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Airways in cystic fibrosis are acidified: detection by exhaled breath condensate.

BACKGROUND: The loss of cystic fibrosis transmembrane conductance regulator (CFTR) mediated chloride conductance does not fully explain the diverse pathologies evident in patients with cystic fibrosis (CF). Bicarbonate (HCO(3)(-)) secretion is also impaired in CFTR expressing tissues and CFTR is thought to regulate HCO(3)(-) secretion at the apical membrane of epithelial cells. We hypothesised that the epithelial lining fluid (ELF) of patients with CF would be acidified and that this may be worsened during an infective exacerbation due to the increased inflammatory burden. METHODS: pH and nitrite levels in exhaled breath condensate (EBC) from 12 healthy non-smoking controls and 30 patients with CF (11 of whom were in an infective exacerbation) were measured. A further nine patients were studied before and after intravenous antibiotic treatment for an exacerbation of CF. RESULTS: The pH of EBC was significantly lower in patients with stable CF than in controls (5.88 (0.32) v 6.15 (0.16), p=0.017), and was further reduced in CF patients with an exacerbation (5.32 (0.38), p=0.001) compared with stable CF patients. EBC pH increased significantly following antibiotic treatment from 5.27 (0.42) to 5.71 (0.42), p=0.049). Nitrite levels in EBC were increased in CF patients with an exacerbation compared with control subjects (4.4 (4.0) micro m v 1.6 (1.6) micro m p=0.047). No correlation was found between EBC pH and nitrite levels. CONCLUSIONS: These findings support the hypothesis that airway acidification occurs in CF. This acidity is in part a function of inflammation as the pH of the EBC of patients increased significantly with treatment of an exacerbation, although not to control levels. Acidic pH of the ELF may play a role in the pathophysiology of CF lung disease and requires further investigation.

Adult↗

Cough frequency in children with stable asthma: correlation with lung function, exhaled nitric oxide, and sputum eosinophil count.

BACKGROUND: A study was undertaken to assess the correlation between cough frequency in asthmatic children with lung function and two non-invasive markers of airway inflammation. METHODS: Thirty two children of median age 12.0 years (interquartile range (IQR) 9.5-13.4) with stable asthma were recruited. They underwent spirometric testing, exhaled nitric oxide (eNO) measurement, sputum induction for differential cell count, and ambulatory cough monitoring over 17 hours and 40 minutes. Coughing episodes were counted both as individual spikes and as clusters. RESULTS: Complete cough frequency data were available in 29 children (90%) and their median forced expiratory volume in 1 second (FEV1) and eNO were 88.5% (IQR 79.5-98) and 23.9 ppb (IQR 11.4-41.5), respectively. The median number of cough episodes was 14 (IQR 7.0-24.0) which was significantly higher than that of normal children (6.7 (IQR 4.1-10.5), p<0.001). Sputum induction was successful in 61% of the subjects; the median induced sputum eosinophil count was 0.05% (IQR 0-9.0). Cough frequency was found to have a significant positive correlation with eNO (Spearman's r =0.781, p<0.001) but not with FEV1 or sputum eosinophil count (r =-0.270, p=0.157; r =0.173, p=0.508, respectively). CONCLUSIONS: Children with stable asthma have increased cough frequency compared with normal controls and cough frequency was greater during the day than at night. Cough may be a more sensitive marker of airway inflammation than simple spirometry.

Adolescent↗

Relationship between exhaled NO, respiratory symptoms, lung function, bronchial hyperresponsiveness, and blood eosinophilia in school children.

