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PubMed1999

Exposure estimates to disinfection by-products of chlorinated drinking water.

Exposure to disinfection by-products (DBPs) of drinking water is multiroute and occurs in households serviced by municipal water treatment facilities that disinfect the water as a necessary step to halt the spread of waterborne infectious diseases. Biomarkers of the two most abundant groups of DBPs of chlorination, exhaled breath levels of trihalomethanes (THMs) and urinary levels of two haloacetic acids, were compared to exposure estimates calculated from in-home tap water concentrations and responses to a questionnaire related to water usage. Background THM breath concentrations were uniformly low. Strong relationships were identified between the THM breath concentrations collected after a shower and both the THM water concentration and the THM exposure from a shower, after adjusting for the postshower delay time in collecting the breath sample. Urinary haloacetic acid excretion rates were not correlated to water concentrations. Urinary trichloroacetic acid excretion rates were correlated with ingestion exposure, and that correlation was stronger in a subset of individuals who consumed beverages primarily within their home where the concentration measurements were made. No correlation was observed between an average 48-hr exposure estimate and the urinary dichloroacetic acid excretion rate, presumably because of its short biological half-life. Valid biomarkers were identified for DBP exposures, but the time between the exposure and sample collection should be considered to account for different metabolic rates among the DBPs. Further, using water concentration as an exposure estimate can introduce misclassification of exposure for DBPs whose primary route is ingestion due to the great variability in the amount of water ingested across a population.

Adult↗
PubMed2003

Early biomarkers of stroke.

BACKGROUND: The diagnosis and management of acute ischemic stroke are limited by the lack of rapid diagnostic assays for use in an emergency setting. Computed tomography (CT) scanning is used to diagnose hemorrhagic stroke but is relatively ineffective (<33% sensitive) in detecting ischemic stroke. The ability to correlate blood-borne protein biomarkers with stroke phenotypes would aid in the development of such rapid tests. METHODS: ELISAs for >50 protein biomarkers were developed for use on a high-throughput robotic workstation. These assays were used to screen plasma samples from 214 healthy donors and 223 patients diagnosed with stroke, including 82 patients diagnosed with acute ischemic stroke. Marker assay values were first compared by univariate analysis, and then the top markers were subjected to multivariate analysis to derive a marker panel algorithm for the prediction of stroke. RESULTS: The top markers from this analysis were S-100b (a marker of astrocytic activation), B-type neurotrophic growth factor, von Willebrand factor, matrix metalloproteinase-9, and monocyte chemotactic protein-1. In a panel algorithm in which three or more marker values above their respective cutoffs were scored as positive, these five markers provided a sensitivity of 92% at 93% specificity for ischemic stroke samples taken within 6 h from symptom onset. CONCLUSION: A marker panel approach to the diagnosis of stroke may provide a useful adjunct to CT scanning in the emergency setting.

Acute Disease↗
PubMed1997

Exhaled pentane levels in acute asthma.

BACKGROUND: Exhaled pentane, a product of lipid peroxidation, has been proposed as an objective, nonspecific, and noninvasive marker of active inflammation. Reactive oxygen species, which elicit lipid peroxidation, are increased in asthma and contribute to airway dysfunction. OBJECTIVE: To determine whether exhaled pentane levels are increased in acute asthma, and whether they decrease once acute asthma subsides. METHODS: Expired air was collected through a mouthpiece into a pentane-impermeable collection bag from 12 patients (40+/-5 years; mean+/-SEM) presenting to the emergency department of the University of Illinois Hospital in Chicago with acute asthma. Exhaled air was also collected after discharge from the hospital once acute asthma subsided. Eleven patients with stable asthma (40+/-5 years) and 17 healthy volunteers (31+/-5 years) served as control subjects. Exhaled air and ambient room air were analyzed for pentane content by gas chromatography. Peak expiratory flow rates were determined in each subject. RESULTS: Peak expiratory flow rates were 202+/-29 L/min during acute asthma and 327+/-26 L/min once acute asthma subsided (p<0.05). Exhaled pentane levels were 8.4+/-2.9 nmol/L during acute asthma and decreased significantly to 3.5+/-0.5 nmol/L once acute asthma subsided (p<0.05). Exhaled pentane levels were similar in patients with stable asthma and normal control subjects (3.6+/-0.4 nmol/L and 2.6+/-0.2 nmol/L, respectively; p>0.05). No pentane was detected in ambient air. CONCLUSION: Exhaled pentane levels are increased in patients with acute asthma and decrease significantly once acute asthma subsides.

