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PubMed2000

Effect of age on the breath methylated alkane contour, a display of apparent new markers of oxidative stress.

Reactive oxygen species (ROS) are toxic byproducts of mitochondrial energy production that inflict oxidative stress, a constant barrage of damage to DNA, proteins, lipids, and other biologically important molecules. Oxidative stress has been implicated as a pathologic mechanism in aging and in several diseases. We developed a display of apparent new markers of oxidative stress in human beings, the breath methylated alkane contour (BMAC). The BMAC is a three-dimensional display of C4 to C20 alkanes and monomethylated alkanes in breath, with x-axis = carbon chain length, z-axis = methylation site, and y-axis = alveolar gradient (relative abundance in breath minus relative abundance in room air). In 102 normal human subjects of 9 to 89 years of age, alveolar gradients of components of the BMAC increased significantly with age. The mean alveolar gradient of all components of the BMAC varied from negative in the youngest quartile (ages 9 to 31 years) to positive in the oldest quartile (ages 74 to 89 years)(P < 2.10(-9)). These findings were consistent with an increase in oxidative stress with advancing age, although an age-related decline in clearance by cytochrome p450 may have contributed. The BMAC provides a display of apparent new markers of oxidative stress with potential applications in aging research, clinical diagnosis, pharmacology, and toxicology.

Adolescent↗
PubMed2002

Levels of exhaled nitric oxide before and after surgical and transcatheter device closure of atrial septal defects in children.

OBJECTIVES: We have shown that exhaled nitric oxide levels decrease after surgical closure of congenital left-to-right cardiac shunts. It remains unclear whether the change in exhaled nitric oxide levels reflects endothelial injury caused by the use of cardiopulmonary bypass or the decrease in pulmonary blood flow attendant on shunt closure. Transcatheter atrial septal defect closure permits shunt closure without the use of cardiopulmonary bypass. Therefore we compared changes in exhaled nitric oxide levels after surgical and transcatheter device closure of atrial septal defects. METHODS: We enrolled sequentially 30 children undergoing atrial septal defect closure. Fifteen patients (age range, 0.4-16 years; median age, 6.5 years) underwent surgical atrial septal defect closure with cardiopulmonary bypass, and 15 patients (age range, 4-17 years; median age, 8.4 years) had device closure of the atrial septal defect in the catheterization laboratory. We measured nitric oxide levels in end-tidal expiratory gas with a rapid-response chemiluminescent analyzer before and after atrial septal defect closure. RESULTS: After surgical repair of the atrial septal defect, exhaled nitric oxide decreased by 21%, from 10.9 +/- 4.4 to 8.4 +/- 3.3 ppb (P <.005), whereas after transcatheter defect closure, exhaled nitric oxide increased by 23%, from 7.6 +/- 2.6 to 9.3 +/- 3.7 ppb (P <.005). Hemoglobin levels in patients undergoing surgical intervention were significantly lower (P =.0001) postoperatively. CONCLUSIONS: We confirmed that exhaled nitric oxide, despite a fall in hemoglobin, decreases after surgical closure of atrial septal defects. In contrast, exhaled nitric oxide levels increase after transcatheter closure. Exhaled nitric oxide levels may reflect bypass-induced endothelial cell injury and are independent of changes in pulmonary blood flow.

Adolescent↗
PubMed2003

Environmental health in Egypt.

Egypt shares most of the environmental problems of developing countries. One of the most important health and environmental problems is air pollution resulting from using fuel, burning operations, and the increase of automobile exhaust in cities. Moreover, the deficiency of efficient sanitation services and water pollution caused by the breaking down of old and consumed water networks, as well as the various problems in construction, designing and maintenance of sewage system resulted in the appearance and prevalence of communicable and non-communicable diseases. There are several examples of exposure to chemical genotoxicants, and lifestyle exposures in the population, which create unique combinations of environmental risk factors for diseases such as cancer. Environmental factors may interact with infection and lead to enhancement of carcinogenicity processes. Currently, there is a growing interest in environmental mutagenicity and carcinogenicity research. The use of different biomarkers and genetic susceptibility testing can contribute effectively to risk assessment. The Government of Egypt recognizes and deals seriously with these problems. The State Ministry of Environment has initiated new policies that include risk minimization, law enforcement, treatment of pollution at source, mitigation procedures and inter-sectorial collaboration. The Ministry of Health and Population recognized the link between economic development, environment and health. It elaborated a national environment health strategy in accordance with the format of the regional and global environmental health policy. This strategy identified priority areas, which requires further action to be taken and to be implemented. Environmental health was included as one of the four main objectives of the strategic Healthy Egyptians 2010 Initiative. Specific objectives and plans for the initiative are presented.

