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Nitric oxide levels in exhaled air and inducible nitric oxide synthase immunolocalization in pulmonary sarcoidosis.

Cytokines such as tumour necrosis factor-alpha and interferon gamma are associated with active pulmonary inflammation in sarcoidosis and they upregulate inducible nitric oxide synthase (iNOS). The objectives of this study were to examine iNOS upregulation in sarcoidosis by showing raised exhaled nitric oxide and increased iNOS activity in lung biopsy specimens of these patients utilizing immunohistochemistry. Exhaled NO was measured by a chemiluminescence analyser in 12 patients with newly diagnosed biopsy-proven sarcoidosis before and after 6 weeks of corticosteroid therapy. Lung biopsy specimens from these patients were subjected to immunohistochemical staining with a specific iNOS antibody. Exhaled NO was raised in newly diagnosed sarcoidosis (mean+/-SEM): 9.8+/-0.4 versus 4.1+/-0.2 parts per billion (ppb) in 21 healthy controls, p<0.001; and fell significantly after 6 weeks treatment with corticosteroids to 5.9+/-1.4 ppb; p<0.01. There was no correlation between exhaled NO and other markers of disease activity. Immunohistochemical staining demonstrated iNOS activity in respiratory epithelium and granulomas in patients with sarcoidosis. Exhaled nitric oxide is raised in patients with active pulmonary sarcoidosis and may be a result of inducible nitric oxide synthase upregulation. The fall in exhaled nitric oxide following corticosteroid therapy may reflect inhibition of inducible nitric oxide synthase in the respiratory epithelium and granulomas.

Adult↗

Exhaled monoxides in asymptomatic atopic subjects.

BACKGROUND: Atopy is a genetically determined condition and some atopic people develop airway hyperresponsiveness and sometimes asthma later in life. Since airway inflammation may be present before the onset of clinical symptoms of asthma, early and noninvasive detection of inflammation would be useful in atopic subjects. Mediators produced by activated inflammatory cells may lead to induction of inducible nitric oxide synthase producing nitric oxide (NO) and inducible heme oxygenase releasing carbon monoxide (CO) in the airways. Both monoxides are present in exhaled air and their levels are elevated in asthma reflecting airway inflammation. OBJECTIVE: We have measured exhaled NO and CO levels in atopic and nonatopic healthy non-smoking subjects to determine whether inflammation is present in the airways. METHODS: Exhaled NO was measured by a chemiluminescence analyser and exhaled CO electrochemically and NO in asymptomatic atopic and age-matched nonatopic normal subjects. RESULTS: Exhaled NO and CO levels were both significantly elevated in 15 atopic subjects compared with 40 nonatopic individuals (means +/- SEM: 18.3+/-3.0 p.p.b. vs. 6.3+/-0.3 p.p.b., P< 0.0001 and 4.7+/-0.3 p.p.m. vs 2.8+/-0.2 p.p.m., P = 0.0005, respectively). CONCLUSION: Increase in exhaled monoxide levels may be an early and noninvasive marker of airway inflammation in asymptomatic atopic subjects.

Adolescent↗

Exhaled nitric oxide in seasonal allergic rhinitis: influence of pollen season and therapy.

Exhaled nitric oxide (eNO) has been proposed as a potential indirect marker of lower airway inflammation in asthma. To investigate the existence of lower airways inflammation in allergic rhinitis eNO measurements were performed in 32 patients with symptomatic and asymptomatic seasonal allergic rhinitis early in and out of pollen seasons and in 80 healthy volunteers. To further define how exhaled NO is modified by therapy, NO levels were detected following 1-month treatment with either inhaled steroids or non-steroids therapy with nedocromil. Exhaled NO (mean +/- SE) was significantly elevated in patients with seasonal allergic rhinitis with and without symptoms (24.2 + 2.5 and 13.9 + 2.9 ppb, respectively) as compared to healthy volunteers (4.5 + 0.3 ppb) both in and out of pollen season (21.2 + 2.1 and 9.0 + 1.4 p.p.b., respectively) with a higher increase during the allergen exposure in season. Higher levels of exhaled NO were detected in patients with symptoms, either from the upper or lower airways, and with bronchial hyperreactivity. The increased exhaled NO in symptomatic patients was reduced only by inhaled steroids and not by nedocromil. These findings possibly suggest the existence of lower airway inflammation in both symptomatic and asymptomatic patients with seasonal allergic rhinitis in and out of pollen season. Thus, exhaled NO may be used as a non-invasive index for early detection of lower airway inflammation and for monitoring the optional treatment in patients with seasonal allergic rhinitis.

