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PubMed1999

The effect of cigarette smoking on exhaled nitric oxide in mild steroid-naive asthmatics.

STUDY OBJECTIVES: It has been demonstrated previously that exhaled nitric oxide (eNO) is increased in steroid-naive asthmatics and that inhaled steroids reduce eNO in these patients. Cigarette smoking has also been reported to reduce the eNO in healthy volunteers. Recently a correlation has been demonstrated between eNO and airway hyperresponsiveness in steroid-naive, mild asthmatics. We hypothesized that cigarette smoking would reduce the eNO level in steroid-naive asthmatics and might, therefore, affect the correlation between eNO and airway hyperresponsiveness. DESIGN: Comparison of eNO in healthy smoking and nonsmoking volunteers with the level of eNO in steroid-naive and steroid-treated asthmatics. Correlate the eNO level with the provocative concentration of histamine causing a 20% fall in FEV1 (PC20hist) in the asthmatic smoking and nonsmoking patients. SETTING: University outpatient asthma clinic. PATIENTS AND METHODS: eNO levels and PC20hist were measured in three different asthmatic patient groups (group A = 29 steroid-naive, nonsmoking asthmatics; group B = 19 steroid-treated, nonsmoking asthmatics; and group C = 13 smoking, steroid-naive asthmatics) and in two healthy volunteer groups (group D = 18 nonsmoking; and group E = 16 smoking). RESULTS: eNO in group A was significantly increased compared with the values in groups B and D (21.8+/-12.7, 12.8+/-4.9, and 10.6+/-2.2 parts per billion [ppb], respectively). Cigarette smoking decreased eNO in healthy volunteers (7.4+/-1.8 ppb, group E) as well as in steroid-naive asthmatics (12.7+/-5.1 ppb, group C). There was a significant correlation between eNO and PC20hist in group A (r = -0.45, p < 0.05); this correlation was, however, lost in both groups B and C. CONCLUSION: Cigarette smoking and inhaled steroids reduce the eNO in patients with mild asthma to a comparable extent. Because the correlation between eNO and airway hyperresponsiveness was lost in steroid-treated and smoking, steroid-naive asthmatics, we question the value of eNO as a marker of airway inflammation, at least in mild asthmatics who are already being treated with inhaled steroids or who are currently smoking.

Administration, Inhalation↗
PubMed2000

Exhaled nitric oxide and exercise in stable COPD patients.

STUDY OBJECTIVE: To evaluate exhaled nitric oxide (eNO) during exercise in patients with stable COPD. SETTING: Outpatient evaluation in a rehabilitation center. PATIENTS: Eleven consecutive male patients with stable COPD (age, 65 +/- 6 years; FEV(1), 56 +/- 10% predicted). Eight healthy (six men; age, 51 +/- 16 years) nonsmoking, nonatopic volunteers served as control subjects. METHODS: In each subject, a symptom-limited cycle ergometry test was performed by monitoring eNO with the tidal-breath method to assess eNO concentration (FENO) and output (VNO) at rest, peak exercise, and recovery time. RESULTS: Resting FENO (9.8 +/- 5.1 and 14.1 +/- 6.3 parts per billion, respectively) and VNO (4.2 +/- 2.0 and 5.9 +/- 3.4 nmol/min, respectively) were lower, although not significantly, in COPD patients than in control subjects. In both groups, FENO significantly decreased whereas VNO significantly increased during exercise. Both variables returned to baseline during the recovery time. Peak exercise VNO, but not FENO, was significantly lower in COPD patients than in control subjects (7.9 +/- 5.4 and 12.7 +/- 6.0 nmol/min, respectively, p < 0.05). The rise in VNO was weakly correlated to oxygen consumption VO(2)) both in control subjects (r = 0.31, p = 0. 002) and in COPD patients (r = 0.22, p = 0.03). FENO showed an inverse correlation to VO(2) in both groups (r = -0.53, p = 0.000; r = -0.31, p = 0.003 in control subjects and COPD patients, respectively). CONCLUSIONS: In patients with mild and moderate COPD, eNO during exercise parallels that observed in normal control subjects. VNO, but not FENO, is significantly reduced at peak exercise in COPD patients as compared with control subjects. The long-term effects of exercise training on eNO has to be evaluated by further studies.

Adult↗
PubMed2001

Exhaled nitric oxide correlated with induced sputum findings in COPD.

