Exhaled Breath Condensate Nitrite Research Articles

Exhaled breath condensate nitrite in premature infants with bronchopulmonary dysplasia.

Tracheal aspirate is the conventional method to measure biomarkers of inflammation and oxidation from premature infants on mechanical ventilation at risk for bronchopulmonary dysplasia (BPD), but this method is invasive. Exhaled breath condensate (EBC) is a novel, non-invasive method that has been used in older populations. Nitrite, a stable metabolite of nitric oxide (NO), is elevated in inflammatory conditions. We aim to investigate the feasibility of EBC nitrite collection from ventilated premature infants and to quantify EBC nitrite in infants with and without BPD. We hypothesize that EBC nitrite correlates with TA nitrite, and that EBC nitrite in the first week of life is higher in infants who will develop BPD than those without BPD. In a pilot prospective cohort study, TA and EBC were collected in the first week of life from mechanically ventilated premature infants. Nitrite levels were measured using chemiluminescence. EBC nitrite significantly correlated with TA nitrite (r = 0.45, p = 0.025). Of 40 infants, 33 (82.5%) developed BPD. EBC and TA nitrite levels collected in the first week of life had a higher trend in infants with BPD than those without BPD (p = 0.23 and 0.38 respectively). Higher trend of EBC nitrite in the first week of life was associated with the development of BPD. Correlation of nitrite level in EBC with that in TA (conventional method) highlights the utility of EBC as an alternative, non-invasive method to measure inflammation. Further refinement of conditions and timing may optimize the predictive value of EBC nitrite.

Effects of dietary nitrate on respiratory physiology at high altitude - Results from the Xtreme Alps study

Nitric oxide (NO) production plays a central role in conferring tolerance to hypoxia. Tibetan highlanders, successful high-altitude dwellers for millennia, have higher circulating nitrate and exhaled NO (ENO) levels than native lowlanders. Since nitrate itself can reduce the oxygen cost of exercise in normoxia it may confer additional benefits at high altitude. Xtreme Alps was a double-blinded randomised placebo-controlled trial to investigate how dietary nitrate supplementation affects physiological responses to hypoxia in 28 healthy adult volunteers resident at 4559 m for 1 week; 14 receiving a beetroot-based high-nitrate supplement and 14 receiving a low-nitrate ‘placebo’ of matching appearance/taste. ENO, vital signs and acute mountain sickness (AMS) severity were recorded at sea level (SL) and daily at altitude. Moreover, standard spirometric values were recorded, and saliva and exhaled breath condensate (EBC) collected. There was no significant difference in resting cardiorespiratory variables, peripheral oxygen saturation or AMS score with nitrate supplementation at SL or altitude. Median ENO levels increased from 1.5/3.0 mPa at SL, to 3.5/7.4 mPa after 5 days at altitude (D5) in the low and high-nitrate groups, respectively (p = 0.02). EBC nitrite also rose significantly with dietary nitrate (p = 0.004), 1.7–5.1 μM at SL and 1.6–6.3 μM at D5, and this rise appeared to be associated with increased levels of ENO. However, no significant changes occurred to levels of EBC nitrate or nitrosation products (RXNO). Median salivary nitrite/nitrate concentrations increased from 56.5/786 μM to 333/5,194 μM with nitrate supplementation at SL, and changed to 85.6/641 μM and 341/4,553 μM on D5. Salivary RXNO rose markedly with treatment at SL from 0.55 μM to 5.70 μM. At D5 placebo salivary RXNO had increased to 1.90 μM whilst treatment RXNO decreased to 3.26 μM. There was no association with changes in any observation variables or AMS score. In conclusion, dietary nitrate supplementation is well tolerated at altitude and significantly increases pulmonary NO availability and both salivary and EBC NO metabolite concentrations. Surprisingly, this is not associated with changes in hemodynamics, oxygen saturation or AMS development.