BACKGROUND: Exhaled nitric oxide (eNO) may serve as a non-invasive marker of airway inflammation but its relationship with other commonly used measures has not been evaluated. METHODS: Levels of eNO in a sample of 450 children aged 7-12 years out of a total sample of 2504 school children living in different urban areas near motorways were determined. The aim of this cross-sectional study was to explore the relationship between eNO, impairment of lung function (PEF, FVC, FEV(1) and MMEF), bronchial hyperresponsiveness (BHR), and blood eosinophilia in children with and without atopy as assessed by skin prick testing. RESULTS: Regression analysis showed that wheezing and nasal discharge and conjunctivitis that had occurred during the previous 12 months were positively associated with eNO levels in atopic children (relative increase of 1.48 and 1.41, respectively; p<0.05) but not in non-atopic children. Similarly, BHR and the number of blood eosinophils per ml were positively associated with eNO levels in atopic children (relative increase of 1.55 and 2.29, respectively; p<0.05) but not in non-atopic children. The lung function indices PEF, FVC, FEV(1) and MMEF were not associated with eNO levels. CONCLUSIONS: In addition to conventional lung function tests and symptom questionnaires, eNO is a suitable measure of airway inflammation and its application may reinforce the power of epidemiological surveys on respiratory health.

Bronchitis↗

Increased leukotriene B4 and 8-isoprostane in exhaled breath condensate of patients with exacerbations of COPD.

BACKGROUND: Exacerbations are an important feature of chronic obstructive pulmonary disease (COPD), accounting for a large proportion of health care costs. They are associated with increased airway inflammation and oxidative stress. METHODS: Concentrations of leukotriene B4 (LTB4), a marker of inflammation, and 8-isoprostane, a marker of oxidative stress, were measured in the exhaled breath condensate of 21 patients (11 M) with COPD during an exacerbation and 2 weeks after treatment with antibiotics. In 12 patients who had no further exacerbations these markers were also measured after 2 months. RESULTS: LTB4 concentrations were raised during the COPD exacerbation (mean (SE) 15.8 (1.1) pg/ml and fell after treatment with antibiotics to 9.9 (0.9) pg/ml (p<0.0001). In 12 patients the level of LTB4 fell further from 10.6 (1.1) pg/ml to 8.5 (0.8) pg/ml (p<0.005) after 2 months. In 12 normal age matched subjects the LTB4 levels were 7.7 (0.5) pg/ml. Concentrations of 8-isoprostane were also increased during the exacerbation (13.0 (0.9) pg/ml) and fell after antibiotic treatment to 9.0 (0.6) pg/ml (p<0.0001). In 12 patients there was a further fall from 9.3 (0.7) pg/ml to 6.0 (0.7) pg/ml (p<0.001) after 2 months compared with normal subjects (6.2 (0.4) pg/ml). CONCLUSIONS: Non-invasive markers of inflammation and oxidative stress are increased during an infective exacerbation of COPD and only slowly recover after treatment with antibiotics.

Adrenal Cortex Hormones↗

Reduced pH and chloride levels in exhaled breath condensate of patients with chronic cough.

BACKGROUND: Increased hydrogen and reduced chloride ionic environments of the airways are conducive to the stimulation of cough. However, the constituents of the local milieu of the airways of patients with chronic cough are unknown. METHODS: The pH and chloride levels in exhaled breath condensate and capsaicin cough threshold (C5) were measured in 50 patients with chronic cough and in 16 healthy controls. pH and chloride measurements were repeated after capsaicin challenge in those with cough. The cause of cough was asthma (n = 13), postnasal drip/rhinitis (n = 7), gastro-oesophageal reflux (n = 5), bronchiectasis (n = 5), but remained unidentified in 20. RESULTS: Compared with controls, patients with chronic cough had lower pH (mean 7.9 v 8.3, 95% CI of difference -0.5 to -0.2, p<0.0001), chloride levels (median 4 v 6 mmol/l, 95% CI -3.1 to -0.2, p = 0.007), and C5 (median 3.9 v 125 micro M, 95% CI -270.0 to -17.6, p = 0.002). The pH levels were different in the six subgroups including controls, and were reduced in all diagnostic subgroups of patients with cough compared with controls but did not differ between them. Chloride levels were significantly different in the six subgroups but were lower than controls in only the gastro-oesophageal reflux subgroup. There was a weak but significant correlation between chloride levels and C5 when all participants were analysed together, but not between pH and C5 or chloride levels. pH and chloride levels did not change after capsaicin challenge. CONCLUSIONS: The epithelial lining fluid of patients with chronic cough has a reduced pH and reduced chloride levels which could contribute to the enhanced cough reflex.

