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The current single exhalation method of measuring exhaled nitric oxide is affected by airway calibre.

The authors have observed that some patients with acute exacerbations of asthma do not have substantially higher levels of exhaled nitric oxide (NO). The study examined whether this could be explained by the effect of airway calibre on exhaled NO. Exhaled NO, height and forced expiratory volume in one second (FEV1) were measured in 12 steroid-naive asthmatics and 17 normal subjects. For comparison, another group of patients with airways disease (34 cystic fibrosis patients) were also studied. In 20 asthmatics (on various doses of inhaled steroids, 0-3,200 microg x day-1), exhaled NO was measured before and after histamine challenge (immediately after reaching the provocative concentration causing a 20% fall in FEV1) and in 12 of these patients, also after nebulized salbutamol to restore FEV1 to baseline. Studies were also conducted to examine possible confounding effects of repeated spirometry (as would occur in histamine challenge) and nebulized salbutamol alone in exhaled NO levels. Exhaled NO was measured using a single exhalation method with a chemiluminescence analyser at a constant flow rate and mouth pressure. There was a significant correlation between FEV1 and exhaled NO in steroid naive asthmatics (r=0.9, p<0.001) and cystic fibrosis patients (r=-0.48, p<0.05) but not in normal subjects (r=-0.13, p=0.61). Exhaled NO decreased significantly after histamine challenge and returned to baseline after bronchodilation by nebulized salbutamol (mean+/-SEM: 23.6+/-3.6 parts per billion (ppb) (prehistamine), 18.2+/-2.7 ppb (posthistamine) and 23.6+/-3.8 ppb (postsalbutamol) p=0.001). Repeated spirometry and nebulized salbutamol did not affect exhaled NO measurements significantly. Exhaled nitric oxide levels appear to be lower in circumstances of smaller airway diameter. Hence, within a subject nitric oxide levels may be artefactually decreased during bronchoconstriction. This may be caused by increased airflow velocity in constricted airways when the exhalation rate is kept constant.

Adult↗

Exhalation flow and pressure-controlled reservoir collection of exhaled nitric oxide for remote and delayed analysis.

BACKGROUND: Expiratory flow rate, soft palate closure, and dead space air may influence exhaled levels of nitric oxide (NO). These factors have not been evaluated in the reservoir collection of NO. METHODS: Exhaled NO was collected into a reservoir during a single flow and pressure controlled exhalation. RESULTS: NO collected in a reservoir containing silica gel was stable for 24 hours. Nasally delivered 4.8% argon measured by mass spectrometry did not contaminate exhaled argon levels (0.1 (0.02)%) in five volunteers during exhalation against a resistance (10 (0.5) cmH2O), hence proving an effective soft palate closure. Exhaled NO in the reservoir was 11 (0.2) ppb, 8.6 (0.1) ppb, 7.1 (0.6) ppb, and 6.6 (0.4) ppb in five normal subjects and 48.3 (18) ppb, 20.3 (12) ppb, 16.9 (0.3) ppb and 10.1 (0.4) ppb in 10 asthmatic subjects at four studied expiratory flows (5-6, 7-8, 10-11, and 12-13 l/min, respectively), with NO levels equal to direct measurement (7.3 (0.5) ppb and 17.4 (0.5) ppb for normal and asthmatic subjects respectively, p < 0.05) at the flow rate 10-11 l/min. Elimination of dead space proved necessary to provide NO levels comparable to the direct measurement. Exhaled NO collected into the reservoir without dead space during flow controlled exhalation against mild resistance provided close agreement (mean (SD) difference -0.21 (0.68), coefficient of variation 4.58%) with direct measurement in 74 patients (NO range 1-69 ppb). CONCLUSIONS: Flow and pressure controlled collection of exhaled NO into a reservoir with silica gel provides values identical to the direct measurement and may be used to monitor asthma at home and where analysers are not on site.