Association of Ozone Exposure With Cardiorespiratory Pathophysiologic Mechanisms in Healthy Adults

Exposure to ozone has been associated with cardiovascular mortality, but the underlying biological mechanisms are not yet understood. To examine the association between ozone exposure and cardiopulmonary pathophysiologic mechanisms. A longitudinal study involving 89 healthy adult participants living on a work campus in Changsha City, China, was conducted from December 1, 2014, to January 31, 2015. This unique quasiexperimental setting allowed for better characterization of air pollutant exposure effects because the participants spent most of their time in controlled indoor environments. Concentrations of indoor and outdoor ozone, along with the copollutants particulate matter, nitrogen dioxide, and sulfur dioxide, were monitored throughout the study period and then combined with time-activity information and filtration conditions of each residence and office to estimate 24-hour and 2-week combined indoor and outdoor mean exposure concentrations. Associations between each exposure measure and outcome measure were analyzed using single-pollutant and 2-pollutant linear mixed models controlling for ambient temperature, secondhand smoke exposure, and personal-level time-varying covariates. Biomarkers indicative of inflammation and oxidative stress, arterial stiffness, blood pressure, thrombotic factors, and spirometry were measured at 4 sessions. Of the 89 participants, 25 (28%) were women and the mean (SD) age was 31.5 (7.6) years. The 24-hour ozone exposure concentrations ranged from 1.4 to 19.4 parts per billion (ppb), corresponding to outdoor concentrations ranging from 4.3 to 47.9 ppb. Within this range, in models controlling for a second copollutant and other potential confounders, a 10-ppb increase in 24-hour ozone was associated with mean increases of 36.3% (95% CI, 29.9%-43.0%) in the level of platelet activation marker soluble P-selectin, 2.8% (95% CI, 0.6%-5.1%) in diastolic blood pressure, 18.1% (95% CI, 4.5%-33.5%) in pulmonary inflammation markers fractional exhaled nitric oxide, and 31.0% (95% CI, 0.2%-71.1%) in exhaled breath condensate nitrite and nitrate as well as a -9.5% (95% CI, -17.7% to -1.4%) decrease in arterial stiffness marker augmentation index. A 10-ppb increase in 2-week ozone was associated with increases of 61.1% (95% CI, 37.8%-88.2%) in soluble P-selectin level and 126.2% (95% CI, 12.1%-356.2%) in exhaled breath condensate nitrite and nitrate level. Other measured biomarkers, including spirometry, showed no significant associations with either 24-hour ozone or 2-week ozone exposures. Short-term ozone exposure at levels not associated with lung function changes was associated with platelet activation and blood pressure increases, suggesting a possible mechanism by which ozone may affect cardiovascular health.

Exhaled Breath Condensate Nitrate Levels are Inversely Associated with the Body Mass Index of Patients without Respiratory Disease

Background: Repeated observations suggest that the incidence and/or severity of the Acute Respiratory Distress Syndrome (ARDS) is lower in mildly obese humans compared to lean subjects, phenomenon called the Obesity-ARDS Paradox. A reduced lung nitrosative stress could contribute to this unexplained protection. We measured levels of nitrate, the most oxidized nitric oxide (NO) metabolite, and other related metabolites in the exhaled breath condensate (EBC) of obese (composed of both overweight or mildly obese) and normal weight patients. Methods: We studied patients without respiratory disease immediately after starting mechanical ventilation for elective surgery. We performed targeted metabolomics analyses of EBC and blood samples. We measured concentrations of arginine, asymmetrical dimethylarginine (ADMA), symmetrical dimethylarginine (SDMA), nitrite, and nitrate and then analyzed their relationship to body mass index (BMI). We compared patients classified as BMI<25 (normal) or 25-34.9 (obese). Results: 21 patients were included in the analysis: 5 with a BMI<25 and 16 with a BMI 25-34.9. Concentrations of nitrate in EBC, but not in plasma, inversely correlated with BMI. EBC nitrate levels positively correlated with EBC nitrite but not with plasma nitrate levels. EBC nitrite levels inversely correlated with plasma nitrite levels. Patients with a BMI 25-34.9 had significantly lower EBC nitrate levels than patients with a BMI<25. Conclusion: Our results suggest a lower nitrosative stress in the lungs of overweight and mildly obese patients compared to normal weight patients. This observation deserves further evaluation as a possible contributing factor to the Obesity ARDS Paradox.

Early effect of tidal volume on lung injury biomarkers in surgical patients with healthy lungs.

