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PubMed2003

Sputum induction leads to a decrease of exhaled nitric oxide unrelated to airflow.

Measurement of exhaled nitric oxide (eNO) and analysis of induced sputum are both established noninvasive methods for studying airway inflammation in asthma. Both methods are often used sequentially within short time frames. The aim of the present study was to evaluate the influence of sputum induction on eNO in adults and to follow the kinetics of airway eNO production after induction in relation to forced expiratory volume in one second (FEV1). eNO and FEV1 were measured in 41 adult patients (aged 29 (range 23-50) yrs, 56% male) with asymptomatic atopy or mild asthma (mean FEV1 97.2+/-3% predicted) prior to and immediately after sputum induction with hypertonic saline (4%). Sputum induction with isotonic saline was also performed in 13 subjects (control group). Repeatability of eNO decrease after sputum induction was also studied in 27 patients on separate occasions and kinetics of eNO production after sputum induction were followed over 24 h in another 10 patients. Sputum induction with hypertonic, but not isotonic, saline led to a marked decrease in eNO (log) immediately after the procedure (pre: 3.85+/-0.13 parts per billion (ppb); post: 3.24+/-0.14 ppb). This decrease was shown to be highly reproducible and not related to a fall in FEV1 following sputum induction. While FEV1 returned to baseline within 1 h, decreased eNO levels were observed over 4 h and returned to baseline after 24 h. Hypertonic saline sputum induction leads to a prolonged reduction in exhaled nitric oxide in adult atopics that is reproducible within subjects and not related to a reduction in airflow following sputum induction. This methodological interference should be taken into account when sputum induction and exhaled nitric oxide measurements are performed in the same subject.

Adult↗
PubMed2004

Comparison between exhaled and sputum oxidative stress biomarkers in chronic airway inflammation.

The aim of the present study was to compare aldehyde levels resulting from lipid peroxidation in exhaled breath condensate (EBC) and induced sputum (IS) supernatant of subjects with asthma and chronic obstructive pulmonary disease (COPD). Aldehydes (malondialdehyde (MDA), acrolein, n-hexanal (C6), n-heptanal (C7), n-nonanal (C9), 4-hydroxynonenal (HNE) and 4-hydroxyhexenal (HHE)) in both biological fluids were measured by liquid chromatography-tandem mass spectrometry. MDA concentrations in sputum were 132.5 nM (82.5-268.8) and 23.7 nM (9-53.7) in EBC. Similarly, C6, C7 and C9 concentrations in IS were 1.5-4.7-fold higher than in EBC. Acrolein levels were 131.1 nM (55.6-264.6) in IS and 45.3 nM (14.4-127.1) in EBC. The concentrations of HNE and HHE in IS were not significantly different from the levels in EBC. Aldehyde levels in EBC did not show any correlation with aldehyde levels in IS or with differential sputum cellular count. In COPD, MDA in EBC, but not its IS counterpart, was negatively correlated with the severity of disease. In conclusion, the data presented here show that aldehydes can be detected in both exhaled breath condensate and supernatant of induced sputum, but that their relative concentrations are different and not correlated with each other. Therefore, with regard to lipid peroxidation products, exhaled breath condensate and induced sputum must be considered as independent techniques.

Adult↗
PubMed2005

Exhaled breath condensate: methodological recommendations and unresolved questions.

Collection of exhaled breath condensate (EBC) is a noninvasive method for obtaining samples from the lungs. EBC contains large number of mediators including adenosine, ammonia, hydrogen peroxide, isoprostanes, leukotrienes, nitrogen oxides, peptides and cytokines. Concentrations of these mediators are influenced by lung diseases and modulated by therapeutic interventions. Similarly EBC pH also changes in respiratory diseases. The aim of the American Thoracic Society/European Respiratory Society Task Force on EBC was to identify the important methodological issues surrounding EBC collection and assay, to provide recommendations for the measurements and to highlight areas where further research is required. Based on the currently available evidence and the consensus of the expert panel for EBC collection, the following general recommendations were put together for oral sample collection: collect during tidal breathing using a noseclip and a saliva trap; define cooling temperature and collection time (10 min is generally sufficient to obtain 1-2 mL of sample and well tolerated by patients); use inert material for condenser; do not use resistor and do not use filter between the subject and the condenser. These are only general recommendations and certain circumstances may dictate variation from them. Important areas for future research involve: ascertaining mechanisms and site of exhaled breath condensate particle formation; determination of dilution markers; improving reproducibility; employment of EBC in longitudinal studies; and determining the utility of exhaled breath condensate measures for the management of individual patients. These studies are required before recommending this technique for use in clinical practice.