Air Pollution↗
PubMedDate not supplied

Exhaled nitric oxide: a novel biomarker of adverse respiratory health effects in epidemiological studies.

The sampling of exhaled breath is a noninvasive procedure that can be performed easily in adults, children, and patients with respiratory disease. Several studies have demonstrated increased exhaled nitric oxide in patients with pulmonary disease, including asthma. In addition, exhaled nitric oxide may be an elegant tool for monitoring of environmental health effects of air pollution and the prevalence of atopy in epidemiological surveys. Recent literature about exhaled nitric oxide is presented in this article. Technical, physiological, and behavioral confounding factors of exhaled nitric oxide measurement are outlined.

Biomarkers↗
PubMedDate not supplied

Quantitation of molecular endpoints for the dose-response component of cancer risk assessment.

Cancer risk assessment involves the steps of hazard identification, dose-response assessment, exposure assessment, and risk characterization. The rapid advances in the use of molecular biology approaches has had an impact on all 4 components, but the greatest overall current and future impact will be on the dose-response assessment because this requires an understanding of the mechanisms of carcinogenesis, both background and induced by environmental agents. In this regard, hazard identification is a qualitative assessment and dose-response is a quantitative estimate. Thus, the latter will ultimately require a quantitative assessment of molecular endpoints that are used to describe the dose-response for cancer. It has been possible for many years to quantitate alterations at the level of the single gene. For example, analysis of mutation frequency by phenotypic selection, analysis of transcription (mRNA) by Northern blot, analysis of translation (proteins) by Western blot, and analysis of kinetics of metabolism from metabolite levels. However, it is becoming clear that it is necessary when considering risk for adverse health outcomes to develop quantitative approaches for whole cell phenotypes or organ effects. For example, cancer is a whole tissue phenotype, not a feature of single gene mutations, in spite of the multistep (multimutation) mode of formation of a tumor. Thus, there is the need to quantitate the circuitry of a cell: the metabolic/biochemical pathways, genetic regulation pathways, and signaling pathways in normal and stressed conditions. The hypothesis presented by Hanahan and Weinberg of the requirement for 6 acquired characteristics for tumor development, independent of tissue type and species or inducer, seems to provide a viable approach. This hypothesis can be addressed through whole cell molecular assessment using microarrays and quantitative PCR together with the emerging proteomic approaches. This is the world of the new computational cell biology.

Animals↗
PubMed2006

Exhaled nitric oxide levels are not correlated with eczema severity in Chinese children with atopic dermatitis.

Asthma is a common atopic disease associated with atopic dermatitis (AD) and allergic rhinitis (AR). Exhaled nitric oxide level (eNO) has been found to be an interesting noninvasive marker of disease severity in children with asthma. However, it is uncertain if eNO may be confounded by any coexisting AD or AR. In this study, eNO in Chinese children with moderate-to-severe AD and no asthma symptoms (n = 53) was measured online by a chemiluminescence analyzer. Severity of AD was assessed using the objective SCORing-Atopic-Dermatitis score and coexisting allergic rhinitis with the Allergic-Rhinitis-Score (ARS). Patients with active symptoms of asthma or inhaled/intranasal corticosteroids were excluded. There was no difference in eNO between genders and no correlation between eNO and AD severity regardless of ARS or bronchial reactivity status. ENO appears to be a noninvasive marker whose level is independent of the two atopic diseases of AD and AR in children old enough to perform exhalation maneuver.

Adolescent↗
PubMed2006

Non-invasive measurement of airway inflammation in asthma.

Assessing the severity and control of a patient's asthma is of great importance to ensure that pharmacotherapy is optimized. Measures such as lung function, symptoms, and reliever use have traditionally been used as objective means of undertaking this assessment, but until now the level of airway inflammation has not been quantified. As asthma is primarily an inflammatory disorder, it would be desirable to include a measure of this process when evaluating disease control. The following article outlines methods of non-invasively measuring asthmatic airway inflammation and highlights their potential role in clinical practice.

Adenosine Monophosphate↗
PubMed2004

Exhaled ethanol and acetaldehyde in human subjects exposed to low levels of ethanol.