The early biological impact of short-term mechanical ventilation on healthy lungs is unknown. The authors aimed to characterize the immediate tidal volume (VT)-related changes on lung injury biomarkers in patients with healthy lungs and low risk of pulmonary complications. Twenty-eight healthy patients for knee replacement surgery were prospectively randomized to volume-controlled ventilation with VT 6 (VT6) or 10 (VT10) ml/kg predicted body weight. General anesthesia and other ventilatory parameters (positive end-expiratory pressure, 5 cm H2O, FIO2, 0.5, respiratory rate titrated for normocapnia) were managed similarly in the two groups. Exhaled breath condensate and blood samples were collected for nitrite, nitrate, tumor necrosis factor-α, interleukins-1β, -6, -8, -10, -11, neutrophil elastase, and Clara Cell protein 16 measurements, at the onset of ventilation and 60 min later. No significant differences in biomarkers were detected between the VT groups at any time. The coefficient of variation of exhaled breath condensate nitrite and nitrate decreased in the VT6 but increased in the VT10 group after 60-min ventilation. Sixty-minute ventilation significantly increased plasma neutrophil elastase levels in the VT6 (35.2 ± 30.4 vs. 56.4 ± 51.7 ng/ml, P = 0.008) and Clara Cell protein 16 levels in the VT10 group (16.4 ± 8.8 vs. 18.7 ± 9.5 ng/ml, P = 0.015). Exhaled breath condensate nitrite correlated with plateau pressure (r = 0.27, P = 0.042) and plasma neutrophil elastase (r = 0.44, P = 0.001). Plasma Clara Cell protein 16 correlated with compliance (r = 0.34, P = 0.014). No tidal volume-related changes were observed in the selected lung injury biomarkers of patients with healthy lungs after 60-min ventilation. Plasma neutrophil elastase and plasma Clara Cell protein 16 might indicate atelectrauma and lung distention, respectively.

Plasma and exhaled breath condensate nitrite–nitrate level in relation to environmental exposures in adults in the EGEA study

This study evaluated the associations between biological markers in the nitrate–nitrite–NO pathway and four environmental exposures among subjects examined in the second survey (2003–2007) of the French Epidemiological study on Genetics and Environment of Asthma (EGEA). Total nitrite and nitrate (NO2- /NO3-) levels were measured both in plasma and in exhaled breath condensate (EBC) in 949 adults. Smoking, diet and exposure to chlorine products were assessed using standardized questionnaires. Exposure to air pollutants was estimated by using geostatistical models. All estimates were obtained with generalized estimating equations for linear regression models. Median levels of NO2-/NO3- were 36.3μM (1st–3rd quartile: 25.7, 51.1) in plasma and 2.0μmol/mg proteins (1st–3rd quartile 0.9, 3.9) in EBC. After adjustment for asthma, age, sex and menopausal status, plasma NO2-/NO3- level increased with leafy vegetable consumption (above versus below median=0.04 (95%CI: 0.001, 0.07)) and decreased in smokers (versus non/ex-smokers=−0.08 (95%CI: −0.11, −0.04). EBC NO2-/NO3- level decreased in smokers (−0.08 (95%CI: −0.16, −0.001)) and with exposure to ambient O3 concentration (above versus below median=−0.10 (95%CI: −0.17, −0.03)). Cured meat, chlorine products, PM10 and NO2 concentrations were not associated with NO2-/NO3- levels. Results suggest that potential modifiable environmental and behavioral risk factors may modify NO2-/NO3- levels in plasma and EBC according to the route of exposure.

In-vehicle Exposures to Traffic and Biomarkers of Airway Oxidative Stress Among Healthy Humans

PP-30-049 Background/Aims: Traffic-related air pollution has been associated with increased pulmonary and cardiovascular morbidity and mortality. Evidence from human, animal, and in vitro studies suggests that oxidative stress may mediate the adverse effects of traffic-related air pollutants. We hypothesized that exposure during passenger vehicle rides simulating a rush-hour commute on a highway would cause measurable acute changes in biomarkers of airway oxidative stress among healthy human volunteers. Methods: Twenty nonsmoking subjects aged 18–45 years will be passengers in a Ford Taurus sedan for two 2-hour car rides at least 1 week apart. To date, 4 subjects have each completed 1 ride with the air intake vent open and 1 ride with the vent closed (recirculation mode) in random order. The route was primarily on the New Jersey Turnpike, a major highway with heavy duty diesel truck traffic. In-vehicle exposure measurements included total particle count, particulate matter less than 2.5 microns (PM2.5), nitrogen dioxide and carbon monoxide, temperature, and humidity. We collected exhaled breath condensate (EBC) using an Ecoscreen device before and 0, 6, and 24 hours after the car rides. We measured the concentration of EBC nitrite, a marker of nitrosative stress, using chemiluminescence detection, and EBC malondialdehyde, a marker oxidative stress, with HPLC with fluorescence detection. Results: Mean particle counts were significantly higher during the vent open rides compared to recirculation mode rides (43,653 vs. 26,362 p/cc, P = 0.03). Among these 4 subjects over 8 car rides, we have observed a 22% increase in EBC MDA from pre- to 0 hour post-ride (95% CI: −24%, 68%), which did not persist at 6-hour post-ride. Conclusion: Having the vent closed substantially reduced total particle counts in the vehicle. To date, these short-term, on-road exposures in traffic were associated with increased oxidative stress in the respiratory tract of healthy humans.

