Changes In Exhaled Nitric Oxide Research Articles

Traffic-related air pollution, chronic stress, and changes in exhaled nitric oxide and lung function among a panel of children with asthma living in an underresourced community

We examined associations between short-term exposure to traffic-related air pollutants (TRAP) and airway inflammation and lung function in children with asthma, and whether these associations are modified by chronic psychological stress. Residents of underresourced port-adjacent communities in New Jersey were concerned about the cumulative impacts of exposure to TRAP, particularly diesel-engine truck emissions, and stress on exacerbation of asthma among children. Children with asthma aged 9–14 (n = 35) were recruited from non-smoking households. We measured each participant's (1) continuous personal exposure to black carbon (BC, a surrogate of TRAP) at 1-min intervals, (2) 24-h integrated personal exposure to nitrogen dioxide (NO2), (3) daily fractional exhaled nitric oxide (FeNO), and (4) lung function for up to 30 consecutive days. Personal BC was recorded by micro-aethalometers. We measured daily FeNO using the NIOX MINO, forced expiratory volume in one second (FEV1), and forced vital capacity (FVC) using Easy One Frontline spirometers. Chronic stress was measured with the UCLA Life Stress Interview for Children. The association was examined using linear mixed-effect models. In the fully adjusted model, an interquartile range (IQR) increase in BC at lag 0–6 h before the FeNO measurement was associated with 8 % (95 % CI: 3 % - 12 %) increase in FeNO, whereas an IQR increase in BC at lag 7–12 h and lag 0–24 h were associated with 6 % (95 % CI: 2 % - 11 %) and 7 % (2 % - 12 %) FeNO increases, respectively. There were no significant lung function changes per IQR increase in BC. No interactions were observed between chronic stress and BC on FeNO. Chronic stress was negatively associated with individual average FeNO levels. Our findings suggest that higher levels of BC exposure within the prior 24 h increased airway inflammation levels in children with asthma, with the strongest effect observed within the first 6 h.

Effectiveness of sublingual immunotherapy with house dust mite drops in asthmatic children at different ages.

Respiratory allergies in children, such as asthma and rhinitis, are becoming progressively common every year. Recent studies found that pediatric patients with asthma receiving regular medication and specific immunotherapy (SIT) had improved therapeutic outcomes in a wide age range. However, there are few studies that have examined the effectiveness of SIT treatment in children with allergic asthma at different ages in terms of the degree of asthma control, improvements in lung function, and changes in exhaled nitric oxide (FeNO). A total of 200 asthmatic pediatric patients who had been receiving regular treatment for at least a year were split into the observation and the control groups, which depended on whether sublingual immunotherapy was added based on conventional treatment medicines. The children who were divided by an age cut-off of 6 years old in these two groups were compared before and after therapy based on the exhaled levels of FeNO, pulmonary function, visual analog scale, medication scores, daytime and nighttime ratings of asthma symptom, and rhinitis symptom scores. Before treatment, there was no significant difference between the observation group and the control group in various indicators of the patients under 6 years old; and in the older children (6-16 years old) group, the scores of FVC, FEV1, and FEF25 in the observation group were significantly lower than those in the control group (P < 0.05). The FEF75, FEF50, FEF25, and MMEF75/MMEF25 indexes in the observation group were significantly higher than those in the control group after treatment (P < 0.05), but there was no statistical significance in other indexes (P > 0.05). The scores of ACT, FEF75, FEF50, MMEF72/MMEF25, and FeNO in the observation group were all higher than those in the control group after treatment (P < 0.05), and the differences in other indexes were not statistically significant (P > 0.05). Between the young-age group and the elder group, there was no significant difference in all indexes in the observation group before and after treatment (P > 0.05). Children with asthma of all ages can considerably benefit from sublingual immunotherapy. Specifically, younger patients showed greater tendency on the improvement of small airway resistance, whereas school-age children with asthma significantly improved their small airway resistance as well as their asthma control and inflammation alleviation.