Adult↗

The relationship between exhaled nitric oxide and allergic sensitization in a random sample of school children.

BACKGROUND: Exhaled nitric oxide (NO) has been proposed as novel a non-invasive marker of airway inflammation. OBJECTIVE: The level of exhaled NO was determined in a random sample of school children (7-12 years old) with the aim of investigating the relationship between exhaled NO and sensitization to common allergens. RESULTS: In the 450 children tested by skin prick tests (SPT), the prevalence of sensitization was 29.5% (overall), 21.9% (sensitization to indoor allergens), and 15.0% (sensitization to outdoor allergens). Regression analysis showed that levels of exhaled nitric oxide were closely associated with various measures of sensitization to aeroallergens. Sensitization to indoor allergens was associated with higher levels of exhaled NO (eNO) than sensitization to outdoor allergens when assessed by IgE but not when assessed by SPT. Children with reported wheeze in the past 12 months had much stronger associations between sensitization and eNO than children without wheeze. CONCLUSION: We conclude that allergic sensitization is strongly associated with increased levels of exhaled NO, especially in children with wheeze.

Air Pollution, Indoor↗

Exhaled nitric oxide in cystic fibrosis patients with allergic bronchopulmonary aspergillosis.

Exhaled nitric oxide (NO) is thought to be a marker of asthmatic inflammation. Levels in cystic fibrosis (CF) are generally low. This study aimed to measure exhaled NO in CF patients at high risk of developing ABPA and patients at low risk. We studied nine patients at high risk of developing ABPA and 36 at low risk. The two groups were similar in age and spirometry. All patients in the high-risk group were taking oral or inhaled glucocorticoids, compared to 56% in the low-risk group (P=0.02). The exhaled NO levels were lower in the high-risk group than in the low-risk group (2.0 vs. 3.6 ppb), mean difference (95% CI) 1.6 (-3.6 to 0.4) ppb, P=0.001. On subgroup analysis of patients on oral glucocorticoids, the exhaled NO levels were significantly lower in patients with a high risk of developing ABPA (n=7) than patients with a low risk (n=8) (P=0.011). The number of patients who were on inhaled, but not oral glucocorticoids was too small to analyse usefully. Exhaled NO levels were lower in CF patients with a high risk of developing ABPA and on glucocorticoids. This may be because oral glucocorticoids exert a greater effect on exhaled NO than inhaled glucocorticoids. Alternatively, inducible nitric oxide synthase may be down-regulated by Aspergillus toxin.

Adolescent↗

Air pollution is associated with increased level of exhaled nitric oxide in nonsmoking healthy subjects.

The authors sought to determine which air pollutant is responsible for the increase in exhaled nitric oxide observed in healthy subjects. Exhaled nitric oxide was measured in 16 nonsmoking healthy subjects on 14 workdays, during which there were varying air-pollution levels. Contamination of samples by ambient nitric oxide was excluded. The baseline value of exhaled nitric oxide, determined at times when outdoor air pollution was low, ranged from 7 to 43 ppb (mean = 28+/-5 ppb). The daily value of exhaled nitric oxide (range = 5-60 ppb) was associated positively with ambient carbon monoxide (r = .85) and nitric oxide (r = .81). Exposure during the morning hours to high levels of outdoor pollution was associated with increased exhaled nitric oxide (i.e., 50% above baseline), which persisted for up to 5 h (i.e., 32% above baseline). These results indicated that exhaled nitric oxide levels represent a useful biomonitor of individual exposure to air pollutants.

Adult↗

Exhaled nitric oxide as a simple assessment of airway hyperresponsiveness in bronchial asthma and chronic cough patients.