STUDY OBJECTIVES: Neutrophilic airway inflammation may underlie the pathogenesis of COPD. We examined repeated measurements of the fractional concentration of exhaled nitric oxide (FENO) and the correlation with cells and mediators in induced sputum (IS) from patients with COPD. PARTICIPANTS: Eleven COPD subjects (9 men and 2 women, aged 46 to 69 years) with predicted FEV(1) of 45 to 70%. SETTING: A hospital research laboratory. DESIGN: Single-cohort, prospective study with four visits at two weekly intervals. INTERVENTIONS: FENO and spirometry were assessed at all visits, and IS for differential cell count, leukotriene-B(4) (LTB(4)) and interleukin (IL)-8, nitrite, and nitrate at visit 1, visit 3, and visit 4. RESULTS: During the study, there were significant declines in mean percent predicted FEV(1), from 55.2 to 51.6% (p = 0.029), and mean FEV(1)/FVC ratio, from 50.4 to 45.4% (p = 0.001), accompanied by a significant increase in FENO geometric mean (95% confidence limits), from 15.2 (10.9 to 21.2) to 23.6 (17.1 to 32.4) parts per billion (p = 0.037), and sputum LTB(4), from 1.79 (1.03 to 3.11) to 3.57 (1.95 to 6.53) ng/mL (p = 0.033), but no significant change in other sputum parameters. From visits 1 to 4, the change in percent neutrophils correlated with the changes in FENO and IL-8 (r = 0.648, p = 0.028; r = 0.60, p = 0.05, respectively). Hypertonic saline solution induction of sputum caused a fall in FEV(1), from 1.83 +/- 0.44 to 1.46 +/- 0.44 L (p = 0.049). CONCLUSIONS: The worsening spirometry results were accompanied by significant increases in FENO and sputum LTB(4). FENO may be related to neutrophilic inflammation driven by the chemoattractant IL-8. FENO and IS may be useful markers of airway inflammation in COPD patients. Sputum induction with hypertonic saline solution causes a significant fall in FEV(1) requiring appropriate caution.

Aged↗
PubMed2001

Dose-response relationship and reproducibility of the fall in exhaled nitric oxide after inhaled beclomethasone dipropionate therapy in asthma patients.

STUDY OBJECTIVES: The fractional concentration of exhaled nitric oxide (FENO) is a marker of asthmatic airway inflammation. We determined the dose response and the reproducibility of the FENO fall following inhaled beclomethasone dipropionate (iBDP) therapy in nonsteroid-treated asthmatic patients. STUDY DESIGN: Study A: For four 1-week periods (period 1 to period 4), the following regimens were administered in sequential order to 15 nonsteroid-treated asthmatic patients: period 1, placebo; period 2, 100 microg/d of iBDP; period 3, 400 microg/D of iBDP; and period 4, 800 microg/d of iBDP. Spirometry, FENO, and provocative concentration of methacholine resulting in a 20% fall in FEV(1) (PC(20)) were measured at each of five visits (visit 1 to visit 5). Study B: During four periods, 12 nonsteroid-treated asthmatic patients received placebo treatment for 7 days (period 1), 200 microg/d of iBDP for 14 days (period 2), washout on placebo treatment until the FENO was within 15% of baseline (period 3), and 200 microg/d of iBDP for 14 days (period 4). RESULTS: Study A: Mean FEV(1) rose progressively from 3.10 L (visit 1) to 3.41 L (visit 5; p = 0.001). All iBDP doses caused a significant FEV(1) rise compared to placebo treatment, but with no significant separation of doses using FEV(1). FENO geometric mean (95% confidence limits) fell progressively from 103.5 parts per billion (ppb) (78.5 to 136.7) to 37.4 ppb (29.1 to 48.0) from visit 1 to visit 5 (p = 0.001). All doses of iBDP resulted in a significant change in FENO from placebo treatment, but with significant separation of only the 100-microg and 800-microg doses by FENO. Geometric mean (95% confidence limits) PC(20) rose progressively from 0.01 mg/mL (0.00 to 0.19) to 0.48 mg/mL (0.01 to 8.1) from visit 1 to visit 5 (p = 0.002). All doses of iBDP resulted in a significant change in PC(20) from baseline or placebo treatment, but with no significant separation of active iBDP doses using PC(20). Study B: FENO fell from 111.56 ppb (80.3 to 155.1) to 66.3 ppb (49.2 to 89.5; p < 0.001) from period 1 to period 2, and from 110.2 ppb (79.3 to 153.1) to 61.7 ppb (42.9 to 88.8; p < 0.001) from period 3 to period 4. There were no significant differences between FENO in period 1 and period 3 (p = 0.83) or between period 2 and period 4 (p = 0.220). CONCLUSIONS: FENO was superior to FEV(1) and PC(20) in separating doses of iBDP. The fall in FENO after two identical administrations of iBDP separated by placebo washout was highly reproducible.

