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PubMed1999

Upright posture and maximal exercise increase platelet aggregability and prostacyclin production in healthy male subjects.

BACKGROUND: It is well accepted that heavy physical exertion can trigger the onset of myocardial infarction, but the mechanism is uncertain. As platelet and endothelial function play an important role in thrombotic events, platelet and prostacyclin responses to maximal treadmill exercise were studied. METHODS/RESULTS: The study subjects were 40 healthy men, mean (SEM) age 29 (5) years. Platelet aggregation was measured on a four channel aggregometer. Plasma 6-keto-prostaglandin F1alpha was analysed using an enzyme immunoassay technique. Upright posture and exercise produced an increase in platelet aggregability, as indicated by a fall in the threshold concentration of adrenaline (epinephrine) from 7.6 (1.5) microM at rest to 4.3 (1.0) microM after exercise (p = 0.002). The collagen lag time became significantly shorter with exercise (from 79.1 (3.1) seconds at rest to 71.9 (2.6) seconds after exercise, p = 0.003). Exercise was also associated with a 55% increase in plasma 6-keto-prostaglandin F1alpha (from 38.1 (75%CI 29.0 to 46.5) pg/ml at rest to 59.2 (47.3 to 66.8) pg/ml after exercise, p<0.001). CONCLUSIONS: In healthy male subjects, upright posture and maximal exercise increased platelet aggregability but this increase was counteracted by an increase in prostacyclin production. In patients with endothelial dysfunction, a reduced prostacyclin response to exercise may promote a transient prothrombotic imbalance that may trigger cardiovascular disease onset.

Adult↗
PubMed2000

Increase in exhaled carbon monoxide during exacerbations of cystic fibrosis.

BACKGROUND: Non-invasive assessment of inflammation is likely to be useful in the management of cystic fibrosis (CF). Exhaled carbon monoxide (CO) concentrations are increased in patients with clinically stable CF. A study was undertaken to determine whether this marker of oxidative damage is further increased during exacerbations of the disease. METHODS: Exhaled CO concentrations were measured in 12 healthy non-smoking control subjects (six men) of mean (SE) age 37 (2) years with forced expiratory volume in one second (FEV(1)) 95 (1)% predicted and in 44 patients with CF (20 men) of mean (SE) age 29 (1) years with FEV(1) 56 (3)% predicted using an on-line CO analyser. RESULTS: Twenty nine patients were in a stable condition while 15 had clinically defined respiratory exacerbations (increased cough and production of sputum, change in the quality of the sputum, shortness of breath, sensation of chest congestion, and deterioration of FEV(1)) and represented the unstable group. Exhaled CO concentrations were 2.0 (0.15) ppm in the control group, were increased in the stable CF group to 2.7 (0.13) ppm (differences between means -0.67 (0.22), 95% confidence interval (CI) 0.22 to 1.12, p<0.01) and further increased in the unstable group to 4.8 (0.3) ppm (differences between means -2.15 (0.32), 95% CI 1.50 to 2.79, p<0.001). A significant correlation was found between the deterioration in FEV(1) and exhaled CO concentrations. CONCLUSIONS: This study shows that the measurement of exhaled CO is of potential value as an indicator of exacerbations in patients with CF and could be used as a simple method to monitor the course of the disease.

Adrenal Cortex Hormones↗
PubMed2000

Exhaled 8-isoprostane as a new non-invasive biomarker of oxidative stress in cystic fibrosis.

