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PubMed2006

Biological monitoring for trimethylbenzene exposure: a human volunteer study and a practical example in the workplace.

This paper presents data from both a human volunteer study looking at exposure to 1,3,5-trimethylbenzene (TMB) and an occupational hygiene study of a printing firm using screen wash containing technical grade TMB. The biomarkers measured were TMB in blood and breath, and urinary dimethylbenzoic acids (DMBAs). The volunteer (N = 4) study showed that TMB was rapidly absorbed into the bloodstream reaching a mean level of 0.85 micromol l(-1) during a 4 h exposure to 25 p.p.m. TMB. There was little decline 1 h post-exposure possibly indicating storage of TMB in adipose tissue. Breath TMB levels peaked within an hour of exposure commencing and averaged 137 nmol l(-1) during exposure. Elimination of TMB in breath was biphasic with an initial half-life of 60 min. Peak excretion of urinary DMBA occurred 4-8 h after the end of exposure and averaged 40 mmol mol(-1) creatinine. Elimination of DMBA in urine was biphasic with half-lives of 13 and 60 h indicating that accumulation of body burden throughout the working week is likely if exposure is repeated. The occupational hygiene study demonstrated an excellent correlation between personal air TMB levels and post-shift urinary DMBA levels (r = 0.997) collected on the third working day. The regression equation from this study indicates that 8 h exposure to 25 p.p.m. TMB would result in a urinary DMBA level of 206 mmol mol(-1) creatinine. All workers showed pre-shift levels of DMBA from exposure to TMB on previous days. Both urinary DMBA and breath TMB levels can be used as biomarkers of TMB exposure. Urine samples should be taken post-shift towards the end of the working week as significant body burden accumulation throughout the working week can be expected. Breath sampling is more suited to task or single-shift monitoring.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2004

Exhaled nitric oxide before and after cardiac surgery with cardiopulmonary bypass--response to acetylcholine and nitroglycerin.

BACKGROUND: Pulmonary endothelial dysfunction may occur after ischaemia-reperfusion injury and can be revealed as a reduced vasodilatory response upon administration of acetylcholine (ACh). ACh also releases the endothelium-derived vasodilator nitric oxide but direct measurements of this gas are difficult to perform in vivo. We wanted to study the effects of i.v. administration of ACh and the endothelium-independent vasodilator nitroglycerin on exhaled nitric oxide in relation to pulmonary endothelial dysfunction after open-heart surgery and cardiopulmonary bypass (CPB). METHODS: Basal exhaled nitric oxide and the response in exhaled nitric oxide to i.v. injections of ACh and nitroglycerin were measured with chemiluminescence in 10 patients before and after open-heart surgery. RESULTS: Exhaled nitric oxide decreased significantly after CPB. I.V. bolus injections of ACh induced a reproducible and dose-dependent increase in exhaled nitric oxide that was unaltered after CPB. In contrast, the increase in exhaled nitric oxide evoked by nitroglycerin was attenuated after CPB. The response in pulmonary vascular resistance index (PVRI) to an infusion of ACh decreased after CPB, indicating endothelial dysfunction. The decrease in PVRI response to ACh correlated to the duration of CPB. CONCLUSIONS: Interestingly, pulmonary vascular dysfunction after CPB was accompanied by a reduction in the exhaled nitric oxide response to nitroglycerin and lower levels of basal exhaled nitric oxide. The ACh-induced responses in exhaled nitric oxide were unchanged, which could indicate nitric oxide-independent mechanisms behind the endothelial dysfunction in this study. The possibility of using exhaled nitric oxide dynamics to investigate pulmonary endothelial dysfunction merits further studies.

Acetylcholine↗
PubMed1999

Validation of the end-expired method for measuring carboxyhaemoglobin levels for the use in occupational and environmental exposure studies.

