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pH increase observed in exhaled breath condensate from welding fume exposure.

OBJECTIVES: We sought to investigate changes in exhaled breath condensate (EBC) pH in healthy workers exposed to welding fumes. METHODS: Fourteen exposed participants (median age 39 years, 5 smokers) and 8 nonexposed controls (median age 44 years, 1 smoker) were monitored at an apprentice welding school. Exposure to fine particulate matter less than 2.5 microm (PM2.5) was assessed using cyclone samplers. EBC samples were collected at baseline and at the end of the work shift. EBC samples were deaerated using argon and pH values were measured using standard pH microelectrodes. RESULTS: Mean +/- SEM PM2.5 levels were 1.17 +/- 0.18 mg/m for exposed subjects and 0.03 +/- 0.01 mg/m for controls. Baseline median (range) EBC pH values for the control and exposed group were similar (P = 0.86), 7.21 (4.91 to 8.26), and 7.39 (4.85 to 7.79), respectively. The exposed subjects had a small-but-marginally significant (P = 0.07) pre- to post-work shift increase in pH of 0.28, whereas the control group showed a minimal increase of only 0.03 (P = 0.56). Compared with the control group, the exposed group had a median cross-shift pH increase of 0.25 (P = 0.49). CONCLUSIONS: The aerosolized fine particulate matter contained in metal fumes may be associated with an acute increase in EBC pH values. Further study is necessary to investigate the acute rise in EBC pH after acute exposure to welding fume.

Adult↗

Accuracy of exhaled nitric oxide measurements for the diagnosis of bronchiolitis obliterans syndrome after lung transplantation.

BACKGROUND: Exhaled nitric oxide (eNO) is increased in patients with bronchiolitis obliterans syndrome (BOS) after lung transplantation. However, the accuracy of eNO measurements in diagnosing BOS is unknown. METHODS: Thirty-two lung-transplant patients were included. Their immunosuppressive regimen consisted of cyclosporin A (tacrolimus), azathioprine (mycophenolate mofetil), and oral but no inhaled steroids. eNO levels and spirometry were prospectively followed until 2 years after transplantation or until the patient developed BOS. RESULTS: Thirteen patients (group A) developed BOS (607 +/- 158 days after transplantation). Their mean eNO level at that time was 24.3 +/- 13.2 parts per billion (ppb), whereas the eNO value in the stable patients at 2 years (group B) was 11.4 +/- 4.9 ppb, P=0.0054. All group A patients had an eNO of 15 or greater ppb. Seven patients of group B also had an eNO of 15 or greater ppb, resulting in a test accuracy for the diagnosis of BOS of 0.78. However, considering only those patients who had two consecutive measurements (3-6 weeks apart) of eNO 15 or greater ppb during the months preceding the diagnosis of BOS or in the whole 2-year evaluation period, only 3 of 19 patients in group B (false-positives) but 12 of 13 in group A (1 false-negative) now fulfilled that criteria, which became positive at a mean of 263 +/- 169 days before the diagnosis of BOS was met, based on the forced expiratory volume in 1 second criteria. This increased the accuracy to 0.88. CONCLUSION: Measurements of eNO appear to be an accurate test for the early diagnosis of BOS.

Adult↗

Tunable diode laser spectroscopy for isotope analysis--detection of isotopic carbon monoxide in exhaled breath.

A high resolution tunable infrared diode laser spectroscopy system was developed for isotope analysis with sensitivity at ppb levels. Such a system is ideally suited for detection and measurement of minute amounts of infrared active compounds present in a huge noninfrared active background such as air. The operation and capabilities of the system were demonstrated by measuring physiological levels of isotopic carbon monoxide, 12C16O and 13C16O, naturally present in exhaled human breath with essentially no sample preparation. The simplicity in obtaining such data suggests that fundamental physiological information may be derived from noninvasive measurements. This makes the system potentially useful for many biomedical applications.

Breath Tests↗

Interpretation of CO2 exhalation rate data from demethylation of aminopyrine and its metabolite monomethylaminoantipyrine.