With the increased use of ethanol-blend gasoline as an alternative to gasoline, there is a demand for new data to assess the potential health risk of ethanol exposure. Currently, there is very limited information from the scientific database on the adverse effects of inhaled low doses of ethanol (ETOH). The aim of this study was to determine the concentration of ETOH and acetaldehyde (ACTDH), a toxic metabolite of ETOH, in the alveolar air (AA) of subjects exposed to low ETOH vapor concentrations by inhalation. Five healthy adults (2 women, 3 men), nonsmoking, 25-55 yr of age, were exposed for 6 consecutive hours to 25, 100, or 1000 ppm ETOH and were asked to provide AA samples at various intervals during and after each exposure session, for ETOH and ACTDH measurements. Results showed that the concentrations of ACTDH and ETOH in AA measured after 2 h of exposure at 25 ppm were 0.06 ppm and 7.5 ppm, respectively. Overall, there was a significant correlation between ETOH exposure and ETOH (R(2) =.92, p <.001) and ACTDH (R(2) =.99, p <.001) in AA. The ratios between ACTDH and ETOH in AA after 4 h of exposure to 25.9 ppm, 101.7 ppm, and 990.8 ppm ETOH were 0.005, 0.008, and 0.006, respectively. In conclusion, this study showed that inhalation of ETOH at low concentrations resulted in measurable levels of ACTDH in AA and suggests that ACTDH may be used, with good toxicological relevance, as an indicator of exposure to low levels of ETOH in air.

Acetaldehyde↗
PubMed2003

Increased levels of ethane, a non-invasive marker of n-3 fatty acid oxidation, in breath of children with attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) comprises a range of behavioural problems including inattention, hyperactivity and impulsivity. Diagnosis and treatment of the disorder is made difficult due to its unknown biological basis. Several studies have identified abnormalities in membrane fatty acids in some subjects with ADHD, and some success has been reported using lipid therapies. We have measured exhalant ethane levels, a non-invasive measure of oxidative damage to n-3 fatty acids, to probe biochemical alterations in ADHD. Patients with ADHD (N = 10) had higher levels of ethane in exhalant than in healthy volunteers (N = 12) with approximately 50% of ADHD cases being above the control range. In contrast, levels of butane, a marker of protein oxidation, were unaltered. Our data, although preliminary, suggests that some patients with ADHD have higher rates of oxidative breakdown of n-3 polyunsaturated fatty acids (PUFAs). Such a biochemical abnormality may underlie the previously observed fatty acid deficiencies, as well as providing further rationale for the use of anti-oxidant and/or lipid supplementation therapy in the treatment of ADHD. Larger studies of ADHD using this non-invasive assessment of oxidative stress appear warranted.

Attention Deficit Disorder with Hyperactivity↗
PubMed2003

Biomarkers in breath condensate: a promising new non-invasive technique in free radical research.

Oxidative stress is associated with a range of inflammatory lung diseases including asthma, adult respiratory distress syndrome, idiopathic pulmonary fibrosis, pneumonia, lung transplantation, chronic obstructive pulmonary disease, cystic fibrosis, bronchiectasis and lung cancer. Increased concentrations of reactive oxygen species (ROS) in the airways of such patients are reflected by elevated concentrations of oxidative stress markers in the breath, airways, lung tissue and blood. Traditionally, the measurement of these biomarkers has involved invasive procedures to procure the samples, or examine the compartments. As a consequence, there is a need for less invasive approaches to measure oxidative stress. Analysis of breath hydrocarbons has partly fulfilled this need, however only gas phase volatile constituents can be assessed by this approach. The collection of exhaled breath condensate (EBC) is a simple, non-invasive approach, which comprehensively samples the lower respiratory tract. It is currently used as a research and diagnostic tool in the free radical field, yielding information on redox disturbance and the degree and type of inflammation in the lung. With further technical developments, such an approach may ultimately have a role in the clinic, in helping to diagnose specific lung diseases. EBC can be exploited to assess a spectrum of potential biomarkers, thus generating a "finger print" characteristic of the disease. By assessing the nature of oxidative stress in this manner, the most appropriate therapy can be selected and the response to treatment monitored.

Biomarkers↗
PubMedDate not supplied

Biomarkers of some pulmonary diseases in exhaled breath.