Exposure to traffic-related air pollution and changes in exhaled nitric oxide and DNA methylation in arginase and nitric oxide synthase in children with asthma

BackgroundTraffic-related air pollution (TRAP) has been associated with increased risk of airway inflammation in children with asthma. While epigenetic changes could potentially modulate TRAP-induced inflammatory responses, few studies have assessed the temporal pattern of exposure to TRAP, epigenetic changes and inflammation in children with asthma. Our goal was to test the time-lag patterns of personal exposure to TRAP, airway inflammation (measured as fractional exhaled nitric oxide, FeNO), and DNA methylation in the promoter regions of genes involved in nitric oxide synthesis among children with asthma.MethodsWe measured personal exposure to black carbon (BC) and FeNO for up to 30 days in a panel of children with asthma. We collected 90 buccal cell samples for DNA methylation analysis from 18 children (5 per child). Methylation in promoter regions of nitric oxide synthase (NOS1, NOS2A, NOS3) and arginase (ARG1, ARG2) was assessed by bisulfite pyrosequencing. Linear-mixed effect models were used to test the associations of BC at different lag periods, percent DNA methylation at each site and FeNO level.ResultsExposure to BC was positively associated with FeNO, and negatively associated with DNA methylation in NOS3. We found strongest association between FeNO and BC at lag 0–6 h while strongest associations between methylation at positions 1 and 2 in NOS3 and BC were at lag 13–24 h and lag 0–24 h, respectively. The strengths of associations were attenuated at longer lag periods. No significant associations between exposure to TRAP and methylation levels in other NOS and ARG isoforms were observed.ConclusionsExposure to TRAP was associated with higher levels of FeNO and lower levels of DNA methylation in the promoter regions of the NOS3 gene, indicating that DNA methylation of the NOS3 gene could be an important epigenetic mechanism in physiological responses to TRAP in children with asthma.

Effects of sublingual-specific immunotherapy on pulmonary function and exhaled nitric oxide levels in asthmatic children with and without allergic rhinitis.

BackgroundAllergic asthma and allergic rhinitis are common chronic respiratory diseases in children. The prevalence rate of disease is increasing year by year. And avoid allergens, drug treatments and special immunotherapy (SIT) is the fundamental treatment for respiratory allergies diseases. But there are few comprehensive studies on the control level of asthma, improvement of lung function, and changes of exhaled nitric oxide (FeNO) after SLIT treatment in children with allergic asthma and rhinitis.MethodsIn all, 71 child asthma patients who received sublingual-specific immune therapy for 1 year or more were divided into an asthmatic rhinitis group (31 cases) and an asthma-alone group (40 cases). The two groups of patients were compared before and after treatment in terms of rhinitis symptom scores, daytime and nighttime asthma symptom scores, visual analog scale (VAS) score, drug score, pulmonary function, and exhaled nitric oxide level (FeNO).ResultsAfter treatment, daytime symptom scores, VAS scores, drug scores, and FeNO levels of the asthma-alone group were all lower than before treatment, and the lung function was significantly improved (P<0.05), while the difference in night symptom scores before and after treatment was not statistically significant (P>0.05). The lung function and FeNO level of children in the asthmatic rhinitis group were lower after treatment than before treatment, with statistically significant differences (P<0.05). The scores of rhinitis and VAS in the asthmatic rhinitis group were higher than those in the asthma-alone group, and the differences were statistically significant. There was no significant difference in other scores between the two groups. There was no significant difference in lung function and FeNO level between the two groups.ConclusionsSLIT for children with or without allergic asthma or with or without rhinitis has a significant effect, but its effect on children with asthma combined with rhinitis is not superior to that of children with asthma alone.