1 Aminopyrine breath tests make use of the commercially available (N-dimethyl-[14C])-aminopyrine. A pharmacokinetic model has been proposed to relate 14CO2 exhalation rates (CER) to the demethylation of ([14C]-methyl)-aminopyrine (AP) and -monomethylaminoantipyrine (MAP). 2 computer simulations based on the model show that the shape of the CER-time profile is largely dependent on the ratio of the MAP to AP elimination rate constants. If this ratio equals 0.5 then the CERs decline in the monoexponential fashion. Ratios less than 0.5 result in concave biexponential curves whereas ratios greater than 0.5 result in convex curves. When demethylation is not complete for both compounds the transfer from biexponential to monoexponential behaviour will only occur at ratios greater than 0.5. 3 The resolution of concave biexponential CER-time profiles to give accurate estimates of AP and MAP elimination rate constants can only be achieved when the length of the experiment is adequate. The commonly employed 2 microCi tracer dose of aminopyrine is insufficient to monitor CER over the necessary time period to detect the proposed biexponential decline.

Aminopyridines↗

High levels and gender difference of exhaled nitric oxide in Chinese schoolchildren.

BACKGROUND: Exhaled nitric oxide (eNO) may represent a useful noninvasive marker of airway inflammation, but data on the reference population values in schoolchildren are limited. No reference eNO study in Asian children has been published. METHODS: Levels of eNO in a sample of 531 schoolchildren aged 11-18 years recruited from five schools (three international schools) in Hong Kong were measured online by a chemiluminescence analyser according to ERS/ATS standard. Each student also completed an International Study of Asthma and Allergic disease in Childhood questionnaire. RESULTS: Among the children without a physician's diagnosis of asthma or symptoms of wheeze, rhinitis and eczema, there were 258 Chinese and 33 Caucasians. In control Chinese children, the eNO level (median: interquantile range) was significantly higher (P<0.001) in males (17.0 parts per billion (p.p.b.); 10.7-36.6) than in females (10.8 p.p.b.; 7.8-17.6). When compared with Caucasian control males (11.6 p.p.b.; 8.2-19.3) and females (9.1 p.p.b.; 7.5-11.9), the Chinese children had significantly higher eNO levels for both males (P=0.011) and females (P=0.037). For Chinese asthmatic males, the median eNO (interquartile range) was 39.8 p.p.b. (12.5-73.8), and for asthmatic females, 18.0 (9.6-56.3). After controlling for sex in Chinese controls, eNO did not have any significant correlation with height, weight and body mass index or body surface area. CONCLUSIONS: This study demonstrates a gender difference of eNO level in healthy Chinese schoolchildren. When compared with Caucasians, Chinese children have significantly higher eNO levels.

Adolescent↗

High fractional concentration of nitric oxide in exhaled air despite steroid treatment in asthmatic children.

BACKGROUND: The fractional concentration of nitric oxide in exhaled air (FENO) is elevated in atopic asthma and typically responds to treatment with inhaled corticosteroids (ICS). However, some patients have persistently high FENO levels despite treatment. OBJECTIVE: We studied how optimizing the inhalation technique and increasing ICS doses would affect FENO in stable atopic asthmatic children who had elevated FENO while using ICS. METHODS: In 41 stable asthmatic children who were treated with ICS (median daily dose 800 microg budesonide equivalent, range 100-1600 microg) and maintained FENO> or =20 p.p.b., we optimized the inhalation technique by thorough instruction and measured FENO 2 weeks later. Then, if FENO remained > or =20 p.p.b., we increased the ICS dose and reassessed FENO 2 weeks later. RESULTS: Improving the inhalation technique did not reduce FENO. Increasing ICS from a daily median dose of 800 to 1200 microg budesonide had no significant effect on FENO. FENO correlated positively with symptom scores in the following 2 and 4 weeks (P=0.001, 0.002) and beta2-agonist use the 2 and 4 weeks following FENO measurement (P=0.02, 0.004). CONCLUSION: We conclude that common steps in asthma treatment, i.e. inhalation instruction and increasing ICS dose, were both ineffective in reducing FENO in atopic asthmatic children with elevated FENO values despite treatment with ICS. This implies that FENO cannot simply be incorporated in current treatment guidelines.

