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At least 505 records · Page 28Linked to original sources
PubMed1999

Non-invasive evaluation of lower airway inflammation in hyper-responsive elite cross-country skiers and asthmatics.

Asthma-like symptoms and bronchial hyper-responsiveness (BHR) to methacholine are prevalent in competitive cross-country skiers. Whether these symptoms (ski asthma) in these athletes are caused by asthma remains uncertain. Bronchial responsiveness to adenosine 5'-monophosphate (AMP) and nitric oxide (NO) concentration in exhaled air, both indirect markers of asthmatic airway inflammation, were investigated in two non-smoking study populations of skiers and asthmatics. Of 18 skiers with ski asthma, 15 non-steroid and 14 steroid-treated asthmatics, BHR to AMP was present in five (28%), six (40%) and 10 (71%) subjects respectively. Although the groups were not significantly different in responsiveness to methacholine, responsiveness to AMP increased in order of magnitude from ski asthma < non-steroid-treated < steroid-treated asthma. Exhaled NO in 44 (nine with ski asthma) skiers was not significantly different from 82 healthy non-atopic controls [median [interquartile range (IQR)] 6.5 (4.1-9.9) vs. 5.2 (4.2-6.5) ppb]. Exhaled NO in 29 subjects with mild intermittent asthma was three-fold greater [median (IQR) 19.2 (5.1-25.6) ppb, P < 0.01] than in skiers. Exhaled NO was two- and four-fold greater in atopic than non-atopic subjects in the skier (P < 0.001) and asthmatic (P < 0.01) groups, respectively, and was correlated to methacholine responsiveness in atopic asthmatics (n = 22, rho = 0.55, P < 0.01). Exhaled NO was not elevated in ski asthma and may be more useful as a marker of atopic status than inflammation in the lower airway in skiers. Few skiers were hyper-responsive to AMP, indicating that pre-activated mucosal mast cells are not a predominant feature in ski asthma.

Adenosine Monophosphate↗
PubMed2001

Patterns and significance of exhaled-breath biomarkers in lung transplant recipients with acute allograft rejection.

BACKGROUND: Obliterative bronchiolitis (OB) remains one of the leading causes of death in lung transplant recipients after 2 years, and acute rejection (AR) of lung allograft is a major risk factor for OB. Treatment of AR may reduce the incidence of OB, although diagnosis of AR often requires bronchoscopic lung biopsy. In this study, we evaluated the utility of exhaled-breath biomarkers for the non-invasive diagnosis of AR. METHODS: We obtained breath samples from 44 consecutive lung transplant recipients who attended ambulatory follow-up visits for the Johns Hopkins Lung Transplant Program. Bronchoscopy within 7 days of their breath samples showed histopathology in 21 of these patients, and we included them in our analysis. We measured hydrocarbon markers of pro-oxidant events (ethane and 1-pentane), isoprene, acetone, and sulfur-containing compounds (hydrogen sulfide and carbonyl sulfide) in exhaled breath and compared their levels to the lung histopathology, graded as stable (non-rejection) or AR. None of the study subjects were diagnosed with OB or infection at the time of the clinical bronchoscopy. RESULTS: We found no significant difference in exhaled levels of hydrocarbons, acetone, or hydrogen sulfide between the stable and AR groups. However, we did find significant increase in exhaled carbonyl sulfide (COS) levels in AR subjects compared with stable subjects. We also observed a trend in 7 of 8 patients who had serial sets of breath and histopathology data that supported a role for COS as a breath biomarker of AR. CONCLUSIONS: This study demonstrated elevations in exhaled COS levels in subjects with AR compared with stable subjects, suggesting a diagnostic role for this non-invasive biomarker. Further exploration of breath analysis in lung transplant recipients is warranted to complement fiberoptic bronchoscopy and obviate the need for this procedure in some patients.