Administration, Inhalation↗
PubMed2002

Effect of salmeterol on seasonal changes in airway responsiveness and exhaled nitric oxide in pollen-sensitive asthmatic subjects.

OBJECTIVE: Using a model of natural allergen exposure, we examined the effect of regular treatment with salmeterol on allergen-induced changes in airway responsiveness and exhaled nitric oxide (ENO). DESIGN: Double-blind, randomized, parallel-group study. SETTING: Specialist allergy unit in a university hospital. PATIENTS: Asthmatic patients sensitized to pollen allergens were randomly allocated to monotherapy with salmeterol (n = 14) or placebo (n = 13). INTERVENTIONS: Salmeterol, 25 micro g, and placebo inhalers, two puffs bid, for 6 weeks. MEASUREMENTS: Spirometry, the level of a provocative concentration of a substance (methacholine) causing a 20% fall in FEV(1) (PC(20)), the PC(20) level for adenosine 5'-monophosphate (AMP), and ENO were measured before the pollen season and were repeated at the height of the pollen season after 6 weeks of treatment with salmeterol or placebo. RESULTS: The decrease in FEV(1) during the pollen season was significantly larger in the placebo group than in the salmeterol group, the mean difference in the change between the groups being 0.20 L (95% confidence interval, 0.03 to 0.35; p = 0.047). Changes in PC(20) for methacholine, PC(20) for AMP, and ENO levels were not significantly different between treatment groups. However, a mean (+/- SEM) decrease in the PC(20) for methacholine of -1.0 +/- 0.4 doubling concentrations was observed within the placebo group (p = 0.03), whereas no significant changes were observed within the salmeterol group. A significant decrease in PC(20) for AMP (doubling concentrations) was observed within the placebo group (-2.1 +/- 0.6; p = 0.003) and the salmeterol group (-1.5 +/- 0.4; p = 0.003). ENO concentrations increased significantly among the placebo and the salmeterol groups during natural pollen exposure. CONCLUSION: These observations indicate that natural allergen exposure and the regular use of salmeterol are not associated with a greater increase in ENO and airway responsiveness than allergen exposure alone.

Adenosine Monophosphate↗
PubMed2002

Modifications of airway responsiveness to adenosine 5'-monophosphate and exhaled nitric oxide concentrations after the pollen season in subjects with pollen-induced rhinitis.

STUDY OBJECTIVE: s: To determine the effect of cessation of exposure to pollen on airway responsiveness to adenosine 5'-monophosphate (AMP) in subjects with pollen-induced rhinitis, and to explore the relationship between changes in airway responsiveness and changes in exhaled nitric oxide (ENO) levels. STUDY DESIGN: Subjects were studied during the pollen season and out of season. SETTING: Specialist allergy unit in a university hospital. PATIENTS: Fourteen subjects without asthma with pollen-induced rhinitis who showed bronchoconstriction in response to methacholine and AMP during the pollen season and 10 healthy nonatopic control subjects. MEASUREMENTS AND RESULTS: In subjects with pollen-induced rhinitis, ENO concentrations, provocative concentration of agonist causing a 20% fall in FEV(1) (PC(20)) methacholine, and PC(20) AMP were determined during the pollen season and out of season. Healthy control subjects were studied during the pollen season. In subjects with allergic rhinitis, PC(20) AMP increased from a geometric mean of 79.4 mg/mL (95% confidence interval [CI], 31.6 to 199.5 mg/mL) during the pollen season to 316.2 mg/mL (95% CI, 158.5 to 400.0 mg/mL) out of season (p = 0.004). The ENO concentrations decreased from 63.1 parts per billion (ppb) [95% CI, 50.1 to 79.4 ppb] during the pollen season to 30.2 ppb (95% CI, 23.4 to 38.0 ppb) out of season (p < 0.001). The ENO concentrations out of pollen season were still significantly increased in subjects with pollen-induced rhinitis when compared with healthy control subjects. There was no relationship between individual changes in ENO levels and changes in either PC(20) methacholine or PC(20) AMP. CONCLUSIONS: In pollen-sensitive subjects with allergic rhinitis, the cessation of exposure to pollen is associated with a significant reduction of airway responsiveness to inhaled AMP. However, no association was found between allergen-induced changes in ENO values and in airway responsiveness to either direct or indirect bronchoconstrictors. These findings suggest that modifications in ENO and in airway responsiveness are the consequence of different alterations induced by allergen exposure on the lower airways.