Exhaled nitric oxide (NO) has been suggested to be a marker of airway inflammation. The aim of this study was to evaluate the role of exhaled NO in bronchial asthma and chronic cough patients to predict bronchial hyperresponsiveness (BHR). We measured the exhaled NO concentration using the chemiluminescence method in 52 asthma patients (group I consisting of 24 without prior inhaled corticosteroid (ICS) use, and group II consisting of 28 previously on ICS and 16 chronic cough patients in group III). In addition to regular examinations, spirometry and methacholine inhalation tests using the Astograph were done. In group I, a significantly negative correlation was observed regarding the exhaled NO concentration with FEV1/FVC%, V50, and BHR that was assessed as Dmin and PD35-Grs, and a positive correlation with peripheral blood eosinophils. In group III, a significantly negative correlation was seen regarding the exhaled NO concentration with BHR. We thus concluded that measuring exhaled NO concentration appears to be a useful noninvasive method to predict the BHR, airway obstruction, and inflammation in asthma and chronic cough patients.

Adult↗

Food restriction suppresses an age-dependent increase in the exhalation rate of pentane from rats: a longitudinal study.

Longitudinal age changes in the exhalation rates of ethane and pentane, which are used as the indices of in vivo lipid peroxidation, from rats under ad libitum feeding and food restriction were measured. The exhalation rate of ethane or pentane from old, ad libitum-fed rats is higher than that of the corresponding hydrocarbon from young, ad libitum-fed rats, as reported previously. There is no difference between the exhalation rates of each hydrocarbon from young, ad libitum-fed and food-restricted rats. However, the exhalation rate of pentane from old, food-restricted rats is significantly lower than that from old, ad libitum-fed rats, while the exhalation rate of pentane from old, food-restricted rats tends to be lower than that from old, ad libitum-fed rats. In addition, the exhalation rate of pentane from old, food-restricted rats is equivalent to that from young, ad libitum-fed rats. These results are consistent with the views that in vivo lipid peroxidation in rats is increased during aging, and that the age-dependent increase in in vivo lipid peroxidation is suppressed by food restriction.

Aging↗

Increase in exhaled nitric oxide in shoe and leather workers at the end of the work-shift.

BACKGROUND: Measurement of nitric oxide (NO) in exhaled air is a non-invasive procedure for assessing airway or pulmonary inflammation, and for evaluating environmental irritant effects of air pollution. The objective of this study was to evaluate exhaled NO levels in synthetic leather workers exposed to organic solvents toluene, xylene and methylethyl ketone. METHODS: Seventeen shoe and leather workers and 10 controls from administrative personnel of the factory were studied. The levels of exhaled NO at baseline and at the end of the work shift were measured using a standardized chemiluminescence technique. Environmental assay of the three solvents was also assessed during the working day. RESULTS: Environmental solvent concentrations were high but within permissible exposure levels. Exhaled NO concentrations increased by 40% in the leather workers at the end of the working day from a mean +/- SD of 9.1 +/- 1.3 p.p.b. to 12.8 +/- 1.7 p.p.b. (P < 0.02), as compared to the controls. CONCLUSION: Exhaled NO is increased in shoe and leather workers exposed to solvents at the end of work shift, while it does not change in unexposed subjects of the same factory. Exhaled NO may be a sensitive tool to monitor sub-clinical effects of occupational pro-inflammatory substances.

Adult↗

General anesthesia and exhaled breath hydrogen peroxide.

To study the role of free radical formation on the impairment of pulmonary function seen with general anesthesia, we measured the hydrogen peroxide (H2O2) concentration in the exhaled breath condensate of 27 patients. Patients were divided into three study groups: a healthy patient group (group 1, n = 15) consisting of ASA physical status 1 and 2 patients undergoing elective noncardiothoracic surgery; a specific anesthetic event group (group 2, n = 6) composed of patients undergoing cardiopulmonary bypass (CPB); and a positive control group (group 3, n = 6) consisting of patients with the adult respiratory distress syndrome (ARDS). The exhaled breath condensate was collected by diverting exhaled breath through a glass condensation coil submerged in an ice/salt water bath. The exhaled breath condensate samples were then assayed using a spectrophotometric method. In group 1, samples were collected before and after the induction of general anesthesia with intravenous drugs, and before and after the administration of the inhalational anesthetics isoflurane (1.5%) (n = 7) or N2O (70%) (n = 8). In group 2, samples were collected pre- and post-CPB, and in group 3, when specific diagnostic criteria for ARDS were met. There was no significantly detectable H2O2 (not significantly different from zero) in any of the samples from the group 1 patients. Similarly, group 2 patients had exhaled breath H2O2 concentrations near zero except for one patient who was positive for the lupus anticoagulant. Group 3 patients had a mean (+/- SE) exhaled breath H2O2 concentration of 0.55 (+/- 0.08) microM, which was significantly greater than zero (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, General↗

Exhaled nitric oxide does not reflect the severity of acute lung injury: an experimental study in a rat model of extracorporeal circulation.