Administration, Inhalation↗

Inflammatory mediators in exhaled breath, induced sputum and saliva.

BACKGROUND AND OBJECTIVE: Airway inflammation is assessed to monitor progression, control and treatment of asthma. The collection of exhaled breath condensate (EBC) provides a non-invasive alternative to induced sputum samples for the monitoring of airway inflammation. Both samples can be confounded by salivary contamination. The aim of this study was to compare the levels of inflammatory mediators in samples of EBC, induced sputum and saliva samples from subjects with asthma. METHOD: EBC, saliva and induced sputum samples were collected from subjects with asthma (n=10). Total protein, IL-8, 8-isoprostane and surfactant protein A (SPA) were assessed in each sample. RESULTS: Total protein, IL-8, 8-isoprostane and SPA were detected in all sputum samples. Only total protein and SPA were consistently measured in EBC, with levels at least 100-fold lower than those measured in induced sputum. In saliva, total protein, SPA and 8-isoprostane were detected in all samples, with IL-8 detected in 60% of samples. CONCLUSIONS: Induced sputum is a reliable technique that can be used to assess markers of airway inflammation. While EBC is a simple and inexpensive technique to collect lower airway secretions, the detection of inflammatory mediators is variable, and further work is required to validate this technique to assess inflammatory mediators.

Adult↗

Intranasal steroid reduces exhaled bronchial cysteinyl leukotrienes in allergic patients.

BACKGROUND: Allergic rhinitis (AR) precedes and is often associated with bronchial asthma. Indeed, local and systemic inflammations in both conditions are very similar. Cysteinyl-leukotrienes (cys-LTs) are generated during early- and late-phase allergic reactions and induce smooth-muscle contraction, microvascular leakage, and mucous hypersecretion. Cys-LTs are detected in exhaled breath condensate (EBC) of asthmatics and regardless of bronchial symptoms, they are also found in EBC of rhinitic patients. OBJECTIVE: To evaluate cys-LTs in EBC of allergic patients and to assess the activity of nasal fluticasone propionate (FP) on EBC cys-LTs levels. METHODS: Cys-LTs coefficient of variation (CV) was evaluated from different EBC in 5 healthy volunteers. Cys-LTs levels from EBCs in 13 healthy controls and 56 allergic rhinitic (n=31) and rhinitic/asthmatic (n=25) patients were also evaluated at baseline. Subsequently patients were randomized to receive either FP 100 microg/day per nostril or placebo for 2 weeks and then re-evaluated for EBC cys-LTs. RESULTS: The CV was 14.12%. EBC cys-LTs in allergic patients were significantly higher than in healthy subjects (70.9 vs. 20.6 pg/mL (median), P<0.05), while it did not differ between asthmatic/rhinitic and purely rhinitic patients. Treatment significantly reduced cys-LTs (from 93.6 to 19.9 pg/mL, P<0.001). This effect was evident both in asthmatic/rhinitic and in rhinitic patients. CONCLUSION: Treatment of AR with FP significantly reduces the levels of cys-LTs, major noninvasive markers of lower airway inflammation, suggesting that upper and lower airway inflammation is present and should be thus treated as a whole in subjects with AR with and without asthma.

Administration, Intranasal↗

Pulmonary infections increase exhaled nitric oxide in lung transplant recipients: a longitudinal study.