Adult↗

Evaluation of exhaled nitric oxide in schoolchildren at different exhalation flow rates.

Nitric oxide (NO) in exhaled air is believed to reflect allergic inflammation in the airways. Measured levels of exhaled NO vary with the exhaled flow rate, which therefore must be standardized. The aim of this study was to estimate the optimal exhalation flow rate when measuring NO in exhaled air. We studied 15 asthmatic children (8-18 y) with elevated NO levels and 15 age-matched controls and focused on how the quality of the NO curve profile, the discriminatory power, and the reproducibility were influenced by the exhalation flow rate. We used an on-line system for NO measurements at six different exhalation flow rates in the interval of 11-382 mL/s. The fraction of exhaled nitric oxide (FENO) was highly flow-dependent as was expected. Intermediate flow rates yielded a flat and stable NO plateau and were considerably easier to interpret than those obtained at the highest and lowest flow rates. The ratio of FENO between asthmatics and controls was lower at higher flow rates and a considerable overlap in NO values was demonstrated at all flow rates except 50 mL/s. The reproducibility was much lower at more extreme flow rates and was best at 50 mL/s. We conclude that a target exhalation flow rate of approximately 50 mL/s is to be preferred using the single-breath method for on-line NO measurements in schoolchildren.

Adolescent↗

Nasal contribution to exhaled nitric oxide during exhalation against resistance or during breath holding.

BACKGROUND: The concentration of nitric oxide (NO) is increased in the exhaled air of patients with inflammation of the airways, suggesting that this may be a useful measurement to monitor inflammation in diseases such as asthma. However, there have been concerns that exhaled NO may be contaminated by the high concentrations of NO derived from the upper airways, and that this may account for differences in reported values of exhaled NO using different techniques. A study was performed, with argon as a tracer, to determine the extent of nasal contamination of exhaled NO using different expiratory manoeuvres. METHODS: Exhaled and nasal NO were measured by a chemiluminescence analyser. Argon (4.8%) was delivered continuously to the nose. Gas was sampled from the posterior oropharynx and argon and carbon dioxide were measured by mass spectrometry at the same time as NO. RESULTS: During a single expiration against a low resistance and during breath holding there was no evidence for nasal contamination, whereas during exhalation without resistance argon concentration in the oropharynx was increased from 0.91% (95% CI 0.84% to 0.98%) in ambient air to 1.28% (0.9% to 2.24%, p < 0.0001) during a single breath or 2.37% (2.29% to 2.51%, p < 0.0001) during tidal breathing. CONCLUSIONS: Collection of exhaled NO in a reservoir during tidal breathing is likely to be contaminated by NO derived from the nose and this may underestimate any increases in NO derived from the lower respiratory tract in inflammatory diseases. However, with slow expiration against a resistance and created back pressure to close the soft palate, there is no contamination of exhaled air which then reflects concentrations of NO in the lower airways.

Adult↗

Challenge from methacholine, natural rubber latex, or 4,4-diphenylmethane diisocyanate in workers with suspected sensitization affects exhaled nitric oxide [change in exhaled NO levels after allergen challenges].

