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PubMed2005

Exercise intolerance in patients with atrial fibrillation: clinical and echocardiographic determinants of exercise capacity.

Although exercise intolerance is a major symptom of patients with atrial fibrillation (AF), the factors limiting these patients' exercise capacity remains uncertain. This study evaluated the correlation of clinical and echocardiographic parameters with exercise capacity of patients with AF. In all, 73 patients (61 men and 12 women; mean age 61 years) with chronic AF were included in this study. Those patients with primary valvular diseases were excluded. Standard 2-dimensional and Doppler echocardiography was performed, and we averaged 10 consecutive measurements of each variable. Patients then underwent a symptom-limited treadmill exercise testing. We also measured patients' plasma levels of B-type natriuretic peptide before exercise testing. Of all clinical and echocardiographic parameters we assessed, age (r = -0.45, P = .006), ratio of early mitral inflow velocity to mitral annular velocity (r = -0.35, P = .032), and baseline heart rate were independent predictors of exercise capacity on multivariate regression analysis. In conclusion, patient's age, averaged ratio of early mitral inflow velocity to mitral annular velocity, and baseline heart rate provided useful information on exercise intolerance for patients with AF. Ratio of early mitral inflow velocity to mitral annular velocity, a noninvasive tool for estimating left ventricular filling pressure, may especially have important value for predicting functional capacity in this population as it has in individuals with in sinus rhythm.

Atrial Fibrillation↗
PubMed1999

[Exhaled nitric oxide of childhood asthma].

Chronic airway inflammation is a central feature of pathology of bronchial asthma. In order to evaluate inflammatory status in asthma, examinations such as bronchoscope or induced sputum test can be done. Because of difficulty of those examinations we need non-invasive and simple measures for childhood asthma. Here we investigated eNO in childhood asthma. Twenty-six of atopic asthma, 13 non-asthmatic atopic children and 12 normal children were enrolled in this study. eNO was measured by chemiluminescence analyzer. eNO was significantly collerated with % FEV 1.0 and blood eosinophil counts (R = -0.494, R = 0.416, respectively). Geometrical mean of eNO in normal, non-asthmatic atopic, asthma without inhaled corticosteroid (ICS) and asthma with ICS was 16.3, 23.7, 71.6, 43.6 ppb, respectively. eNO was significantly higher in asthma than in normals. eNO in patients without ICS were significantly higher than in non-asthmatic atopic. We concluded that eNO might be useful marker for evaluation of airway inflammation in asthmatic children.

Asthma↗
PubMed2001

High levels of nitric oxide in individuals with pulmonary hypertension receiving epoprostenol therapy.

Lack of vasodilator substances, such as nitric oxide (NO), has been implicated in the development of pulmonary hypertension, but the pathogenesis of the disease remains speculative. We hypothesized that NO plays a role in the pathogenesis of primary pulmonary hypertension (PPH), and may serve as a sensitive and specific marker of disease progression and/or severity. To test this, exhaled NO and pulmonary artery pressure were measured in individuals with PPH and secondary pulmonary hypertension (SPH) on various therapies, including the potent vasodilator epoprostenol (prostacyclin), compared with healthy controls. NO in exhaled breath of individuals with PPH was lower than SPH or control (p<0.05). In contrast, exhaled NO of individuals with PPH or SPH receiving epoprostenol was strikingly higher than PPH or SPH individuals not receiving epoprostenol, or controls. Concomitant with higher NO levels, right ventricular systolic pressure of individuals significantly decreased with epoprostenol. Importantly, in paired measures of exhaled NO before and after epoprostenol, NO increased in all pulmonary hypertensive individuals 24 h after initiation of epoprostenol therapy (p<0.05). NO may be a useful noninvasive marker of pulmonary hypertension severity and response to prostacyclin therapy.

Adolescent↗
PubMed2005

Clinical use of noninvasive measurements of airway inflammation in steroid reduction in children.