Change in exhaled nitric oxide during peanut challenge is related to severity of reaction

BackgroundPeanut allergy affects 3% of Australian children and has a higher risk of anaphylaxis than most food allergies. Predicting who is likely to develop anaphylaxis is still an inexact science. The fraction of exhaled nitric oxide (FeNO) shows promise as a biomarker involved in peanut allergy, as nitric oxide plays a role in inhibiting mast cell degranulation which is relevant in anaphylaxis, where mast cell degranulation plays a mediator role. The aim of this study was to assess the change in FeNO in children during peanut challenge.MethodsThirty-six children aged from 5 to 17 years were recruited for open-labelled peanut challenge. Participants had skin prick test to peanut performed, and serum collected for Ara h2 specific IgE and peanut specific IgE. FeNO was measured by portable device (NIOX VERO) prior to and throughout the peanut challenge.ResultsWhen grouped according to reaction type at peanut challenge (anaphylaxis, clinical allergy not anaphylaxis and tolerant), there were significant differences in the mean change in FeNO measurement between the anaphylaxis group and the clinical allergy, not anaphylaxis group (p = 0.005), and between the anaphylaxis group and tolerant group (p < 0.0001).ConclusionsFeNO decreased more significantly in those who subsequently developed anaphylaxis than in those with clinical allergy, not anaphylaxis or negative peanut challenge (tolerance). As a bedside test that can be used in children, it has potential for further research into mechanisms of anaphylaxis in food allergy and potentially assists in predicting an imminent anaphylactic reaction in some patients.Trial registration ClinicalTrials.gov: PEAnut Anaphylaxis Predictors (PEAAP) NCT02424136.

What is a clinically meaningful change in exhaled nitric oxide for children with asthma?

Fractional exhaled nitric oxide (FE NO) may be a useful objective measurement to guide asthma treatment. What remains uncertain is what change in FE NO is clinically significant. An individual patient data analysis was performed using data from seven randomized clinical trials which used FE NO to guide asthma treatment. The absolute and percentage intra-subject change in FE NO measurements over "stable" and also "unstable" 3-month periods were described. Data were available in 1112 randomized controlled trial participants and ≥1 stable period was present for 665 individuals. The interquartile range (IQR) and limits of agreement (LoA) for change in absolute FE NO among individuals whose initial FE NO was <50 parts per billion (ppb) were -7 to +9 ppb and -43 to +50 ppb, and for those with initial FE NO ≥50 ppb IQR was -29 to +17 ppb and LoA was -80 to +76 ppb. For percentage change in FE NO, the IQR and LoA for individuals whose initial FE NO was <50 ppb were -33% to +51% and -157% to +215%, and for those with initial FE NO ≥50 ppb were -33% to +35% and -159% to +192%. The variation in FE NO values for a stable period was similar irrespective of whether it was followed by a stable or unstable period. Over a 3-month period where FE NO is initially <50 ppb, a rise of <10 ppb or of <50% (based on IQR) is unlikely to be related to asthma. When FE NO is initially ≥50 ppb an percentage change of <50% (based on IQR) is unlikely to be asthma-related.

Time-Lag Pattern of Short-Term Exposure to Traffic-Related Air Pollution and Changes in Exhaled Nitric Oxide in Asthmatic Children

Background/Aim: Short-term exposure to traffic-related air pollution (TRAP) has been associated with asthma exacerbation and increases in exhaled nitric oxide (FeNO), a biomarker of airway inflammation, with time lags ranging from several hours to a few days. Very few studies have examined TRAP-FeNO associations on less than 24-hour timescale. Moreover, most of the previous studies have used central-site exposure data. We aimed to investigate the lag structure of changes in FeNO in response to black carbon (BC), a marker for diesel exhaust particulate matter exposure, at hourly resolution measured by personal monitors from 35 asthmatic children in seaport-adjacent communities in New Jersey.Methods: Thirty five children with mild-to-moderate physician-diagnosed asthma wore micro-aethalometers (AE51, Aethlabs) for around 30 days (1071 observations in total). FeNO was measured daily in late afternoon using a NIOX MINO. Linear-mixed effect model was applied to quantify the BC-FeNO association after adjusting for day-of-week, temperature, age and gender. The lag was stratified as every two hours within 24-hour before the time of FeNO measurement.Results: Based on data from the first 9 subjects, FeNO level was positively associated with 24-hour average BC exposure (0.69% [95%CI: -1.62%, 3.05%] per one &amp;#956;g/m3 increase in BC) in the adjusted model. However, we observed inverse associations between BC and FeNO within 24 hour prior to FeNO measurement, and the association was strongest at lag 14-16 hours (-5.5% [95%CI: -9.38%, -1.44%] per one &amp;#956;g/m3 increase in BC) The strength of negative associations increased from lag 4-6 hours to lag 16-18 hours, and then decreased and becoming positive, over lags 18-20, 20-22 and 22-24 hours.Conclusions: Given the known high spatial and temporal variation in exposure to TRAP, the preliminary results support the need for further study of time-lag patterns between exposure to TRAP and acute asthma outcomes.