Adult↗

Exhaled breath condensate pH assays are not influenced by oral ammonia.

BACKGROUND: Measurement of pH in exhaled breath condensate (EBC) is robust and simple. Acidic source fluid (airway lining fluid) traps bases while volatilising acids, leading to EBC acidification in many lung diseases. Lower airway ammonia is one determinant of airway lining fluid pH, raising the concern that addition of the base ammonia by contamination from the mouth might confound EBC pH assays. METHODS: Three discrete methods were used to limit oral ammonia contamination of EBC collections: endotracheal intubation, oral rinsing, and -40 degrees C condenser temperatures. Separately, ammonia was removed from collected EBC samples by lyophilisation and resuspension. Intraweek and intraday variability of ammonia concentration was determined in 76 subjects, and ammonia and pH from a further 235 samples were graphically compared. Ammonia was assayed spectrophotometrically and pH was assessed after deaeration. RESULTS: Data from 1091 samples are presented. Ammonia was reduced in EBC by all methods. Endotracheal intubation decreased EBC ammonia from a mean (SD) of 619 (124) microM to 80 (24) microM (p<0.001, n=32). Oral rinsing before collection also led to a decline in EBC ammonia from 573 (307) microM to 224 (80) microM (p=0.016, n=7). The colder the condensation temperature used, the less ammonia was trapped in the EBC. Lyophilisation removed 99.4 (1.9)% of ammonia. Most importantly, the pH of EBC never decreased after removal of ammonia by any of these methods. Intraweek and intraday coefficients of variation for ammonia were 64 (27)% and 60 (32)%, which is substantially more variable than EBC pH assays. CONCLUSIONS: Although ammonia and pH appear to correlate in EBC, the oral ammonia concentration is not an important determinant of EBC pH. No precautions need to be taken to exclude oral ammonia when EBC pH is of interest. The low pH and low ammonia found in EBC from patients with lung diseases appear to be independent effects of volatile compounds arising from the airway.

Adult↗

Exhaled nitric oxide predicts asthma relapse in children with clinical asthma remission.

BACKGROUND: Nitric oxide in exhaled air (FE(NO)) is a marker of eosinophilic airway inflammation. A study was undertaken to determine whether FE(NO) predicts asthma relapse in asymptomatic asthmatic children in whom inhaled corticosteroids are discontinued. METHODS: Forty children (21 boys) of mean age 12.2 years on a median dose of 400 mug budesonide or equivalent (range 100-400) were included. FE(NO) was measured before and 2, 4, 12, and 24 weeks after withdrawal of steroids. A relapse was defined as more than one exacerbation per month, or need for beta agonist treatment on 4 days per week for at least 2 weeks, or diurnal peak flow variability of >20%. FE(NO) measurements were performed online with an expiratory flow of 50 ml/s. RESULTS: Nine patients relapsed. Two and 4 weeks after withdrawal of steroids geometric mean FE(NO) in children who were about to relapse was higher than in those who did not relapse: 35.3 ppb v 15.7 ppb at 2 weeks (ratio 2.3; 95% CI 1.2 to 4.1; p = 0.01) and 40.8 ppb v 15.9 ppb at 4 weeks (ratio 2.6; 95% CI 1.3 to 5.1). An FE(NO) value of 49 ppb at 4 weeks after discontinuation of steroids had the best combination of sensitivity (71%) and specificity (93%) for asthma relapse. CONCLUSION: FE(NO) 2 and 4 weeks after discontinuation of steroids in asymptomatic asthmatic children may be an objective predictor of asthma relapse.

Administration, Inhalation↗

Exhaled nitric oxide in the diagnosis of asthma: comparison with bronchial provocation tests.

