levels and platelet counts (P < .05 for all). Patients in the PICU were more likely to require high-flow nasal cannula (P = .0001) and were more likely to have received Remdesivir through compassionate release (P < .05). Severe sepsis and septic shock syndromes were observed in 7 (53.8%) patients in the PICU. Acute respiratory distress syndrome was observed in 10 (77%) PICU patients, 6 of whom (46.2%) required invasive mechanical ventilation for a median of 9 days. Of the 13 patients in the PICU, 8 (61.5%) were discharged home, and 4 (30.7%) patients remain hospitalized on ventilatory support at day 14. One patient died after withdrawal of life-sustaining therapy because of metastatic cancer.. We describe a higher than previously recognized rate of severe disease requiring PICU admission in pediatric patients admitted to the hospital with COVID-19.

Topics: Adenosine Monophosphate; Adolescent; Alanine; Antiviral Agents; Asthma; Betacoronavirus; Blood Urea Nitrogen; C-Reactive Protein; Child; Child, Preschool; Coronavirus Infections; COVID-19; Creatinine; Critical Illness; Dyspnea; Female; Hospitalization; Hospitals, Pediatric; Humans; Infant; Infant, Newborn; Intensive Care Units, Pediatric; Male; Natriuretic Peptide, Brain; New York City; Pandemics; Pediatric Obesity; Platelet Count; Pneumonia, Viral; Procalcitonin; Respiration, Artificial; Retrospective Studies; SARS-CoV-2; Sepsis; Shock, Septic; Tertiary Care Centers; Young Adult

Little is known about the characteristics and impact of acute pulmonary embolism (PE) during episodes of asthma exacerbation. We aimed to characterize patients diagnosed with acute PE in the setting of asthma exacerbation, develop a prediction model to help identify future patients and assess the impact of acute PE on hospital outcomes.. We included 758 patients who were treated for asthma exacerbation and underwent a computed tomographic pulmonary angiography (CTA) during the same encounter at a university-based hospital between June 2011 and October 2018. We compared clinical characteristics of patients with and without acute PE and developed a machine learning prediction model to classify the PE status based on the clinical variables. We used multivariable regression analysis to evaluate the impact of acute PE on hospital outcomes.. Twenty percent of the asthma exacerbation patients who underwent CTA had an acute PE. Factors associated with acute PE included previous history of PE, high CHA. It is important to consider acute PE, a potentially life-threatening event, in the setting of asthma exacerbation especially when other risk factors are present.

Topics: Adult; Aged; Asthma; Body Mass Index; Case-Control Studies; Clinical Decision Rules; Comorbidity; Computed Tomography Angiography; Creatinine; Disease Progression; Female; Fibrin Fibrinogen Degradation Products; Heart Rate; Hospitals, University; Humans; Intensive Care Units; International Normalized Ratio; Length of Stay; Machine Learning; Male; Middle Aged; Natriuretic Peptide, Brain; Oxygen; Pulmonary Embolism

Topics: Asthma; C-Reactive Protein; Chest Pain; Eosinophilia; Female; Granulomatosis with Polyangiitis; Humans; Leukocytosis; Lupus Erythematosus, Discoid; Magnetic Resonance Imaging, Cine; Middle Aged; Natriuretic Peptide, Brain; Pericarditis; Troponin T

Topics: Arterial Occlusive Diseases; Asthma; Betacoronavirus; Catheterization; Computed Tomography Angiography; Coronavirus Infections; COVID-19; Extracorporeal Membrane Oxygenation; Fibrin Fibrinogen Degradation Products; Fibrinolytic Agents; Heparin; Humans; Lung; Natriuretic Peptide, Brain; Pandemics; Pneumonia, Viral; Pulmonary Artery; Respiration, Artificial; SARS-CoV-2; Thrombolytic Therapy; Thrombosis; Tissue Plasminogen Activator; Ventricular Dysfunction, Right