Carbon monoxide is one of the most common toxins encountered in work settings, the gas being emitted in situations where there is incomplete combustion of carbon-containing substances. Its acute and chronic health effects have been well-documented. While identification of dangerous situations and evaluation of control measures are conducted by environmental monitoring, the body burden due to inhalation of carbon monoxide is measured by an individual's blood carboxyhaemoglobin level. Carboxyhaemoglobin level can be measured directly from a blood sample or, indirectly, by measuring the end-expired carbon monoxide level and using the charts provided to read the corresponding carboxyhaemoglobin level. As the end-expired method is not an intervention method, and is therefore easy to conduct, it is being used widely in epidemiological studies and it could also be used for individual measurements. This study presents a better statistical method for validating the end-expired method than the correlation method used and described in previous studies.

Bias↗
PubMed1998

Tumour necrosis factor alpha as a predictor of impaired peak leg blood flow in patients with chronic heart failure.

Tumour necrosis factor alpha (TNF alpha) is increased in patients with cardiac cachexia, a condition associated with reduced peripheral blood flow both at rest and after interventions causing vasodilation. By contrast, in patients with chronic heart failure (CHF), higher TNF levels are associated with a greater capacity for vasodilation in the arm. To clarify the relationship between peripheral blood flow and TNF in CHF, we studied the relation between TNF alpha and blood flow in the leg (plethysmography, post maximal exercise and 5 min ischaemia) in 34 patients (age 63 +/- 2 years, ejection fraction 29 +/- 3%, peak VO2 16.6 +/- 1.1 ml/kg/min, mean +/- SEM). Peak leg blood flow correlated significantly with total TNF alpha (r = 0.68, p < 0.0001, peak VO2 (r = 0.54), and soluble TNF receptors 1 (r = 0.56) and 2 (r = 0.52, all p < 0.002). TNF alpha, soluble TNF receptors 1 and 2 and aldosterone correlated with peak blood flow independently of age, ejection fraction, peak VO2 and functional NYHA class. TNF alpha was the only parameter that showed strong correlations for peak blood flow in all clinically relevant subgroups (severe vs. mild, ischaemic vs. dilated, cachectic vs. non-cachectic patients). This study shows a close and inverse relationship between peak leg blood flow and the plasma concentration of TNF alpha, suggesting a pathophysiological role for TNF alpha in reducing peak peripheral blood flow in CHF.

Adult↗
PubMed2003

Dermal, oral, and inhalation pharmacokinetics of methyl tertiary butyl ether (MTBE) in human volunteers.

Methyl tertiary butyl ether (MTBE), a gasoline additive used to increase octane and reduce carbon monoxide emissions and ozone precursors, has contaminated drinking water and can lead to exposure by oral, inhalation, and dermal routes. To determine its dermal, oral, and inhalation kinetics, 14 volunteers were exposed to 51.3 microg/ml MTBE dermally in tap water for 1 h, drank 2.8 mg MTBE in 250 ml Gatorade(R), and inhaled 3.1 ppm. MTBE for 1 h. Blood and exhaled breath samples were then obtained. Blood MTBE peaked between 15 and 30 min following oral exposure, at the end of inhalation exposure, and ~5 min after dermal exposure. Elimination by each route was described well by a three-compartment model (Rsq >0.9). The Akaike Information Criterion for the three-compartment model was smaller than the two-compartment model, supporting it over the two-compartment model. One metabolite, tertiary butyl alcohol (TBA), measured in blood slowly increased and plateaued, but it did not return to the pre-exposure baseline at the 24-h follow-up. TBA is very water-soluble and has a blood:air partition ratio of 462, reducing elimination by exhalation. Oral exposure resulted in a significantly greater MTBE metabolism into TBA than by other routes based on a greater blood TBA:MTBE AUC ratio, implying significant first-pass metabolism. The slower TBA elimination may make it a better biomarker of MTBE exposure, though one must consider the exposure route when estimating MTBE exposure from TBA because of first-pass metabolism. Most subjects had a baseline blood TBA of 1-3 ppb. Because TBA is found in consumer products and can be used as a fuel additive, it is not a definitive marker of MTBE exposure. These data provide the risk assessment process of pharmacokinetic information relevant to the media through which most exposures occur-air and drinking water.

Administration, Cutaneous↗
PubMed2006

A comparison of transcriptomic and metabonomic technologies for identifying biomarkers predictive of two-year rodent cancer bioassays.