The use of noninvasive methods of monitoring airway inflammation, such as exhaled nitric oxide (eNO) and induced sputum, has been shown to improve asthma monitoring and optimize treatment in adult patients with asthma. There is a lack of comparable data in children. Forty children with stable asthma eligible for inhaled steroid reduction were reviewed every 8 weeks, and their inhaled steroid dose halved if clinically indicated. eNO, sputum induction combined with bronchial hyperreactivity testing, and exhaled breath condensate collection were performed at each visit to predict success or failure of reduction of inhaled steroids. Thirty of 40 (75%) children tolerated at least one dose reduction, 12 of 40 (30%) were successfully weaned off, and in total, 15 of 40 (38%) children experienced loss of asthma control. Treatment reduction was successful in all children who had no eosinophils in induced sputum before the attempted reduction. Using multiple logistic regression, increased eNO (odds ratio, 6.3; confidence interval, 3.75-10.58) and percentage of sputum eosinophils (odds ratio, 1.38; confidence interval, 1.06-1.81) were significant predictors of failed reduction. These findings suggest that monitoring airway inflammation may be useful in optimizing treatment in children with asthma.

Administration, Inhalation↗
PubMed1999

[A sensitive enzyme immunoassay for the measurement of small quantities of erythrocyte-associated IgG in patients with systemic lupus erythematosus who had negative direct antiglobulin test].

To measure the amount of erythrocyte-associated IgG (EAIgG) molecules from 70 patients with systemic lupus erythematosus (SLE) who had negative direct antiglobulin test (DAT), we employed a sensitive enzyme-linked immunosorbent assay (ELISA) technique. Ninety-five percent of healthy individuals were less than 65 molecules of EAIgG per red cell (RBC). About 51 percent of these patients with SLE were positive (over 65 molecules of EAIgG per RBC) by this technique that showed more sensitive than the DAT. EAIgG levels of these patients were inversely proportional to RBC count (r = -0.369, p < 0.005), and EAIgG positive patients were recognized by 88 percent in patients group who were less than 4 x 10(6)/microliter RBC counts. These results suggest that even a few EAIgG, as of a DAT shows negative, are related to the catabolism of erythrocytes in patients with SLE. EAIgG determination value in this method calculated and converted with CRM 470 that is the IFCC international reference preparation for plasma protein.

Biomarkers↗
PubMed2005

Collection of exhaled breath condensate and analysis of hydrogen peroxide as a potential marker of lower airway inflammation in cats.

The objective of this study was to describe a standardised and non-invasive method for exhaled breath condensate (EBC) collection in cats and to test whether determination of hydrogen peroxide (H(2)O(2)) in EBC might be used as marker of lower airway inflammation. The technique of barometric whole body plethysmography for cats was combined with a system to condense the effluent air from the plethysmograph, allowing simultaneous EBC collection and respiratory pattern measurement. H(2)O(2) was determined spectrophotometrically. Eighteen experimental cats were used to investigate the impact on EBC volume and EBC H(2)O(2) of plethysmograph ventilation rate, collection duration, sample stability, within-day and day-to-day variability. After determination of a standardised EBC collection procedure, correlation analyses between EBC H(2)O(2) and bronchoalveolar lavage (BAL) cytology of healthy and allergen-challenged Ascaris suum (AS)-sensitised cats were performed. A significant and positive correlation between EBC H(2)O(2) and bronchoalveolar lavage (BAL) neutrophil% was found in healthy cats (P < 0.001, r = 0.55), whereas in AS-sensitised cats, correlation with BAL eosinophil% was significant (P < 0.005, r = 0.61). H(2)O(2) was increased after an allergen challenge in AS-sensitised cats (n = 6, 0.56+/-0.12 versus 1.08+/-0.35 micromol/L, P < 0.05). This study proposes a non-invasive, well tolerated and repeatable method of EBC collection for cats and suggests that EBC H(2)O(2) might be used as non-invasive biomarker for monitoring lower airway inflammation.

Airway Obstruction↗
PubMed2005

Exhaled breath condensate cytokine patterns in chronic obstructive pulmonary disease.