Bronchial asthma may lead to pulmonary hypertension, right ventricular (RV) dysfunction, and cor pulmonale due to elevated afterload on the RV later in life. The aim of this study was to determine whether serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) might serve as a biomarker for detecting subclinical RV dysfunction using echocardiography during the early stages of bronchial asthma.. Sixty-eight pediatric patients with asthma (asthma group) and 69 age- and sex-matched healthy children (control group) were enrolled. The study was conducted in a tertiary woman and child diseases education and research hospital from January 2013 to December 2013. RV function (2-D and tissue-Doppler echocardiography), pulmonary function (spirometry) and serum NT-proBNP concentration were evaluated.. Mean age was 10.5 ± 2.8 years in the asthma group and 10.2 ± 2.7 years in the control group (P = 0.522). RV diastolic function was significantly decreased in the asthma group (ratio of tricuspid lateral annular early diastolic peak velocity to tricuspid lateral annular late diastolic peak velocity [E'/A'], 1.29 ± 0.68 vs 1.74 ± 0.89, P = 0.001). RV myocardial performance index was significantly higher in the asthma group than in the control group (0.28 ± 0.06 vs 0.24 ± 0.07, respectively; P = 0.003). Finally, serum NT-proBNP concentration was significantly higher in the asthma group than in the control group (292.3 ± 142.2 pg/mL vs 208.2 ± 70.1 pg/mL, respectively; P = 0.003).. Increased serum NT-proBNP is associated with subclinical RV dysfunction in asthmatic children. RV function is significantly affected in children with bronchial asthma.

Topics: Adolescent; Asthma; Biomarkers; Case-Control Studies; Child; Echocardiography, Doppler; Female; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Severity of Illness Index; Ventricular Dysfunction, Right

During the attacks of acute severe bronchial asthma there are marked cardiopulmonary changes leading to hypoxia. The study aims to find the incidence of myocardial dysfunction in patients of acute severe bronchial asthma based on cardiac enzyme levels at admission and see whether the myocardial damage is transient or persistent even after stabilization of the patient based on enzyme levels at discharge.. This prospective, case control study was done at Department of Pediatrics, Institute of Medical Sciences, Banaras Hindu University between October 2016 to May 2018. Sixty pediatric patients of acute severe bronchial asthma were taken as cases and 15 age and sex matched children served as controls. Blood samples were collected in Ethylene diamine tetra acetic acid vials before the start of treatment, for measurement of cardiac biomarkers Troponin I (TnI), Brain natriuretic peptide (BNP) and Creatine Kinase-muscle/brain (CK-MB) and repeat samples were taken before discharge.. Fifty percent of the cases had abnormal TnI levels, 15% had abnormal CK-MB levels and 8.3% had abnormal BNP levels at admission. At discharge, only 1 (1.7%) case had abnormal levels of CK-MB, whereas the levels of TnI and BNP normalized in all. The level of cardiac biomarkers were significantly raised at admission when compared to discharge values (p value < 0.001).. The raised cardiac biomarkers suggest myocardial stress during acute exacerbation of bronchial asthma. Though, the present study showed that the changes are of transient nature, larger follow up studies are required to document any permanent damage to myocardium.

Topics: Adolescent; Asthma; Biomarkers; Case-Control Studies; Child; Child, Preschool; Creatine Kinase, MB Form; Female; Follow-Up Studies; Humans; India; Male; Myocardial Infarction; Natriuretic Peptide, Brain; Prevalence; Prospective Studies; Severity of Illness Index; Troponin I; Troponin T

The etiologic diagnosis of acute dyspnea in the emergency department (ED) remains difficult, especially for elderly patients or those with previous cardiorespiratory medical history. This may lead to inappropriate treatment and potentially a higher mortality rate. Our objective was to evaluate the performance of cardiopulmonary ultrasound compared with usual care for the etiologic diagnosis of acute dyspnea in the ED.. Patients admitted to the ED for acute dyspnea underwent upon arrival a cardiopulmonary ultrasound performed by an emergency physician, in addition to standard care. The performances of the clinical examination, chest x-ray, N-terminal brain natriuretic peptide (NT-proBNP), and cardiopulmonary ultrasound were compared with the final diagnosis made by 2 independent physicians.. One hundred thirty patients were analyzed. For the diagnosis of acute left-sided heart failure, cardiopulmonary ultrasound had an accuracy of 90% (95% confidence interval [CI], 84-95) vs 67% (95% CI, 57-75), P = .0001 for clinical examination, and 81% (95% CI, 72-88), P = .04 for the combination "clinical examination-NT-proBNP-x-ray". Cardiopulmonary ultrasound led to the diagnosis of pneumonia or pleural effusion with an accuracy of 86% (95% CI, 80-92) and decompensated chronic obstructive pulmonary disease or asthma with an accuracy of 95% (95% CI, 92-99). Cardiopulmonary ultrasound lasted an average of 12 ± 3 minutes.. Cardiopulmonary ultrasounds performed in the ED setting allow one to rapidly establish the etiology of acute dyspnea with an accuracy of 90%.