Two-year rodent bioassays play a central role in evaluating the carcinogenic potential of both commercial products and environmental contaminants. The bioassays are expensive and time consuming, requiring years to complete and costing $2-4 million. In this study, we compare transcriptomic and metabonomic technologies for discovering biomarkers that can efficiently and economically identify chemical carcinogens without performing a standard two-year rodent bioassay. Animals were exposed subchronically to two chemicals (one genotoxic and one nongenotoxic) that were positive for lung and liver tumors in a standard two-year bioassay, two chemicals that were negative, and two control groups. Microarray analysis performed on liver and lung tissues identified multiple biomarkers in each tissue that could discriminate between carcinogenic and noncarcinogenic treatments. The discriminating biomarkers shared a common expression profile among carcinogenic treatments despite different genotoxicity categories and potential modes of action, suggesting that they reflect underlying cellular changes in the transition toward neoplasia. Statistical classification analysis exhibited 100% accuracy in both tissues when the number of genes was less than 5000. Additional genes reduced the predictive accuracy of the model. Serum samples were analyzed by 1H nuclear magnetic resonance (NMR) spectroscopy, and chemical-specific metabolites were removed from the spectra. The statistical classification analysis of the endogenous serum metabolites showed relatively low predictive accuracy with few metabolites in the model, but the accuracy increased to a maximum of 94% when all metabolites were added. These results suggest that individual endogenous metabolites are relatively poor biomarkers, but the metabolite profile as a whole is altered following carcinogen treatment.

Animals↗
PubMed1999

Molecular and genetic targets in early detection.

Recent research has revealed the existence of specific mutations in cancer. These mutations are being investigated as targets to find subjects at high risk for cancer, to detect early cancer, to detect the early recurrence of established cancer, and to find micrometastasis. These mutations are reviewed for the major anatomic sites. Some of the clinical issues related to the application of these mutations and the limitations of using molecular targets are also considered. Current methods for determining the risk of cancer are reviewed. Risk assessment is essential for defining cohorts for chemoprevention and other interventions. The concept of using surrogate anatomic and functional sites for estimating risk is introduced. Finally, the increasing complexity of molecular genetic analysis and the biologic heterogeneity of cancer are discussed in relation to early detection.

Biomarkers↗
PubMed2000

Exhaled nitric oxide level decreases after cardiopulmonary bypass in adult patients.

OBJECTIVE: To measure exhaled nitric oxide (NO) and compare it with lung function after cardiopulmonary bypass (CPB) in adult patients. Pulmonary dysfunction is sometimes observed after CPB. Impaired production of NO may account for this dysfunction. DESIGN: Prospective, single-center, observational study. SETTING: University hospital operating room, intensive care unit. PATIENTS: Sixteen adult patients undergoing cardiac surgery with CPB. INTERVENTIONS: None except cardiac surgery with CPB. MEASUREMENTS AND MAIN RESULTS: Exhaled NO was measured continuously by the chemiluminescence method and was expressed as the peak and mean NO concentrations, and the NO output (VNO). These parameters were calculated by averaging four sequential tidal NO values. The data were obtained serially from before CPB to 16 hrs after CPB. Lung function was evaluated by monitoring lung compliance, pulmonary artery pressure, and alveolar-arterial oxygen difference (P(A-a)O2). The cardiac index did not change except for a significant increase at 16 hrs compared with 6 hrs after CPB. Peak NO, mean NO, and VNO decreased from 15.4 +/- 2.0 ppb (before CPB) to 8.2 +/- 0.8 ppb (6 hrs after CPB), from 5.7 +/- 0.7 ppb to 2.8 +/- 0.6 ppb, and from 29.2 +/- 3.1 nL/min to 15.7 +/- 2.2 nL/min, respectively. These changes were associated with the increases in pulmonary artery pressure and alveolar-arterial oxygen difference, and the decrease in lung compliance. VNO recovered to the level measured before CPB 16 hrs after CPB, which was consistent with the physiologic recovery in pulmonary hypertension, lung compliance, and gas exchange. CONCLUSION: Measurement of exhaled NO as VNO, which was associated with lung dysfunction, may be an indicator of lung injury in adult patients after cardiopulmonary bypass.