BACKGROUND: Bronchial provocation tests such as exercise, methacholine (MCH), and adenosine-5'-monophosphate (AMP) challenges are used extensively in the diagnosis of asthma. A study was undertaken to determine whether exhaled nitric oxide (eNO) can be used to diagnose asthma in patients with non-specific respiratory symptoms and to compare this test with conventional provocation tests. METHODS: Patients with non-specific respiratory symptoms and normal spirometric parameters were included in the study. eNO was measured and exercise, MCH and AMP challenges performed in all subjects. Patients were defined as asthmatic based on clinical follow up 24 months after testing. RESULTS: Forty patients were considered asthmatic and 45 were not. The area under receiver operating characteristic curves gave values of 0.896 for eNO, 0.781 for exercise, 0.924 for MCH, and 0.939 for AMP (p = 0.033, 0.575 and 0.085 for eNO v exercise, MCH and AMP respectively). From our data, a cut off value of NO > 7 ppb at a flow rate of 250 ml/s best differentiates between asthmatics and non-asthmatics (sensitivity 82.5%, specificity 88.9%). Optimal cut off values for other tests were exercise: deltaFEV1 > or = 10% (sensitivity 57.9%, specificity 100%); PC20-MCH: < or = 3 mg/ml (sensitivity 87.5%, specificity 86.7%); and PC20-AMP: < or = 150 mg/ml (sensitivity 89.5%, specificity 95.6%). CONCLUSIONS: Measurement of eNO can be used as a safe, simple and rapid test for the diagnosis of asthma and is as good as bronchial provocation tests.

Adenosine Monophosphate↗

Exhaled nitric oxide measurements: clinical application and interpretation.

The use of exhaled nitric oxide measurements (F(E)NO) in clinical practice is now coming of age. There are a number of theoretical and practical factors which have brought this about. Firstly, F(E)NO is a good surrogate marker for eosinophilic airway inflammation. High F(E)NO levels may be used to distinguish eosinophilic from non-eosinophilic pathologies. This information complements conventional pulmonary function testing in the assessment of patients with non-specific respiratory symptoms. Secondly, eosinophilic airway inflammation is steroid responsive. There are now sufficient data to justify the claim that F(E)NO measurements may be used successfully to identify and monitor steroid response as well as steroid requirements in the diagnosis and management of airways disease. F(E)NO measurements are also helpful in identifying patients who do/do not require ongoing treatment with inhaled steroids. Thirdly, portable nitric oxide analysers are now available, making routine testing a practical possibility. However, a number of issues still need to be resolved, including the diagnostic role of F(E)NO in preschool children and the use of reference values versus individual F(E)NO profiles in managing patients with difficult or severe asthma.

Asthma↗

Effect of simple carbohydrates, casein hydrolysate, and a lipid test meal on ethane exhalation rate.

To determine the potential differences in the effect of various nutrients on lipid peroxidation, the ethane exhalation (EE) rate, an index of lipid peroxidation, was measured in rats at 4 (young), 18 (intermediate age), and 24 (aged) mo of age at fasting conditions and after acute ingestion of various test meals. The EE rate (means +/- SD) after a 15-h fast was significantly reduced in 24-mo-old rats (2.45 +/- 0.44 pmol.min-1.100 g body wt-1) and 18-mo-old rats (3.51 +/- 0.55 pmol.min-1.100 g body wt-1) compared with 4-mo-old rats (4.44 +/- 0.66 pmol.min-1.100 g body wt-1; P < 0.01). The EE rate significantly increased in 4-mo-old rats after ingestion of 50% (wt/vol) dextrose (8.59 +/- 2.9 pmol.min-1.100 g body wt-1), 50% casein hydrolysate (6.77 +/- 1.23 pmol.min-1.100 g body wt-1), and 20% neutral lipid emulsion (7.33 +/- 1.96 pmol.min-1.100 g body wt-1; P < 0.01). The response of aged rats to these nutrients compared with young rats was reduced by approximately 50%. A 25% dextrose solution or a 50% solution of sucrose, fructose, maltose, or galactose did not significantly alter EE rate. It is concluded that various macronutrients have a diverse potential of inducing lipid peroxidation. The responsiveness of aged rats to meal-induced enhancement of EE and presumably lipid peroxidation is significantly reduced.

Aging↗

Effect of age on L-3,5,3'-triiodothyronine-induced ethane exhalation.