Acute Disease↗
PubMed2000

Nasal and exhaled nitric oxide is reduced in adult patients with cystic fibrosis and does not correlate with cystic fibrosis genotype.

STUDY OBJECTIVES: Inducible nitric oxide synthase (iNOS) is upregulated in a number of inflammatory lung conditions, and exhaled nitric oxide (NO) concentration is increased. However, previous studies in children with cystic fibrosis (CF) have shown that exhaled NO is reduced. The purpose of this investigation was to study exhaled NO concentration in adults with CF, and to investigate the effect of CF genotype and respiratory tract infection on this measurement. DESIGN: Exhaled and nasal NO levels were measured in 54 adult CF subjects and 37 healthy nonsmoking age-matched subjects using a chemiluminesence analyzer. Spirometry (FEV(1) and FVC), CF genotype, and bacterial colonization were also recorded. SETTING: This study was conducted at a national CF center. RESULTS: The mean age of patients was 26.9 years, and the mean FEV(1) was 50.5% predicted (range, 17 to 104%). Nasal NO in the CF patients (mean, 520 parts per billion [ppb]; confidence interval [CI], 452 to 588) was significantly lower (p < 0.001) than in control subjects (987 ppb; CI, 959 to 1,015). Exhaled NO was significantly lower (p < 0. 001) in CF patients (5.0 ppb; CI, 4.1 to 6.1) than in control subjects (7.3 ppb; CI, 6.8 to 7.8). FEV(1) did not correlate with nasal or exhaled NO. No association was observed between genotype and NO values or colonization with Pseudomonas aeruginosa. CONCLUSIONS: Despite the airway inflammation that is characteristic of CF, both nasal and exhaled NO were reduced. There was no association with genotype or infection status. As NO has bacteriostatic effects and may augment mucociliary clearance, this observation may be of clinical importance.

Adolescent↗
PubMed2000

Oxidative stress after lung resection therapy: A pilot study.

STUDY OBJECTIVES: To investigate whether oxidative stress occurs following lobectomy and pneumonectomy and to evaluate whether markers of oxidative stress might be of value in the assessment of the diagnosis, course, and prognosis of postoperative complications. DESIGN: A prospective study. SETTING: A specialized thoracic surgical unit in a large referral hospital. PATIENTS: Twenty-eight patients with lung carcinoma undergoing thoracotomy. MEASUREMENTS: Exhaled H(2)O(2) concentrations in breath condensate were measured by spectrophotometry, while malondialdehyde (MDA) levels in urine samples collected every 24 h were measured by reversed-phase, ion-pair high-performance liquid chromatography using ultraviolet detection. RESULTS: Our results show increased H(2)O(2) and MDA levels in lobectomy patients compared with pneumonectomy patients. A strong correlation was found between the levels of H(2)O(2) and MDA. CONCLUSION: The present data support the hypothesis that oxidative stress may occur following pulmonary resection.

Aged↗
PubMed2003

Prospective evaluation of the validity of exhaled nitric oxide for the diagnosis of asthma.

STUDY OBJECTIVE: Exhaled nitric oxide (NO) levels are significantly elevated in patients with inflammatory airways disorders such as asthma, and the measurement of exhaled NO has been proposed as a noninvasive marker of airways inflammation. The aim of this study was to assess the accuracy of exhaled NO levels for the diagnosis of asthma. METHODS: Two hundred forty consecutive, nonsmoking, steroid-naive patients, who were referred to our outpatient clinic with symptoms suggestive of obstructive airways disease, were investigated. Asthma was diagnosed in 160 patients on the basis of the presence of significant airways reversibility (DeltaFEV(1) > 12% predicted) and/or airways hyperresponsiveness (provocative concentration of histamine causing a 20% fall in FEV(1) < or = 8 mg/mL). Prior to lung function measurements, exhaled NO was measured during a single-breath exhalation, according to European Respiratory Society and American Thoracic Society guidelines. RESULTS: The measurement of exhaled NO in our study population showed, at a cutoff level of 16 parts per billion, a specificity for the diagnosis of asthma of 90% and a positive predictive value of > 90%. CONCLUSIONS: These findings suggest that the simple and absolutely noninvasive measurement of exhaled NO can be used as an additional diagnostic tool for the screening of patients with a suspected diagnosis of asthma.