Acetone↗
PubMed2001

The effect of low-dose inhaled fluticasone propionate on exhaled nitric oxide in asthmatic patients and comparison with oral zafirlukast.

BACKGROUND: Exhaled nitric oxide (ENO) is a noninvasive marker of ongoing inflammation in asthmatic patients. Comparison between inhaled and oral anti-inflammatory medications in reduction of ENO in asthmatic patients has not been performed. OBJECTIVE: We measured changes in ENO, spirometry, need for rescue medication, quality of life (QOL), and diary scores (DS) after inhaled and oral anti-inflammatory therapy in adults with moderate asthma. METHODS: A randomized, double-blind, placebo-controlled, crossover design with 4-week washout periods was used. A plateau level of ENO, measured in parts per billion (ppb), was obtained by chemiluminescence with a Sievers 280NOA as per American Thoracic Society recommendations. Eighteen asthmatic adults (15 Hispanic, with a percentage predicted forced expiratory volume in 1 second (FEV1%) of 50% to 85%) on bronchodilators (beta2) only were studied. Subjects used fluticasone propionate (FP) metered-does inhaler (44 microg), two puffs twice daily, and matching placebo (PB) for 4 weeks. Eight of the asthmatic patients (7 Hispanic, FEV1% 50% to 85%) on bronchodilators only then received blinded zafirlukast (ZK) 20 mg and matching PB twice daily for 4 weeks. RESULTS: Low-dose inhaled FP resulted in significant improvements in ENO, spirometry, QOL, DS, and beta2 use. A significant difference in mean ENO was found (P < 0.01) before and after FP from 34+/-7 ppb to 13+/-3 ppb. A significant improvement was found (P < 0.05) with FEV1% from 75+/-3 to 85+/-3 with FP treatment. The other measured parameters, percentage predicted of peak expiratory flow rate, beta2 need, DS, and QOL measurements, were improved with low-dose FP treatment. No significant reduction was found in ENO with oral ZK for 4 weeks. After oral ZK washout and the second extension arm of placebo, ENO significantly increased back to 47+/-14 ppb (P < 0.05), but spirometry measures did not worsen. Significant improvements were found with DS and beta2 use with oral ZK therapy. CONCLUSIONS: These results reveal ENO is reduced with only low-dose inhaled FP in asthmatic patients not on anti-inflammatory medication. In the smaller extension study, ENO was reduced with FP and not with oral ZK treatment, and ENO levels increased back to near prestudy levels after ZK washout and the second extension arm of placebo. As a marker of inflammation, ENO levels reveal an improvement with anti-inflammatory medication and worsening when it is discontinued.

Administration, Inhalation↗
PubMed1999

Comparison of exhaled nitric oxide to spirometry during emergency treatment of asthma exacerbations with glucocorticoids in children.

BACKGROUND: Asthma is characterized as a chronic inflammatory process; however, there is no easily measured marker for airway inflammation. Such a marker, particularly in children, would be very helpful in the management of asthma even in the acute setting. OBJECTIVE: The purposes of this study were to determine whether asthmatic children have (1) elevation of exhaled breath nitric oxide (ENO) during acute exacerbations when presenting to the emergency room, (2) reduction of ENO following glucocorticoid treatment, or (3) improvement in spirometry and clinical examination accompanying reduction of ENO levels. METHODS: Peak ENO levels were measured by chemiluminescence during exhalation into the NO analyzer. Ten asthmatic children (mean age 10 years) who presented to the Pediatric Special Care Unit at National Jewish Medical and Research Center in acute respiratory distress with an asthma exacerbation were studied. The subjects were recruited, after informed consent was obtained from the parent, on the basis of specific inclusion/exclusion criteria. Measurements of ENO in parts per billion (ppb) and spirometry, including percentiles of forced expiratory volume in one second (FEV1%) and peak expiratory flow (PEF%), were performed before and after at least 5 days of glucocorticoid therapy. RESULTS: The mean ENO level in the asthmatic children prior to glucocorticoid treatment was 48 +/- 8ppb, and after glucocorticoid treatment the ENO level was 17 +/- 1ppb; (P < .002). Prior to glucocorticoid treatment, the mean FEV1% value was 68 +/- 3% compared with the postglucocorticoid treatment FEV1% value of 100 +/- 5%; (P < .0001). Prior to glucocorticoid treatment, the mean PEF% value was 81 +/- 7%, compared with the postglucocorticoid treatment PEF% value of 105 +/- 6%; (P < .02). CONCLUSIONS: The mean peak ENO level after glucocorticoid therapy was significantly less than that measured before treatment in children with acute asthma exacerbations. Concomitant with the decrease in ENO levels, there was improvement in the spirometry values and physical examination in the asthmatic children; thus, ENO is a sensitive marker for response to anti-inflammatory treatment in children.