OBJECTIVE: Nitric oxide (NO) levels in the exhaled air of asthmatic patients have been shown to be increased. This observation has also been reported in workers who are allergic to laboratory animals. To determine if a challenge test with natural rubber latex (NRL) or 4,4'-diphenylmethane diisocyanate (MDI) would also produce an increase of NO exhalation in sensitized patients, we carried out this study. METHODS: Nine subjects with suspected occupational asthma were exposed to MDI, and 18 took part in a challenge test with gloves powdered with NRL. Nineteen subjects underwent a challenge test with methacholine (MCh). Exhaled NO was measured by a modified chemiluminescence analyzer according to the European Respiratory Society guidelines. RESULTS: We found that there was a decrease in exhaled NO concentrations 16-18 h after MCh challenge testing and subsequent bronchodilation with salbutamol, in three subjects. Three of nine participants had a significant immediate bronchial obstruction after exposure to MDI, of those three, two had MDI-specific IgE antibodies. After 22 h, their levels of exhaled NO had increased > 10 parts per billion (ppb). Eight of the 18 subjects participating in the NRL challenge test displayed an NO concentration increase of at least 10 ppb after 22 h (seven had NRL-specific IgE antibodies). A significant decrease in the one-second forced expiratory volume (FEV1) was documented in four of those eight participants after NRL challenge. CONCLUSIONS: There was no clear relationship between bronchial response, substance-specific IgE antibodies and an increase in exhaled NO levels. However, there was a tendency for subjects with substance-specific IgE antibodies and bronchial reaction to develop an increase in exhaled NO concentration. Further studies are needed to determine if analysis of NO from the lower respiratory tract can become a useful non-invasive tool for detecting lower airway inflammatory response even before clinical symptoms occur.

Adolescent↗

Relationship between exhaled air temperature and exhaled nitric oxide in childhood asthma.

Airway inflammation is a characteristic of asthma. Exhaled nitric oxide (eNO) has been demonstrated to be related to actual levels of airway inflammation in asthmatic patients. The purpose of this study was to investigate whether the temperature of exhaled air is related to eNO levels. Temperature of exhaled air and eNO were measured in 52 asthmatic children with a cross-sectional design. A significant relationship was demonstrated between eNO and temperature of peak and plateau exhaled air temperature. The relationship between both the peak and the plateau values and eNO was more evident when it was corrected for environmental temperature. These results suggest a relationship between exhaled nitric oxide and the temperature of exhaled air in asthmatic patients not treated with systemic steroids.

Adolescent↗

Exhaled monoxides as a pulmonary function test: use of exhaled nitric oxide and carbon monoxide.

Although there has been tremendous improvement in the technologic ability to measure exhaled gases and monitor biologic processes in the lung, it has not yet found a clinical role outside the research laboratory. Common themes seem to be significant overlap in the amount of exhaled gases in clinically distinct populations, confounding variables such as infection, smoking, and environmental exposure, and lack of consistent change with disease management. If these tests are ever to be used by the general pulmonologist, consistent links between the measurements and the response to disease modification will need to be demonstrated at the very least and, ideally, the clinician would like to see improved outcomes when these noninvasive tests are employed regularly.

Breath Tests↗

Comparison of exhaled and nasal nitric oxide and exhaled carbon monoxide levels in bronchiectatic patients with and without primary ciliary dyskinesia.

BACKGROUND: Primary ciliary dyskinesia (PCD) is associated with chronic airway inflammation resulting in bronchiectasis. METHODS: The levels of exhaled nitric oxide (eNO), carbon monoxide (eCO) and nasal NO (nNO) from bronchiectatic patients with PCD (n=14) were compared with those from patients with non-PCD bronchiectasis without (n=31) and with cystic fibrosis (CF) (n=20) and from normal subjects (n=37) to assess the clinical usefulness of these measurements in discriminating between PCD and other causes of bronchiectasis. RESULTS: Exhaled NO levels were lower in patients with PCD than in patients with non-PCD non-CF bronchiectasis or healthy subjects (median (range) 2.1 (1.3-3.5) ppb v 8.7 (4.5-26.0) ppb, p<0.001; 6.7 (2.6-11.9) ppb, p<0.001, respectively) but not lower than bronchiectatic patients with CF (3.0 (1.5-7.5) ppb, p>0.05). Nasal levels of nNO were significantly lower in PCD patients than in any other subjects (PCD: 54.5 (5.0-269) ppb, non-PCD bronchiectasis without CF: 680 (310-1000) ppb, non-PCD bronchiectasis with CF: 343 (30-997) ppb, control: 663 (322-1343) ppb). In contrast, eCO levels were higher in all patient groups than in control subjects (PCD: 4.5 (3.0-24.0) ppm, p<0.01, other bronchiectasis without CF: 5.0 (3.0-15.0) ppm, p<0.001; CF: 5.3 (2.0-23.0) ppm, p<0.001 v 3.0 (0.5-5.0) ppm). Low values in both eNO and nNO readings (<2.4 ppb and <187 ppb, respectively) identified PCD patients from other bronchiectatic patients with a specificity of 98% and a positive predictive value of 92%. CONCLUSION: The simultaneous measurement of eNO and nNO is a useful screening tool for PCD.