Adolescent↗
PubMed2003

Exhaled breath condensate nitrite and its relation to tidal volume in acute lung injury.

STUDY OBJECTIVE: Mechanical ventilation may damage the lung. Low tidal volume (VT) is protective, but VT is scaled to body weight (BW) and may be high in functionally small ARDS lungs. We hypothesized that exhaled breath condensate (EBC) nitrite (NO(2)(-)) concentration may increase with lung distension. DESIGN: Prospective, noncontrolled study. SETTING: University hospital and medical ICU. PATIENTS: Thirty-five ICU patients requiring mechanical ventilation (severe pneumonia, n = 31; exacerbated COPD, n = 4). Patients were scored according to American and European Consensus Conference on ARDS criteria (AECC) [no lung injury, n = 7; acute lung injury, n = 13; ARDS, n = 15], as well as the Murray lung injury severity score (LISS) [score 0, n = 3; score 0.1 to 2.5, n = 19; score > 2.5, n = 13]. INTERVENTIONS: EBC was collected and analyzed for NO(2)(-), interleukin (IL)-6, and IL-8. Serum was analyzed for IL-6, IL-8, and procalcitonin. RESULTS: and measurements: EBC NO(2)(-) correlated well with VT (milliliters per kilogram of BW; r = 0.79, p < 0.0001) and expiratory minute volume (r = 0.60, p < 0.0001) but not with other ventilatory parameters or parameters of pulmonary (EBC IL-6, EBC IL-8) or systemic (serum IL-6, IL-8, and procalcitonin) inflammation. The ratio of EBC NO(2)(-) and the size of the VT correlated directly with lung injury (AECC, r = 0.66, p < 0.0001; LISS, r = 0.84, p < 0.0001). CONCLUSION: EBC NO(2)(-) increased linearly with VT. The ratio of EBC NO(2)(-) to VT is assumed to reflect NO(2)(-) release at a given VT. An increase in this ratio indicates an inappropriate increase of NO(2)(-) production most likely due to mechanical stress of the remaining open lung units in injured lungs. We conclude that the EBC NO(2)(-)/VT ratio may help to identify situations of critical mechanical stress.

Acute Disease↗
PubMed2003

Effect of montelukast on exhaled nitric oxide and nonvolatile markers of inflammation in mild asthma.

STUDY OBJECTIVES: Leukotriene receptor antagonists appear to exert anti-inflammatory activity in asthma. We undertook the present study to evaluate the effect of montelukast on levels of exhaled nitric oxide (ENO) and two inflammatory markers, hydrogen peroxide (H(2)O(2)), and cysteinyl leukotrienes (cys-LTs), in the exhaled breath condensate of subjects with mild asthma. PATIENTS: Twenty stable subjects with mild asthma (15 women and 5 men; mean [+/- SD] age, 34.8 +/- 12.6 years) were included in the study. INTERVENTION: A 1-week run-in period was followed by 2 weeks of treatment (with montelukast or placebo) that was administered in randomized, double-blind, crossover fashion. One week of washout followed each treatment arm. RESULTS: Montelukast significantly reduced the levels of ENO from baseline (median, 52.5 parts per billion [ppb]; 25th to 75th percentile, 37.8 to 101.8 ppb) during the entire treatment period (ie, day 1 to day 14), with the effect measurable as early as day 1 (median, 45.9 ppb; 25th to 75th percentile, 29.3 to 92.5 ppb) and with the maximal effect being observed on day 7 (median, 35.7 ppb; 25th to 75th percentile, 27.6 to 66.6 ppb). The levels of ENO did not change significantly with placebo therapy. Montelukast improved symptom score and reduced peak expiratory flow (PEF) variability. Changes in PEF variability correlated positively with changes in ENO (r = 0.46; p = 0.04). No significant changes in FEV(1) or concentration of H(2)O(2) in the exhaled breath condensate were observed. Levels of cys-LTs were undetectable in the exhaled breath condensate. CONCLUSIONS: We concluded that montelukast reduces the levels of ENO in patients with mild asthma, a finding that is compatible with an anti-inflammatory effect of montelukast, and that ENO appears to be more sensitive in detecting this effect than FEV(1) and H(2)O(2) levels in the exhaled breath condensate.