The effect of age on thyroid hormone-induced lipid peroxidation in rats was determined by measuring ethane exhalation (EE) rate. The mean basal EE rates (in pmol.min-1 x 100 g-1) at room air in 25-mo-old aged rats [3.07 +/- 0.26 (SE)] and in intermediate age (18-mo-old) rats (3.42 +/- 0.18) were significantly lower than that in young (3- to 5-mo-old) rats (4.44 +/- 0.27) (P < 0.01). After 8 days of L-3,5,3'-triiodothyronine (T3) administration, EE rates in aged rats (4.10 +/- 0.25) and in intermediate-age rats (4.16 +/- 0.35) were significantly lower than that in young rats (5.61 +/- 0.36) (P < 0.01). T3-treated young rats pair-fed with aged rats for 2 wk had EE rates (5.53 +/- 0.18) comparable to ad libitum-fed young rats, although the basal rate of EE was significantly reduced with partial food restriction (4.44 +/- 0.27 vs. 3.50 +/- 0.24) (P < 0.01). These observations indicate that reduced food intake with age cannot account for the age-related changes in T3-stimulated peroxidation rate of lipids.

Aging↗

Tidal exhaled nitric oxide in healthy, unsedated newborn infants with prenatal tobacco exposure.

Tidal fractional exhaled nitric oxide (FE(NO)) changes were investigated in healthy, unsedated infants with or without prenatal tobacco exposure. Tidal flow (V), FE(NO), and CO(2) were measured in 20 healthy, unsedated infants [age: 25-58 days, length: 56.5 +/- 2.5 (SE) cm]. NO output (VNO) was calculated (VNO = FE(NO) x V). Two approaches were used to investigate within-breath changes of FE(NO) and VNO. First, we identified phases II and III from the expiratory capnogram. Second, we divided expiration into time-based quartiles. Tidal FE(NO) (range: 14.5 +/- 1.6 to 17.6 +/- 2.1 parts/billion: quartile 4 and phase II, respectively) was not different between portions and exhibited significant negative V dependence. VNO was significantly dependent on the expiratory portion, with quartile 4 being significantly lower than the remaining expiratory portions. Infants exposed to prenatal cigarette smoke (n = 7) exhibited significantly lower FE(NO) and VNO compared with nonexposed (n = 13) infants. We conclude that tidal FE(NO) is V dependent and that VNO may be a more suitable outcome parameter in variable V conditions. Prenatal tobacco exposure resulted in a decreased FE(NO) and VNO in infants.

Carbon Dioxide↗

Exhaled oral and nasal nitric oxide during L-arginine infusion in preeclampsia.

OBJECTIVE: To determine the effects of the nitric oxide (NO) precursor L-arginine on the airway NO concentration in patients with preeclampsia. METHODS: NO was measured by a noninvasive chemiluminescence technique in air sampled directly from nasal and oral cavities during expiration before and during L-arginine infusion in 9 preeclamptic and 10 control pregnancies. Maternal blood pressure and heart rate were simultaneously recorded, and blood was sampled for analyses of cyclic guanosine monophosphate (cGMP) and nitrate. RESULTS: Basal nasal and orally exhaled NO and the increment in nasal NO concentration during L-arginine infusion were similar in both groups. Basal plasma and platelet cGMP concentrations were similar in both groups. Following L-arginine infusion, plasma cGMP levels were significantly higher in preeclamptics (p < 0.01), while platelet cGMP was unaffected in both groups. Basal plasma nitrate was significantly higher in preeclamptics (p < 0.01), and this difference was not altered following infusion. Blood pressure and heart rate remained unaffected by the procedure in both groups. CONCLUSIONS: Blood pressure did not decrease in the preeclamptics following L-arginine infusion, despite a significant increase in nasal NO sampled during breathhold and a concomitant increase in plasma cGMP, possibly reflecting an endogenous NO production. These results do not support the idea of a generalized decrease in NO production being a major cause of hypertension in preeclampsia.

Adult↗

Volatile alkanes and increased concentrations of isoprene in exhaled air during hemodialysis.