The aim of this longitudinal study was to test whether pulmonary infections influence fractional exhaled nitric oxide levels (FENO) in otherwise clinically-stable lung transplant recipients. Levels of FENO were measured at least on 11 occasions in nine lung transplant recipients who attended for routine or urgent clinical review over 27.0 +/- 3.2 months period. Diagnosis of infection was based on clinical symptoms, functional measurements and radiological findings. Concentrations of FENO were also determined in 12 healthy volunteers. During follow-up, six patients had one, two had three, and one had four episodes of pulmonary infections. Overall, six upper and 10 lower respiratory tract infections were noted. Recipients with active infections developed increased FENO levels as compared with their own baseline levels measured in the clinically well period (10.8 +/- 1.3 vs. 7.6 +/- 1.1 ppb, p < 0.05). After antibiotic treatment, elevated FENO concentrations returned to baseline in association with full clinical recovery. Baseline FENO levels in lung transplant recipients and in healthy volunteers (6.0 +/- 0.5 ppb) were similar. The sensitivity and specificity of FENO measurement in detecting pulmonary infections were 57 and 96%, respectively. Our data suggest that pulmonary infections are associated with increased FENO levels in patients with lung allografts. Nevertheless, the measurement of FENO by itself as a screening tool for infections seems to be limited by its low sensitivity.

Adult↗

Exhaled NO and eosinophil markers in blood, nasal lavage and sputum in children with asthma after withdrawal of budesonide.

BACKGROUND: There is a need for controlled trials among children with asthma to evaluate and compare different markers of inflammation. OBJECTIVE: Our goal was to investigate the effect of withdrawal of inhaled budesonide on repeated measurements of exhaled NO (ENO), peripheral blood eosinophils (PBE), sputum/NAL/serum-eosinophil cationic protein (ECP), bronchial hyperresponsiveness (BHR) and forced expiratory volume in 1 s (FEV(1)) in children with allergic asthma. METHODS: Eighteen asthmatic children were randomly allocated to continue or discontinue use of inhaled budesonide. They were followed up, at six visits for 4 months with regular blood, serum, sputum, and NAL samples. Sixteen age-matched healthy children served as controls. RESULTS: ENO, PBE, and S-ECP increased significantly in the withdrawal group (p < 0.05) but not in the continuous treatment group. No trend could be observed during the study for markers in sputum or in NAL in either group. CONCLUSION: The present data provide evidence for the clinical usefulness of measuring ENO, PBE, and S-ECP and when combined they could help to avoid over- and undertreatment with corticosteroids in the growing child.

Adolescent↗

Peak expiratory flow during a passive exhalation: an index of expiratory resistance during anesthesia.

During a passive exhalation performed between (FRC + VT) and FRC, peak expiratory flow (VmaxE) varies as a function of the respiratory system expiratory resistance, RT, with the following relationship: VmaxE = VT/(RT . CT), where Cr is the total respiratory system compliance (static). This expression assumes: (1) a laminar flow regimen during expiration, and (2) a constant CT value over the range of VT. Both these conditions are usually attained during controlled ventilation in the apneic patient. VmaxE can be monitored continuously with relative ease, and may represent a simple and useful index of the mechanical properties of the respiratory system in the anesthetized patient.

Adult↗

Quantitative measurements of the alcohol concentration and the temperature of breath during a prolonged exhalation.

After healthy men drank a moderate dose of alcohol their breath-alcohol concentrations and breath-temperatures were quantitatively determined as a function of expired-volume. All test were made in the post-adsorptive phase of ethanol metabolism and breath samples were analysed by gas-liquid chromatography. The temperatures of breath rose steadily from start to end of exhalation with a mean of 34.48 degrees C after a forced vital capacity (FVC) maneuver. The standard deviation of a single measurement of breath-temperature in randomly selected subjects was +/- 0.402 degrees C. No statistically significant increases in the temperature of breath were noted after an expired volume of 70% FVC. At average expired-breath volumes of 13.5%, 26.2%, 52.2%, 71.7% and 94.2% FVC the breath-temperatures were 33.3 degrees C, 33.5 degrees C, 33.9 degrees C, 34.1 degrees C and 34.4 degrees C whereas breath-alcohol concentration were 79.7%, 85.9%, 90.5%, 95.9% and 98.8% of the 100% FVC alcohol levels. When I corrected for the lower temperatures of breath in the early stages of expiration, the concentrations of alcohol were 86.6%, 90.8%, 93.5%, 96.5% and 98.5% of the 100% FVC levels. These results show that at least 70% of a man's vital capacity must be discarded before a breath-concentration plateau for ethanol develops. But even after a discard breath-volume of 10% FVC the concentration of alcohol reaches 80% of the level in end-expiratory breath. I suspect that ethanol dissolves in the mucous-membranes of the upper respiratory tract and equilibrates with breath in the airway dead-space and in the mouth.