BACKGROUND: Cystic fibrosis is characterised by oxidative stress in the airways. Isoprostanes are prostaglandin isomers formed by free radical catalysed peroxidation of arachidonic acid. 8-Isoprostane is increased in interstitial lung diseases, asthma, chronic obstructive pulmonary disease, and adult respiratory distress syndrome. Exhaled nitric oxide (NO) and carbon monoxide (CO) are biomarkers of inflammation and oxidative stress in the airways, respectively. METHODS: Concentrations of 8-isoprostane in the breath condensate of 10 normal subjects and 19 patients with stable cystic fibrosis were measured using an enzyme immunoassay (EIA). Breath condensate is a non-invasive method of collecting airway secretions. Exhaled nitric oxide (NO) and carbon monoxide (CO) levels were measured by a chemiluminescence analyser. RESULTS: Concentrations of 8-isoprostane in the breath condensate of patients with stable cystic fibrosis were increased about threefold compared with normal subjects (42.7 (4.5) pg/ml vs 15.2 (1.7) pg/ml; p<0.005, 95% CI 14.6 to 40.9). 8-Isoprostane concentrations were negatively correlated with forced expiratory volume in one second in patients with cystic fibrosis (r = -0.61; p<0.005). Exhaled CO was also increased in patients with cystic fibrosis compared with normal subjects (6.7 (1.2) ppm vs 2.9 (0.3) ppm; p<0.05, 95% CI 0.2 to 7.4). 8-Isoprostane concentrations were significantly correlated with CO levels (r = 0.66; p<0.002). CONCLUSIONS: The results of this study show that oxidative stress is increased in cystic fibrosis and may be quantified by measuring 8-isoprostane concentrations in breath condensate.

Adult↗
PubMed2000

Dissociation between exhaled nitric oxide and hyperresponsiveness in children with mild intermittent asthma.

BACKGROUND: Bronchial hyperresponsiveness and airway inflammation are distinctive features of asthma. Evaluation of nitric oxide (NO) levels in expired air have been proposed as a reliable method for assessing the airway inflammatory events in asthmatic subjects. A study was undertaken to evaluate whether airway hyperresponsiveness is related to levels of exhaled NO. METHODS: Thirty two steroid-naive atopic children with mild intermittent asthma of mean (SD) age 11.8 (2.3) years and 28 age matched healthy controls were studied to investigate whether baseline lung function or airway hyperresponsiveness is related to levels of exhaled NO. Airway responsiveness was assessed as the dose of methacholine causing a 20% decrease in forced expiratory volume in one second (FEV(1)) from control (PD(20) methacholine) and exhaled NO levels were measured by chemiluminescence analysis of exhaled air. RESULTS: At baseline asthmatic children had significantly higher NO levels than controls (mean difference 25.87 ppb (95% CI 18.91 to 32.83); p<0.0001) but there were no significant differences in lung function parameters (forced vital capacity (FVC), FEV(1) (% pred), and forced expiratory flows at 25-75% of vital capacity (FEF(25-75%))). In the asthmatic group exhaled NO levels were not significantly correlated with baseline lung function values or PD(20) methacholine. CONCLUSIONS: These results suggest that levels of exhaled NO are not accurate predictors of the degree of airway responsiveness to inhaled methacholine in children with mild intermittent asthma.

Adolescent↗
PubMed2002

Exhaled nitric oxide correlates with airway eosinophils in childhood asthma.

BACKGROUND: Exhaled nitric oxide has been proposed as a marker for airway inflammation in asthma. The aim of this study was to compare exhaled nitric oxide levels with inflammatory cells and mediators in bronchoalveolar lavage fluid from asthmatic and normal children. METHODS: Children were recruited from elective surgical lists and a non-bronchoscopic bronchoalveolar lavage (BAL) was performed after induction of anaesthesia. Exhaled nitric oxide (parts per billion) was measured by two techniques: tidal breathing and restricted breath. RESULTS: Median (interquartile range) exhaled nitric oxide measured by restricted breath was increased in asthmatics compared with normal children (24.3 (10.5-66.5) v 9.7 (6.5-16.5), difference between medians 14.6 (95% CI 5.1 to 29.9), p=0.001). In asthmatic children exhaled nitric oxide correlated significantly with percentage eosinophils (r=0.78, p<0.001 (tidal breathing) and r=0.78, p<0.001 (restricted breath)) and with eosinophilic cationic protein (r=0.53, p<0.01 (restricted breath)), but not with other inflammatory cells in the BAL fluid. The area under the receiver operator characteristic curves for the prediction of the presence of eosinophilic airways inflammation by exhaled nitric oxide (tidal and restricted) was 0.80 and 0.87, respectively. CONCLUSIONS: Exhaled nitric oxide correlates closely with percentage eosinophils in BAL fluid in asthmatic children and is therefore likely to be a useful non-invasive marker of airway inflammation.

Asthma↗
PubMed2002

Nitric oxide in chronic airway inflammation in children: diagnostic use and pathophysiological significance.