Perioperative changes in exhaled nitric oxide during oesophagectomy

Introduction: Oesophagectomy is a major surgical procedure, associated with high rates of postoperative cardiopulmonary morbidity, that is in part due to the frequent requirement for periods of intraoperative one-lung ventilation (OLV). The current pilot study aims to investigate variation in exhaled NO levels during oesophagectomy with emphasis on the response to OLV and correlation to physiological variables and clinical outcomes. Methods: Breath-to-breath concentrations of NO were analysed in patients undergoing oesophagectomy at various stages of two-lung ventilation. Furthermore, we also analysed the effects of OLV both in the selectively ventilated and collapsed lungs. Results: Twenty-four patients were recruited to the study (17 male, 60.2 ± 12.8 years). Regarding two-lung ventilation, the baseline levels of NO (2.9 ppb), tended to increase after re-inflation of the collapsed lung (3.5 ppb, P = 0. 888) and decreased at 2 h (2.1 ppb, P = 0.022) and 12 h (2.2 ppb, P = 0.733) postoperatively. Compared to baseline, selective measurements of NO at the end of OLV demonstrated a significant reduction of NO levels in the ventilated lung (1.6 versus 3.1 ppb, P = 0.028), whereas re-inflation of the collapsed lung revealed higher levels of NO (3.4 versus 2.7 ppb, P = 0.657). Exhaled NO correlated significantly with systolic blood pressure and lactate (P < 0.007). Exhaled NO levels tended to be higher at all perioperative time points in patients who developed postoperative respiratory complications (P > 0.05). Conclusion: This study highlights effects of oesophagectomy and OLV on exhaled concentrations of NO. The observed variations may be related to differential ventilation during OLV altering the complex balance between synthesis and consumption of NO as well as local and generalised tissue injury associated with this surgery. Findings should prompt further larger studies to establish the relationship between exhaled NO and lung injury both during and after oesophagectomy and one-lung ventilation.

Biomarkers of Human Cardiopulmonary Response After Short-Term Exposures to Medical Laser-Generated Particulate Matter From Simulated Procedures: A Pilot Study.

We conducted an exposure chamber study in humans using a simulated clinical procedure lasing porcine tissue to demonstrate evidence of effects of exposure to laser-generated particulate matter (LGPM). We measured pre- and post-exposure changes in exhaled nitric oxide (eNO), spirometry, heart rate variability (HRV), and blood markers of inflammation in five volunteers. Change in pre- and post-exposure measurements of eNO and spirometry was unremarkable. Neutrophil and lymphocyte counts increased and fibrinogen levels decreased in four of the five subjects. Measures of HRV showed decreases in the standard deviation of normal between beat intervals and sequential 5-minute intervals. These data represent the first evidence of human physiologic response to LGPM exposure. Further exploration of coagulation effects and HRV is warranted.

Exhaled nitric oxide and carbon monoxide in mechanically ventilated brain-injured patients