Adult↗

Effects of expiratory pressure on nitric oxide in exhaled breath. Is exhaled nitric oxide really unaffected by pressure?

The measurements of exhaled nitric oxide (ENO) concentrations in several previous reports have been quite disparate but the cause of this variability is unclear. In the present study, we have attempted to elucidate the effects of expiratory pressure upon ENO values by taking measurements at pressures ranging from 2 to 10 cmH2O in control subjects and in both smokers and asthmatics. Differences in ENO concentrations (delta pNO) were then estimated and the concentration levels were found to increase with elevated expiratory pressure levels in both the control volunteers and in the asthmatics (under 2 and 3 L/min flow rates). These results indicate that changes in expiratory pressure indeed affect ENO concentrations. The measurement of ENO concentrations in human patients must therefore be undertaken using standard procedures that must incorporate expiratory pressure levels in order to properly interpret ENO values.

Adolescent↗

Corticosteroids decrease exhaled nitric oxide in children with acute asthma.

OBJECTIVES: Nitric oxide (NO) produced in human airways seems to have both homeostatic and proinflammatory actions in the respiratory system. NO production has been shown to be higher in the exhaled air of asthmatic adults than in normal subjects. The aim of this study was to evaluate exhaled NO production during asthma exacerbation in children and the effect of a rescue course of oral steroid therapy. STUDY DESIGN: We measured NO in the exhaled air of 16 children (8 girls and 8 boys, aged 6 to 13 years) with an acute asthmatic episode before and after 5 days of therapy with prednisone, and in 16 healthy children. To measure NO, children inhaled NO-free air and, breathing at tidal volume, exhaled in a circuit from which a chemiluminescence analyzer sampled continuously. To assess the effect of acute changes in bronchial caliber on exhaled NO levels, we measured NO before and after a positive bronchodilation test result with albuterol in seven children with asthma whose disease was stable. RESULTS: In the group with acute asthma (forced expiratory volume in 1 second 62% +/- 4.4% predicted, mean +/- SEM), NO levels were significantly higher (31.3 +/- 4.2 parts per billion [ppb]) than in healthy children (5.4 +/- 0.4 ppb, p < 0.001). Administration of prednisone (1 mg/kg per day orally) for 5 days resulted in a mean decrease of 46% +/- 4% in exhaled NO concentrations (16.5 +/- 2.3 ppb, p < 0.001) compared with baseline, accompanied by a significant improvement in lung function (forced expiratory volume in 1 second 90.7% +/- 4.3% predicted). However, in patients with asthma exhaled NO levels remained significantly higher than in control children (p < 0.001) after steroid treatment. When exhaled NO was measured before and after a positive result after bronchodilator reversibility testing, we found no difference in exhaled NO levels (24 +/- 3.8 ppb vs 23.8 +/- 3 ppb; difference not significant). This demonstrates that inhaled albuterol and acute changes in bronchial caliber do not affect exhaled NO measurement. CONCLUSIONS: These data show that children with asthma exacerbation have high levels of exhaled NO that rapidly decrease with oral steroid therapy. We suggest that measurement of exhaled NO may represent a noninvasive method of monitoring airway inflammation in children with asthma.

Acute Disease↗

Characterization of exhaled nitric oxide: introducing a new reproducible method for nasal nitric oxide measurements.