Topics: Aged; Aged, 80 and over; Asthma; Cohort Studies; Disease Progression; Dyspnea; Echocardiography; Emergency Service, Hospital; Female; Heart Failure; Humans; Lung; Male; Natriuretic Peptide, Brain; Peptide Fragments; Physical Examination; Pleural Effusion; Pneumonia; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Radiography, Thoracic; Sensitivity and Specificity

The airway epithelium acts as a barrier and provides a critical interface between the body and the external environment. Brain natriuretic peptide (BNP) plays an important role in several bronchial functions, including relaxation. BNP relaxes airways by binding and activating natriuretic peptide receptor-A expressed from the airway epithelium. Although relaxation effect has been extensively investigated, less is known about BNP-regulated intracellular biomolecular pathways leading to bronchial relaxation. To this aim, we investigated BNP effects on gene signalling of airway smooth muscle cells (ASM) obtained from donors with asthma by using a RT(2) profiler™ PCR array. When compared with control, treatment for 2 h with supernatant from BNP-treated (1 μM) bronchial epithelial cells (BEAS-2B) induced in asthmatic ASM cells a rapid reduction of transcription of EGFR and genes involving in actin and calcium homeostasis, as those of Protein kinase C (PKC) and RhoA-ROCK gene pathways. Immunofluorescence and western blotting did not shown any difference comparing control and ASM cells treated with conditioned medium from BNP-treated BEAS-2B. This study provides evidence that the effect of BNP on relaxing bronchial in ASM cells is mediated from epithelium and associates to rapid changes of EGFR and calcium homeostasis-associated gene levels.

Topics: Asthma; Bronchi; Calcium; Epithelial Cells; Genes, erbB-1; Homeostasis; Humans; Muscle Relaxation; Myocytes, Smooth Muscle; Natriuretic Peptide, Brain; Protein Kinase C; rho-Associated Kinases; rhoA GTP-Binding Protein; Transcription, Genetic

Brain natriuretic peptide (BNP) relaxes airways by activating natriuretic peptide receptor-A and elevating cyclic guanosine monophosphate. BNP is more effective in passively sensitized human bronchi compared with control airways. The molecular and cellular patterns involved in this signaling are unknown. The aim of this study was to investigate the influence of BNP on airway smooth muscle (ASM) cells obtained from donors with asthma and healthy donors and to identify the mechanisms involved in BNP-mediated relaxation. The contractile response of ASM cells was microscopically assessed in vitro in the presence of 1 μM BNP or with supernatant from human bronchial epithelial (BEAS-2B) cells pretreated with 1 μM BNP. We investigated the role of muscarinic M2 receptors and inducible nitric oxide synthase (iNOS), quantified the release of acetylcholine and nitric oxide (NO), and assessed the gene/protein expression of iNOS and myosin phosphatase target subunit 1 (MYPT1). Supernatant from BEAS-2B cells treated with BNP reduced the hyperreactivity of asthmatic ASM cells by shifting the potency of histamine by 1.19-fold but had no effect in healthy ASM cells. BNP was not effective directly on ASM cells. Blocking muscarinic M2-receptors and iNOS abolished the protective role of supernatant from BEAS-2B treated with BNP. BNP stimulated the release of acetylcholine (210.7 ± 11.1%) from BEAS-2B cells that in turn increased MYPT1 and iNOS gene/protein expression and enhanced NO levels in asthmatic ASM supernatant (35.0 ± 13.0%). This study provides evidence that BNP protects against bronchial hyperresponsiveness via an interaction between respiratory epithelium and ASM in subjects with asthma.