OBJECTIVE: This study was undertaken to determine whether an increase in exhaled nitric oxide would reflect the severity of the acute lung injury caused by extracorporeal circulation. DESIGN: Prospective, controlled animal laboratory investigation. SETTING: University laboratory. SUBJECTS: Male, anesthetized, paralyzed, and mechanically ventilated Wistar rats (n = 34). INTERVENTIONS: Twenty-three Wistar rats underwent a partial (100 mL.kg(-1).min(-1)) femoro-femoral extracorporeal circulation in normothermia for 90 mins. Eleven time-matched rats formed the sham group. MEASUREMENTS AND MAIN RESULTS: Exhaled nitric oxide was monitored with a chemiluminescence analyzer. Acute lung injury was assessed by blood gas analysis and lung water content. Lung Evans blue dye content, lung myeloperoxidase, and heme oxygenase activities were determined. Compared with the sham rats, extracorporeal circulation was responsible for acute lung injury characterized by an increased lung water content (82.4 +/- 1.3% vs. 77.9 +/- 1.1%; p<.05), an increased Evans blue dye content (191.8 +/- 15.8 vs. 112.5 +/- 16.8 mg/g tissue wet weight; <.01), and an increased pulmonary heme oxygenase activity (332.9 +/- 107 vs. 113.7 +/- 46.5 pmol. hr(-1).mg of protein(-1); p<.05). Exhaled nitric oxide remained stable throughout the experiment in all sham rats. Among the 23 rats that underwent extracorporeal circulation, eight rats (35%) experienced an increase in exhaled nitric oxide concentration (16.9 +/- 12.7 ppb). There was no significant difference between rats that did or did not experience an increase in exhaled nitric oxide regarding each index of acute lung injury. CONCLUSIONS: An increase in exhaled nitric oxide did not reflect the severity of the acute lung injury caused by extracorporeal circulation. Its significance remains to be determined.

Animals↗

Detection of nitric oxide in exhaled air during administration of nitroglycerin in vivo.

1. Direct evidence for nitric oxide (NO) formation from nitroglycerin (GTN) was obtained by measurements of NO concentrations in exhaled air in artificially-ventilated, pentobarbitone-anaesthetized rabbits. 2. The concentration of endogenously formed NO was 23 +/- 5 parts per billion (p.p.b.). Infusions of GTN (1-100 micrograms kg-1 min-1, i.v.) induced dose-dependent and biphasic increments in exhaled NO and concomitant reductions in systemic blood pressure. 3. Tolerance to the blood pressure reduction developed in parallel with a decrease in GTN-induced exhaled NO, a pattern which was unaffected by administration of N omega-nitro-L-arginine methyl ester (L-NAME, 30 mg kg-1), L-cysteine (200 mg kg-1), N-acetylcysteine (200 mg kg-1) or glutathione (200 mg kg-1). 4. Intravenous infusions of adenosine (0.7 mg ml-1, 250 microliters kg-1 min-1) and GTN (1 mg ml-1, 250 microliters kg-1 min-1) elicited similar decrements in pulmonary vascular resistance. GTN elicited a substantial increase in exhaled NO (50 +/- 10 p.p.b.) whereas adenosine evoked a markedly smaller increase (7 +/- 1 p.p.b.). L-NAME (30 mg kg-1, i.v.) abolished NO in exhaled air, and evoked an increase in pulmonary vascular resistance from 116 +/- 19 to 147 +/- 9 pulmonary vascular resistance units. After L-NAME the change in pulmonary vascular resistance induced by adenosine or GTN was increased to a similar degree. However, while the increase in exhaled NO induced by nitroglycerin was unaffected, the response to adenosine was abolished. 5. The present data demonstrate that NO is formed from GTN in vivo. Furthermore, thiol availability,or nitric oxide synthase activity are not limiting factors in the conversion of nitroglycerin to NO in vivo.Finally, pulmonary haemodynamic changes per se do not explain the observed increase in NO upon nitroglycerin infusion.