Acetates↗
PubMed2005

Clinical implications of the ethane in exhaled breath in patients with acute paraquat intoxication.

STUDY OBJECTIVES: Pulmonary fibrosis due to lipid peroxidation is a major symptom of paraquat intoxication. Ethane in the expired breath (exEth) reflects lipid peroxidation and may be a measure of the damage effected by oxygen radicals in acute lung injury. The purpose of this study was to evaluate the clinical efficacy of exEth as a measure of exposure to paraquat and as an indicator of lung damage. DESIGN: Exposure levels were evaluated by the amount ingested, semiquantitative measurement of urine paraquat levels, and plasma paraquat concentration. End-tidal breath was collected for measurement of ethane 24 h after paraquat ingestion. Renal function and blood gas analyses were conducted on the same day as the breath collection, and the final clinical outcome was defined as either recovery or death. Associations between exEth and paraquat exposure profiles and clinical outcomes were assessed using linear regression models. PATIENTS: Twenty-one patients poisoned by paraquat were selected for the study during 2001 and 2002. RESULTS: exEth could not be used as a predictor of laboratory parameters such as Pa(O2), Pa(CO2), serum creatinine, and lung injury (as graded by high-resolution CT). A logistical analysis revealed that only the amount of paraquat ingested was a significant predictor of fatality (p = 0.021). The strength of the association between exEth and fatality was unaffected by the addition of potential confounders such as age, sex, and time interval and paraquat concentration. CONCLUSION: exEth cannot be used as either an independent predictor of survival or a specific marker of lung injury in patients with acute paraquat poisoning.

Adult↗
PubMed2005

Exhaled ethane: an in vivo biomarker of lipid peroxidation in interstitial lung diseases.

BACKGROUND: Oxidative stress plays a role in the pathogenesis and progression of interstitial lung disease (ILD). Exhaled ethane is a product of lipid peroxidation that has been proposed as a biomarker of oxidative stress in vivo. OBJECTIVES: To determine whether the exhaled ethane level is elevated in patients with ILD and to compare it with other clinical parameters. METHODS: Breath samples were collected from 34 patients with ILD, including 13 with idiopathic pulmonary fibrosis (IPF), 9 patients with cryptogenic organizing pneumonia, 6 patients with collagen vascular disease-associated interstitial pneumonia, and 6 patients with pulmonary sarcoidosis. Gas samples were obtained at hospital admission and after 3 weeks. After each expired sample was concentrated using a trap-and-purge procedure, the ethane level was analyzed by gas chromatography. RESULTS: Exhaled ethane levels were elevated in ILD patients (n = 34, mean +/- SD, 8.5 +/- 8.0 pmol/dL) compared with healthy volunteers (n = 16, 2.9 +/- 1.0 pmol/dL; p < 0.001). Serial measurements revealed that increase and decrease of ethane levels were largely consistent with the clinical course. Four patients with IPF who had persistently high ethane levels died or deteriorated, whereas those with ethane levels < 5.0 pmol/dL remained stable or improved. Exhaled ethane concentrations were positively correlated with levels of lactate dehydrogenase (Spearman rank correlation coefficient [rs], 0.28, p = 0.026) and C-reactive protein (rs, 0.38, p = 0.025) and were inversely correlated with Pa(O2) (rs, - 0.40, p = 0.0026). Patients showing increased uptake on (67)Ga scintigraphy demonstrated higher ethane levels (n = 19, 7.5 +/- 5.7 pmol/dL) compared with those who did not show increased uptake on scintigraphy (n = 10, 3.0 +/- 2.4 pmol/dL; p < 0.01). CONCLUSIONS: Exhaled ethane is elevated in patients with ILD and is correlated with the clinical outcome, suggesting that it provides useful information about ongoing oxidative stress, and thereby disease activity and severity in ILD.