Topics: Acetylcholine; Anti-Asthmatic Agents; Asthma; Bronchial Hyperreactivity; Bronchoconstriction; Bronchoconstrictor Agents; Case-Control Studies; Cell Communication; Cells, Cultured; Coculture Techniques; Culture Media, Conditioned; Dose-Response Relationship, Drug; Epithelial Cells; Humans; Muscle, Smooth; Myocytes, Smooth Muscle; Myosin-Light-Chain Phosphatase; Natriuretic Peptide, Brain; Nitric Oxide; Nitric Oxide Synthase Type II; Receptor, Muscarinic M2; Respiratory Mucosa; Signal Transduction

Dyspnea is a subjective experience of breathing discomfort; patients experience qualitatively distinct sensations that vary in intensity. Acute dyspnea might be secondary to an acute problem, or it might be an exacerbation of an existing disease (eg, asthma, chronic obstructive pulmonary disease, heart failure). It also accompanies a variety of illnesses at the end of life. New information has changed differentiation between respiratory and cardiovascular etiologies of acute dyspnea, as well as rapid diagnosis of pulmonary embolism. Management of acute dyspnea from hypercapnic failure also has changed. Patients presenting with dyspnea most commonly have underlying cardiovascular and/or respiratory etiologies, and differentiating between the two can be challenging. B-type natriuretic peptide (BNP) and N-terminal proB-type natriuretic peptide (NT-proBNP) are elevated when ventricular wall tension increases (eg, during a heart failure exacerbation). BNP and NT-proBNP are most useful for identifying patients with dyspnea who do not have heart failure. A BNP level less than 50 pg/mL has a negative predictive value of 96%, effectively ruling out heart failure; a serum BNP level less than 100 pg/mL has a negative likelihood ratio of 0.11. Patients with pulmonary embolism often present with dyspnea, and this condition needs to be diagnosed and managed expeditiously. When pulmonary embolism is suspected, use a clinical decision rule (eg, the Wells rule, the Geneva rule) to establish the probability of this condition. For patients with a low probability, obtain a D-dimer test; if the D-dimer result is negative, monitor the patient. A positive D-dimer result requires further investigation. For patients with intermediate or high probability, obtain computed tomography pulmonary angiography for a definitive diagnosis. Patients who have dyspnea from a chronic obstructive pulmonary disease exacerbation can experience hypercapnic failure. As an adjunct to usual medical treatment, noninvasive positive pressure ventilation decreases the need for mechanical ventilation and is particularly useful in patients who have chosen not to be resuscitated with intubation.

Topics: Acute Disease; Asthma; Biomarkers; Decision Support Systems, Clinical; Diagnosis, Differential; Dyspnea; Female; Fibrin Fibrinogen Degradation Products; Heart Failure; Humans; Middle Aged; Natriuretic Peptide, Brain; Oxygen Inhalation Therapy; Peptide Fragments; Pulmonary Disease, Chronic Obstructive; Pulmonary Embolism; Respiratory Tract Diseases

Topics: Asthma; Bronchi; Epithelial Cells; Humans; Muscle, Smooth; Natriuretic Peptide, Brain; Pulmonary Disease, Chronic Obstructive