Differences in cytokine patterns in stable chronic obstructive pulmonary disease (COPD), exacerbated COPD, smokers without apparent COPD, and healthy volunteers should be of interest for pathophysiological and therapeutic reasons. Methods including lavage, biopsy and sputum have been employed to investigate cytokines in the lung. For asystematic comparison, exhaled breath condensate (EBC) appears to be well suited. We investigated healthy volunteers, smokers without apparent COPD, stable and exacerbated COPD patients (+/- inhalative steroids) and finally those whose exacerbation made mechanical ventilation inevitable, for a more complete picture of inflammatory cytokines in COPD. We chose EBC because it is non-invasive and can be used repeatedly in spontaneous breathing individuals and during mechanical ventilation. EBC cytokines (IL-1 beta, IL-6, IL-8, IL-10, IL-12 p 70, TNF-alpha) were assayed from a single sample using a multiplex array test kit. We observed a significant increase of all cytokines in acute exacerbation compared to stable COPD, smokers, and volunteers. Stable COPD and volunteers exhibited only small differences in cytokine pattern with respect to IL-1 beta and IL-12 (P<0.01). Smokers had increased levels of all investigated cytokines (P<0.01) compared to non-smokers and, with the exception of IL-1 beta, to stable COPD. Inhaled steroids resulted in reduced levels of IL-1 beta, IL-6, IL-8, IL-10, and IL-12 (all: P<0.01) in stable COPD (all: ex-smokers) with dose dependency for IL-8, IL-1 beta and IL-12. EBC analysis successfully characterized important differences in stable COPD compared to exacerbation or smoking and non-smoking healthy individuals.

Adult↗
PubMed2006

A critical reappraisal of the WHO classification of the chronic myeloproliferative disorders.

Following the introduction of the WHO classification of chronic myeloproliferative disorders (MPDs), after approximately 5 years, a critical reappraisal appears to be warranted. Retrospective clinico-pathological evaluations conducted in the meantime, as well as the detection of new biomarkers, may aid in testing the validity of these new criteria. Based on a large series of patients with chronic myeloid leukemia (CML), an analysis of bone marrow (BM) features and risk classifications revealed that the fiber content exerted a most important and independent impact on prognosis. This finding was also supported in a prospective randomized study and therefore myelofibrosis should be included in any staging system in CML related to survival. Moreover, it is important to emphasize the dynamics of the disease process in MPDs, especially in polycythemia vera (PV) and chronic idiopathic myelofibrosis (CIMF). Latent-stage PV is difficult to recognize when adhering to the proposed limits for hemoglobin (or red cell mass) without regarding the erythropoietin (EPO) level, endogenous erythroid colonies (EECs) or BM histopathology. Initial PV may firstly present with complications and, when accompanied by a high platelet count, mimics essential thrombocythemia (ET). Consequently, BM morphology and EPO level should be entered as major diagnostic criteria for PV. To document more accurately the progress of disease, a simplified scoring system concerning myelofibrosis has to be included in the histological description of CIMF. The diagnostic guidelines of BM features in ET should be improved because, usually, there is neither a significant proliferation nor left-shifting of the granulo- and erythropoiesis detectable and no relevant increase in reticulin. A comparison of clinical data and BM morphology reveals that biomarkers (EPO, EECs, PRV-1, JAK2) show an overlapping pattern of positivity between the different subtypes of MPDs.

Chronic Disease↗
PubMed2005

The role of radiotracer imaging in Parkinson disease.

Radiotracer imaging (RTI) of the nigrostriatal dopaminergic system is a widely used but controversial biomarker in Parkinson disease (PD). Here the authors review the concepts of biomarker development and the evidence to support the use of four radiotracers as biomarkers in PD: [18F]fluorodopa PET, (+)-[11C]dihydrotetrabenazine PET, [123I]beta-CIT SPECT, and [18F]fluorodeoxyglucose PET. Biomarkers used to study disease biology and facilitate drug discovery and early human trials rely on evidence that they are measuring relevant biologic processes. The four tracers fulfill this criterion, although they do not measure the number or density of dopaminergic neurons. Biomarkers used as diagnostic tests, prognostic tools, or surrogate endpoints must not only have biologic relevance but also a strong linkage to the clinical outcome of interest. No radiotracers fulfill these criteria, and current evidence does not support the use of imaging as a diagnostic tool in clinical practice or as a surrogate endpoint in clinical trials. Mechanistic information added by RTI to clinical trials may be difficult to interpret because of uncertainty about the interaction between the interventions and the tracer.