Analysis of various biomarkers in exhaled breath allows completely non-invasive monitoring of inflammation and oxidative stress in the respiratory tract in inflammatory lung diseases, including asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), bronchiectasis and interstitial lung diseases. The technique is simple to perform, may be repeated frequently, and can be applied to 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, ammonia), and many non-volatile molecules (mediators, oxidation and nitration products, proteins) may be measured in exhaled breath condensate. Exhaled breath analysis may be used to quantify inflammation and oxidative stress in the respiratory tract, in differential diagnosis of airway disease and in the monitoring of therapy. Most progress has been made with exhaled nitric oxide (NO), which is increased in atopic asthma, is correlated with other inflammatory indices and is reduced by treatment with corticosteroids and antileukotrienes, but not (beta 2-agonists. In contrast, exhaled NO is normal in COPD, reduced in CF and diagnostically low in primary ciliary dyskinesia. Exhaled carbon monoxide (CO) is increased in asthma, COPD and CF. Increased concentrations of 8-isoprostane, hydrogen peroxide, nitrite and 3-nitrotyrosine are found in exhaled breath condensate in inflammatory lung diseases. Furthermore, increased levels of lipid mediators are found in these diseases, with a differential pattern depending on the nature of the disease process. In the future it is likely that smaller and more sensitive analyzers will extend the discriminatory value of exhaled breath analysis and that these techniques may be available to diagnose and monitor respiratory diseases in the general practice and home setting.

Ammonia↗
PubMedDate not supplied

A review of the USEPA's single breath canister (SBC) method for exhaled volatile organic biomarkers.

Exhaled alveolar breath can provide a great deal of information about an individual's health and previous exposure to potentially harmful xenobiotic materials. Because breath can be obtained non-invasively and its constituents directly reflect concentrations in the blood, its use has many potential applications in the field of biomarker research. This paper reviews the utility and application of the single breath canister (SBC) method of alveolar breath collection and analysis first developed by the US Environmental Protection Agency (USEPA) in the 1990s. This review covers the development of the SBC technique in the laboratory and its application in a range of field studies. Together these studies specifically show how the SBC method (and exhaled breath analysis in general) can be used to clearly demonstrate recent exposure to volatile organic compounds, to link particular activities to specific exposures, to determine compound-specific uptake and elimination kinetics, and to assess the relative importance of various routes of exposure (i.e. dermal, ingestion, inhalation) in multi-pathway scenarios. Specific investigations covered in this overview include an assessment of exposures related to the residential use of contaminated groundwater, exposures to gasoline and fuel additives at self-service gas stations, swimmers' exposures to trihalomethanes, and occupational exposures to jet fuel.

Biomarkers↗
PubMedDate not supplied

A human exposure study to investigate biological monitoring methods for 2-butoxyethanol.

2-Butoxyethanol is a glycol ether widely used in printing inks, varnishes and cleaning fluids. As skin absorption can be significant, biological monitoring is useful in monitoring worker exposure. A number of analytes and matrices have been used previously, including 2-butoxyethanol in blood and free and total 2-butoxyacetic acid in urine. Using a combination of a volunteer study and samples from exposed workers, we compared the applicability of some of the biological monitoring markers available. We conclude that 2-butoxyethanol in blood is not a suitable marker for biological monitoring due to sampling problems. In view of the low-level exposures reported in occupational surveys, 2-butoxyethanol in breath is also unsuitable because of a lack of sensitivity. Measuring 2-butoxyacetic acid in blood is possible, although non-invasive urine samples are preferred. Free 2-butoxyacetic acid in urine has previously been widely used; however, we found that the extent of conjugation of 2-butoxyacetic acid in urine varied from 0 to 100% both within and between individuals and is not related to time, concentration or urine pH. Data from 48 exposed workers suggested that an estimated 57% (95% confidence interval 44-70%) of the total 2-butoxyacetic acid is excreted in the conjugated form, and that conjugation may be activated above a certain exposure level. Using total 2-butoxyacetic acid significantly reduced inter-individual variation. Elimination half-lives for free and total 2-butoxyacetic acid were similar ( approximately 6 h) and there was no delay in excretion of the conjugated metabolite (peak excretion for both free and total was between 6 and 12 h after the end of exposure). In conclusion, we propose that total butoxyacetic acid (after acid hydrolysis) in urine is the biomarker of choice for monitoring exposure to 2-butoxyethanol. Urine samples should be collected post-shift towards the end of the working week.

Adult↗
PubMedDate not supplied

Impact of inspired substance concentrations on the results of breath analysis in mechanically ventilated patients.