The inflammatory influence and biological markers of prolonged mechanical-ventilation in uninjured human lungs remains controversial. We investigated exhaled nitric oxide (NO) and carbon monoxide (CO) in mechanically-ventilated, brain-injured patients in the absence of lung injury or sepsis at two different levels of positive end-expiratory pressure (PEEP).Exhaled NO and CO were assessed in 27 patients, without lung injury or sepsis, who were ventilated with 8ml kg−1 tidal volumes under zero end-expiratory pressure (ZEEP group, n = 12) or 8 cm H2O PEEP (PEEP group, n = 15). Exhaled NO and CO was analysed on days 1, 3 and 5 of mechanical ventilation and correlated with previously reported markers of inflammation and gas exchange.Exhaled NO was higher on day 3 and 5 in both patient groups compared to day 1: (PEEP group: 5.8 (4.4–9.7) versus 11.7 (6.9–13.9) versus 10.7 (5.6–16.6) ppb (p < 0.05); ZEEP group: 5.3 (3.8–8.8) versus 9.8 (5.3–12.4) versus 9.6 (6.2–13.5) ppb NO peak levels for days 1, 3 and 5, respectively, p < 0.05). Exhaled CO remained stable on day 3 but significantly decreased by day 5 in the ZEEP group only (6.3 (4.3–9.0) versus 8.1 (5.8–12.1) ppm CO peak levels for day 5 versus 1, p < 0.05). The change scores for peak exhaled CO over day 1 and 5 showed significant correlations with arterial blood pH and plasma TNF levels (rs = 0.49, p = 0.02 and rs = −0.51 p = 0.02, respectively). Exhaled NO correlated with blood pH in the ZEEP group and with plasma levels of IL-6 in the PEEP group.We observed differential changes in exhaled NO and CO in mechanically-ventilated patients even in the absence of manifest lung injury or sepsis. These may suggest subtle pulmonary inflammation and support application of real time breath analysis for molecular monitoring in critically ill patients.

Effect of a Soy Isoflavone Supplement on Lung Function and Clinical Outcomes in Patients With Poorly Controlled Asthma

Soy isoflavone supplements are used to treat several chronic diseases, although the data supporting their use are limited. Some data suggest that supplementation with soy isoflavone may be an effective treatment for patients with poor asthma control. To determine whether a soy isoflavone supplement improves asthma control in adolescent and adult patients with poorly controlled disease. Multicenter, randomized, double-blind, placebo-controlled trial conducted between May 2010 and August 2012 at 19 adult and pediatric pulmonary and allergy centers in the American Lung Association Asthma Clinical Research Centers network. Three hundred eighty-six adults and children aged 12 years or older with symptomatic asthma while taking a controller medicine and low dietary soy intake were randomized, and 345 (89%) completed spirometry at week 24. Participants were randomly assigned to receive soy isoflavone supplement containing 100 mg of total isoflavones (n=193) or matching placebo (n=193) in 2 divided doses administered daily for 24 weeks. The primary outcome measure was change in forced expiratory volume in the first second (FEV1) at 24 weeks. Secondary outcome measures were symptoms, episodes of poor asthma control, Asthma Control Test score (range, 5-25; higher scores indicate better control), and systemic and airway biomarkers of inflammation. Mean changes in prebronchodilator FEV1 over 24 weeks were 0.03 L (95% CI, -0.01 to 0.08 L) in the placebo group and 0.01 L (95% CI, -0.07 to 0.07 L) in the soy isoflavone group, which were not significantly different (P = .36). Mean changes in symptom scores on the Asthma Control Test (placebo, 1.98 [95% CI, 1.42-2.54] vs soy isoflavones, 2.20 [95% CI, 1.53-2.87]; positive values indicate a reduction in symptoms), number of episodes of poor asthma control (placebo, 3.3 [95% CI, 2.7-4.1] vs soy isoflavones, 3.0 [95% CI, 2.4-3.7]), and changes in exhaled nitric oxide (placebo, -3.48 ppb [95% CI, -5.99 to -0.97 ppb] vs soy isoflavones, 1.39 ppb [95% CI, -1.73 to 4.51 ppb]) did not significantly improve more with the soy isoflavone supplement than with placebo. Mean plasma genistein level increased from 4.87 ng/mL to 37.67 ng/mL (P < .001) in participants receiving the supplement. Among adults and children aged 12 years or older with poorly controlled asthma while taking a controller medication, use of a soy isoflavone supplement, compared with placebo, did not result in improved lung function or clinical outcomes. These findings suggest that this supplement should not be used for patients with poorly controlled asthma. clinicaltrials.gov Identifier: NCT01052116.

Across-shift changes of exhaled nitric oxide and spirometric indices among cotton textile workers.