Biomarkers↗
PubMed1998

Breath pentane as a marker for lipid peroxidation and adverse outcome in preterm infants.

AIM: To test the hypothesis that complications of neonatal intensive care are related to increased oxygen derived free radical activity, using breath pentane as a marker of lipid peroxidation. METHODS: Exhaled breath was collected daily from 57 ventilated preterm infants and pentane concentration measured by gas chromatography. RESULTS: High peak pentane exhalation was significantly associated with low gestational age, mortality, intraventricular haemorrhage and retinopathy of prematurity. Peak pentane was not significantly associated with the development of chronic lung disease. CONCLUSIONS: The demonstration that pentane exhalation is related to the course of neonatal disease and its outcome is consistent with the hypothesis that lipid peroxidation is associated with these illnesses, and may contribute to their severity. If this is a causal relation, antioxidant treatments could prove useful in reducing their severity. Measurement of breath pentane might assist in the assessment of antioxidant strategies prior to more extensive clinical trials.

Biomarkers↗
PubMed2005

Passive smoking does not increase hydrogen peroxide (H2O2) levels in exhaled breath condensate in 9-year-old healthy children.

Environmental tobacco smoke, also called passive smoking, was shown to have adverse effects on the health of children. Hydrogen peroxide (H2O2) is proposed as a sensitive marker of oxidative injury and inflammatory processes in the airways, being increased in adult active cigarette smokers. We tested whether passive smoking had an influence on H2O2 exhalation in healthy children. Thirty healthy passive smoking and 24 nonexposed healthy children aged 9 years were included in the study. Exhaled breath condensate (EBC) was obtained by spontaneous tidal volume breathing with EcoScreen (Jaeger, Germany). All subjects underwent flow-volume measurements immediately after EBC collection. Levels of H2O2 were measured fluorimetrically with the homovanillic acid method. Lung function did not differ between the passive smoking and nonexposed children groups. In the passive smoking group, EBC H2O2 concentration (median and range) was 0.32 (0.00-1.20) microM, and did not differ significantly (P >0.05) from that found in the nonexposed group, i.e., 0,22 (0.00-0.68) microM. Exhaled H2O2 did not correlate with spirometric parameters (FEV1, FEV1%FVC, and MEF50%FVC) in either group. We conclude that passive smoking does not increase H2O2 exhalation in healthy children.

Biomarkers↗
PubMed2006

[Nocturnal secretion of melatonin in subjects with asymptomatic and symptomatic Helicobacter pylori infection].

UNLABELLED: Melatonin is synthesized not only in the pineal gland, but also in gastrointestinal tract by enterochromaffin cells (EC) and it has a gastroprotective properties. Helicobacter pylori infection causes functional and organic changes of gastric mucosa, particularly in endocrine cells (D, G, ECL, EC). AIM: The aim of own studies was to evaluate nocturnal secretion of Melatonin in subjects with asymptomatic and symptomatic (dyspepsia, duodenal ulcer disease) H. pylori infection (Hp). MATERIAL AND METHODS: 116 subjects, aged 19-61 years were included in this study. Four groups were distinguished: group I (n=30) healthy subjects, Hp (-), group II (n=26)--subjects with asymptomatic infection Hp, group III (n=32) patients with ulcer-like dyspepsia, Hp (+), and group IV (n=28) patients with duodenal ulcer Hp(+). H. pylori infection was diagnosed by using urea breath test (UBT-(13)C) and rapid urease test. The concentration of melatonin in serum was measured with ELISA method, before and after eradication of H. pylori. Blood samples were taken for examination at 10:00 p.m., 2:00 a.m. and 6:00 a.m. RESULTS: The average melatonin concentration at night hours was found in group I--34.74 +/- 4.77 pg/ml, in group II--48.29 +/- 12.22 pg/ml (p < O.005), in group III--41.56 +/- 12.31 pg/ml (p > 0.05) and in group IV--26.16 +/- 6.89 pg/ml p < 0.01). Such statistical differences were not observed in all group after eradication H. pylori. CONCLUSIONS: (1) Nocturnal secretion of melatonin in subjects with asymptomatic infection of H. pylori is higher than in patients with ulcer-like dyspepsia and with duodenal ulcer disease. (2) Lower nocturnal secretion of melatonin probably may play role in pathogenesis of upper digestive tract diseases.