Adult↗
PubMed2005

Time-dependent effect of nitrate-rich meals on exhaled nitric oxide in healthy subjects.

BACKGROUND: Exhaled nitric oxide (eNO) is a convenient noninvasive marker for airway inflammation in several pulmonary diseases. However, external factors such as nitrate-rich nutrition can affect the levels of eNO and thus compromise its diagnostic value. STUDY OBJECTIVES: The objective of this investigation was to have a better understanding of the time-dependent effect of nitrate-rich meals on eNO in healthy subjects. STUDY DESIGN: Forty-two healthy, nonsmoking volunteers (age range, 25 to 62 years) were recruited for the study. They had no recent respiratory tract infections and were free of pulmonary history, rhinitis, and atopic disorders. eNO was measured before, and 0.5, 2, 4, 12, 15, and 20 h after the intake of a nitrate-rich meal equivalent to 230 mg of nitrate. RESULTS: The intake of a nitrate-rich meal increased eNO by 60% 2 h after the meal. Even after 15 h, the mean eNO value was still 22% higher than the baseline value. Only after 20 h did eNO return to the normal baseline level. CONCLUSION: This finding stresses the importance of advising patients to avoid nitrate-rich nutrition at least 20 h before a scheduled measurement of eNO.

Adult↗
PubMed2006

Normative data for pH of exhaled breath condensate.

INTRODUCTION: Measurement of pH is one of the simplest and most technically validated biomarkers studied in exhaled breath condensate (EBC). The pH of EBC has been found to be lower than controls in many respiratory disorders. Published data from normal control subjects have been reasonably consistent, but the data sets are not large. This study was undertaken to establish normative EBC pH reference values. PARTICIPANTS: Four hundred four healthy subjects of all ages were enrolled. INTERVENTIONS: Each participant provided a single EBC sample using a disposable collector at modest temperature so that EBC was collected as a liquid. MEASUREMENTS AND RESULTS: Samples of EBC were bubbled with argon gas to standardize for carbon dioxide, and pH was recorded with a calibrated and validated glass microelectrode on stabilization. The median EBC pH was 8.0 with interquartile (25 to 75%) range of 7.8 to 8.1. There were no differences based on age, sex, or race. The distribution is skewed, with 6.4% of EBC samples having a pH range < 7.4. CONCLUSIONS: An extensive normal data set now exists that reveals EBC pH is maintained in a modestly alkaline and tight range in subjects who consider themselves healthy.

Adolescent↗
PubMed2006

Exhaled metallic elements and serum pneumoproteins in asymptomatic smokers and patients with COPD or asthma.

STUDY OBJECTIVES: The aim of this study was to characterize the elemental composition of exhaled breath condensate (EBC) in order to identify new biomarkers of exposure and susceptibility in COPD patients. Serum pneumoproteins were used as lung-specific biomarkers of effect. DESIGN: EBC was obtained from 50 healthy subjects, 30 healthy smokers, 30 asthmatics, and 50 patients with stable COPD, and was collected by cooling exhaled air. Trace elements and toxic metals in the samples were measured by means of inductively coupled plasma-mass spectrometry and electrothermal atomic absorption spectroscopy. The serum pneumoproteins were immunoassayed. RESULTS: The EBC of COPD subjects had higher levels of such toxic elements as lead, cadmium, and aluminum, and lower levels of iron and copper, than that of the nonsmoking control subjects. There were no between-group differences in surfactant protein (SP)-A and SP-B levels. Clara-cell protein and SP-D levels were negatively and positively influenced, respectively, by tobacco smoke. CONCLUSIONS: Our results show that toxic metals and transition elements are detectable in the EBC of studied subjects. We propose new biomarkers of exposure as a means of assessing the target tissue dose of carcinogenic and pneumotoxic substances from tobacco smoke or polluted workplaces, and the use of the transition elements involved in redox systems of oxidative stress as disease biomarkers associated with effect or susceptibility. Together with biomarkers of effect, such as serum pneumoproteins, the elemental composition of EBC may be clinically useful in distinguishing similar diseases.