Adult↗

Postprandial changes in the exhalation rate of radon produced in vivo.

The rate of exhalation of radon by persons with long-standing radium burdens increases about twofold shortly after a meal. The increase is short-lived and "normal" values are regained in 1.5 to 2 hours. The effect may account in part for the poor reproducibility in estimates of the freely emanating part of the radium content.

Adult↗

Exhaled nitric oxide in chronically ventilated preterm infants.

Exhaled nitric oxide (eNO) levels were measured in eight ventilated infants, mean gestational age 25.8 (SD 1.7) weeks and postnatal age 55 (SD 39) days, before and after three days of dexamethasone treatment. The eNO levels fell from a mean of 6.5 (SD 3.4) to 4.2 (SD 2.6) parts per billion (p = 0.031) and the mean supplementary oxygen levels from 62% to 45% (p = 0.0078).

Anti-Inflammatory Agents↗

Extra intestinal influences on exhaled breath hydrogen measurements during the investigation of gastrointestinal disease.

During the clinical investigation of patients with gastrointestinal disease by exhaled breath hydrogen measurement, the occurrence of inexplicable variations in recorded hydrogen values led to a search for extra intestinal factors which were capable of adversely influencing breath hydrogen concentration and impairing the diagnostic accuracy of the test. Serial breath samples were collected from normal subjects under a variety of conditions which might occur during routine clinical study, including, hyperventilation, exercise, cigarette smoking, and carbohydrate ingestion. Breath hydrogen concentrations were consistently reduced by hyperventilation (p less than 0.01) and exercise (p less than 0.05). Cigarette smoking, in contrast, caused a marked rise in measured breath hydrogen (p less than 0.01), as did oral carbohydrate (p less than 0.05). Prior bactericidal mouthwash abolished this carbohydrate associated rise, suggesting that the hydrogen was the result of fermentation by oropharyngeal bacteria. Because, in all instances, the changes in breath hydrogen were of sufficient magnitude to interfere with data interpretation, it is recommended that these factors are eliminated, whenever possible, from conditions of study.

Bacteria, Anaerobic↗

The effect of sulphurous air pollutant exposures on symptoms, lung function, exhaled nitric oxide, and nasal epithelial lining fluid antioxidant concentrations in normal and asthmatic adults.

AIMS: To explore the effects in normal and asthmatic adults of exposure to 200 ppb sulphur dioxide (SO2) and 200 microg/m3 and 2000 microg/m3 aerosols of ammonium bisulphate (AB) and sulphuric acid (SA) (MMD 0.3 microm). METHODS: Exposures were placebo controlled, for one hour at rest, double blind in random order. DeltaFEV1 was the primary outcome; secondary outcomes included symptoms, ventilation, exhaled nitric oxide (NO) concentrations, and nasal lavage fluid ascorbic (AA) and uric acid (UA) concentrations. RESULTS: There were no significant changes in spirometry or symptoms with any exposure in either group. SO2 exposure was associated with an increased respiratory rate relative to air exposure in the asthmatic group (SO2: 958.9 breaths/hour; air: 906.8 breaths/hour) but the mean volume breathed did not differ significantly (SO2: 318.8 litres; air: 311.4 litres). AB exposures were associated with a significant rise in [NO] in the asthmatic (+1.51 ppb, and +1.39 ppb), but not in the normal group. Mean pre- and post-exposure [AA] tended to be higher in the normal than in the asthmatic group. Within each group, [AA] did not change significantly with any exposure. Post-exposure [UA] were greater than pre-exposure concentrations for all exposures, significantly so in the normal group for all exposures except SO2. There were no significant differences in the mean change in [UA] for any exposure relative to air. CONCLUSIONS: The pollutant exposure concentrations employed in this study were generally much greater than ambient. It is unlikely that short lived exposures at lower concentrations would show significant effects, but effects of longer term lower concentration exposures cannot be ruled out.