Adenosine Monophosphate↗
PubMed2003

Exhaled nitric oxide as a predictor of exercise-induced bronchoconstriction.

INTRODUCTION: Exercise-induced bronchoconstriction (EIB) is present in 40 to 90% of patients with asthma. Exhaled NO (eNO) levels have been correlated with bronchial hyperresponsiveness to methacholine, and have correlated with the degree of decrease in FEV(1) with exercise. The purpose of our study was to examine whether eNO measurements prior to or after exercise could be used as a surrogate marker of exertional bronchoconstriction in a population referred specifically for the evaluation of EIB. METHODS: We studied 50 consecutive subjects without a history of asthma who were referred for the clinical evaluation of EIB. eNO levels were measured prior to exercise challenge and every 5 min for a total of 30 min after exercise. Forced expiratory flows were measured prior to and serially after exercise challenge. RESULTS: Seven subjects had a decrease in FEV(1) of > or = 15% with exercise. The mean eNO level prior to exercise was 41 parts per billion (ppb) [median +/- SD, 23 +/- 42.2 ppb] in the EIB group and 25.6 ppb (median, 19.95 +/- 18.47 ppb) in the group without EIB. A receiver operator characteristic curve yielded a value of 0.636. When using an eNO level of < 12 ppb, the sensitivity, specificity, negative predictive value, and positive predictive value for EIB were 1.0, 0.31, 0.19, and 1.0, respectively; therefore, no one with a baseline eNO of < 12 ppb demonstrated EIB. CONCLUSIONS: No subjects with very low pre-exercise eNO levels (< 12 ppb) demonstrated bronchial hyperresponsiveness to exercise. eNO measurement may obviate the need for bronchoprovocation testing in patients who complain of exertional dyspnea.

Adult↗
PubMed2003

Exhaled breath condensate nitrite and its relation to tidal volume in acute lung injury.

STUDY OBJECTIVE: 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. DESIGN: Prospective, noncontrolled study. SETTING: University hospital and medical ICU. PATIENTS: 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]. INTERVENTIONS: EBC was collected and analyzed for NO(2)(-), interleukin (IL)-6, and IL-8. Serum was analyzed for IL-6, IL-8, and procalcitonin. RESULTS: 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). CONCLUSION: 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.

Acute Disease↗
PubMed2004

Markers of inflammation in exhaled breath condensate of young healthy smokers.

INTRODUCTION: Although a strong correlation exists between long-term cigarette smoking, pulmonary inflammation, and COPD, efforts to identify populations at risk of acquiring COPD have so far been unsuccessful. To this end, noninvasive detection and monitoring of biomarkers of pulmonary inflammation in young healthy smokers may assist in this task. STUDY OBJECTIVES: The purpose of this study was to determine the concentrations of total protein, nitrites, interleukin (IL)-1beta, and tumor necrosis factor (TNF)-alpha, and neutrophil chemotactic activity in exhaled breath condensate (EBC) collected from healthy college student smokers and nonsmokers. DESIGN: EBC was collected from 20 volunteers (9 nonsmokers and 11 smokers) during tidal breathing for 20 min. EBC was also collected from smokers 30 min after smoking one filtered cigarette. The concentrations of total protein, nitrite, IL-1beta, and TNF-alpha in EBC was determined by enzyme-linked immunosorbent assay. Neutrophil chemotactic activity in EBC was determined in vitro using the blind-well technique. RESULTS: The concentrations of total protein and nitrite, and neutrophil chemotactic activity were significantly higher in EBC of smokers in comparison to nonsmokers (p < 0.05). The concentrations of total protein and nitrite in the condensate of smokers did not change significantly after smoking one cigarette. The concentrations of IL-1beta and TNF-alpha in EBC were similar in nonsmokers and smokers. CONCLUSIONS: Concentrations of certain inflammatory mediators and neutrophil chemotactic activity are increased in EBC of young healthy smokers. Collection and analysis of EBC may assist in early detection of cigarette smoke-induced pulmonary inflammation and identifying populations at risk for acquiring COPD.

Adult↗
PubMed2005

Effect of spirometric maneuver, nasal clip, and submaximal inspiratory effort on measurement of exhaled nitric oxide levels in asthmatic patients.