The prognostic value of NT-proBNP levels in patients admitted to hospital due to acute exacerbations of chronic pulmonary diseases (CPDs) is unknown.. Internal Medicine units at two general hospitals.. NT-proBNP levels were obtained within 72 h after admission in 192 consecutive patients with acute exacerbations of CPDs and no history of heart failure or diuretic treatment. Clinical characteristics and main outcomes were assessed over a 12-month follow-up. NT-proBNP cut-points for outcomes were obtained by ROC (receiver operating characteristics) curve analysis.. Chronic obstructive lung disease (69.3%) and chronic asthma (22.4%) were the most prevalent CPDs, and non-pneumonic acute respiratory infection (72.4%) and pneumonia (22.9%) were the most frequent causes of exacerbation. Atrial flutter or fibrillation rate was 11%. During the one-year follow-up period, 22 patients died, 42 were re-admitted, 46 received new long-term oxygen therapy, and 39 received new diuretic treatment. NT-proBNP values correlated with hospitalisation days. NT-proBNP values over 587.9 pg/ml were associated with significantly raised one-year mortality (OR=3.90; 95% IC 1.46-10.47; p=0.006) and over 782.2 pg/ml with cardio-pulmonary deaths (OR=6.38; 95% IC 1.91-21.3; p=0.002). That association persisted after adjustment for age, gender, creatinine levels and cardiac rhythm. NT-proBNP values over 628.7 pg/ml were associated with significantly higher probability of new diuretic treatment (OR=4.38; IC 95% 2.07-9.25; p<0.001). The negative predictive values for these cut-points ranged from 89% to 97%.. NT-proBNP levels below 587.9 pg/ml in patients with acute exacerbations of CPD were associated with favourable one-year outcomes.

Topics: Adult; Aged; Aged, 80 and over; Asthma; Chronic Disease; Female; Follow-Up Studies; Humans; Lung Diseases; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pneumonia; Prevalence; Prognosis; Protein Precursors; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Infections; ROC Curve; Severity of Illness Index

The diagnosis and treatment of dyspnea in the emergency department and in the prehospital setting is a challenge faced by the emergency physician and other prehospital care providers. While the use of lung ultrasound as a diagnostic tool in dyspneic patients has been well researched, there has been limited evaluation of its use in the prehospital setting. In the previous issue of Critical Care, Prosen and colleagues study the accuracy of lung ultrasound compared with both N-terminal pro-brain natriuretic peptide and the clinical examination for differentiating between acute decompensated congestive heart failure and chronic obstructive pulmonary disease exacerbations for patients in the prehospital setting. Their article adds to the growing body of evidence demonstrating the diagnostic efficacy of lung ultrasound in differentiating between these two disease processes in the acutely dyspneic patient.

Topics: Asthma; Dyspnea; Emergency Medical Services; Female; Heart Failure; Humans; Lung; Male; Natriuretic Peptide, Brain; Pulmonary Disease, Chronic Obstructive; Ultrasonography

We conducted a cross-sectional study to investigate which factors have a significant impact on wheezing and QOL in the elderly of a Japanese local community.. In 2008, 527 participants (250 participants aged 45 to 64 years and 277 participants aged 65 to 88 years) responded to the questionnaire regarding wheezing and disease history. QOL was evaluated by the Short Form-8. The participants underwent airway reversibility testing. The plasma levels of IgE were measured. The plasma levels of N-terminal-pro-B-type natriuretic peptide were measured in twenty-one participants with a history of ischemic heart disease and in thirty-five age-matched participants without that history.. Wheezing was reported by 50 (9.5%) participants and was associated with a lower score of QOL. In multivariate analysis, wheezing was associated with sex (OR 3.12, CI 1.10-9.67) and a history of bronchial asthma (OR 22.3, CI 6.50-84.0) among participants aged 45 to 64 years. Among participants aged 65 and over, wheezing was associated with a history of bronchial asthma (OR 4.86, CI 1.39-15.1) and ischemic heart disease (OR 5.12, CI 1.61-15.0). Participants with both a history of ischemic heart disease and wheezing showed higher levels of N-terminal-pro-B-type natriuretic peptide. Airway reversibility was only associated with a history of ischemic heart disease (OR 4.65, CI 1.26-17.6).. It is suggested that bronchial asthma and heart disease are both significant causes of wheezing and affect the QOL in the elderly of a Japanese local community.