Biomarkers↗
PubMed2005

Effects of exacerbations and seasonality on exhaled nitric oxide in COPD.

Exhaled nitric oxide (eNO) appears to be associated with airway inflammation seen in chronic obstructive pulmonary disease (COPD). The present authors studied the effects of exacerbation, season, temperature and pollution on eNO. eNO was measured seasonally and at exacerbations in 79 outpatients suffering from COPD (mean forced expiratory volume in one second=42%). The effects of exacerbation symptoms, physiological and environmental parameters were analysed. Stable eNO levels were correlated positively with arterial oxygen tension. Median levels were found to be lower in smokers (5.3 ppb) than in ex- or nonsmokers (6.8 ppb). Levels were higher during October to December (6.9 ppb) than in April to June (4.6 ppb). Levels were also higher during 68 exacerbations in 38 patients (7.4 ppb) than in stable conditions (5.4 ppb), independent of the effects of smoking. The rise in eNO was greater in exacerbations that were associated with colds, a sore throat or dyspnoea combined with a cold. In conclusion, exhaled nitric oxide levels were higher in colder weather and in the autumn, perhaps related to the increased prevalence of viral infection at this time of year. The levels were lower in more severe chronic obstructive pulmonary disease. Exhaled nitric oxide levels were raised at the onset of exacerbation, particularly in the presence of a cold.

Age Distribution↗
PubMed2005

The effects of Aspergillus fumigatus challenge on exhaled and nasal NO levels.

Several studies have previously shown that exposure to indoor air microbes from moisture-damaged buildings can cause adverse health effects. Aspergillus fumigatus is one of the best-documented moulds causing health problems to those exposed. In this study, inhalation of a commercial A. fumigatus solution was assessed, to establish if it would have effects on fractional exhaled (FeNO) and nasal (FnNO) nitric oxide levels and on lung function. The results were compared with placebo challenge. A total of 28 subjects were divided into three study groups: group 1 had been exposed to occupational mould; group 2 consisted of atopic subjects; and group 3 was a control group. Some 3 h after A. fumigatus challenge, there was a considerable increase in FeNO, and a significant difference was observed between the A. fumigatus and placebo inhalations. The difference was seen in all study groups. No such differences were found in the levels of FnNO or nitrite in nasal lavage fluid. Subjects reported significantly more frequent respiratory tract symptoms after the A. fumigatus inhalation compared with placebo challenge. In conclusion, it was shown here that inhalation challenge of Aspergillus fumigatus elevated fractional exhaled nitric oxide levels. An increase in fractional exhaled nitric oxide may serve as an indicator of respiratory inflammation of acute mould exposure.

Adult↗
PubMed2005

Reproducibility of exhaled breath condensate pH in chronic obstructive pulmonary disease.

Increasingly, exhaled breath condensate (EBC) is being used to sample airway fluid from the lower respiratory tract. EBC pH may be a biomarker of airway inflammation in chronic obstructive pulmonary disease (COPD). In this study, the reproducibility of EBC pH in COPD was investigated. A total of 36 COPD patients and 12 healthy nonsmoking subjects participated in several investigations: duration of argon deaeration, within-sample variability, effect of freezing, leaving samples at room temperature, nose-peg use, within- (WD) and between-day (BD) variability. Analysis of repeated measurements was performed using the Bland-Altman method with limits of agreement (LOA; mean difference+/-2 SD). Wider LOA indicate greater variability. EBC pH became significantly higher with argon deaeration for < or =5 min. Variability during sample analysis was minimal; LOA of within-sample variability, freezing for 3 months and leaving at room temperature for 3 h were -0.29-0.45, -0.37-0.42 and -0.13-0.09, respectively. In contrast, variability due to nose-peg use (LOA -1.46-1.99), WD (LOA -1.50-2.48) and BD variability (LOA -2.52-3.02) were higher in COPD. In healthy nonsmoking subjects, nose-peg use (LOA -0.27-0.23), WD (LOA -0.33-0.40) and BD variability (LOA -0.46-0.44) were more reproducible. In conclusion, the variability of exhaled breath condensate pH in chronic obstructive pulmonary disease patients is mainly due to changes in airway pH over time, which are not seen in healthy nonsmoking subjects. Reasons for these fluctuations in exhaled breath condensate pH are unclear and require further investigation.