BACKGROUND: The levels of exhaled and nasal nitric oxide (eNO and nNO) in groups of patients with inflammatory lung diseases are well documented but the diagnostic use of these measurements in an individual is unknown. METHODS: The levels of nNO and eNO were compared in 31 children with primary ciliary dyskinesia (PCD), 21 with non-CF bronchiectasis (Bx), 17 with cystic fibrosis (CF), 35 with asthma (A), and 53 healthy controls (C) using a chemiluminescence NO analyser. A diagnostic receiver-operator characteristic (ROC) curve for PCD using NO was constructed. RESULTS: The median (range) levels of nNO in parts per billion (ppb) in PCD, Bx, CF, and C were 60.3 (3.3-920), 533.6 (80-2053), 491.3 (31-1140), and 716 (398-1437), respectively; nNO levels were significantly lower in PCD than in all other groups (p<0.05). The median (range) levels of eNO in ppb in PCD, Bx, CF, A, and C were 2.0 (0.2-5.2), 5.4 (1.0-22.1), 2.6 (0.8-12.9), 10.7 (1.6-46.7), and 4.85 (2.5-18.3), respectively. The difference in eNO levels in PCD reached significance (p<0.05) when compared with those in Bx, A and C but not when compared with CF. Using the ROC curve, nNO of 250 ppb showed a sensitivity of 97% and a specificity of 90% for the diagnosis of PCD. CONCLUSIONS: eNO and nNO cannot be used diagnostically to distinguish between most respiratory diseases. However, nNO in particular is a quick and useful diagnostic marker which may be used to screen patients with a clinical suspicion of PCD.

Adolescent↗
PubMed2003

Multiple roles of nitric oxide in the airways.

Nitric oxide is endogenously released in the airways by nitric oxide synthase. Functionally, two isoforms of this enzyme exist: constitutive and inducible. The former seems to protect airways from excessive bronchoconstriction while the latter has a modulatory role in inflammatory disorders of the airways such as asthma. This review explores the physiological and pathophysiological role of endogenous nitric oxide in the airways, and the clinical aspects of monitoring nitric oxide in exhaled air of patients with respiratory disease.

Biomarkers↗
PubMed2003

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↗
PubMed2003

Exhaled nitric oxide rather than lung function distinguishes preschool children with probable asthma.

BACKGROUND: Respiratory function and airway inflammation can be evaluated in preschool children with special techniques, but their relative power in identifying young children with asthma has not been studied. This study was undertaken to compare the value of exhaled nitric oxide (FE(NO)), baseline lung function, and bronchodilator responsiveness in identifying children with newly detected probable asthma. METHODS: Ninety six preschool children (age 3.8-7.5 years) with asthmatic symptoms or history and 62 age matched healthy non-atopic controls were studied. FE(NO) was measured with the standard online single exhalation technique, and baseline lung function and bronchodilator responsiveness were measured using impulse oscillometry (IOS). RESULTS: Children with probable asthma (n=21), characterised by recent recurrent wheeze, had a significantly higher mean (SE) concentration of FE(NO) than controls (22.1 (3.4) ppb v 5.3 (0.4) ppb; mean difference 16.8 ppb, 95% CI 12.0 to 21.5) and also had higher baseline respiratory resistance, lower reactance, and larger bronchodilator responses expressed as the change in resistance after inhalation of salbutamol. Children with chronic cough only (n=46) also had significantly raised mean FE(NO) (9.2 (1.5) ppb; mean difference 3.9 ppb, 95% CI 0.8 to 7.0) but their lung function was not significantly reduced. Children on inhaled steroids due to previously diagnosed asthma (n=29) differed from the controls only in their baseline lung function. The analysis of receiver operating characteristics (ROC) showed that FE(NO) provided the best power for discriminating between children with probable asthma and healthy controls, with a sensitivity of 86% and specificity of 92% at the cut off level of 1.5 SD above predicted. CONCLUSIONS: FE(NO) is superior to baseline respiratory function and bronchodilator responsiveness in identifying preschool children with probable asthma. The results emphasise the presence of airway inflammation in the early stages of asthma, even in young children.

Airway Resistance↗
PubMed2003

Cysteinyl leukotrienes and 8-isoprostane in exhaled breath condensate of children with asthma exacerbations.