Topics: Aged; Aged, 80 and over; Asian People; Asthma; Cross-Sectional Studies; Female; Humans; Immunoglobulin E; Japan; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Quality of Life; Respiratory Sounds; Surveys and Questionnaires

Early diagnosis of chronic obstructive pulmonary disease (COPD) with latent pulmonary hypertension (PH) and cor pulmonale is important because the prognosis of this condition is poor.. To investigate the utility of brain natriuretic peptide (BNP) for prognostication of COPD, plasma BNP was measured in patients with COPD without symptoms or physical findings of PH or cor pulmonale.. Plasma BNP was measured in 60 patients with COPD, 10 asthmatics, and 30 healthy subjects. Echocardiography, arterial blood gas analysis, and spirometry were also performed. Mortality and exacerbation were compared between COPD patients with high and low plasma BNP levels over a 3-year follow-up period.. Plasma BNP (mean +/- SEM, pg/mL) in COPD patients (41.0+/-6.6) was significantly higher than in normal subjects (14.8+/-2.7) and asthmatics (17.4+/-4.5) (p<0.0001 and p<0.05, respectively). No significant correlations were observed between plasma BNP level and pulmonary function or hypoxia. There was, however, a significant correlation between plasma BNP level and % ejection fraction (r=-0.41, p=0.0197) and pulmonary artery systolic pressure (r=0.5, p=0.004). The period until initial COPD exacerbation in subjects with a high plasma BNP level was significantly shorter (p<0.05). Plasma BNP level during exacerbations (79.9+/-16.2) was also significantly higher than during stable disease (41.2+/-8.7) (p=0.004).. We suggest that plasma BNP is a non-invasive biomarker that can be used as a screening parameter for latent PH and left ventricular dysfunction, and also as a predictor of exacerbation in stable COPD.

Topics: Adult; Aged; Asthma; Biomarkers; Bronchodilator Agents; Carbon Dioxide; Case-Control Studies; Disease Progression; Echocardiography; Female; Follow-Up Studies; Humans; Hypertension, Pulmonary; Japan; Male; Middle Aged; Natriuretic Peptide, Brain; Oxygen; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Pulmonary Heart Disease; Smoking; Spirometry; Stroke Volume

We evaluate results from amino-terminal pro-brain natriuretic peptide (NT-proBNP) testing with or without those of clinical judgment for the evaluation of dyspneic patients with previous chronic obstructive pulmonary disease or asthma.. As a secondary analysis of previously collected observational data from a convenience sample of 599 breathless patients, 216 patients with previous chronic obstructive pulmonary disease or asthma who presented to the emergency department were analyzed according to results of NT-proBNP, clinical impression, and their final diagnosis. Test performance of NT-proBNP in these patients with chronic obstructive pulmonary disease or asthma was examined for the group as a whole, as well as in patients with and without previous heart failure. NT-proBNP results were compared to clinician-estimated likelihood for heart failure using receiver operating curves and as a function of NT-proBNP plus clinical evaluation. The final diagnosis was determined by 2 independent cardiologists blinded to NT-proBNP using all available data from the 60-day follow-up period.. Overall, 55 patients (25%) had acute heart failure; the median value of NT-proBNP was higher in these patients compared with those without acute heart failure (2,238 vs 178 pg/mL); use of cut points of 450 pg/mL for patients younger than 50 years and 900 pg/mL for patients 50 years or older yielded a sensitivity of 87% (95% confidence interval [CI] 72% to 93%) and a specificity of 84% (95% CI 76% to 88%). In patients without previous heart failure (n=164), median NT-proBNP levels were also higher in patients with heart failure of new onset compared with those with chronic obstructive pulmonary disease or asthma exacerbation (1561 versus 168 pg/mL). High clinical suspicion for acute heart failure (probability >80%) detected only 23% of patients with new-onset heart failure, whereas 82% of these patients had elevated NT-proBNP levels. In patients who had both previous acute heart failure and chronic obstructive pulmonary disease or asthma (n=52), median NT-proBNP levels were significantly higher in those with acute heart failure (4,435 pg/mL) than patients with chronic obstructive pulmonary disease or asthma exacerbation (536 pg/mL). In patients with acute-on-chronic heart failure, NT-proBNP levels were elevated in 91%, whereas clinical impression considered only 39% of cases as high likelihood for acute heart failure.. NT-proBNP may be a useful adjunct to standard clinical evaluation of dyspneic patients with previous obstructive airway disease.