Adult↗
PubMed2002

Cardiac troponin I: a potential marker of exercise intolerance in patients with moderate heart failure.

BACKGROUND: In severe heart failure, increased values of cardiac troponins have been detected during decompensation. In this study, we investigated whether an increase of cardiac troponin I can be observed after symptom-limited exercise and after an exercise training session in patients with moderate heart failure. METHODS: Twenty-seven patients with moderate heart failure (New York Heart Association II-III, ejection fraction 31% +/- 8%) were compared with 9 patients with mild heart failure and 10 subjects without heart failure. They underwent a symptom-limited exercise test and a bicycle exercise training session at >80% of maximal heart rate over 20 to 30 minutes. Plasma cTnI levels were measured at baseline, after symptom-limited exercise (hourly for 5 hours), and after training (4 and 10 hours). RESULTS: Patients with moderate heart failure showed an increase of cTnI from 37 +/- 49 pg/mL to 73 +/- 59 pg/mL (P <.001) after symptom-limited exercise. Four patients with moderate and 1 with mild heart failure and normal cTnI values at rest showed an increase of cTnI above 100 pg/mL after acute exercise but not after training. Subjects without heart failure had lower cTnI levels at rest and significantly lower values after symptom-limited exercise and training (P <.05 for each). CONCLUSION: Patients with symptomatic heart failure reveal an increase of cTnI after symptom-limited exercise at levels that indicate minor myocardial damage. The prognostic impact of this finding should, therefore, be further investigated.

Adult↗
PubMed2006

An approach to the validation of biomarkers of harm for use in a tobacco context.

There is both a call and a need for biomarkers of harm that are validated for use in a tobacco context. Currently, there are no validated biomarkers and there is no consensus about which ones may be suitable for this purpose. To advance the science in this area a working definition of biomarkers of harm and a shortlist of candidate biomarkers are proposed. A framework for the validation of biomarkers of harm using of a series of epidemiological studies culminating in a targeted prospective study is outlined. The candidate biomarkers have advanced to preliminary testing although this does not imply that any on the shortlist will become validated. This framework could also be used for the evaluation of proteomic, genomic, transcriptosomic or metabonomic profiles, which may turn out to be the preferred biomarkers for use in harm prediction. Biomarker studies would complement data that are generated from specific in vitro tests and from animal studies to evaluate tobacco products.

Animals↗
PubMed2006

A fast, simple, and inexpensive method to collect exhaled breath condensate for pH determination.

BACKGROUND: Exhaled breath condensate (EBC) analysis is a noninvasive method for assessing lower airway inflammation. Various methods of collecting EBC have been described. However, they are often time-consuming or involve expensive equipment. OBJECTIVE: To evaluate the efficiency and repeatability of a simple, fast, and inexpensive method of EBC collection for pH determination. METHODS: Twenty-four mild asthmatic patients, 18 moderate-to-severe asthmatic patients, and 26 controls were asked to slowly exhale for 45 seconds into a -80 degrees C cooled metal cylinder covered with protective rubber and attached to a piece of tubing. The EBC was collected using a syringe's plunger. The groups were compared regarding EBC pH. Reproducibility tests were also performed. Induced sputum samples were obtained for inflammatory cell counts. RESULTS: We obtained approximately 50 microL of EBC for pH determination. Mild asthmatic patients had lower mean +/- SD pH values than controls (5.97 +/- 0.48 vs 6.36 +/- 0.34; P = .008), and corticosteroid-treated, moderate-to-severe asthmatic patients had mean +/- SD pH values similar to controls (6.23 +/- 0.38; P > .05). Mean +/- SD sputum eosinophil percentages were higher in both asthmatic groups than in controls (3.42% +/- 5.37% and 4.14% +/- 4.98% vs 0.04% +/- 0.12%; P < .001) and were not correlated with pH values in all groups. The mean intraday coefficient of variation for the method was 4.8% (range, 0.9%-8.8%). No correlation was found in all groups between sputum neutrophils and pH. CONCLUSIONS: We developed a useful device for collecting EBC for pH evaluation that could provide an alternative to other methods when pH is the main variable evaluated.