For the purpose of evaluation of exhaled NO as an index of airway inflammation, we assessed changes in fractional exhaled NO (FeNO) across a work shift and its relationship with respiratory complaints. Chronic and work-aggravated respiratory complaints were assessed using a questionnaire in 89 male textile workers. FeNO and spirometry were performed before and after a work shift and all the changes were registered. A significant increase in FeNO after a work shift was observed. Post-shift FeNO was significantly higher among the subjects with chronic respiratory complaints. There was an obvious decrease in FVC, and FEV1 after a work shift; however, we couldn't find a significant relationship between changes in respiratory parameters and concentration of inhalable dusts. FeNO increase after a work shift along with pulmonary function decrement and higher post-shift FeNO among subjects with respiratory complaints makes across-shift FeNO a non-invasive test for assessment of airway hyper-responsiveness in textile workers.

The association between exhaled nitric oxide and sleep apnea: The role of BMI

Obstructive sleep apnea syndrome is associated with airway inflammation. Measurement of exhaled nitric oxide is a non-invasive method for evaluation of airway diseases. It seems that obesity is an exacerbating factor for airway inflammation. We aimed to evaluate the changes of exhaled nitric oxide after sleep in patients suffering from OSA regarding BMI. In 54 patients referred for polysomnography, exhaled nitric oxide measurements were performed before and after sleep. Subjects were divided into three categories: normal, obese with sleep apnea and non-obese, based on polysomnographic recordings and BMI. 47 subjects had abnormal apnea/hypopnea index (AHI mean = 39.7) and 7 were normal regarding AHI (AHI mean = 3.0). BMI was significantly correlated to AHI, number of desaturations and hypoxia. Among those with apnea, 31 subjects were obese and 16 were non-obese. Exhaled nitric oxide levels in normal and OSA subjects showed no significant change, but a significant increase was found in obese patients with apnea (14.7 pre-sleep mean, 20.0 post-sleep mean). Obesity is an effective factor in the inflammation of airways in patients with obstructive apnea.

Study of the interaction of glutamatergic and nitrergic signalling in conditions of the experimental airways hyperreactivity

BackgroundGlutamatergic and nitrergic system participate in the control of respiratory system functions. It is only little information regarding a possible interaction of both systems in the airways hyperractivity. We investigated the effect of agents modulating the activity of these systems on the experimental ovalbumin-induced airways hyperreactivity as well as on the changes of exhaled nitric oxide (eNO) levels. MethodsWe used the agonists of NMDA receptors – N-methyl-D-aspartic acid (NMDA) and monosodium glutamate (MSG), selective competitive antagonist (DL-2-amino-5-phosphonovaleric acid – AP-5) and selective non-competitive antagonist (dizocilpine – MK-801) of these receptors. We used also non-specific inhibitor of NO synthases Nω-nitro-L-arginine methyl ester (L-NAME). The airways responsiveness to histamine or acetylcholine was evaluated under in vitro conditions. ResultsNMDA administration caused the increase of tracheal smooth muscle response in ovalbumin-induced hyperreactivity to acetylcholine. The effect of MSG was less pronounced. MK-801 as well as AP-5 provoked the decrease of reactivity mainly to acetylcholine in tracheal smooth muscle. We recorded the changes in eNO levels. The activation of NMDA receptor with NMDA or MSG increased eNO levels. The inhibition of NO synthase with L-NAME caused the fall of eNO levels. MK-801 shows (within the group) the more expressive effect in the eNO levels during sensitization than AP-5 group. ConclusionThe results confirm the possibility of NMDA receptors participation in the experimental airways hyperreactivity.

Exhaled nitric oxide as biomarker of acute lung injury: an unfulfilled promise?