Adult↗
PubMed2006

Exhaled biomarkers.

Assessing airway and lung inflammation is important for investigating the underlying mechanisms of asthma and COPD. Yet these cannot be measured directly in clinical research and practice because of the difficulties in monitoring inflammation. Noninvasive monitoring may assist in early recognition of asthma and COPD, assessment of its severity, and response to treatment, especially during disease exacerbations. There is increasing evidence that breath analysis may have an important place in clinical management of asthma and COPD. The article reviews the role of current noninvasive measurements of exhaled gases, such as nitric oxide (NO), inflammatory markers in exhaled breath condensate (EBC), and exhaled breath temperature, as well as novel methods in monitoring and management of asthma and COPD.

Asthma↗
PubMed2006

Increased leukotriene E4 in the exhaled breath condensate of children with mild asthma.

BACKGROUND: Chronic airway inflammation is a feature of asthma. Increased levels of cysteinyl leukotrienes (cys-LTs; leukotriene [LT]C(4), LTD(4), LTE(4)) have been shown in the exhaled breath condensate (EBC) of children with moderate-to-severe asthma. The aim of this study was to examine the relationship between EBC cys-LTs (LTE(4)) levels and bronchial hyperreactivity in children with mild asthma in order to evaluate the clinical utility of measuring EBC cys-LTs levels. METHODS: We measured LTE(4) levels in the EBC of children aged 8 to 18 years, including healthy nonasthmatic children (n = 6) and children with mild asthma (n = 37). Patients with mild asthma were classified into the following three groups: group 1, participants who had been asymptomatic (no wheezing/symptoms of asthma) for > 6 months prior to examination (n = 12); group 2, participants who were asymptomatic but had had wheezing/symptoms of asthma within 6 months before examination (n = 18); and group 3, patients with current wheeze and/or mild symptoms of asthma exacerbation at the time of examination. RESULTS: Exhaled LTE(4) levels were increased in all children with mild asthma compared with nonasthmatic control subjects (5.69 +/- 9.62 pg/20 min vs 0.74 +/- 0.79 pg/20 min, p < 0.05) [mean +/- SD]. In particular, the EBC LTE(4) levels in group 2 (4.99 +/- 6.70 pg/20 min) and group 3 (14.66 +/- 17.11 pg/20 min) were increased compared with control subjects and group 1 (1.50 +/- 1.69 pg/20 min). The EBC LTE(4) levels negatively correlated with the provocative concentration of methacholine causing a 15% fall in FEV(1) (r = - 0.454, p = 0.012). CONCLUSION: EBC cys-LTs may be useful as a noninvasive marker assessing airway inflammation and hyperreactivity in children with asthma.

Adolescent↗
PubMed2004

Effects of corticosteroids on noninvasive biomarkers of inflammation in asthma and chronic obstructive pulmonary disease.

Exhaled breath analysis may be used to quantify inflammation and oxidative stress in the respiratory tract, in the differential diagnosis of airway diseases, and in the monitoring of therapy. The greatest progress has been made with standardized measurement of exhaled nitric oxide (NO). Bronchial NO is increased in asthma, correlated with other markers of inflammation, and reduced by treatment with corticosteroids and antileukotrienes. Alveolar NO is increased in chronic obstructive pulmonary disease (COPD), reflecting disease severity and progression. Exhaled carbon monoxide and ethane are increased in both asthma and COPD. Increased concentrations of 8-isoprostane, hydrogen peroxide, nitrite, and nitrotyrosine are found in exhaled breath condensate from patients with inflammatory lung diseases. Increased levels of lipid mediators are also found, and the pattern depends on the nature of the disease process. Additional biomarkers are exhaled breath temperature, which is elevated in asthma and reduced in COPD, and bronchial blood flow. It is likely that smaller and more sensitive analyzers will extend the discriminatory value of exhaled breath analysis and that new techniques will become available to diagnose and monitor respiratory diseases in the family practice and home settings.

Administration, Inhalation↗