STUDY OBJECTIVES: The measurement of exhaled nitric oxide (eNO) in asthmatic patients is increasingly being used to aid diagnosis and management. To standardize the measurement techniques, the American Thoracic Society and European Respiratory Society guidelines were published, but these were based mainly on expert opinions without strong clinical evidence on many aspects. We investigated the effect of three different factors on the on-line measurement of eNO. In a clinical setting, we evaluated the effect of prior spirometry, the use of nasal clips, and the influence of submaximal inspiratory effort on on-line eNO readings. Recommended guidelines on these factors have been published but have been supported by scanty research data. METHODS: Three groups of stable asthmatic patients (30 patients in each group) had eNO measurements made on-line (NIOX; Aerocrine AB; Solna, Sweden) before and 5 min after performing spirometric maneuvers, without and with a nasal clip, or with maximal and then submaximal inspiratory efforts. RESULTS: There were no significant differences in mean eNO levels among all three groups, before and after spirometry (68.2 vs 66.0 parts per billion [ppb], respectively; mean difference, 2.2 ppb; 95% confidence interval [CI], -0.4 to 4.9; p = 0.090), without use of a nasal clip compared with its use (46.7 vs 45.6 ppb, respectively; mean difference, 1.1 ppb; 95% CI, -0.7 to 2.8; p = 0.234), and maximal or submaximal inspiratory effort (52.6 vs 51.2 ppb, respectively; mean difference, 1.4 ppb; 95% CI, -0.3 to 3.0; p = 0.096). CONCLUSION: We conclude that on-line eNO measurements in clinical practice are not significantly affected by prior spirometry maneuver, use of a nasal clip, or submaximal inspiratory effort.

Adolescent↗
PubMed2005

The effect of montelukast on exhaled nitric oxide and lung function in asthmatic children 2 to 5 years old.

OBJECTIVE: The study was undertaken to investigate the influence of once-daily treatment with montelukast (Singulair; MSD; Glattbrugg, Switzerland) on levels of exhaled nitric oxide (eNO) and lung function in preschool children with asthma. METHODS: A total of 30 children (19 girls), 2 to 5 years of age, in whom asthma had been newly diagnosed, who had a positive first-degree family history of asthma and a positive allergy test result, were allocated to undergo a 1-week run-in period of montelukast treatment. eNO and airway resistance were measured in all patients before (visit 1) and after the run-in period (visit 2), and after treatment with montelukast (4 mg once daily) for 4 weeks (visit 3). RESULTS: There were no significant differences in all parameters before and after the run-in period. However, the mean (SD) levels of eNO and the mean (SD) levels of airway resistance after treatment at visit 3 were 11.6 parts per billion (ppb) [9.5 ppb] and 1.15 kPa/L/s (0.26 kPa/L/s), respectively, and were significantly lower compared to values of 33.1 ppb (12.0 ppb) and 1.28 kPa/L/s (0.23 kPa/L/s), respectively, before treatment (p < 0.001) and at visit 2 (p = 0.01). There was no significant change in mean bronchodilator responsiveness between visit 3 (13.2%; SD, 6.8%) and visit 1/visit 2 (13.3%; SD, 7.0%; p = 0.47). CONCLUSION: We have shown that montelukast has a positive effect on lung function and airway inflammation as measured by nitric oxide level in preschool children with allergic asthma.

Acetates↗
PubMed2005

Leukotriene B4 in exhaled breath condensate and sputum supernatant in patients with COPD and asthma.

STUDY OBJECTIVES: Some patients with COPD present with significant reversibility of airflow limitation after receiving bronchodilation therapy. Leukotriene B(4) (LTB(4)) has been implicated in the pathophysiology of both COPD and asthma. We tested the hypothesis that COPD patients with airflow reversibility and asthmatic patients who smoke might have similar levels of LTB(4) in exhaled breath condensate (EBC) and sputum supernatant. The repeatability and stability of LTB(4) measurements were additionally studied. DESIGN: Prospective, cross-sectional study. PATIENTS OR PARTICIPANTS: We studied 30 patients with COPD (15 smokers [FEV(1), 56% predicted; SD, 6% predicted]; 15 patients with significant reversibility in airway obstruction after bronchodilation [FEV(1), 14% predicted; SD, 2% predicted]). Fifteen asthmatic patients who smoked, with similar FEV(1) and reversibility were also studied. Ten healthy smokers served as control subjects. SETTING: A hospital research laboratory. INTERVENTIONS: Spirometry and reversibility testing were performed on the first visit. On the following day, EBC was collected for the measurement of LTB(4), and induced sputum was collected for differential cell counts and LTB(4) measurement in the sputum supernatant. MEASUREMENTS AND RESULTS: LTB(4) levels in EBC [mean (SD)] were increased in COPD patients (mean, 86.7 pg/mL; SD, 19 pg/mL) and asthmatic patients (mean, 97.5 pg/mL; SD, 15 pg/mL) compared to control subjects (mean, 32.3 pg/mL; SD, 10 pg/mL; p < 0.0001 for both groups). COPD patients with airflow reversibility (mean, 99.8 pg/mL; SD, 12 pg/mL) had values similar to those of asthmatic patients (mean, 97.5 pg/mL; SD, 15 pg/mL; p = 0.2) and higher than those of COPD patients without airflow reversibility (mean, 73.7 pg/mL; SD, 17 pg/mL; p = 0.002). Similar results were observed in the sputum supernatant. Measurements of LTB(4) in EBC and sputum were repeatable on two consecutive days, but measurements in the frozen samples of EBC and sputum were not stable after 3 weeks. CONCLUSIONS: Patients with asthma and reversible COPD presented with higher LTB(4) values compared to patients with nonreversible COPD and healthy smokers. This difference may be mainly attributed to the presence of reversibility in airway obstruction, probably as part of a common underlying inflammatory process.