Acetylcysteine↗

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↗

Effect of nebulised L- and D-arginine on exhaled nitric oxide in steroid naive asthma.

BACKGROUND: Nitric oxide (NO) is a product of the enzyme nitric oxide synthase (NOS) and is found in normal and asthmatic human airways. The administration of L-arginine results in an increase in airway NO production in asthmatic subjects. This is thought to occur because L-arginine is the substrate for NOS. However, studies in the systemic vasculature suggest that other mechanisms may be responsible. METHODS: Eight patients with steroid naive asthma each received 2.5 g L-arginine, 2.5 g D-arginine, and 2.0% saline by ultrasonic nebuliser on separate days in a randomised, single blind manner. Exhaled NO was measured by chemiluminescence and spirometric tests were performed before and for 3 hours after each administration. The mean concentration of NO after exposure was calculated from the area under the curve. RESULTS: L-arginine, D-arginine, and 2.0% saline induced a mean (95% CI) maximal bronchoconstriction of 11.9% (-1.7 to 25.4), 10.0% (2.8 to 17.2), and 8.5% (-2.5 to 19.5) of the starting forced expiratory volume in one second (FEV(1)), respectively. Exhaled NO declined in proportion to the degree of bronchoconstriction (r=0.60, p<0.01). Bronchoconstriction and the acute reduction in exhaled NO resolved within 15 minutes. The mean post-exposure concentration of NO was 15.75 parts per billion (ppb) after L-arginine, 15.16 ppb after D-arginine, and 12.74 ppb after 2.0% saline. The mean (95% CI) difference between L-arginine and placebo was 3.01 (0.32 to 5.7) ppb, between D-arginine and placebo 2.42 (0.10 to 4.74) ppb, and between L- and D-arginine 0.59 (-1.56 to 2.74) ppb. CONCLUSIONS: Exhaled NO decreased with acute bronchoconstriction and returned to baseline with the resolution of bronchoconstriction. Exhaled NO increased following the administration of both L-arginine and D-arginine. Since NOS is stereospecific, this finding suggests that the increase in exhaled NO is not entirely mediated through an increase in NOS enzyme activity. We suggest that arginine may react in a non-stereospecific fashion with reactive oxygen species present in asthmatic airways.

Administration, Inhalation↗

Longitudinal study of grass pollen exposure, symptoms, and exhaled nitric oxide in childhood seasonal allergic asthma.

BACKGROUND: Exhaled nitric oxide (NO) has been proposed as a marker of airway eosinophilic inflammation in asthma. There is currently a paucity of longitudinal data relating it to allergen exposure and asthma symptoms. METHODS: Forty four children (6-16 years) with seasonal allergic asthma were sequentially followed before and during the grass pollen season. Asthma symptoms, lung function, NO levels, and pollen counts were recorded. The relationship between exhaled NO and both the pollen levels and asthma control were assessed longitudinally, comparing a subject's measurements with their previous ones. RESULTS: The median exhaled NO concentration was significantly increased during the pollen season (6.2 v 9.2 parts per billion (ppb), p<0.002; median change 2.9 ppb, 95% confidence interval 1.5 to 5.4). Exhaled NO was best associated with the mean pollen count in the week before measurement. It was also significantly associated with asthma control. CONCLUSIONS: The results suggest that, within a longitudinal model, the exhaled NO concentration is related to preceding allergen exposure and asthma control. It may be clinically more useful to compare exhaled NO values with a subject's previous values than to compare them with a population based normal range.

Adolescent↗

Gas chromatography/mass spectrometry analysis of exhaled leukotrienes in asthmatic patients.