Adult↗
PubMedDate not supplied

An integrated approach to prenatal smoking cessation interventions.

This article encourages the incorporation of smoking cessation activities into routine nursing care in the prenatal period. A brief background is given regarding the problem of smoking in women--especially pregnant women and adolescents. A model is suggested that integrates the Stages of Change framework with a program for planning, implementing, and evaluating smoking cessation activities in the clinical setting. The use of biochemical testing for cotinine, a biomarker of nicotine, is also explored as an evaluation tool and a method of self-report confirmation. The nurse is uniquely poised to reduce both the healthcare and economic burden of smoking during pregnancy. Because cigarette smoking is a major public health problem in the United States today, it is important for nurses to have a background in smoking assessment, cessation, and evaluation methods. It is critical for all nurses in obstetric, pediatric, hospital, and clinic settings to use this knowledge to assist vulnerable clients in achieving lifetime abstinence from cigarettes.

Adolescent↗
PubMedDate not supplied

Biological markers in diagnosing, monitoring, and treating asthma: a focus on noninvasive measurements.

Asthma is a major concern for society, healthcare professionals, and individuals and families directly affected by asthma due to rising morbidity rates and costs associated with the disease. The pathological hallmark of asthma is airway inflammation that is considered to be a major cause of exacerbations and persistent structural alterations of the airways. Assessing airway inflammation is important for investigating the underlying mechanisms of the disease and possibly for following the progression and resolution of the disease. The presence and type of airway inflammation can be difficult to detect clinically, and may result in delays in initiating appropriate therapy. The purpose of this article is to review noninvasive methods for assessing biological markers of airway inflammation and their potential role in the future for diagnosing, monitoring, and treating asthma. The article reviews the noninvasive measurements of induced sputum and exhaled nitric oxide as indicators of airway inflammation.

Adrenergic beta-Agonists↗
PubMed2003

Noninvasive biomarkers of airway inflammation in cystic fibrosis.

PURPOSE OF REVIEW: Airway inflammation plays a central role in the lung disease of cystic fibrosis (CF). Biomarkers of inflammation may be useful for monitoring disease progression and evaluating response to therapy. Much of our knowledge of the chronic inflammatory process in the CF airway derives from studies of bronchoscopy and bronchoalveolar lavage. A number of noninvasive approaches have been recently developed to more readily assess airway inflammation including sputum induction, collection of exhaled air, analysis of systemic markers of inflammation, and computed tomography imaging. RECENT FINDINGS: While measurements of biomarkers of inflammation continue to advance our understanding of the underlying disease process, there is as yet no established role for these markers in clinical practice. This review summarizes the current state of knowledge of various inflammatory markers relevant to CF lung disease, with an eye towards application as surrogate outcome measures in CF clinical trials. SUMMARY: It is hoped that biomarkers obtained by noninvasive means will be useful in determining specific pathways of injury (ie, oxidative or proteolytic) in individual persons with CF and in assessing response to antiinflammatory treatments.

Biomarkers↗
PubMed2004

Asthma severity and asthma control: symptoms, pulmonary function, and inflammatory markers.

PURPOSE OF REVIEW: Asthma severity and asthma control are distinct yet related concepts. Asthma severity describes the underlying disease in the absence of therapy and is ideally defined without concurrent treatment confounding its assessment. Asthma control describes the clinical status of disease in the face of intervention. However, the individual parameters by which we define asthma severity and asthma control overlap significantly. A MEDLINE search between July 1, 2002, and June 30, 2003, was performed using keywords related to concepts of asthma severity of illness and asthma control. From these articles the author selected the articles most relevant for discussion. RECENT FINDINGS: Asthma is a complex syndrome. Although correlations exist between the various parameters used in clinical assessment, no single parameter can accurately classify all individuals. Assessment of multiple parameters including physiologic measures, symptoms, and activity limitation are necessary to categorize asthma clinical status accurately. In addition, the role biomarkers play in the assessment of disease status is an area of increasing interest. Several validated multidimensional measures for assessing asthma control are now available. Each of these measures includes the parameters of symptoms, activity limitation, and rescue medication use, yet they vary on inclusion of other important components such as physiologic measures and biomarkers. SUMMARY: Asthma is a complex syndrome. Currently available instruments demonstrate an improved understanding of the multidimensional approach required to assess asthma control accurately. However, debate continues on the optimal parameters to be included and the role biomarkers play in the clinical assessment of asthma.