Anti-Asthmatic Agents↗
PubMed1999

An evaluation of styrene genotoxicity using several biomarkers in a 3-year follow-up study of hand-lamination workers.

A study employing several biomarkers of styrene exposure and genotoxicity was carried out in a group of lamination (reinforced plastic) workers and controls, who had been repeatedly sampled during a 3-year period. Special attention will be paid to the last sampling (S.VI), reported here for the first time. Styrene concentration in the breathing zone, monitored by personal dosimeters, and urinary mandelic acid (MA) were measured as indicators of external exposure. Blood samples were assayed for styrene-specific O6-guanine adducts in DNA, N-terminal valine adducts of styrene in haemoglobin, DNA single-strand breaks (SSB), determined by use of the single cell gel electrophoresis (Comet) assay), and hypoxanthine guanine phosphoribosyl transferase (HPRT) mutant frequencies (MF) in T-lymphocytes. O6-styrene guanine adduct levels were significantly higher in the exposed group (5.9 +/- 4.9 adducts/10(8) dNp) as compared to laboratory controls (0.7 +/- 0.8 adducts/10(8) dNp; P = 0.001). DNA adduct levels significantly correlated with haemoglobin adducts, SSB parameters and years of employment. Styrene-induced N-terminal valine adducts were detected in the lamination workers (1.7 +/- 1.1 pmol/g globin), but not in the control group (detection limit 0.1 pmol/g globin). N-terminal valine adducts correlated strongly with external exposure indicators, DNA adducts and HPRT MF. No significant correlation was found with SSB parameters. A statistically significant difference in HPRT MF was observed between the laminators (22.3 +/- 10.6/10(6)) and laboratory controls (14.2 +/- 6.5/10(6), P = 0.039). HPRT MF in the laminators significantly correlated with styrene concentration in air, MA and haemoglobin adducts, as well as with years of employment and age of the employees. No significant difference (P = 0.450) in MF between the laminators and the factory controls was observed. Surprisingly, we detected differences in MF between sexes. When data from all measurements were combined, women showed higher MF (geometric mean 15.4 vs. 11.2 in men, P = 0.020). The styrene-exposed group exhibited significantly higher SSB parameters (tail moment (TM), tail length (TL) and the percentage of DNA in the tail (TP)) than the control group (P < 0.001). SSB parameters correlated with indicators of external exposure and with O6-styrene guanine adducts. No significant correlation was found between SSB parameters and haemoglobin adducts or HPRT MF. The data encompassing biomarkers from repeated measurements of the same population over a 3-year period are discussed with respect to the mechanisms of genotoxic effects of styrene and the interrelationship of individual biomarkers.

Adult↗
PubMed2003

Hepatitis C virus genotypes in Hungarian and Austrian patients with chronic hepatitis C.