The discovery of nitric oxide (NO) as a signalling and regulatory molecule and its subsequent detection in the exhaled breath has not only yielded new mechanistic insights but also diagnostic opportunities and therapeutic targets in several important medical conditions. In diseases involving chronic pulmonary inflammation such as asthma that affects millions worldwide, exhaled NO has achieved spectacular successes with patients currently owning handheld devices and monitoring inflammatory aspects of their conditions in their own homes. This has been facilitated by recognition by regulatory bodies, scientific and clinical societies and insurance companies. While characteristic changes in exhaled NO have also been observed in acute lung injury (ALI), the promise of exhaled NO as a surrogate biomarker of this life-threatening disease has not been achieved. In this work, we have analysed factors contributing to successes of exhaled NO in the asthma field and contrasted these on the ALI field. We provide a snapshot of current status of exhaled NO field in ALI and propose a framework for definite evaluation of exhaled NO as a clinically useful biomarker.

Inflammatory response to acute exposure to welding fumes during the working day

To investigate cardiorespiratory and inflammatory responses in male workers following exposure to welding fumes and airborne particles in actual workplace conditions. We measured blood leukocytes and their differential counts, platelet count, hemoglobin, sensitive C-reactive protein, fibrinogen, E-selectin, IL-(interleukin)1β, IL-6, IL-8, tumor necrosis factor alpha (TNF-α) and endothelin-1 in blood samples of twenty workers before and after their working day. We also studied peak expiratory flow (PEF), forced expiratory volume in one second (FEV1), and exhaled nitric oxide (NO). We assessed heart rate variability (HRV) by obtaining 24-hour ambulatory electrocardiograms. The total blood leukocytes and neutrophils increased after the work shift, whereas IL-1β and E-selectin decreased significantly. There were no statistically significant changes in exhaled NO, FEV1, PEF or HRV. Occupational exposure to welding fumes and particles caused a slight, acute inflammatory effect estimated based on the increased values of leukocytes and neutrophils in blood and a decrease in the interleukin 1β and E-selectin values, but no changes in the pulmonary function (exhaled NO, FEV1, PEF) or HRV during the working day were observed.

Initial Cooperative Group Experience of Bevacizumab (Bev) Plus Concomitant Chemoradiation Therapy (CRT) in Patients With Inoperable Locally Advanced Stage III Non-small Cell Lung Cancer (LA-NSCLC): Preliminary Results of S0533

Purpose/Objective(s): Radiation pneumonitis (RP) is the most common toxicity following stereotactic ablative radiation therapy (SABR) for lung tumors, but methods to predict which patients will develop this side effect remain lacking. We performed a prospective clinical trial to assess the feasibility and potential of measuring levels of exhaled nitric oxide (NO), carbon monoxide (CO), nitrous oxide (N2O), and carbon dioxide (CO2) as predicative biomarkers of RP in patients receiving SABR to the lung. Materials/Methods: Twenty patients with lung tumors receiving SABR were enrolled in this pilot study. Exhaled concentrations of NO, CO, N2O, and CO2 were simultaneously measured with a real time laser based instrument immediately prior to and following each fraction. Patients were followed for development of symptomatic RP (Grade 2 or higher, CTCAE v4.0). RP incidence was evaluated for correlation with acute changes in exhaled gas concentrations, baseline concentrations, and dosimetric and demographic factors. Results: Five of twenty patients developed RP at an average of 5.4 months following SABR. Average acute changes in NO were 4.10 6.66% (mean standard error) for symptomatic and 33.5 9.31% for asymptomatic patients. Average acute changes in CO were -0.77% 1.53% for symptomatic and -7.32% 1.81% for asymptomatic patients. Average acute change in NO 12.5% and CO -5.5% correlated with RP incidence (p Z 0.036 and p Z 0.035, respectively). Bivariate analysis showed acute change in NO 12.5% combined with acute change in CO -5.5% strongly correlated with RP incidence (p Z 0.003). Baseline NO 24 parts per billion also correlated with RP incidence (p Z 0.036). N2O and CO2 concentrations were not predicative of symptomatic RP. Dosimetric parameters did not predict for the development of RP. Conclusions: Acute changes in exhaled NO and CO concentrations following SABR were found to predict development of RP. Evaluating changes in exhaled NO and CO concentrations immediately following radiation therapy represents a promising method for identifying individuals at highest risk for developing RP. Author Disclosure: J.M. More: None. N.C. Eclov: None. M. Chung: None. J.H. Shorter: A. Employee; JHS is affiliated with Aerodyne Research Inc., which designed the breath analysis instrument used in this study. R. Burmeister: Q. Leadership; RB is affiliated with Kos Systems, which seeks to develop applications for breath analysis. P. Banos: Q. Leadership; PB is affiliated with Kos Systems, which seeks to develop applications for breath analysis. P. Maxim: None. B.W. Loo: None. M. Diehn: None.