In this study we examined breath volatile hydrocarbon concentrations in exhaled air of hemodialysis patients. We assessed both C(2)-C(5) alkanes - among them ethane and pentane the production of which in man is essentially due to the action free radicals exert on polyunsaturated fatty acids - and isoprene, an unsaturated hydrocarbon the biosynthesis and biological effects of which are the subject of controversy and mounting interest. Twenty patients were studied. Evaluation was performed intrapatient in the breath of patients with chronic renal failure, before and after dialysis (20 patients) and, in the same cases, during hemodialytic treatment (10 patients). Breath concentrations of these volatile hydrocarbons, determined before dialysis, were not different from those of normal subjects. Dialysis did not modify the levels of the C(2)-C(5) saturated hydrocarbons ethane, propane, butane and pentane. Instead, there was a marked increase in isoprene in all patients (basal values rose by a mean of 270%). Since isoprene was not present in the fluids or filters used for dialysis and there were only traces in the ambient air, the isoprene must have been produced endogenously during hemodialysis. As no situation has previously been reported to increase endogenous production of isoprene in humans, patients in hemodialysis offer a unique opportunity to investigate in depth the medical, biological and toxicological aspects of isoprene.

Adult↗

Acute exudative inflammation and nasally exhaled nitric oxide are two independent phenomena.

BACKGROUND: Increased levels of nitric oxide (NO) and the exudations of plasma proteins to the airway lumen have both been considered characteristics of airway inflammation. The aim of the present study was to investigate a possible relationship between nasal NO concentrations and acutely induced exudative inflammation of the nasal mucosa. METHODS: Twelve healthy non-allergic subjects participated. Nasal challenges with saline, histamine 40 microg/ml (H1), histamine 400 microg/ml (H2), oxymethazoline, 0.25 mg/ml (OXY), and a combination of oxymethazoline 0.25 mg/ml and histamine 800 microg/ml (OXYH), were performed on separate occasions. Exhaled NO was measured after each challenge, and alpha(2)-macroglobulin (as a marker of plasma exudation) was measured in nasal lavage fluids after the H1 and H2 challenges. RESULTS: The mean baseline NO in all measurements was 164 plus minus 10.3 ppb. Saline and H1 challenge did not change NO and alpha(2)-macroglobulin levels. H2 challenge showed a tendency to reduce NO levels, and the most pronounced decrease was seen after 10 min (-36.3 +/- 16.3%, p = 0.07). This reduction was sustained throughout the registration period. Simultaneously with the decrease in NO, alpha(2)-macroglobulin levels were increased significantly. OXY challenge alone reduced NO significantly throughout the whole registration period. Maximum decrease was seen at 40 min (-21.3 plus minus 3.4%, p = 0.03). The OXYH challenge also reduced NO, with a maximal reduction recorded at 10 min (-29.4 +/- 6.4%, p = 0.03). The reduction of NO was sustained throughout the registration period (p < 0.01). CONCLUSION: Histamine 400 microg/ml induced a prompt plasma exudation response whereas a decrease in nasal NO was registered, suggesting that these two events are not necessarily linked. Furthermore it was shown that the vasoconstrictor oxymethazoline reduced nasal NO, which could be related to reduced mucosal blood flow, whereas the reduction of nasal NO after histamine challenge remains to be elucidated.

Acute-Phase Reaction↗

Correlations between exhaled nitric oxide levels and pH-metry data in asthmatics with gastro-oesophageal reflux.