Nitric oxide (NO) is present in the human nasal airways and has been suggested to originate primarily from the paranasal sinuses. The aim of this study was to establish a new and reproducible method for measurement of nasal NO. Through repeated single-breath measurements the intra- and inter-individual variations of NO levels in nasally (into a tightly fitting mask covering the nose) and orally exhaled air were determined in healthy humans. Variations due to the methods used were investigated. The contribution of oral NO to the nasal exhalations by introducing a mouthwash procedure was also studied. This study shows distinct individual values of NO in nasally and orally exhaled air of healthy humans. Some diurnal variability was also found with a rise in NO in nasally and orally exhaled air over the day, but no, or little, day-to-day variability when comparing the results from separate mornings. There was no correlation between NO levels in nasally and orally exhaled air, whereas there was a strong correlation between NO levels in air exhaled through the left and right nostril. The levels of NO in air exhaled at 0.17 L x s(-1) through either nostril separately were higher than in air exhaled at the same flow rate through both nostrils simultaneously. After the introduction of a mouthwash procedure the level of NO in orally, but not nasally exhaled air was reduced. To conclude the method using nasal exhalation into a nose mask is highly reproducible. It is also suggested that subtracting the level of NO in orally exhaled air, after mouthwash, from that in nasally exhaled air, would adequately reflect nasal NO levels.

Adult↗

Increased carbon monoxide in exhaled air of patients with seasonal allergic rhinitis.

BACKGROUND: Carbon monoxide (CO) can be detected in exhaled air and is increased in asthmatic patients. However, it is uncertain whether exhaled CO is increased in patients with allergic rhinitis. OBJECTIVE AND METHODS: To study whether exhaled CO is increased in patients with allergic rhinitis, exhaled CO concentrations were measured on a CO monitor by vital capacity manoeuvre in 86 patients with seasonal allergic rhinitis during and out of the cedar pollen season. RESULTS: During the season, exhaled CO concentrations were 3. 6 +/- 0.3 p.p.m. and decreased to 1.2 +/- 0.1 p.p.m. out of the season. The values of exhaled CO out of the season were similar to those in age-matched non-smoking healthy control subjects (1.2 +/- 0. 1 p.p.m.). Exhaled CO concentrations were significantly higher in patients with symptoms than in those without symptoms (P < 0.01). Exhaled CO concentrations in patients did not differ significantly among oral and nasal exhalation, and oral exhalation with an expiratory resistance (P > 0.20). CONCLUSION: These findings suggest that allergic rhinitis increases the concentration of CO in exhaled air and increases in exhaled CO may be derived from lower airways.

Adult↗

A small dose of ethanol increases the exhalation of mercury in low-level-exposed humans.

Inorganic mercury is mainly eliminated by urinary and fecal excretion, but it is also eliminated by exhalation and sweat. There are only a few reports on exhalation of mercury in humans. In volunteers with short-term mercury exposure, an increased exhalation of mercury was found after alcohol intake. The aim of this study was to determine mercury in end-exhaled air and the influence of ethanol on mercury exhalation in subjects with long-term mercury exposure from diet, amalgam fillings, or the work environment. Fourteen subjects, with different grades of mercury exposure, were given 0.2 g ethanol/kg body weight. Measurements of mercury in end-exhaled air were performed before and after alcohol intake. Mercury in end-exhaled air could be detected in all subjects. In 10 individuals without amalgam fillings the mercury concentration was 3 to 12 pg/L. A marked increase, in general about fivefold, in mercury concentrations in end-exhaled air was seen in all subjects 30 min after intake of alcohol, regardless of the level of mercury exposure. Higher ethanol doses resulted in higher mercury levels in end-exhaled air and longer time periods before a return to background levels. An increase was seen even after an ethanol dose of only 0.1 g ethanol/kg body weight (about 0.08 L wine). The decrease in exhaled mercury at higher alcohol doses followed approximately zero-order kinetics and probably reflects the elimination of ethanol in tissues. In conclusion, low levels of mercury can be detected in end-exhaled air also in individuals without amalgam fillings. About a fivefold increase was seen 30 min after alcohol intake, and the relative increase seemed to be independent of the body burden of mercury. Exhalation of mercury represents only a small percentage of the total elimination of mercury.