Adolescent↗
PubMed2005

Telomere length in white blood cells is not associated with morbidity or mortality in the oldest old: a population-based study.

Cross-sectional studies have repeatedly suggested peripheral blood monocyte telomere length as a biomarker of aging. To test this suggestion in a large population-based follow-up study of the oldest old, we measured telomere length at baseline in 598 participants of the Leiden 85-plus Study (mean age at baseline 89.8 years). We also obtained second telomere measurements from 81 participants after an average time span of between 3.9 and 12.9 years. Telomere length at baseline was not predictive for mortality (P > 0.40 for all-cause, cardiovascular causes, cancer or infectious diseases, Cox regression for gender-adjusted tertiles of telomere length) or for the incidence of dementia (P = 0.78). Longitudinally, telomere length was highly unstable in a large fraction of participants. We conclude that blood monocyte telomere length is not a predictive indicator for age-related morbidity and mortality at ages over 85 years, possibly because of a high degree of telomere length instability in this group.

Aged, 80 and over↗
PubMed2006

Comprehensive phenotyping in multiple sclerosis: discovery based proteomics and the current understanding of putative biomarkers.

Currently, there is no single test for multiple sclerosis (MS). Diagnosis is confirmed through clinical evaluation, abnormalities revealed by magnetic resonance imaging (MRI), and analysis of cerebrospinal fluid (CSF) chemistry. The early and accurate diagnosis of the disease, monitoring of progression, and gauging of therapeutic intervention are important but elusive elements of patient care. Moreover, a deeper understanding of the disease pathology is needed, including discovery of accurate biomarkers for MS. Herein we review putative biomarkers of MS relating to neurodegeneration and contributions to neuropathology, with particular focus on autoimmunity. In addition, novel assessments of biomarkers not driven by hypotheses are discussed, featuring our application of advanced proteomics and metabolomics for comprehensive phenotyping of CSF and blood. This strategy allows comparison of component expression levels in CSF and serum between MS and control groups. Examination of these preliminary data suggests that several CSF proteins in MS are differentially expressed, and thus, represent putative biomarkers deserving of further evaluation.

Autoantibodies↗
PubMed2006

Chlorine in breath condensate--a measure of airway affection in pollinosis?

BACKGROUND: Infiltration of inflammatory cells in bronchial mucosa and glandular hypersecretion are hallmarks of asthma. It has been postulated that exhaled breath condensate (EBC) mirrors events in epithelial lining fluid of airways, such as presence of local inflammation as well as glandular hypersecretion. It is also well known that eosinophil cationic protein (ECP) and cysteinyl-leukotrienes (cys-LT) are released by circulating inflammatory cells when triggered by antigen stimulation in asthma patients. OBJECTIVES: The aim of this study was to evaluate whether chlorine and/or cys-LT in EBC would reflect changes of exposure of airborne pollen in patients with asthma. METHODS: EBC and serum were collected from 23 patients with allergic asthma during a pollen season and repeated 5 months later during a period with no aeroallergens. Chlorine was measured by means of a sensitive coulometric technique and cys-LT by an EIA technique. Serum ECP was measured and lung function tests were performed and symptoms noted during both occasions. RESULTS: Significantly higher concentrations of chlorine in EBC (p = 0.007) and ECP in serum (p = 0.003) were found during the pollen season compared to post-season. Chlorine levels tended to be higher in patients who reported of chest symptoms compared to those who denied symptoms during the pollen season (p = 0.06). Areas under the receiver-operated characteristic curves (AUC(ROC)) were compared and similar discriminative power to identify exacerbations of asthma was recorded by chlorine in EBC (range 0.67-0.78) and ECP in serum (range 0.64-0.78). CONCLUSION: It is concluded that chlorine in EBC and ECP in serum decreased significantly post-season, and this is suggested to mirror the decrement in airborne antigen. It is furthermore proposed that chlorine in EBC and ECP in serum tend to have a similar capacity to identify seasonal variations in airborne pollen in patients with asthma.

Adult↗