Adult↗

Association between air pollution exposure and exhaled nitric oxide in an elderly population.

BACKGROUND: Animal models suggest that the cardiovascular effects of air pollution result in part from inflammation caused by proinflammatory mediators originating in the lung. In a human study of the cardiovascular effects of air pollution, we aimed to evaluate the potential association between air pollution levels and the fraction of exhaled nitric oxide (FE(NO)), a non-invasive measure of airway inflammation. METHODS: Breath samples were collected weekly between September and December 2000 in a community based group of elderly subjects (median age 70.7 years) in Steubenville, Ohio. The samples were analysed for NO. Air pollution levels were measured concurrently at a central site monitor. RESULTS: An increase in the 24 hour average PM(2.5) concentration of 17.7 micro g/m(3) was associated with an increase in FE(NO) of 1.45 ppb (95% CI 0.33 to 2.57) in models adjusted for subject, week of study, day of the week, hour of the day, ambient barometric pressure, temperature, and relative humidity. This represents a change of approximately 15% compared with the mean FE(NO) in the cohort (9.9 ppb). A significant association was also observed for a 24 hour moving average of ambient NO (0.83 ppb increase, 95% CI 0.26 to 1.40). In two-pollutant models, the magnitude and precision of the PM(2.5) effect was not reduced and the ambient NO effect was no longer significant. The associations between FE(NO) and PM(2.5) were significantly higher in subjects with a doctor's diagnosis of COPD (p value for interaction = 0.03). CONCLUSIONS: Ambient pollution may lead to airway inflammation as measured by FE(NO). These subclinical inflammatory changes may be an important step in the pathogenesis of the cardiopulmonary effects induced by exposure to air pollution.

Aged↗

Exhaled nitric oxide levels in non-allergic and allergic mono- or polysensitised children with asthma.

BACKGROUND: Increased fractional exhaled NO concentrations (FENO) and blood/tissue eosinophilia are frequently reported in allergic children with mild asthma and are thought to reflect the intensity of the inflammation characterising the disease. The aim of this study was to investigate possible differences in FENO levels or in the intensity of the blood eosinophilia in allergic and non-allergic asthmatic children. METHODS: 112 children with stable, mild, intermittent asthma with a positive bronchial challenge to methacholine were consecutively enrolled in the study; 56 were skin prick test and RAST negative (non-sensitised) while 56 were sensitised to house dust mites (23 only to house dust mites (monosensitised) and 33 were sensitised to mites and at least another class of allergens (pollens, pet danders, or moulds)). Nineteen sex and age matched healthy children formed a control group. RESULTS: Compared with non-allergic patients, allergic children had a significantly higher rate of blood eosinophilia (p=0.0001) with no differences between mono- and polysensitised individuals. Forced expiratory volume in 1 second (FEV(1)), forced vital capacity (FVC), forced expiratory flow at 25-75% of vital capacity (FEF(25-75%)), and the degree of bronchial reactivity to methacholine were similar in non-atopic and atopic children, with no differences between mono- and polysensitised individuals. FENO levels measured by chemiluminescence analyser were higher in asthmatic children (15.9 (14.3) ppb) than in the control group (7.6 (1.6) ppb, p=0.04) and higher in allergic patients (23.9 (2.1) ppb) than in non-allergic patients (7.9 (0.8) ppb, p=0.0001), but there were no differences between mono- and polysensitised individuals (p>0.1). Significant correlations between blood eosinophilia and FENO levels were seen only in allergic (r=0.35, p<0.01) and in polysensitised individuals (r=0.45, p<0.05). CONCLUSIONS: In children with mild asthma, a similar degree of functional disease severity may be associated with a higher inflammatory component in allergic than in non-allergic subjects.

Adolescent↗