Adult↗

Basal and nitroglycerin-induced exhaled nitric oxide before and after cardiac surgery with cardiopulmonary bypass.

BACKGROUND: Exhaled nitric oxide (NO) may reflect NO production and consumption but the pulmonary origin of NO in exhaled gas is not clear. There are also conflicting data on exhaled NO after cardiopulmonary bypass (CPB). Because intravenous nitrovasodilators increase exhaled NO by conversion to NO in the lung, we measured basal and nitroglycerin (GTN)-induced exhaled NO in patients having low-risk coronary artery bypass graft (CABG) operations using routine CPB. We reasoned that GTN-induced exhaled NO would be a primarily vascular mechanism, which would contrast with the airway epithelial origin of basal exhaled NO, and that they might be differentially influenced by CPB. METHODS: Breath-to-breath concentrations of gas phase NO were measured in 12 CABG patients before and 1, 3 and 6 h after CPB. After the baseline measurements, three increasing doses of 1, 2 and 3 micro g kg(-1) intravenous GTN were given by a central venous catheter and exhaled NO and haemodynamic responses were recorded. RESULTS: Intravenous administration of 1, 2 and 3 micro g kg(-1) doses of GTN produced a dose-dependent increase in exhaled NO and a reduction in systemic blood pressure. Baseline exhaled NO remained unchanged. Exhaled NO but not blood pressure responses were reduced 1 and 3 h after CPB. CONCLUSIONS: The capacity of the lungs to increase exhaled NO in response to intravenous GTN is reduced after CPB, suggesting microvascular injury and/or atelectasis after routine open-heart surgery.

Aged↗

Exhaled nitric oxide production by nitric oxide synthase-deficient mice.

Nitric oxide (NO) is produced in the nasal cavities, airways, and lungs and is exhaled by normal animals and humans. Although increased exhaled NO concentrations in airway inflammation have been associated with increased airway expression of nitric oxide synthase 2 (NOS 2), it is uncertain which NOS isoform is responsible for baseline levels of exhaled NO. We therefore studied wild-type mice and mice with a congenital deficiency of NOS 1, NOS 2, or NOS 3. By studying a closed chamber in which the exhaled gas of a group of mice was collected, gaseous NO production rates were measured. Wild-type mice exhaled 362 +/- 35 x 10(-15) mol g(-1) min(-1) NO (mean +/- SE, n = 16 groups of five mice), NOS 1-deficient mice exhaled 592 +/- 74 x 10(-15) mol g(-1) min(-1) NO (n = 15 groups, p < 0.05 versus wild-type and NOS 2-deficient mice), NOS 2-deficient mice 330 +/- 74 x 10(-15) mol g(-1) min(-1) NO (n = 14 groups) and NOS 3-deficient mice 766 +/- 101 x 10(-15) mol g(-1) min(-1) NO (n = 16 groups, p < 0.001 versus wild-type and NOS 2-deficient mice). Pharmacological NOS inhibition with L-NAME decreased (p < 0.05) the exhaled NO production rate of wild-type and NOS 3-deficient but not of NOS 2-deficient mice. L-Arginine administration increased exhaled NO production rate in all but NOS 2-deficient mice. Absence of NOS 1 or 3 is associated with increased murine exhaled NO production rates. Since NOS 2-deficient mice were the only genotype to lack substrate- and inhibitor-regulated changes of NO exhalation, we suggest that NOS 2 is an important isoform contributing to exhaled NO exhalation in healthy mice.

Animals↗

Effect of short- and long-acting inhaled beta2-agonists on exhaled nitric oxide in asthmatic patients.