A well-defined relationship has to exist between substance concentrations in blood and in breath if blood-borne volatile organic compounds (VOCs) are to be used as breath markers of disease or health. In this study, the impact of inspired substances on this relationship was investigated systematically. VOCs were determined in inspired and expired air and in arterial and mixed venous blood of 46 mechanically ventilated patients by means of SPME, GC/MS. Mean inspired concentrations were 25% of expired concentrations for pentane, 7.5% for acetone, 0.7% for isoprene and 0.4% for isoflurane. Only if inspired concentrations were <5% did substance disappearance rates from blood and exhalation rates correlate well. Exhaled substance concentrations depended on venous and inspired concentrations. Patients with sepsis had higher n-pentane and lower acetone concentrations in mixed venous blood than patients without sepsis (2.27 (0.37-8.70) versus 0.65 (0.33-1.48) nmol L-1 and 69 (22-99) versus 18 (6.7-56) micromol L-1). n-Pentane and acetone concentrations in breath showed no differences between the patient groups, regardless whether or not expired concentrations were corrected for inspired concentrations. In mechanically ventilated patients, concentration profiles of volatile substances in breath may considerably deviate from profiles in blood depending on the relative amount of inspired concentrations. A simple correction for inspired substance concentrations was not possible. Hence, substances having inspired concentrations>5% of expired concentrations should not be used as breath markers in these patients without knowledge of concentrations in blood and breath.

Acetone↗
PubMed2005

Inhibition of progenitor dendritic cell maturation by plasma from patients with peripartum cardiomyopathy: role in pregnancy-associated heart disease.

Dendritic cells (DCs) play dual roles in innate and adaptive immunity based on their functional maturity, and both innate and adaptive immune responses have been implicated in myocardial tissue remodeling associated with cardiomyopathies. Peripartum cardiomyopathy (PPCM) is a rare disorder which affects women within one month antepartum to five months postpartum. A high occurrence of PPCM in central Haiti (1 in 300 live births) provided the unique opportunity to study the relationship of immune activation and DC maturation to the etiology of this disorder. Plasma samples from two groups (n = 12) of age- and parity-matched Haitian women with or without evidence of PPCM were tested for levels of biomarkers of cardiac tissue remodeling and immune activation. Significantly elevated levels of GM-CSF, endothelin-1, proBNP and CRP and decreased levels of TGF-beta were measured in PPCM subjects relative to controls. Yet despite these findings, in vitro maturation of normal human cord blood derived progenitor dendritic cells (CBDCs) was significantly reduced (p < 0.001) in the presence of plasma from PPCM patients relative to plasma from post-partum control subjects as determined by expression of CD80, CD86, CD83, CCR7, MHC class II and the ability of these matured CBDCs to induce allo-responses in PBMCs. These results represent the first findings linking inhibition of DC maturation to the dysregulation of normal physiologic cardiac tissue remodeling during pregnancy and the pathogenesis of PPCM.

Adolescent↗
PubMed2002

Ethene and other biomarkers of oxidative stress in hypertensive disorders of pregnancy.

OBJECTIVE: An increase in reactive oxygen species (ROS) and lipid peroxides and a comprised antioxidant status has been implicated in the pathophysiology of severe preeclampsia. This study investigates whether oxidative stress and impaired antioxidant systems also contribute to milder forms of hypertensive disorders in pregnancy. Furthermore, ethene in exhaled air, a noninvasive measure for oxidative stress, was evaluated and compared with two other more established biomarkers. METHODS: Ethene in exhaled air, plasma protein carbonyls, and the ratio of free glutathione/oxidized glutathione (GSHfree/GSHox) as markers for oxidative stress as well as the antioxidants vitamins C and E, uric acid, glutathione, and the oxygen radical absorbance capacity (ORAC) in plasma were measured in 30 healthy nonpregnant, 14 normal pregnant, 9 women with pregnancy-induced hypertension (PIH), and 14 preeclamptic women. Pregnant participants were measured during pregnancy and after delivery. RESULTS: Women suffering from PIH and preeclampsia showed higher levels of the antioxidants vitamin E and uric acid, and lower levels of vitamin C compared with normal pregnant and nonpregnant women. All markers for oxidative stress were comparable between groups. Ethene levels showed a positive correlation with protein carbonyls but no correlation could be demonstrated with the free glutathione/oxidised glutathione ratio. CONCLUSIONS: PIH and preeclampsia are associated with minor alterations in antioxidant levels without signs of oxidative stress. Detection of ethene in exhaled air seems a promising noninvasive method to study lipid peroxidation but further research in more severe preeclampsia is needed.

Antioxidants↗