Structural lung changes, lung function, and non‐invasive inflammatory markers in cystic fibrosis

Cystic fibrosis (CF) lung disease is characterized by chronic airway inflammation and recurrent infections, resulting in (ir)reversible structural lung changes and a progressive decline in lung function. The objective of this study was to investigate the relationship between non-invasive inflammatory markers (IM) in exhaled breath condensate (EBC), lung function indices and structural lung changes, visualized by high resolution computed tomography (HRCT) scans in CF. In 34 CF patients, lung function indices (forced expiratory volume in 1 s, forced vital capacity [FVC], residual volume, and total lung capacity [TLC]) and non-invasive IM (exhaled nitric oxide, and condensate acidity, nitrate, nitrite, 8-isoprostane, hydrogen peroxide, interferon-gamma) were assessed. HRCT scans were scored in a standardized and validated way, a composite score and component scores were calculated. In general, the correlations between non-invasive IM and structural lung changes, and between IM and lung function were low (correlation coefficients <0.40). Patients with positive sputum Pseudomonas cultures had higher EBC nitrite levels and higher parenchymal HRCT subscores than patients with Pseudomonas-negative cultures (p < 0.05). Multiple linear regression models demonstrated that FVC was significantly predicted by hydrogen peroxide in EBC, and the scores of bronchiectasis and mosaic perfusion (Pearson correlation coefficient R = 0.78, p < 0.001). TLC was significantly predicted by 8-isoprostane, nitrate, hydrogen peroxide in EBC, and the mucous plugging subscore (R = 0.92, p < 0.01). Static and dynamic lung function indices in this CF group were predicted by the combination of non-invasive IM in EBC and structural lung changes on HRCT imaging. Future longitudinal studies should reveal whether non-invasive monitoring of airway inflammation in CF adds to better follow-up of patients.

Exhaled breath condensate collection for nitrite dosage: a safe and low cost adaptation

Standardization of a simple and low cost technique of exhaled breath condensate (EBC) collection to measure nitrite. Two devices were mounted in polystyrene boxes filled either with crushed ice/salt crystals or dry ice/crushed ice. Blood samples were stored at -70 degrees C for posterior nitrite dosages by chemiluminescence and the Griess reaction. a) The use of crushed ice/dry ice or salt revealed sufficient EBC room air collection, but was not efficient for patients under ventilation support; b) the method using crushed ice/salt collected greater EBC volumes, but the nitrite concentrations were not proportional to the volume collected; c) The EBC nitrite values were higher in the surgical group using both methods; d) In the surgical group the nasal clip use diminished the EBC nitrite concentrations in both methods. The exhaled breath condensate (EBC) methodology collection was efficient on room air breathing. Either cooling methods provided successful EBC collections showing that it is possible to diminish costs, and, amongst the two used methods, the one using crushed ice/salt crystals revealed better efficiency compared to the dry ice method.

Melatonin improves sleep and reduces nitrite in the exhaled breath condensate in cystic fibrosis – a randomized, double‐blind placebo‐controlled study

Cystic fibrosis (CF) is a chronic progressive disorder characterized by repeated episodes of respiratory infection. Impaired sleep is common in CF leading to reduced quality of life. Melatonin, a secretory product of the pineal gland, has an important function in the synchronization of circadian rhythms, including the sleep-wake cycle, and has been shown to possess significant anti-oxidant properties. To evaluate the effects of exogenous melatonin on sleep and inflammation and oxidative stress markers in CF, a randomized double-blind, placebo-controlled study initially involving 20 patients with CF was conducted. One individual failed to conclude the study. All subjects were clinically stable when studied and without recent infectious exacerbation or hospitalization in the last 30 days. Groups were randomized for placebo (n = 10; mean age 12.1 +/- 6.0) or 3 mg melatonin (n = 9; mean age 16.6 +/- 8.26) for 21 days. Actigraphy was performed for 6 days before the start of medication and in the third week (days 14-20) of treatment. Isoprostane and nitrite levels were determined in exhaled breath condensate (EBC) at baseline (day 0) and after treatment (day 21). Melatonin improved sleep efficiency (P = 0.01) and tended to improve sleep latency (P = 0.08). Melatonin reduced EBC nitrite (P = 0.01) but not isoprostane. In summary, melatonin administration reduces nitrite levels in EBC and improves sleep measures in clinically stable CF patients. The failure of melatonin to reduce isoprostane levels may have been a result of the low dose of melatonin used as a treatment.