Hepatitis C virus (HCV) genotypes are relevant to epidemiological questions, vaccine development, and clinical management of chronic HCV infection. The aim of this study was to determine HCV genotypes of South Hungarian and Southeast Austrian patients with chronic hepatitis C. Results were obtained by the largely automated TruGene HCV 5'NC Genotyping Kit (Visible Genetics, Toronto, Ontario) and by phylogenetic analysis. All of the 20 Hungarian patients and 15 out of 20 Austrian patients were infected with genotype 1. The remaining Austrian patients were infected with genotypes 3 or 2. With the commercially available assay, it was not possible to determine the HCV subtype in a total of three patients. The TruGene HCV 5'NC Genotyping assay for the determination of HCV genotypes proved to be useful for a high-throughput routine diagnostic laboratory.

Alanine Transaminase↗
PubMed2001

Breath isoprene in patients with heart failure.

BACKGROUND: Chronic heart failure (CHF) is characterised by increased vascular resistance. This increased after load on the left ventricle contributes to the vicious cycle that leads to progression of myocardial failure, multiple organ failure and death. There is evidence for increased oxidative stress in heart failure, which will influence the myocardium but also peripheral vasculature endothelium. AIMS: The aim of the present study was to examine the production of isoprene, reputed to reflect oxidative stress, in patients with CHF compared to control subjects. METHODS: Twelve patients with CHF and thirty-one healthy control subjects free from heart disease were studied. Breath was collected via a two-way non-re-breathing valve into a 60-l gas collection bag. A sample of ambient air was collected at the same time. A measured aliquot of patient breath and ambient air (approx. 1.5 l) was adsorbed onto a gas adsorption tube packed with poropak-Q. Isoprene was measured using GC/MS and the production rate calculated. All samples of breath were collected at 10.00 h after subjects had been sitting at rest for 15 min. RESULTS: Breath isoprene production in subjects with CHF was significantly reduced compared to controls 83(23) vs. 168(20) pmol min(-1) kg(-1). CONCLUSION: Breath isoprene does not directly reflect oxidative stress in CHF.

Adult↗
PubMed1999

Effect of treatment for 6 months with human parathyroid hormone (1-34) peptide in ovariectomized cynomolgus monkeys (Macaca fascicularis).

A potential negative side effect of intermittent parathyroid hormone (PTH) therapy to treat osteoporosis is the loss of cortical bone concomitant with increased cancellous bone mass. We addressed this issue by studying the effects of PTH on whole-body, axial, and appendicular bone mass in an animal model with haversian cortical bone remodeling. Ovariectomized, young adult female cynomolgus monkeys were assigned to placebo (n = 9) or PTH groups (n = 10). The PTH group received 10 microg/kg synthetic human PTH(1-34) peptide by subcutaneous injection, 3 days/week for 6 months, and the placebo group received vehicle. Multiple endpoints of bone mass, strength, and turnover in the axial and appendicular skeleton were assessed, including dual-energy X-ray absorptiometry (DEXA), quantitative computed tomography (qCT), analysis of serum (calcium, phosphorus, alkaline phosphatase, osteocalcin, and tartrate-resistant acid phosphatase) and urinary (calcium and creatinine) biomarkers, histomorphometry, and biomechanical testing. Compared with placebo-treated animals, PTH-treated monkeys had no change in whole-body bone mass, but a 6.7% increase in spinal areal bone mineral density (aBMD) was observed. Cortical bone mass measured by qCT at appendicular sites was not affected by PTH treatment, but there were significant increases in cancellous bone mass in the proximal tibia, and a similar trend in the distal radius. Small, transient increases in serum and urinary calcium were observed, but there were no treatment-related effects on other biochemical endpoints. Increased bone formation rate (BFR/BV) in the midradius and midfemur was accompanied by a nonsignificant increase in midfemur porosity. Increased vertebral cancellous bone volume (BV/TV) was associated with greater trabecular and interstitial thickness with no effect on wall thickness. Increases in bone strength were observed in both axial (vertebral maximum stress and load at fracture) and appendicular (femoral neck fracture load) skeleton. Together, these results indicate that PTH therapy in the cynomolgus monkey results in a net gain of spinal and appendicular cancellous bone mass with no adverse effect on cortical bone.