Adult↗
PubMed2005

Time-dependent effect of nitrate-rich meals on exhaled nitric oxide in healthy subjects.

BACKGROUND: Exhaled nitric oxide (eNO) is a convenient noninvasive marker for airway inflammation in several pulmonary diseases. However, external factors such as nitrate-rich nutrition can affect the levels of eNO and thus compromise its diagnostic value. STUDY OBJECTIVES: The objective of this investigation was to have a better understanding of the time-dependent effect of nitrate-rich meals on eNO in healthy subjects. STUDY DESIGN: Forty-two healthy, nonsmoking volunteers (age range, 25 to 62 years) were recruited for the study. They had no recent respiratory tract infections and were free of pulmonary history, rhinitis, and atopic disorders. eNO was measured before, and 0.5, 2, 4, 12, 15, and 20 h after the intake of a nitrate-rich meal equivalent to 230 mg of nitrate. RESULTS: The intake of a nitrate-rich meal increased eNO by 60% 2 h after the meal. Even after 15 h, the mean eNO value was still 22% higher than the baseline value. Only after 20 h did eNO return to the normal baseline level. CONCLUSION: This finding stresses the importance of advising patients to avoid nitrate-rich nutrition at least 20 h before a scheduled measurement of eNO.

Adult↗
PubMed2006

Inflammatory mediators in exhaled breath condensate of children with obstructive sleep apnea syndrome.

BACKGROUND: Upper airway inflammation is now recognized in adults with obstructive sleep apnea (OSA) syndrome. However, the role played by eicosanoids such as leukotrienes and prostaglandins is unclear. OBJECTIVE: To investigate whether eicosanoids are measurable in exhaled breath condensate (EBC), and to determine whether differences in these inflammatory mediators emerge among children with and without sleep-disordered breathing (SDB). METHODS: EBC was collected from 50 consecutive snoring children undergoing overnight polysomnography for suspected SDB, and from 12 nonsnoring control subjects. Prostaglandin E2 (PGE2), leukotriene B4 (LTB4), and cysteinyl leukotrienes (cys-LTs: leukotriene C4 [LTC4]/leukotriene D4 [LTD4]/leukotriene E4 [LTE4]) EBC levels were analyzed using enzyme-linked immunosorbent assay. RESULTS: LTB4 levels were elevated in children with an apnea-hypopnea index (AHI) > 5/h (SDB; 97.6 +/- 6.3 pg/mL) compared to children with an AHI < 5/h (mild SDB; 66.4 +/- 19.1 pg/mL; p < 0.01) and control subjects (27.8 +/- 3.7 pg/mL; p < 0.01). Similarly, cys-LT (LTC4/LTD4/LTE4) concentrations were also increased in SDB (45.1 +/- 10.6 pg/mL in SDB vs 27.6 +/- 8.3 pg/mL in mild SDB, and 15.7 +/- 7.6 pg/mL in control subjects; p < 0.01). In contrast, PGE2 concentrations were similar among the three groups. CONCLUSIONS: Inflammatory mediators such as leukotrienes and prostaglandins can be readily quantified in EBC collected from the upper airway of children. Disease severity-dependent increases in leukotriene concentrations (LTB4 and LTC4/LTD4/LTE4) emerge among children and may serve as a noninvasive tool in the clinical assessment of these children.

Adolescent↗
PubMed1987

Rest and exercise cardiac output and diffusing capacity assessed by a single slow exhalation of methane, acetylene, and carbon monoxide.