BACKGROUND: Cysteinyl leukotrienes (Cys-LTs) and isoprostanes are inflammatory metabolites derived from arachidonic acid whose levels are increased in the airways of asthmatic patients. Isoprostanes are relatively stable and specific for lipid peroxidation, which makes them potentially reliable biomarkers for oxidative stress. A study was undertaken to evaluate the effect of a course of oral steroids on Cys-LT and 8-isoprostane levels in exhaled breath condensate of children with an asthma exacerbation. METHODS: Exhaled breath condensate was collected and fractional exhaled nitric oxide (FE(NO)) and spirometric parameters were measured before and after a 5 day course of oral prednisone (1 mg/kg/day) in 15 asthmatic children with an asthma exacerbation. Cys-LT and 8-isoprostane concentrations were measured using an enzyme immunoassay. FE(NO) was measured using a chemiluminescence analyser. Exhaled breath condensate was also collected from 10 healthy children. RESULTS: Before prednisone treatment both Cys-LT and 8-isoprostane concentrations were higher in asthmatic subjects (Cys-LTs, 12.7 pg/ml (IQR 5.4-15.6); 8-isoprostane, 12.0 pg/ml (9.4-29.5)) than in healthy children (Cys-LTs, 4.3 pg/ml (2.0-5.7), p=0.002; 8-isoprostane, 2.6 pg/ml (2.1-3.0), p<0.001). After prednisone treatment there was a significant decrease in both Cys-LT (5.2 pg/ml (3.9-8.8), p=0.005) and 8-isoprostane (8.4 pg/ml (5.4-11.6), p=0.04) concentrations, but 8-isoprostane levels remained higher than in controls (p<0.001). FE(NO) levels, which fell significantly after prednisone treatment (p<0.001), did not correlate significantly with either Cys-LT or 8-isoprostane concentrations. CONCLUSION: After a 5 day course of oral prednisone there is a reduction in Cys-LT and 8-isoprostane levels in EBC of children with an asthma exacerbation, although 8-isoprostane levels remain higher than in controls. This finding suggests that corticosteroids may not be fully effective in reducing oxidative stress in children with an exacerbation of asthma.

Adolescent↗
PubMed2005

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↗
PubMed2005

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↗
PubMed1997

Nasal contribution to exhaled nitric oxide during exhalation against resistance or during breath holding.

BACKGROUND: The concentration of nitric oxide (NO) is increased in the exhaled air of patients with inflammation of the airways, suggesting that this may be a useful measurement to monitor inflammation in diseases such as asthma. However, there have been concerns that exhaled NO may be contaminated by the high concentrations of NO derived from the upper airways, and that this may account for differences in reported values of exhaled NO using different techniques. A study was performed, with argon as a tracer, to determine the extent of nasal contamination of exhaled NO using different expiratory manoeuvres. METHODS: Exhaled and nasal NO were measured by a chemiluminescence analyser. Argon (4.8%) was delivered continuously to the nose. Gas was sampled from the posterior oropharynx and argon and carbon dioxide were measured by mass spectrometry at the same time as NO. RESULTS: During a single expiration against a low resistance and during breath holding there was no evidence for nasal contamination, whereas during exhalation without resistance argon concentration in the oropharynx was increased from 0.91% (95% CI 0.84% to 0.98%) in ambient air to 1.28% (0.9% to 2.24%, p < 0.0001) during a single breath or 2.37% (2.29% to 2.51%, p < 0.0001) during tidal breathing. CONCLUSIONS: Collection of exhaled NO in a reservoir during tidal breathing is likely to be contaminated by NO derived from the nose and this may underestimate any increases in NO derived from the lower respiratory tract in inflammatory diseases. However, with slow expiration against a resistance and created back pressure to close the soft palate, there is no contamination of exhaled air which then reflects concentrations of NO in the lower airways.

Adult↗
PubMed1998

Increased levels of exhaled carbon monoxide in bronchiectasis: a new marker of oxidative stress.