Absorptiometry, Photon↗
PubMed2003

Application of low-temperature glassy carbon-coated macrofibers for solid-phase microextraction analysis of simulated breath volatiles.

With increasing interest in the detection of disease-related volatile organic compounds (VOCs) found in human breath, breath analysis could prove to be a very useful diagnostic tool, especially for the early detection of lung cancer. Solid-phase microextraction (SPME) is a technique well suited for breath analysis and has been applied to studying VOCs in the nanomolar concentration range. However, many compounds of interest in human breath are excreted at picomolar concentrations and may be unsuitable for analysis using conventional SPME sorbent phases. To extend the concentration range of conventional SPME, a novel 4-cm-long, low-temperature glassy carbon (LTGC) macrofiber was developed. The LTGC SPME macrofibers were used to extract five lung cancer-related VOCs (2-methylheptane, styrene, propylbenzene, decane, undecane) at conditions simulating human breath, and they were analyzed via gas chromatography/mass spectrometry. Results show that detection limits are lower using the SPME macrofibers compared to a conventional SPME fiber, in the low- to sub-picomolar range for the compounds of interest, which should be adequate for the analysis of these compounds in human breath. Also, the LTGC SPME macrofibers demonstrate significantly greater extraction efficiencies, sensitivity, and peak identification accuracy compared to that of commercial PDMS/DVB fibers without excessive chromatographic peak broadening. The use of SPME macrofibers broadens the potential range of application of SPME where the rapid extraction of very low levels of volatile compounds is required.

Alkanes↗
PubMed2005

[Acute chest pain--it's not always the heart! What additional laboratory and diagnostic imaging is needed].

Few diagnostic decisions in medicine have been more heavily researched and debated than the approach to patients with acute chest pain. In addition, the question is which patients with acute chest pain have a presentation benign enough to make discharge from the emergency department safe and appropriate despite the advances in diagnostic tests. There is always the possibility of missed diagnosis which may cause substantial morbidity and mortality. The use of algorithms or protocols is not always sufficient to avoid missed diagnosis and the individual physicians's diagnostic performance and clinical experience is as important as the best algorithm for atypical chest pain! Patients with atypical symptoms are most likely to be mistakenly discharged. This article does mainly focus on diagnostic tests including ECG and biomarkers such as troponin and D-dimer as well as the investigation by helical CT scan in patients with suspected pulmonary embolism. The article also discuss the importance of repeated assessments of biomarkers and the determination of the exact time interval between the first clinical symptoms and the presentation to the emergency department. This time interval can be very crucial for the diagnostic work-up of patients with acute chest pain.

Acute Disease↗
PubMed1999

Flow-dependency of exhaled nitric oxide in children with asthma and cystic fibrosis.

The concentration of nitric oxide in exhaled air, a marker of airway inflammation, depends critically on the flow of exhalation. Therefore, the aim of this study was to determine the effect of varying the flow on end-expiratory NO concentration and NO output in children with asthma or cystic fibrosis (CF) and in healthy children. Nineteen children with stable asthma, 10 with CF, and 20 healthy children exhaled from TLC while controlling expiratory flow by means of a biofeedback signal at approximately 2, 5, 10 and 20% of their vital capacity per second. NO was measured in exhaled air with a chemiluminescence analyser. Comparisons between the three groups were made by analysing the NO concentration at the endexpiratory plateau and by calculating NO output at different flows. Exhaled NO decreased with increasing flow in all children. Children with asthma had significantly higher NO concentrations than healthy children, but only at the lowest flows. Asthmatics using inhaled steroids (n=13) tended to have lower median exhaled NO than those without steroids. The slope of linearized (log-log transformed) NO/flow plots was significantly steeper in asthmatics than in healthy controls. CF patients had a significantly lower NO concentration and output over the entire flow range studied, compared to asthmatic and control subjects, with a similar NO/flow slope as control subjects. In conclusion, the nitric oxide concentration in exhaled air is highly flow-dependent, and the nitric oxide-flow relationship differs between asthmatics versus cystic fibrosis patients and control subjects. Assessment of the nitric oxide/flow relationship may help in separating asthmatics from normal children.