BACKGROUND: In gastro-oesophageal reflux (GER), micro-aspirations of gastric fluid may damage the epithelial surface of the airways, an important source of endogenous nitric oxide (NO). OBJECTIVES: The aim of the study was to evaluate the possible influence of GER on fractional exhaled nitric oxide (FE(NO)) release. METHODS: FE(NO) levels were compared in two age-matched groups of allergic children: (1) 20 with mild asthma, responding to standard anti-asthma pharmacologic therapy (asthmatic children) and (2) 12 with mild 'asthma-like symptoms' and GER. RESULTS: No differences in pulmonary functions parameters (FEV(1), FVC and FEF(25-75%)) were found between the two groups of children (p > 0.1); FE(NO) levels were higher in asthmatic children compared with GER children (p = 0.0001). GER children underwent 24-hour oesophageal pH-metry, and possible correlations between pH-metry data, pulmonary functions and FE(NO) levels were evaluated. No correlations were found between pulmonary functions and pH-metry data (p > 0.05, each correlation). In contrast, correlations were observed between FE(NO) levels and pH-metry data, including (1) percentage of study time with pH < 4 (r = -0.80, p = 0.008), (2) number of episodes with pH < 4 (r = -0.76, p = 0.012), and (3) number of episodes >5 min with pH < 4 (r = -0.69, p = 0.02). CONCLUSIONS: Thus, FE(NO) levels are lower in allergic children with 'asthma-like symptoms' and GER as compared to asthmatic children. The correlations between FE(NO) levels and pH-metry data suggest that inhalation of acid gastric content may interfere with NO production in the airways.

Asthma↗

Relationship between exhaled breath condensate volume and measurements of lung volumes.

BACKGROUND: Exhaled breath condensate (EBC) is proving to be a technique which can sample markers of lung inflammation; however, many factors affect the collection process. OBJECTIVES: We hypothesised that lung volumes--tidal volume, minute volume and total lung capacity (TLC)--would dictate the volume of the EBC sample that could be collected. METHODS: First, the volume of EBC collected was measured while measuring the tidal volume and minute volume in normal, asthmatic and chronic obstructive pulmonary disease subjects. Second, the volume of EBC was compared between breathing at tidal volumes and breathing at vital capacity in normal subjects. TLC was measured by plethysmography. RESULTS: The mean EBC volume was 5.55 +/- 0.50 microl/breath in normal subjects (n = 23), 3.56 +/- 0.33 microl/breath in chronic obstructive pulmonary disease patients (n = 25) and 5.77 +/- 0.50 microl/breath in asthmatic subjects (n = 17). EBC volume was significantly correlated with both tidal volume (Pearson's r = 0.775, p < 0.0005) and minute volume (Pearson's r = 0.425, p < 0.0005), but importantly, EBC volume was not significantly affected by age, gender or disease status. There was a significant difference in EBC volume when tidal breathing was compared with breathing at vital capacity (5.55 +/- 0.50 vs. 20.59 +/- 1.72 microl; p < 0.0001). No significant correlation was found between EBC volume and TLC (21 normal subjects). CONCLUSIONS: These results suggest that tidal and minute volume can predict the amount of EBC that can be expected to be collected. No significant differences in the volume of EBC were seen between normal subjects and those with airway diseases.

Adult↗

Increased exhalation of hydrogen peroxide in patients with stable and unstable chronic obstructive pulmonary disease.

An imbalance between oxidative stress and antioxidative capacity is thought to play an important role in the development and progression of chronic obstructive pulmonary disease (COPD). To assess the lung oxidative status in patients with COPD, we studied whether exhaled hydrogen peroxide (H2O2) is increased in breath condensate of patients with stable COPD (n = 12, mean FEV1 51% pred) and in patients with exacerbated COPD (n = 19, actual FEV1 36% pred) compared with a healthy control group (n = 10, FEV1 108% pred). Expired breath condensate during 15 min of tidal breathing was collected by cooling. The concentration of H2O2 was measured spectrophotometrically by means of horse radish peroxidase-catalyzed oxidation of tetramethylbenzidine. Concentrations of H2O2 (mean +/- SEM) were significantly elevated at 0.205 +/- 0.054 microM in patients with stable COPD compared with 0.029 +/- 0.012 microM in the control group (p < 0.05) and were further increased to 0.600 +/- 0.075 microM in patients with acutely exacerbated COPD (p < 0.001 compared with patients with stable COPD). Patients with pulmonary infiltrates on chest radiograph showed similar values compared with patients without obvious infiltrates. These findings demonstrate that patients with stable COPD exhibit increased oxidant production in the airways and that oxidant production increases further during exacerbations.

Aged↗