BACKGROUND: Bronchiectasis is a chronic inflammatory lung disease associated with increased production of oxidants due mostly to neutrophilic inflammation. Induction of heme oxygenase (HO-1) by reactive oxygen species is a general cytoprotective mechanism against oxidative stress. HO-1 catabolises heme to bilirubin, free iron and carbon monoxide (CO). Exhaled CO measurements may therefore reflect an oxidative stress and be clinically useful in the detection and management of inflammatory lung disorders. METHODS: The levels of exhaled CO of 42 non-smoking patients with bronchiectasis treated or not treated with inhaled corticosteroids were compared with CO levels in 37 normal non-smoking subjects. RESULTS: Levels of exhaled CO were raised in patients with bronchiectasis, both those treated with inhaled corticosteroids (n = 27, median 5.5 ppm, 95% CI 5.16 to 7.76) and those not treated with inhaled corticosteroids (n = 15, median 6.0 ppm. 95% CI 4.74 to 11.8), compared with normal subjects (n = 37, median 3.0 ppm, 95% CI 2.79 to 3.81, p = 0.0024). There was no correlation between exhaled CO and HbCO levels (r = 0.42, p = 0.12) in normal subjects (n = 7), nor between the urine cotinine concentration and exhaled CO levels (r = 0.2, p = 0.12). CONCLUSIONS: Increased levels of exhaled CO may reflect induction of HO-1 and oxidative stress in bronchiectasis. Measurement of exhaled CO may be useful in the management of bronchiectasis and possibly other chronic inflammatory lung disorders.

Androstadienes↗
PubMed1998

Endogenous nitric oxide in patients with stable COPD: correlates with severity of disease.

BACKGROUND: Increased levels of exhaled nitric oxide (eNO) have been reported in asthmatic subjects but little information is available on eNO in patients with advanced chronic obstructive pulmonary disease (COPD). A study was undertaken to evaluate the levels of eNO in patients with stable COPD of different degrees of severity. METHODS: Peak and plateau values of eNO (PNO and PLNO, respectively) were evaluated in 53 patients with COPD and analysed according to the level of forced expiratory volume in one second (FEV1) and the presence of cor pulmonale (CP) (group 1, FEV1 < 35% predicted with CP, n = 15; group 2, FEV1 < 35% predicted without CP, n = 15; group 3, FEV1 > 35% predicted, n = 23). Seventeen normal subjects served as controls. RESULTS: All the patients with COPD had reduced levels of PLNO compared with the controls (mean (SD) 6.3 (3.0) and 9.4 (2.8) ppb, respectively). In groups 1 and 2 PLNO levels were significantly lower than in subjects in group 3 (5.5 (2.9), 5.7 (3.5), and 7.1 (2.7) ppb, respectively; p < 0.01 ANOVA). In all subjects % predicted FEV1 correlated slightly with PLNO but not with PNO. CONCLUSION: Patients with severe stable COPD have reduced levels of eNO compared with normal subjects. eNO levels are slightly related to the severity of airflow obstruction.

Aged↗
PubMed1998

Increase in exhaled nitric oxide levels in patients with difficult asthma and correlation with symptoms and disease severity despite treatment with oral and inhaled corticosteroids. Asthma and Allergy Group.

BACKGROUND: Patients with difficult asthma suffer chronic moderate to severe persistent asthma symptoms despite high doses of inhaled and oral corticosteroid therapy. These patients suffer a high level of treatment and disease related morbidity but little is known about the degree of airway inflammation in these patients. METHODS: Fifty two patients were examined to assess levels of exhaled nitric oxide (NO) as a surrogate marker of inflammatory activity in this condition. From this group, 26 patients were defined with severe symptoms and current physiological evidence of reversible airway obstruction requiring high dose inhaled (> or = 2000 micrograms beclomethasone dipropionate (BDP) equivalent) or oral steroid therapy to maintain disease control. RESULTS: Exhaled NO levels were higher in subjects with difficult asthma (mean 13.9 ppb, 95% CI 9.3 to 18.5) than in normal controls (7.4 ppb, 95% CI 6.9 to 7.8; p < 0.002), but lower than levels in steroid naive mild asthmatics (36.9 ppb, 95% CI 34.6 to 39.3; p < 0.001). Prednisolone treated patients had higher exhaled NO levels than patients only requiring inhaled corticosteroids (17.5 ppb, 95% CI 11.1 to 24.0 versus 7.2 ppb, 95% CI 4.6 to 9.8; p = 0.016), suggesting greater disease severity in this group. Non-compliance with prednisolone treatment was observed in 20% of patients but this did not explain the difference between the treatment groups. Exhaled NO levels were closely correlated with symptom frequency (p = 0.03) and with rescue beta agonist use (p < 0.002), but they did not correlate with lung function. CONCLUSIONS: Exhaled NO may serve as a useful complement to lung function and symptomatology in the assessment of patients with chronic severe asthma, and in the control and rationalisation of steroid therapy in these patients.