Adult↗
PubMed2006

Safety and feasibility of exhaled breath condensate collection in ventilated infants and children.

The aim of this study was to develop a technique for the collection of exhaled breath condensate (EBC) from ventilated children and assess its safety and feasibility. Collection of EBC is used to investigate markers of oxidative stress in the lower airway. No studies have assessed its safety in ventilated children. An in vitro model was developed by connecting a ventilator to an artificial lung; 14 clinical and ventilatory parameters were measured during EBC collection from ventilated children. Levels of 8-isoprostane were measured following collection with and without humidification of the inhaled gas. Amount of water vapour collected was linearly related to time and to minute ventilation in the in vitro model. EBC collections (n = 68) were made from ventilated children. In the nonhumidified group, the mean (range) positive end-expiratory pressure increased by 4.1% (2.8-5.5%) and the peak inspiratory flow decreased by 6.1% (11.0-1.3%) during collection. Detectable levels of 8-isoprostane were only found in 10 out of 18 nonhumidified EBC samples (median (range) 4.7 pg x mL(-1) (0-5.8)). Collection of exhaled breath condensate from ventilated infants and children is feasible and safe. Discontinuation of humidification is likely to be important in standardising the measurement of inflammatory parameters in exhaled breath condensate collected from ventilated children.

Air↗
PubMed2004

Source of exhaled nitric oxide in primary biliary cirrhosis.

BACKGROUND: Exhaled nitric oxide (NO) levels may be elevated in patients with liver cirrhosis and autoimmune diseases. Primary biliary cirrhosis (PBC) is often associated with keratoconjunctivitis sicca (Sjogren syndrome [SS]), an extrahepatic autoimmune manifestation. The aim of this study was to evaluate the source of increased exhaled NO (ie, alveolar vs airway) in patients with PBC, whether associated with SS or not, and to evaluate its impact on oxygenation abnormalities. DESIGN: Observational controlled study. SETTING: University hospital. METHODS: The fractional alveolar NO concentration (FANO) and airway flux of NO (QbrNO) were measured by the multiple flows technique in 34 patients with PBC, 12 with associated SS, and were compared to 20 control subjects and 12 patients with primary SS. RESULTS: FANO was significantly higher in patients with PBC, associated with SS (mean [+/- SEM], 8.9 +/- 0.8 parts per billion [ppb]) or not (mean, 7.7 +/- 0.7 ppb) compared to healthy control subjects (mean, 4.6 +/- 0.5 ppb; p < 0.001) and to patients with primary SS (mean, 4.3 +/- 0.5 ppb; p < 0.001). FANO was significantly higher in cirrhotic patients with increased alveolar-arterial oxygen pressure difference (P[A-a]O(2)) compared to patients with normal P(A-a)O(2) values (9.8 +/- 0.8 vs 7.3 +/- 0.7, respectively; p = 0.018). When compared with control subjects and with patients with PBC not associated with SS, QbrNO was significantly increased in patients with both primary SS and SS associated with PBC. CONCLUSIONS: Increased exhaled NO levels found in PBC are from both alveolar and airway sources in patients with associated SS, but only FANO is associated with oxygenation impairment.

Exhalation↗
PubMed2006

Exhaled biomarkers.

Assessing airway and lung inflammation is important for investigating the underlying mechanisms of asthma and COPD. Yet these cannot be measured directly in clinical research and practice because of the difficulties in monitoring inflammation. Noninvasive monitoring may assist in early recognition of asthma and COPD, assessment of its severity, and response to treatment, especially during disease exacerbations. There is increasing evidence that breath analysis may have an important place in clinical management of asthma and COPD. The article reviews the role of current noninvasive measurements of exhaled gases, such as nitric oxide (NO), inflammatory markers in exhaled breath condensate (EBC), and exhaled breath temperature, as well as novel methods in monitoring and management of asthma and COPD.