BACKGROUND: Leukotriene-like immunoreactivity has been detected in exhaled breath condensate (EBC), but definitive evidence for the presence of leukotrienes (LTs) in this biological fluid is not available. A study was undertaken to determine whether LTC(4), LTD(4), LTE(4), and LTB(4) are measurable in EBC by gas chromatography/mass spectrometry and to quantify exhaled LTs in adults and children with asthma and in control subjects. METHODS: Twenty eight adults and 33 children with mild to moderate persistent asthma treated with inhaled corticosteroids and age matched healthy controls (50 adults and 50 children) were studied. LTB(4), LTC(4), LTD(4), and LTE(4) in EBC were measured by gas chromatography/mass spectrometry. RESULTS: LTD(4), LTE(4), and LTB(4) were detectable in all samples. Concentrations of LTC(4) in EBC were either close to or below the detection limit of 1 pg/ml. Median exhaled LTD(4), LTE(4), and LTB(4) concentrations in asthmatic adults were increased 4.1-fold (p<0.001), 1.8-fold (p<0.01), and 2.6-fold (p<0.001), respectively, compared with values in healthy adults. Median exhaled LTD(4), LTE(4), and LTB(4) concentrations in asthmatic children were increased 2.8-fold (p<0.001), 1.3-fold (p<0.001), and 1.6-fold (p<0.001), respectively, compared with those in healthy children. In patients with asthma there was a correlation between exhaled LTD(4) and LTE(4) in both adults (r = 0.87, p<0.0001) and children (r = 0.78, p<0.0001). CONCLUSIONS: Gas chromatography/mass spectrometry can be used to accurately quantify exhaled LTs which are increased in asthmatic adults and children compared with controls.

Administration, Inhalation↗

Small airways function and molecular markers in exhaled air in mild asthma.

BACKGROUND: Several studies suggest that the periphery of the lung is the major site of inflammation in asthma. Fractional exhaled nitric oxide (Feno) and 8-isoprostane have been proposed as biomarkers of inflammation and oxidative stress. We therefore hypothesised that small airway dysfunction in asthma is of inflammatory origin that can be detected by molecular markers in exhaled air. To test this hypothesis, we examined the relationship of Feno and 8-isoprostane in exhaled air with small airways function as assessed by the single breath nitrogen test. METHODS: Sixteen patients (14 women) with mild atopic asthma (forced expiratory volume in 1 second >80% predicted) of mean (SD) age 23.0 (5.5) years participated in a cross sectional study. Feno was recorded by chemiluminescence and 8-isoprostane was measured by ELISA in concentrated exhaled breath condensate. The slope of phase III (deltaN2) and the closing volume (CV) were assessed from the single breath washout curve. RESULTS: The median Feno level was 30.4 ppb (range 10.1-82.8), the median 8-isoprostane concentration in exhaled breath condensate was 2.2 pg/ml (range 1.6-2.7), and the mean (SD) deltaN2 value was 1.1 (0.4)% N2/l. Feno was positively associated with deltaN2 (r(s) = 0.54, p = 0.032) while 8-isoprostane was inversely correlated with FEV1% predicted (rs= -0.58; p = 0.017) and CV as a percentage of vital capacity (rs= 0.58; p = 0.019). CONCLUSIONS: Feno and 8-isoprostane in exhaled air are associated with small airways function in mild asthma. This suggests that these markers reflect small airway inflammation and favours a role for them as disease markers that is complementary to spirometry in the monitoring of patients with asthma.

Adult↗

Measurement of transfer factor during constant exhalation.

BACKGROUND: Transfer factor of the lung for carbon monoxide (TLCO) was measured by a new method based on analysis of the ratio of the concentrations of carbon monoxide to an inert gas (methane) relative to lung volume during a constant exhalation. Since this new technique is based solely upon exhalation, anomalies associated with inspiration and breath holding do not affect results. Additionally, because prolonged breath holding is not required, measurements can readily be made in dyspnoeic patients. METHODS: Exhalation TLCO (TLCO,ex) was compared with the standard (Jones and Meade) 10 second breath holding TLCO (TLCO,bh) in 100 consecutive patients. Patients did not practise the exhalation manoeuvre prior to testing. RESULTS: The comparative results were very close; mean difference (bias) +/- standard deviation (precision) was 0.05 (0.84) mmol/min/kPa. The relation was equally strong in patients with severe pulmonary disease; for patients with FEV1 < 1.51 the mean difference was 0.21 (0.80) mmol/min/kPa. CONCLUSIONS: Since the results were essentially identical between the techniques, it seems that comparable pathophysiological factors affect TLCO during breath holding and constant exhalation. Constant exhalation may therefore be a useful alternative to the breath holding technique for clinical measurement of TLCO.

Adult↗