Mediators in Exhaled Breath Condensate after Hypertonic Saline Challenge

Background. Airway narrowing after hypertonic saline challenge (HSC) is postulated to be mediated by bronchoconstrictors and inflammatory mediators. Objective. To study the mechanism of this challenge by using exhaled breath condensate (EBC). Methods. Fifty-six subjects (9 to 72 years of age) performed an HSC, with EBC collection and exhaled nitric oxide (FENO) measurements before and after the challenge. Bronchial hyper-reactivity (BHR) was defined if forced expiratory volume in 1 second (FEV1) decreased by 10% compared with baseline (PD10). EBC volume was recorded and was analyzed for mucin, histamine, nitrite/nitrate, and pH. Results. Those with BHR had a significant rise in EBC volume/5-minute collection period after challenge (286.3 ± 25.6 μl vs 402.2 ± 31.3 μl, p = 0.0002), while BHR(−) subjects did not show this change (387.6 ± 29.7 μl vs 364.1 ± 30.1 μl, p = 0.55). FENO showed a significant decrease in both BHR(+) and BHR(−) groups after challenge (p = < 0.0001). In BHR(+) subjects histamine increased significantly (1.3 ± 0.1 μM vs 1.5 ± 0.1 μM, p = 0.006) compared with baseline, while EBC pH and mucin increased significantly after HSC in both groups. EBC nitrite did not change in either group. Conclusion. EBC analysis suggests that HSC causes an increase in pH and mucin in both groups, but EBC volume and histamine only increased in the BHR(+) group. This suggests that mast cells are activated and fluid flux is associated with the positive response, while mucin release is independent of BHR in HSC.

Time-dependent effects of inhaled corticosteroids on lung function, bronchial hyperresponsiveness, and airway inflammation in asthma

Exhaled nitric oxide (F(ENO)) and exhaled breath condensate (EBC) are noninvasive markers that directly measure airway inflammation and may potentially be useful in assessing asthma control and response to therapy. To examine the time-dependent effects of inhaled corticosteroids on F(ENO) and EBC markers concomitantly with lung function and bronchial hyperresponsiveness. Eleven steroid-naive adults with mild-to-moderate persistent asthma were treated with mometasone furoate dry powder inhaler, 400 microg/d, for 8 weeks, followed by a 4-week washout. Forced expiratory volume in 1 second (FEV1), the concentration of methacholine calculated to cause a 20% decline in FEV1 (PC20), F(ENO), EBC pH, and EBC nitrite measurements before, during, and after treatment were analyzed and compared. The mean (SEM) FEV1 increased from 3.01 (0.13) L (82% predicted) to 3.24 (0.18) L (87% predicted) by week 8 (P < .05). The PC20 level increased from 1.28 (0.31) mg/mL to 2.99 (0.51) mg/mL by treatment week 8 (P < .05) and remained relatively stable through washout week 4 (P < .05). The F(ENO) level decreased from 31.1 (4.1) ppb to 20.6 (4.5) ppb by treatment week 1 (P < .01), remained low through treatment week 8 (P < .01), then trended back to the baseline level by washout week 1 (P < .01). The median EBC pH increased from 7.81 (interquartile range, 7.49-8.09) to 8.02 (interquartile range, 7.87-8.12) by treatment week 4, but did not achieve statistical significance. The EBC nitrite level decreased from 17.6 (1.6) microM to 9.3 (0.9) microM by treatment week 8 (P < .01), and remained low throughout washout week 4 (P < .05). There was a negative correlation between F(ENO) and PC20 (Spearman rank correlation coefficient = -0.50, P < .001). The F(ENO) level responded the earliest to treatment and withdrawal of inhaled corticosteroids, whereas changes in EBC markers were delayed but more sustained.