Asthma↗
PubMed2004

Measurement of exhaled nitric oxide.

Assessment of the value of exhaled NO (eNO) is an attractive tool for studying pulmonary disease, considering its wide advantages (i.e., fast analysis, noninvasive sampling, ability to measure large numbers of subjects [including children], and inexpensive in use). Increased concentrations of eNO have been observed in asthmatic patients' airway infections, allergic rhinitis, and bronchiectasis. During inflammation, specific and nonspecific stimuli elicit expression and de novo synthesis of inducible nitric oxide (iNOS). Once generated in the bronchiolar cells, NO is released from the tissue and diffuses to the lumen of the bronchiolis. Of the two sampling ways (on-line and off-line), the off-line method is suitable for monitoring environmental health effects of air pollution and for obtaining an impression of the prevalence of atopy in epidemiological surveys. For this off-line measurement, a balloon method is developed (sampling exhaled air at location) that includes a sample device assuring inflation of balloons at a controlled flow rate and back-pressure. Cigarette smoking and alcohol consumption significantly reduces NO levels in exhaled air because of downregulation of iNOS. Although eNO can be reliably measured and analyzed, the prospective value to detect asthma or allergy is rather low (low sensitivity and low specificity), which makes the diagnostic value of eNO for predicting either allergy or asthma doubtful. Promising results have, however, been observed in corticoid-sparing therapies under guidance of eNO. In addition, measurement of eNO helps to understand the mechanisms of pulmonary disease and may be useful in detecting adverse effects of air pollution.

Adolescent↗
PubMedDate not supplied

[Volatile hydrocarbons in exhaled air: preliminary data on the characteristic profile associated with lung tumors].

The aim of this pilot study was to identify and quantify selected volatile organic compounds (VOCs), such as aliphatic and aromatic hydrocarbons in exhaled air from patients with non small cells lung cancer (NSCLC) as compared to healthy subjects, either smokers or non smokers. Exhaled air has been collected by repeated expirations in Tedlar bags. VOCs were sampled by solid phase micro-extraction (SPME) and analyzed by gascromatography/mass spectometry. NSCLC patients showed higher levels of pentane, 2-metilpentane, 2,4-dimetilheptane in the exhaled air as compared to smokers and non smokers. BTEX (benzene, toluene, etilbenzene and xylenes) concentrations were higher in smokers compared to other groups, whereas no differences were observed between subjects with NSCLC and smokers for heptane and octane. In summary, selected VOCs have sufficient diagnostic power to differentiate among the three groups we examined. These differences might be exploited to identify characteristic fingerprints of various lung diseases.

Adult↗
PubMed2004

[Reproducibility of exhaled nitric oxide (FENO) measurements in healthy subjects].

UNLABELLED: The aim of the study was to evaluate the short-term variability of FENO in healthy subjects. METHODS: 33 healthy volunteers (26 F, 7 M) aged 32.6 +/- 9.5 yrs with body mass index (BMI) of 23.3 +/- 3 kg/m2 participated in the study. Exhaled nitric oxide was analyzed on 5 consecutive days with a chemiluminescence analyzer (NIOX, Aerocrine, Sweden) according to the ATS recommendations. The exhalation flow was between 0.045 and 0.055 l/s. The measurements were performed at the same time of the day and the subjects were asked to refrain from eating and drinking for at least one hour before the analysis. RESULTS: The mean value of FENO for the whole group was 13.9 +/- 5.4 ppb, there were no correlations between FENO and age, BMI, sex or the concentration of ambient nitric oxide. Day-to-day coefficient of variation was 13.3 +/- 5.3% (range 4.6 - 23.9%), the value of pooled SD - 2.1 ppb and ICC (intraclass correlation coefficient) was 0.84. No relationship was observed between variability of FENO and intervals between measurement of exhaled nitric oxide and intake of food or beverages. CONCLUSION: Chemiluminescence analysis of FENO with NIOX is a highly reproducible method, however one has to take into account the possibility of about 13% variability of FENO within 5 days.

Adult↗
PubMed2005

[The role of measurement of exhaled nitric oxide in asthma patients].