Sputum inflammatory phenotypes are not stable in children with asthma

BackgroundTwo distinct, stable inflammatory phenotypes have been described in adults with asthma: eosinophilic and non-eosinophilic. Treatment strategies based on these phenotypes have been successful. This study evaluated sputum cytology in...

Circulating nitric oxide products do not solely reflect nitric oxide release in cirrhosis and portal hypertension

Patients with cirrhosis often develop a systemic vasodilatation and a hyperdynamic circulation with activation of vasoconstrictor systems such as the renin-angiotensin-aldosterone system (RAAS), and vasopressin. Increased nitric oxide (NO) synthesis has been implicated in the development of this state of vasodilation and pulmonary dysfunction including increased exhaled NO concentrations. Circulating metabolites (NO(x)) may affect the systemic and pulmonary NO-generation. However, the relations of these abnormalities to the haemodynamic changes remain unclear. The aims of the present study were to measure changes in exhaled NO in relation to circulating NO(x), RAAS, and haemodynamics. Twenty patients (eight child class A and 12 class B patients) underwent a liver vein catheterization with determination of splanchnic and systemic haemodynamics. Circulating NO(x) and exhaled NO were determined in the supine and sitting positions and related to haemodynamics, RAAS and lung diffusing capacity (D(L)CO). Eight matched healthy individuals served as controls. All patients with cirrhosis had portal hypertension. We found no significant difference in exhaled NO between patients and controls and no changes from the supine to the sitting position. Exhaled NO in the patients correlated significantly with plasma volume, heart rate and D(L)CO. NO(x) concentrations were not significantly increased in the patients. NO(x) correlated with portal pressure and haemodynamic indicators of vasodilatation, but not with exhaled NO concentrations. In patients with moderate cirrhosis, exhaled NO is normal. Circulating NO(x) do not seem to reflect pulmonary and systemic NO release, but NO(x) seems to reflect systemic and splanchnic haemodynamic changes in cirrhosis.

Subclinical responses in healthy cyclists briefly exposed to traffic-related air pollution: an intervention study

BackgroundNumerous epidemiological studies have demonstrated adverse health effects of a sedentary life style, on the one hand, and of acute and chronic exposure to traffic-related air pollution, on the other. Because physical exercise augments the amount of inhaled pollutants, it is not clear whether cycling to work in a polluted urban environment should be encouraged or not. To address this conundrum we investigated if a bicycle journey along a busy commuting road would induce changes in biomarkers of pulmonary and systematic inflammation in a group of healthy subjects.Methods38 volunteers (mean age: 43 ± 8.6 years, 26% women) cycled for about 20 minutes in real traffic near a major bypass road (road test; mean UFP exposure: 28,867 particles per cm3) in Antwerp and in a laboratory with filtered air (clean room; mean UFP exposure: 496 particles per cm3). The exercise intensity (heart rate) and duration of cycling were similar for each volunteer in both experiments. Exhaled nitric oxide (NO), plasma interleukin-6 (IL-6), platelet function, Clara cell protein in serum and blood cell counts were measured before and 30 minutes after exercise.ResultsPercentage of blood neutrophils increased significantly more (p = 0.004) after exercise in the road test (3.9%; 95% CI: 1.5 to 6.2%; p = 0.003) than after exercise in the clean room (0.2%; 95% CI: -1.8 to 2.2%, p = 0.83). The pre/post-cycling changes in exhaled NO, plasma IL-6, platelet function, serum levels of Clara cell protein and number of total blood leukocytes did not differ significantly between the two scenarios.ConclusionsTraffic-related exposure to particles during exercise caused a small increase in the distribution of inflammatory blood cells in healthy subjects. The health significance of this isolated change is unclear.