Oral bacteria – The missing link to ambiguous findings of exhaled nitrogen oxides in cystic fibrosis

Nitrite in exhaled breath condensate (EBC) has been shown to be elevated in cystic fibrosis (CF), while exhaled nitric oxide (FENO) is paradoxically low. This has been argued to reflect increased metabolism of NO while its diffusion is obstructed by mucus. However, we wanted to study the possible influence of salivary nitrite and bacterial nitrate reduction on these parameters in CF patients by the intervention of an anti-bacterial mouthwash. EBC and saliva were collected from 15 CF patients (10-43 years) and 15 controls (9-44 years) before and 5 min after a 30s chlorhexidine mouthwash, in parallel with measurements of FENO. Nitrite and nitrate concentrations were measured fluorometrically. EBC nitrite, but not nitrate, was significantly higher in the CF patients (median 3.6 vs 1.3 microM in controls, p<0.05) and decreased after mouthwash in both groups (3.6-1.4 microM, p<0.01; 1.3-0.5 microM, p<0.01). Salivary nitrite correlated significantly to EBC nitrite (r=0.60, p<0.001) and decreased correspondingly after chlorhexidine, whereas salivary nitrate increased. FENO was lower in CF and the difference between patients and controls was accentuated after mouthwash (5.4 vs 8.4 ppb in controls, p<0.05). EBC nitrite mainly originates in the pharyngo-oral tract and its increase in CF is possibly explained by a regional change in bacterial activity. The limited lower airway contribution supports the view of a genuinely impaired formation and metabolism of NO in CF, rather than poor diffusion of the molecule.

Normative values for exhaled breath condensate pH and its relationship to exhaled nitric oxide in healthy African Americans

Exhaled breath condensate (EBC) pH and exhaled nitric oxide (FeNO) have been proposed as markers of asthma severity. EBC pH values below 6.5 have been associated with asthma exacerbations. Protonation of airway nitrite occurs at low pH and may contribute to FeNO. To establish normative EBC pH values and to determine the contribution of EBC pH to FeNO in healthy African Americans. Two hundred seventy healthy African American subjects without asthma between 18 and 40 years old were evaluated. Subjects had simultaneous measurement of EBC pH, EBC nitrite, nitrate, and FeNO. The median EBC pH was 8.14 (interquartile range, 7.83-8.28). Of subjects, 11.9% had an EBC pH < or = 6.5. In subjects with EBC pH values below 6.5, there was an inverse correlation between EBC pH and FeNO (r(2) = 0.158; P = .0245; n = 32). In the entire cohort, there was a direct correlation between EBC pH and EBC nitrite (r(2) = 0.163; P < .0001), but there was no correlation between EBC nitrite and FeNO. In multivariate analyses, EBC pH and nitrite did not contribute significantly to FeNO variation while controlling for other confounders of FeNO. There was an increased prevalence (11.9%) of low EBC pH (less than 6.5) in healthy African American subjects compared with white subjects (<5%). EBC pH and nitrite were directly correlated, but there was no correlation between EBC nitrite and FeNO. FeNO correlated with EBC pH at pH values less than 6.5 in univariate but not multivariate analyses. This suggests that EBC pH and nitrite are not significant determinants of FeNO in healthy subjects.

Increased exhaled nitrite in children with allergic asthma is not related to nitric oxide formation

Nitrite sampled from the upper airways could originate from inflammation-induced nitric oxide (NO), as reports of elevated nitrite in exhaled breath condensate (EBC) from asthmatics suggest, but also through bacterial action in the pharyngo-oral tract. To correlate EBC nitrite and nitrate to exhaled NO (FENO, fraction of expired NO) and other markers of disease activity in children with allergic asthma and thereby further investigate their role and origin. EBC was collected from 27 asthmatic subjects (ages 6-17 years, all immunoglobulin E-positive for aeroallergens) and 21 age-matched non-atopic healthy controls for fluorometric analysis of nitrite and nitrate. These markers were compared with measurements of FENO, blood eosinophil count (EOS), methacholine reactivity (PD(20)) and baseline spirometry. EBC nitrite, in contrast to nitrate, was significantly increased (P < 0.01) in the asthmatic children. They also had increased levels of FENO (P < 0.001) and EOS (P < 0.001) along with decreased PD(20) (P < 0.001) and FEV1/FVC (P < 0.01). However, there was no correlation between EBC nitrite and FENO (r = 0.05) or any other marker of disease activity in the asthmatic children, whereas between the other markers correlations could be established. EBC nitrite is elevated in childhood asthma but the lack of correlation to FENO and other markers, together with simultaneously normal levels of nitrate, make its origin as a metabolite of inflammation-induced NO questionable.