To study rest and exercise pulmonary capillary blood flow (Qc) and diffusing capacity (DLexh) assessed by the rapid analysis of methane, acetylene, and carbon monoxide during a single, slow exhalation, we evaluated 36 subjects during first-pass radionuclide angiography (RNA). At rest (N = 36) and at exercise (N = 21) there was no difference in the respective measurements of cardiac output (Qc = 6.0 +/- 1.7 and CORNA = 6.9 +/- 2.5 at rest; Qc = 13.7 +/- 3.2 and CORNA = 14.5 +/- 4.1 at exercise, L/min, mean +/- SD, r = .80). Mild maldistribution of ventilation, as manifested by an increased phase 3 alveolar slope for methane (CH4 slope), did not significantly influence the results. CH4 slope and DLexh did increase significantly with exercise, while total lung capacity remained unchanged (CH4 slope: 6.2 +/- 5.0 vs 12.5 +/- 6.8% delta CH4/L, mean +/- SD, p less than 0.001; Dsb: 27.7 +/- 9.2 vs 42.0 +/- 17.9 ml/min/mm Hg, mean +/- SD, p less than 0.001; TLC: 5.47 +/- .20 vs 5.96 +/- 1.20 L, mean +/- SD). DLexh was related to CORNA (r = .68) and RNA stroke volume (r = .50). Qc was significantly less than CORNA in the subset of studies with valvular regurgitation (VHD) (N = 7). On the other hand, Qc was significantly greater than CORNA in the setting of coronary artery disease (CAD) and severe wall motion abnormalities (N = 7). These differences may be attributed to regurgitant fractions in VHD, and the influence of wall motion abnormalities on the estimation of left ventricular volume by the area-length method in CAD. These two noninvasive methods compare well at rest and exercise in clinical subjects and may provide complementary information in certain cardiopulmonary diseases.

Acetylene↗
PubMed2004

Exhaled nitric oxide in children with asthma receiving Xolair (omalizumab), a monoclonal anti-immunoglobulin E antibody.

OBJECTIVE: To evaluate the effect of a humanized monoclonal antibody to immunoglobulin E, omalizumab (Xolair, Novartis Pharmaceuticals, East Hanover, NJ; Genentech Inc, South San Francisco, CA), on airway inflammation in asthma, as indicated by the fractional concentration of exhaled nitric oxide (FE(NO)), a noninvasive marker of airway inflammation. Xolair was approved recently by the US Food and Drug Administration for moderate-to-severe allergic asthma in adolescents and adults. STUDY DESIGN: As an addendum at 2 sites to a randomized, multicenter double-blind, placebo-controlled trial, FE(NO) was assessed in children with allergic asthma over 1 year. There were 3 consecutive study periods: 1) stable dosing of inhaled beclomethasone dipropionate (BDP) when the dose was optimized (period of 16 weeks); 2) inhaled steroid-reduction phase (period of 12 weeks), during which BDP was tapered if subjects remained stable; and 3) open-label extension phase, during which subjects receiving placebo were switched to active omalizumab (period of 24 weeks). The primary outcome was area under the FE(NO) versus time curve (AUC) for adjusted FE(NO), defined as the ratio of FE(NO) at each time point compared with the value at baseline. RESULTS: Twenty-nine subjects participated and were randomized to omalizumab (n = 18) and placebo (n = 11) treatment groups in a 2:1 ratio dictated by the main study. There was a significant difference for age, resulting in a difference in absolute forced expiratory volume in 1 second but no difference in asthma severity based on the forced expiratory volume in 1 second percentage predicted. Baseline BDP dose was comparable between groups, as were baseline values of mean FE(NO) (active: 38.6 +/- 25.6 ppb; placebo: 52.7 +/- 52.9 ppb). The degree of BDP dose reduction during the steroid-reduction and open-label phases was equivalent between the omalizumab and placebo-treated groups; subjects in the omalizumab- and placebo-treated groups had reduced their BDP dose by an average of 51% and 60%, respectively, at the end of the steroid-reduction phase and by 68% and 94%, respectively, by the end of the open-label period. In the active and placebo groups, 44% and 27% and 75% and 73% of subjects had stopped use of inhaled corticosteroids at the end of the steroid-reduction and open-label phases, respectively. There was no significant difference between the active and placebo groups during the steroid-stable phase for AUC of adjusted nitric oxide (1.31 +/- 1.511 vs 1.45 +/- 0.736). However, during the steroid-reduction phase, the variability of adjusted FE(NO) in the placebo-treated group was greater than that of the omalizumab-treated group at most visits, with a significant difference between groups for AUC of adjusted nitric oxide (0.88 +/- 0.69 vs 1.65 +/- 1.06). FE(NO) fell from 82.1 +/- 55.6 ppm at the end of the steroid-reduction phase to 33.3 +/- 21.6 ppb at the end of the open-label period in the placebo group who were placed on active omalizumab. This decrease occurred while the mean dose of BDP remained very low. Analysis of FE(NO) over 52 weeks of omalizumab treatment in the active group demonstrated that there was a significant reduction from baseline to the end of the open-label period (41.9 +/- 29.0 to 18.0 +/- 21.8 ppb) despite a high degree of steroid reduction. CONCLUSION: In this preliminary study based on FE(NO), a noninvasive marker of airway inflammation, treatment with omalizumab may inhibit airway inflammation during steroid reduction in children with allergic asthma. The degree of inhibition of FE(NO) was similar to that seen for inhaled corticosteroids alone, suggesting an antiinflammatory action for this novel therapeutic agent in asthma. This is in keeping with recent evidence that omalizumab inhibits eosinophilic inflammation in induced sputum and endobronchial tissue.