Administration, Inhalation↗
PubMed1998

Raised levels of exhaled carbon monoxide are associated with an increased expression of heme oxygenase-1 in airway macrophages in asthma: a new marker of oxidative stress.

BACKGROUND: Chronic inflammatory diseases are associated with an increased production of oxidants. Induction of a stress protein, heme oxygenase (HO) HO-1, is a cytoprotective mechanism against oxidative cellular injury. HO-1 catabolises heme to bilirubin, free iron, and carbon monoxide (CO). METHODS: Exhaled CO and sputum bilirubin levels were measured and HO-1 protein expression in airway macrophages was determined by Western blotting in asthmatic patients as levels of oxidants are raised in asthma and may induce HO-1. RESULTS: Exhaled CO was significantly increased in 37 non-steroid treated asthmatic patients compared with 37 healthy subjects (5.8 (95% CI 5.20 to 6.39) ppm vs 2.9 (2.51 to 3.28) ppm; p < 0.0001) but was similar to normal in 25 patients who received corticosteroids (3.3 (95% CI 2.92 to 3.67) ppm; p > 0.05). In non-treated asthmatic patients more HO-1 protein was expressed in airway macrophages than in normal subjects. Bilirubin levels in induced sputum were also higher than in normal subjects. Inhalation of hemin, a substrate for HO, significantly increased exhaled CO from 3.8 (95% CI 2.80 to 4.87) ppm to 6.7 (95% CI 4.95 to 8.38 CI) ppm (p < 0.05) with a concomitant decrease in exhaled nitric oxide levels, suggesting an interaction between the two systems. CONCLUSIONS: Increased exhaled CO levels and HO-1 expression may reflect induction of HO-1 which may be inhibited by steroids. Measurement of exhaled CO, an index of HO activity in non-smoking subjects, may therefore be clinically useful in the detection and management of asthma and possibly other chronic inflammatory lung disorders.

Adult↗
PubMed1998

Nitrite levels in breath condensate of patients with cystic fibrosis is elevated in contrast to exhaled nitric oxide.

BACKGROUND: Nitric oxide (NO) is released by activated macrophages, neutrophils, and stimulated bronchial epithelial cells. Exhaled NO has been shown to be increased in patients with asthma and has been put forward as a marker of airways inflammation. However, we have found that exhaled NO is not raised in patients with cystic fibrosis, even during infective pulmonary exacerbation. One reason for this may be that excess airway secretions may prevent diffusion of gaseous NO into the airway lumen. We hypothesised that exhaled NO may not reflect total NO production in chronically suppurative airways and investigated nitrite as another marker of NO production. METHODS: Breath condensate nitrite concentration and exhaled NO levels were measured in 21 clinically stable patients with cystic fibrosis of mean age 26 years and mean FEV1 57% and 12 healthy normal volunteers of mean age 31 years. Breath condensate was collected with a validated method which excluded saliva and nasal air contamination and nitrite levels were measured using the Griess reaction. Exhaled NO was measured using a sensitive chemiluminescence analyser (LR2000) at an exhalation rate of 250 ml/s. Fourteen patients with cystic fibrosis had circulating plasma leucocyte levels and differential analysis performed on the day of breath collection. RESULTS: Nitrite levels were significantly higher in patients with cystic fibrosis than in normal subjects (median 1.93 microM compared with 0.33 microM). This correlated positively with circulating plasma leucocytes and neutrophils (r = 0.6). In contrast, exhaled NO values were not significantly different from the normal range (median 3.8 ppb vs 4.4 ppb). There was no correlation between breath condensate nitrite and lung function and between breath condensate nitrite and exhaled NO. CONCLUSIONS: Nitrite levels in breath condensate were raised in stable patients with cystic fibrosis in contrast to exhaled NO. This suggests that nitrite levels may be a more useful measure of NO production and possibly airways inflammation in suppurative airways and that exhaled NO may not reflect total NO production.

Adult↗