O60. Exhaled breath condensate nitrite and plasma nitrite. Pre- and post-operative comparative study in patients submitted to cardiopulmonary bypass

O60. Exhaled breath condensate nitrite and plasma nitrite. Pre- and post-operative comparative study in patients submitted to cardiopulmonary bypass

Breath condensate nitrite correlates with hyperinflation in chronic obstructive pulmonary disease

Estimating the degree of pulmonary hyperinflation in chronic obstructive pulmonary disease (COPD) is not always straight forward. Standard pulmonary function tests provide only a crude estimate of this important aspect of COPD. In addition, good patient cooperation cannot always be achieved and therefore adds to the uncertainties with regard to the extent of hyperinflation of the lung. The aim of this investigation was to characterize exhaled breath condensate nitrite in volunteers, healthy smokers, and stable COPD (GOLD-stages 0-4) and to compare this parameter with inflammatory markers in exhaled breath condensate and with lung function in order to test the hypothesis that elevated exhaled breath condensate nitrite reflects hyperinflation in COPD. We found a logarithmic correlation of exhaled breath condensate nitrite to residual volume (r=0.75, p<0.0001), total lung capacity (r=0.51, p<0.0001), and thoracic gas volume (r=0.71, p<0.0001) but no correlation of exhaled breath condensate nitrite concentrations with levels of inflammatory cytokines in exhaled breath condensate (interleukin (IL)-8, IL-1beta, IL-6, IL-10, IL-12, and tumor necrosis factor-alpha). Analysis of COPD subgroups revealed a logarithmic correlation of EBC nitrite to residual volume, total lung capacity, and intrathoracic gas volume exclusively for patients characterized by GOLD classes 2, and higher. Our results confirm a relation of exhaled breath condensate nitrite levels and hyperinflation measured by conventional pulmonary function tests. Investigations using isolated lung models and cells stretched in culture also provide insight into this relation. Exhaled breath condensate nitrite may be a biochemical indicator of pulmonary overdistension.

The effect of specific immunotherapy on exhaled breath condensate nitrite levels

The effect of specific immunotherapy on exhaled breath condensate nitrite levels

Exhaled Breath Condensate Nitrite and Its Relation to Tidal Volume in Acute Lung Injury

Mechanical ventilation may damage the lung. Low tidal volume (VT) is protective, but VT is scaled to body weight (BW) and may be high in functionally small ARDS lungs. We hypothesized that exhaled breath condensate (EBC) nitrite (NO(2)(-)) concentration may increase with lung distension. Prospective, noncontrolled study. University hospital and medical ICU. Thirty-five ICU patients requiring mechanical ventilation (severe pneumonia, n = 31; exacerbated COPD, n = 4). Patients were scored according to American and European Consensus Conference on ARDS criteria (AECC) [no lung injury, n = 7; acute lung injury, n = 13; ARDS, n = 15], as well as the Murray lung injury severity score (LISS) [score 0, n = 3; score 0.1 to 2.5, n = 19; score > 2.5, n = 13]. EBC was collected and analyzed for NO(2)(-), interleukin (IL)-6, and IL-8. Serum was analyzed for IL-6, IL-8, and procalcitonin. and measurements: EBC NO(2)(-) correlated well with VT (milliliters per kilogram of BW; r = 0.79, p < 0.0001) and expiratory minute volume (r = 0.60, p < 0.0001) but not with other ventilatory parameters or parameters of pulmonary (EBC IL-6, EBC IL-8) or systemic (serum IL-6, IL-8, and procalcitonin) inflammation. The ratio of EBC NO(2)(-) and the size of the VT correlated directly with lung injury (AECC, r = 0.66, p < 0.0001; LISS, r = 0.84, p < 0.0001). EBC NO(2)(-) increased linearly with VT. The ratio of EBC NO(2)(-) to VT is assumed to reflect NO(2)(-) release at a given VT. An increase in this ratio indicates an inappropriate increase of NO(2)(-) production most likely due to mechanical stress of the remaining open lung units in injured lungs. We conclude that the EBC NO(2)(-)/VT ratio may help to identify situations of critical mechanical stress.

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 (HCO3−) secretion...