Increased concentrations of exhaled nitric oxide (NO) occur in patients with asthma, and exhaled NO may be useful for assessing the effect of drug therapy on airway inflammation. Beta2-agonists have been proposed to have both proinflammatory and anti-inflammatory effects. We therefore assessed exhaled NO after beta2-agonists in asthmatic patients. Two randomized, double-blind, placebo-controlled studies were conducted. Firstly, exhaled NO was measured in 18 asthmatics (9 taking inhaled glucocorticosteroids (GCS)) before and after nebulized salbutamol (5 mg), or identical placebo (0.9% saline). Exhaled NO and forced expiratory volume in one second (FEV1) were measured at 15 min intervals for 1 h (Study 1). Secondly, the effect of 1 week of treatment with the long-acting beta2-agonist, salmeterol (50 microg b.i.d.), added to either budesonide (800 microg b.i.d.) or placebo, was studied in eight mild asthmatic subjects (Study 2). Exhaled NO was measured by a chemiluminescence analyser, adapted for on-line recording. In Study 1, exhaled NO showed no significant change at any time-point in patients not taking inhaled GCS. In asthmatics on inhaled GCS, exhaled NO increased compared to placebo at 15 and 30 min, but this did not reach statistical significance. In Study 2, treatment with salmeterol increased FEV1, but exhaled NO levels were not significantly changed, either after budesonide treatment (143+/-35 to 179+/-67 ppb), or after placebo (201+/-68 to 211+/-65 ppb). Our results confirm that single high dose salbutamol does not increase exhaled nitric oxide in asthmatics not taking inhaled glucocorticosteroids. Salbutamol may increase exhaled nitric oxide in asthmatics taking inhaled glucocorticosteroids. However, regular use of salmeterol resulted in no change in exhaled nitric oxide, either used alone or in combination with inhaled glucocorticosteroids.

Administration, Inhalation↗

Increased exhaled nitric oxide in chronic bronchitis: comparison with asthma and COPD.

STUDY OBJECTIVES: To test the hypothesis that exhaled nitric oxide (NO) is increased in patients with chronic bronchitis, and to compare the results with exhaled NO in patients with asthma and COPD. STUDY DESIGN: Cross-sectional survey. SETTING AND PATIENTS: Veterans Administration pulmonary function laboratory. Patients (n = 179) were recruited from 234 consecutive patients. Two nonsmoking control groups of similar age, with normal spirometry measurements and no lung disease, were used (18 patient control subjects and 20 volunteers). MEASUREMENTS: Participants completed questionnaires and spirometry testing. Exhaled NO was measured by chemiluminescence using a single-breath exhalation technique. RESULTS: Current smoking status was associated with reduced levels of exhaled NO (smokers, 9. 2 +/- 0.9 parts per billion [ppb]; never and ex-smokers, 14.3 +/- 0. 6 ppb; p < 0.0001). Current smokers (n = 57) were excluded from further analysis. Among nonsmokers, the levels of exhaled NO were significantly higher in patients with chronic bronchitis (17.0 +/- 1. 1 ppb; p = 0.035) and asthma (16.4 +/- 1.3 ppb; p = 0.05) but not in those with COPD (14.7 +/- 1.0 ppb; p = 0.17) when compared with either control group (patient control subjects, 11.1 +/- 1.6 ppb; outside control subjects, 11.5 +/- 1.5 ppb). The highest mean exhaled NO concentration occurred in patients with both chronic bronchitis and asthma (20.2 +/- 1.6 ppb; p = 0.005 vs control subjects). CONCLUSIONS: Exhaled NO is increased in patients with chronic bronchitis. The increase of exhaled NO in patients with chronic bronchitis was similar to that seen in patients with asthma. The highest mean exhaled NO occurred in patients with both chronic bronchitis and asthma. Exhaled NO was not increased in patients with COPD. Although chronic bronchitis and asthma have distinct histopathologic features, increased exhaled NO in patients with both diseases suggests common features of inflammation.

Asthma↗