Topics: Acute Disease; Aged; Asthma; Biomarkers; Diagnosis, Differential; Dyspnea; Female; Heart Failure; Humans; Logistic Models; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Disease, Chronic Obstructive; Retrospective Studies; ROC Curve; Sensitivity and Specificity

Plasma B-type natriuretic peptide (BNP) can reliably identify acute congestive heart failure (CHF) in patients presenting to the emergency department (ED) with acute dyspnea. Heart failure, asthma, and chronic obstructive pulmonary disease (COPD) are syndromes where dyspnea and wheezing are overlapping signs, and hence, these syndromes are often difficult to differentiate.. To determine whether BNP can distinguish new-onset heart failure in patients with COPD or asthma presenting with dyspnea to the ED.. The BNP Multinational Study was a seven-center prospective study of 1,586 adult patients presenting to the ED with acute dyspnea who had blinded BNP levels measured on arrival with a rapid, point-of-care device. This study evaluated the 417 patients with no previous history of heart failure and a history of asthma or COPD as a subgroup from the 1,586 adult patients in the BNP Multinational Study. The reference standard for CHF was adjudicated by two independent cardiologists, also blinded to BNP results, who reviewed all clinical data and standardized CHF scores.. A total of 417 subjects (mean age 62.2 years, 64.4% male) had a history of asthma or COPD without a history of CHF. Of these, 87/417 (20.9%, 95% CI = 17.1% to 25.1%) were found to have CHF as the final adjudicated diagnosis. The emergency physicians identified a minority, 32/87 (36.8%), of these patients with CHF. The mean BNP values (+/- SD) were 587.0 +/- 426.4 and 108.8 +/- 221.3 pg/mL for those with and without CHF (p < 0.0001). At a cutpoint of 100 pg/mL, BNP had the following decision statistics: sensitivity 93.1%, specificity 77.3%, positive predictive value 51.9%, negative predictive value 97.7%, accuracy 80.6%, positive likelihood ratio 4.10, and negative likelihood ratio 0.09. If BNP would have been added to clinical judgment (high > or = 80% probability of CHF), at a cutpoint of 100 pg/mL, 83/87 (95.4%) of the CHF subjects would have been correctly diagnosed. Multivariate analysis found BNP to be the most important predictor of CHF (OR = 12.1, 95% CI = 5.4 to 27.0, p < 0.0001). In the 87 subjects found to have CHF, 39.0%, 22.2%, and 54.8% were taking angiotensin-converting enzyme inhibitors (ACEIs), beta-blockers (BBs), and diuretics on a chronic basis, respectively.. The yield of adding routine BNP testing in patients with a history of asthma or COPD in picking up newly diagnosed CHF is approximately 20%. This group of patients presents a substantial therapeutic opportunity for the initiation and chronic administration of ACEI and BB therapy, as well as other CHF management strategies.

Topics: Aged; Asthma; Atrial Natriuretic Factor; Cardiotonic Agents; Comorbidity; Female; Heart Failure; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Prospective Studies; Pulmonary Disease, Chronic Obstructive

We compared the effects of natriuretic peptides on antigen-induced bronchoconstriction and airway microvascular leakage in sensitized guinea pigs. Anesthetized male guinea pigs, ventilated via a tracheal cannula, were placed in a plethysmograph to measure pulmonary mechanics for 10 min after challenge with 1 mg/kg of ovalbumin, and then Evans blue dye was extravasated into airway tissue in order to indicate and evaluate microvascular leakage. Three separate intravenous pretreatments using atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) significantly inhibited the ovalbumin-induced bronchoconstriction and microvascular leakage in a dose-dependent manner. These inhibitory effects were mimicked by 8-bromoguanosine 3',5'-cyclic monophosphate. We showed that the rank order of inhibitory potencies, which were mediated by cyclic guanosine 3',5'-monophosphate, was BNP > or = ANP > or = CNP. These results gave us some clues for the clinical application of the natriuretic peptides.

Topics: Animals; Antigens; Asthma; Atrial Natriuretic Factor; Blood Pressure; Bronchi; Bronchoconstriction; Capillary Permeability; Cyclic GMP; Disease Models, Animal; Guinea Pigs; Leukotriene D4; Male; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Nerve Tissue Proteins; Ovalbumin; Proteins; Trachea