The aim of the study was to evaluate exhaled nitric oxide levels (F(ENO)) in asthmatics and to establish the possible correlation of these measurements with clinical symptoms, disease severity, anti-inflammatory treatment and spirometric indices. The measurement of exhaled NO was performed using NO analyser model 280i, Sievers Instruments, Inc., USA. This measurement was based on the gas phase chemiluminescence reaction between NO and ozone. The investigations were performed on the group of 85 asthmatic patients (34 with chronic mild asthma, 31 with chronic moderate asthma, 20 with chronic severe asthma). F(ENO) level in healthy, non-smoking volunteers (46 persons--control group) was mean 12.9 +/- 4.6 ppB and it was statistically significant lower than in all groups of asthmatics. The highest F(ENO) levels were observed in patients with severe asthma (74 +/- 72 ppB). Statistically significant lower levels of ENO were obtained in patients with moderate (42 +/- 31 ppB) and mild asthma (49 +/- 43 ppB). In all groups of asthmatic patients higher levels of F(ENO) were observed in subjects with allergic asthma. In patients with mild and moderate asthma ENO levels were negatively correlated with the used dosage of inhaled steroids. Similar dependences were not noticed in patients with severe asthma. The measurement of exhaled nitric oxide levels provides a rapid, reproducible, non-invasive and reliable test, which is very useful in diagnosis and treatment monitoring in asthmatic patients.

Adult↗
PubMed1998

Effect of salmeterol treatment on nitric oxide level in exhaled air and dose-response to terbutaline in children with mild asthma.

The aim of this study was to investigate whether regular treatment with inhaled salmeterol modifies the dose-response curve to the inhaled short-acting beta2-agonist terbutaline or affects the concentration of nitric oxide (NO) in exhaled air of children with asthma. Twenty-two children aged 7 to 15 years (mean = 11.6 years) with mild asthma were treated with inhaled 50 microg salmeterol twice daily or placebo for 3 weeks in a randomized double-blind cross-over study. These treatments were followed by treatment with inhaled 200 microg budesonide twice daily for 3 weeks. On the last day of each period, NO level was measured in exhaled air and a cumulative dose-response experiment with terbutaline (cumulative dose: 1,475 microg) was performed. Baseline lung functions after salmeterol treatment were significantly higher than baseline after placebo (P + 0.05). Salmeterol treatment flattened out the dose-response curve to terbutaline such that higher doses of terbutaline were required to produce the same degree of bronchodilation (ED50 for FEV1 was increased by an estimated factor of 70 (95% CI: 0.8-6307) and ED50 for FEF25-75 by a factor of 41 (95% CI: 6.7-254); P < 0.05). NO levels were unaffected by salmeterol treatment (12.7 ppb; placebo = 10.7 ppb), but were significantly reduced during budesonide therapy (5.2 ppb; P < 0.001). The corresponding maximal NO levels were 19.5 (placebo), 22.9 (salmeterol), and 9.4 ppb (budesonide). We conclude that 3 weeks treatment with salmeterol does not affect NO levels in exhaled air, but it significantly changes the dose-response curve to terbutaline.

Adolescent↗
PubMed1990

Exhalation of malondialdehyde from the smoke of high grade cigarettes and effectiveness of filtering it.

It has been found that malondialdehyde penetrates during smoking through filters and exhales with smoke from cigarettes such as: "Pall Mall", "Winston", "Camel", "Lucky Strike", "Kansas", "Mustang", "Ronson", "Chesterfield", "Rally", "Oscar" and "Marlboro". These cigarettes exhale malondialdehyde in a different way, in free form in the amount from 8.5 to 23.5 mg/kg cigarettes on an average of 13.3 mg/kg for the whole group and totally (in free and bounded form) from 9.5 to 26.5 mg/kg (average 16.9 mg/kg). Moreover, it has been found that filters retain this aldehyde in free form on an average of 9.9 mg/kg and totally (in free and bounded form) of 19.0 mg/kg. Without filters these amounts would increase aldehyde contents in smoke by 42.7 and 52.9%, respectively. Low malonalogenic properties of tobacco, high effectiveness of cigarette filters, high degree of tar deposition before inhaling into lungs and slow (6 min and longer) smoking decide about low level of exhalation of malondialdehyde in cigarette smoke.