Asthma↗
PubMed1999

Influence of atopy on exhaled nitric oxide in patients with stable asthma and rhinitis.

The level of exhaled NO is increased in patients with allergic asthma and seasonal rhinitis. The aim of this study was to investigate the significance of atopy on NO production in the lower airways. Measurements of exhaled NO were performed in 131 stable asthmatic patients with chronic mild asthma (95 atopics and 36 nonatopics), 72 patients with perennial rhinitis (57 atopics and 15 nonatopics) and 100 healthy controls (20 atopics and 80 non-atopics). Patients with either asthma or rhinitis had higher exhaled NO values (13.3+/-1.2 parts per billion (ppb) and 11.7+/-1.1 ppb) than control subjects (4.8+/-0.3 ppb, p<0.01). Exhaled NO levels were significantly higher in atopic asthmatics (19+/-3.6 ppb) compared with nonatopic patients (5.6+/-0.8 ppb, p<0.001). Similar findings were observed in patients with rhinitis (13.3+/-1.3 ppb in atopics and 5.8+/-1.2 ppb in nonatopics, p<0.001). No difference was found in NO levels between atopic and nonatopic control subjects (4.8+/-0.8 ppb, and 4.5+/-0.3 ppb). In summary, this study has shown that increased exhaled NO levels are detected only in atopic patients with asthma and/or rhinitis and not in nonatopic patients. These findings may suggest that it is rather the allergic nature of airways inflammation, which is mainly responsible for the higher NO production in the lower airways.

Adult↗
PubMed1997

Incorporating biomarkers of exposure and genetic susceptibility into smoking cessation treatment: effects on smoking-related cognitions, emotions, and behavior change.

In this article the authors report on the short-term impact of incorporating biomarker feedback about exposure and genetic susceptibility into minimal-contact quit-smoking counseling (QSC). Four hundred and twenty-seven smokers were randomized to 1 of 3 treatments: (a) QSC, (b) QSC + exposure biomarker feedback (EBF) about carbon monoxide in exhaled breath, or (b) QSC + EBF + biomarker feedback about genetic susceptibility to lung cancer (SBF). We observed significant immediate positive effects of SBF, compared with EBF and QSC on perceived risk, perceived quitting benefits, and fear arousal. However, at the 2-month follow-up, there were no group differences in quit rates. SBF did lead to significant reductions in the number of cigarettes smoked for smokers who were in the preparation stage. Smokers in the EBF and QSC conditions showed reductions in depressive symptoms by 2 months, but smokers in the SBF condition did not. In the context of QSC, genetic feedback may heighten vulnerability and possibly promote distress, but may not immediately enhance quitting in most smokers.

Adolescent↗
PubMed2002

Recent advances in the molecular diagnosis of lung cancer.

Despite extensive effort in improvement of diagnosis and treatment of patients with lung cancer in past three decades, the overall survival of patients with the disease remains dismal. Because the development of lung cancer takes a few decades, early diagnosis of the disease or identification of truly high-risk populations may provide us opportunity to successfully cure or prevent the disease. Recent advances in understanding biological basis of lung tumorigenesis provide new tools for detecting malignant cells or the process of malignant transformation and progression. Along with identification of molecular abnormalities in the early lung tumorigenesis, advanced molecular analytic technologies have been emerged, which may facilitate development of rapid and effective methods for early diagnosis and risk assessment. Here, I discuss recent progresses in understanding of early molecular abnormalities in lung cancer, efforts of translating laboratory findings to clinical tests, and prospective of biomarkers in lung cancer diagnosis and risk assessment.

Genetic Techniques↗