Asthma↗
PubMed2002

Non-invasive assessment of airway inflammation in occupational lung diseases.

The clinical investigation of occupational asthma is currently based on the demonstration of functional changes after exposure to occupational agents, but it does not yet include any monitoring of airway inflammation, one of the hallmarks of this disease. Methods permitting a non-invasive assessment of airway inflammation, such as induced sputum and exhaled nitric oxide, are currently under investigation for research purposes in occupational asthma. Their role in clinical practice has not yet been established. The advantages and limitations of these methods for occupational airway diseases, and more particularly occupational asthma, are discussed in this review.

Asthma↗
PubMed2001

Exhaled markers of inflammation.

Exhaled markers of inflammation allow completely noninvasive monitoring of inflammation and oxidative stress in the respiratory tract in inflammatory lung diseases, including asthma, chronic obstructive pulmonary disease, cystic fibrosis, bronchiectasis and interstitial lung diseases. Such noninvasive techniques are simple to perform, may be repeated frequently and can be applied in children, including neonates and patients with severe disease in whom more invasive procedures are not possible. Several volatile chemicals can be measured in the breath (nitric oxide, carbon monoxide, hydrocarbons), and many nonvolatile molecules (mediators, oxidation and nitration products, proteins) may be measured in exhaled breath condensate.

Biomarkers↗
PubMedDate not supplied

Inflammation at a glance: erythrocyte adhesiveness/aggregation test to reveal the presence of inflammation in people with atherothrombosis.

The erythrocyte adhesiveness/aggregation test is a new biomarker to detect low-grade inflammation in patients with atherothrombosis. In a group of 30 individuals with an acute ischemic event, the variability of EAAT during a follow-up period was similar to those obtained for other commonly used markers of the acute phase response, suggesting the potential clinical use of this novel marker.

Aged↗
PubMed2003

Heterogeneity of FeNO response to inhaled steroid in asthmatic children.

BACKGROUND: Nitric oxide in exhaled air is regarded as an inflammation marker, and may be used to monitor the anti-inflammatory control from inhaled corticosteroids (ICSs). However, this response to ICSs exhibits a heterogeneous pattern. OBJECTIVE: The study aimed to describe the independent variables associated with the heterogeneity in the response of exhaled nitric oxide to ICSs. METHODS: Exhaled nitric oxide (FeNO), lung function, bronchial hyper-responsiveness (BHR), specific IgE to common inhalant allergens, blood eosinophils, other atopic manifestations and variants in nitric oxide synthethase 1 (NOS1) gene were studied in a double-blind, placebo-controlled crossover comparison of budesonide (BUD) Turbohaler 1600 mcg daily vs. placebo in asthmatic schoolchildren. RESULTS: Forty children were included in the study from a screening of 184 asthmatic children with moderately persistent asthma, well controlled on regular BUD 400 mcg daily: 20 children with normal FeNO and 20 with raised FeNO. FeNO, BHR and forced expiratory volume in 1 s improved significantly after BUD 1600 mcg (BUD1600). However, FeNO after ICS treatment exhibited a Gaussian distribution and FeNO was significantly raised in 15 children. Allergy and BHR, but none of the other independent variables under study were significantly related to FeNO after BUD1600. CONCLUSION: Exhaled nitric oxide exhibited a heterogeneous response to ICS in asthmatic schoolchildren. Allergy and BHR were driving FeNO level independently of high-dose steroid treatment. This should be considered when using FeNO for steroid dose titration and monitoring of ICS anti-inflammatory control in asthmatic children.

Administration, Inhalation↗