Filtration↗
PubMed1992

Design and evaluation of an exhaled breath sampler for biological monitoring of organic solvents.

We designed a breath sampler based on a tube which collects the final portion of exhaled air. The passage of successive fractions through a layer of activated charcoal is controlled by a three-way valve. This system was validated in a controlled atmosphere of n-hexane and toluene at four concentrations between 12 and 110 mg m-3 and 12 and 115 mg m-3, respectively. Uptake volumes of 0.1, 0.2 and 0.31 were tested at relative humidities of 46% and 98%. There were no significant differences in the recoveries obtained under any of the conditions tested. We confirmed the reproducibility between successive samples in volunteers and exposed workers, and found no significant differences between the different sampling conditions studied. Our system enriches the sample in an adsorbent cartridge by collecting successive fractions of end-exhaled breath from one or more exhalations until the amount required by the analytical method has been accumulated. It is portable, economical and highly operative in the field.

Breath Tests↗
PubMed2005

Methodological issues related to exhaled nitric oxide measurement in children aged four to six years.

This study was designed to test five methodological issues related to measurement of fractional exhaled nitric oxide (FE(NO)) in children aged 4-6 years using commercially available apparatus. Participants attended two randomly selected schools. A respiratory questionnaire was completed. Measurements of FE(NO) were made on successive days, using a NIOX analyzer employing standard or modified methodologies. Ninety-one children participated in the study (mean age, 5.3 years; 46 boys). Using a standard methodology (n = 61), FE(NO) was successfully measured in 28 (46%) children, 1/12 aged 4 years, 12/25 aged 5 years, and 15/24 aged 6 years (trend test P = 0.01). On the first assessment, FE(NO) could be determined in more boys than girls (64% vs. 30%, respectively, P = 0.008), but this gender difference was not apparent on the second assessment. Exhaled NO was reproducible over a 24-hr period; the mean difference between repeated measurements of natural log (ln) FE(NO) was 0.016 parts per billion (ppb) (95% confidence limits, -0.479, 0.511), n = 20. Data from 35 assessments showed that values of FE(NO) did not alter over nine individual, successive measurements. Use of a modified methodology in 30 children increased success in obtaining FE(NO), but these values were unreliable. In conclusion, measurements of FE(NO) can be obtained in the majority of 5- and 6-year-old but not 4-year-old children. Exhaled NO measurements were reproducible over a 24-hr interval, and did not change over up to nine expiratory maneuvers in these young children.

Age Factors↗
PubMed2005

Biomarkers of neutrophilic inflammation in exhaled air of cystic fibrosis children with bacterial airway infections.

Leukotriene B(4) (LTB(4)) and interleukin-8 (IL-8) are inflammatory mediators involved in the neutrophil response to pulmonary bacterial colonization in cystic fibrosis (CF). The aim of this study was to investigate whether the LTB(4) and IL-8 levels in exhaled breath condensate (EBC) could be related to the type of bacterial colonization in CF patients. The pH level in EBC was analyzed as an estimate of airway acidification. Forty children were evaluated: 10 CF patients with P. aeruginosa, 10 CF patients with S. aureus, 10 not colonized CF patients, and 10 healthy children. LTB(4) and IL-8 in EBC were analyzed by specific enzyme immunoassay kits (EIA). The pH of EBC was measured with a pH-meter after deareation by bubbling with argon. Exhaled LTB(4) was higher in CF children with P. aeruginosa compared to those with S. aureus (P < 0.01), not colonized (P < 0.001), and healthy children (P < 0.01). Exhaled IL-8 was elevated in CF patients colonized by P. aeruginosa compared with other subgroups (vs. not colonized, P < 0.05; vs. healthy children, P < 0.001). IL-8 levels were higher in CF children with S. aureus than in healthy children (P < 0.05). There was an increase in IL-8 levels in not colonized CF patients compared with healthy children (P < 0.05). EBC pH was higher in healthy children compared to CF patients not colonized (P < 0.05). Our data suggest that EBC is suitable for evaluating neutrophil inflammatory mediators (LTB(4), IL-8, and pH) involved in the response to pulmonary bacterial colonization in CF children.

Biomarkers↗