Anti-Asthmatic Agents↗
PubMed2002

Exhaled nitric oxide collected with two different mouthpieces: a study in asthmatic patients.

Techniques for collecting exhaled nitric oxide (ENO) recommend the use of antibacterial filters of 0.3 m. The aim of the present study was to compare the measurements of ENO obtained with two different filtering devices. Air samples from 17 asthmatic and 17 non-asthmatic subjects were collected by a recommended off-line technique using two different mouthpieces: 1) the Sievers disposable tool (A) under a breathing pressure of 18 cmH2O, and 2) a mouthpiece containing a HEPA filter (B) under a breathing pressure of 12 cmH2O. The nitric oxide samples were collected into an impermeable reservoir bag. Values for ENO were compared using two-way repeated measures ANOVA followed by the Tukey test. Agreement was assessed by Bland-Altman analysis. ENO values obtained with mouthpieces A and B were comparable for asthmatic (mean +/- SEM, 42.9 +/- 6.9 vs 43.3 +/- 6.6 ppb) and non-asthmatic (13.3 +/- 1.3 vs 13.7 +/- 1.1 ppb) subjects. There was a significant difference in ENO between asthmatics and non-asthmatics using either mouthpiece A (P<0.001) or B (P<0.001). There was a positive correlation between mouthpiece A and mouthpiece B for both groups. The Bland-Altman limits of agreement were considered to be acceptable. Mouthpiece B was less expensive than A, and these data show that it can be used without compromising the result. Our data confirm reports of higher ENO values in the presence of airway inflammation.

Analysis of Variance↗
PubMed1983

Nutritional aspect of methionine isomers studied by pulmonary exhalation of dimethyl sulfide and urinary excretion of alpha-keto-gamma-methiolbutyrate in humans.

With the view of evaluating the relative utilization of methionine isomers, the pulmonary exhalation of dimethyl sulfide and methyl mercaptan and the urinary excretion of alpha-keto-gamma-methiolbutyrate were studied in normal healthy subjects following oral or intravenous administration of L- or D-isomer of methionine. Dimethyl sulfide concentration in the expired alveolar gas (mean +/- SD) before methionine loading was 2.1 +/- 1.4 ng/dl (N = 23). Maximum concentrations of dimethyl sulfide in oral methionine loading tests were: 56.0 +/- 24.9 ng/dl (D-2g) (n = 4), 66.0 +/- 42.1 (D-1g) (N = 6) and 4.6 +/- 2.6 (L-2g) (N = 4); and in intravenous loading tests: 60.0 +/- 19.9 (D-Ig) (N = 4) and 4.2 +/- 2.1 (L-2g) (N = 3), respectively. The changes in methyl mercaptan in the expired alveolar gas were small and were disproportional to the changes in dimethyl sulfide following administration of both isomers. Preloading concentration of alpha-keto-gamma-methiolbutyrate in urine was 0.15 +/- 0.10 microgram/mg Creatinine (mean +/- SD) (N = 5). Postloading values during the initial two hours were 578 and 156 micrograms/mg Creatinine following 3g of D- and 0.20 and 29.7 micrograms/mg Creatinine following 3g of L-methionine ingestion. In view of the results obtained, significant amounts of D-methionine seem to be metabolized through the transaminative pathway of methionine metabolism.

Adult↗