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Biomarkers of some pulmonary diseases in exhaled breath.

Analysis of various biomarkers in exhaled breath allows completely non-invasive monitoring of inflammation and oxidative stress in the respiratory tract in inflammatory lung diseases, including asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), bronchiectasis and interstitial lung diseases. The technique is simple to perform, may be repeated frequently, and can be applied to children, including neonates, and patients with severe disease in whom more invasive procedures are not possible. Several volatile chemicals can be measured in the breath (nitric oxide, carbon monoxide, ammonia), and many non-volatile molecules (mediators, oxidation and nitration products, proteins) may be measured in exhaled breath condensate. Exhaled breath analysis may be used to quantify inflammation and oxidative stress in the respiratory tract, in differential diagnosis of airway disease and in the monitoring of therapy. Most progress has been made with exhaled nitric oxide (NO), which is increased in atopic asthma, is correlated with other inflammatory indices and is reduced by treatment with corticosteroids and antileukotrienes, but not (beta 2-agonists. In contrast, exhaled NO is normal in COPD, reduced in CF and diagnostically low in primary ciliary dyskinesia. Exhaled carbon monoxide (CO) is increased in asthma, COPD and CF. Increased concentrations of 8-isoprostane, hydrogen peroxide, nitrite and 3-nitrotyrosine are found in exhaled breath condensate in inflammatory lung diseases. Furthermore, increased levels of lipid mediators are found in these diseases, with a differential pattern depending on the nature of the disease process. In the future it is likely that smaller and more sensitive analyzers will extend the discriminatory value of exhaled breath analysis and that these techniques may be available to diagnose and monitor respiratory diseases in the general practice and home setting.

Ammonia↗

Performance when breathing through different respirator inhalation and exhalation resistances during hard work.

Respirator inspiratory and expiratory breathing resistances impact ventilation and performance when studied independently. However, it is less clear as to how various combinations of inhalation and exhalation resistance affect user performance. The present study investigated the performance of 11 individuals during constant load, demanding work to exhaustion while wearing respirators with eight different combinations of inhalation and exhalation resistance. Exercise performance time, performance rating, minute volume, and peak inspiratory and expiratory airflow were recorded at the end of each test trial, and independent correlations with inhalation resistance and exhalation resistance were assessed. The combined impacts of respirator inhalation and exhalation resistances were quantified as the total external work of breathing (WOB(tot)) and correlations between the test variables and WOB(tot) were also examined. Significantly linear decreases in performance were found with increased inhalation resistances independent of exhalation resistance (R(2) = 0.99; p < 0.001) and with increased WOB(tot) (R(2) = 0.92; p < 0.001). Performance also decreased with increased exhalation resistance but no significant relationships were found. Minute volume decreased linearly with increased inhalation resistance independent of exhalation resistance (R(2) = 0.99; p < 0.001), but the linear decrease observed between minute volume and WOB(tot) was weak (R(2) = 0.36; p < 0.05). These findings suggest that WOB(tot) serves as a reliable estimate of the combined impacts of respirator inhalation and exhalation resistances on user performance during hard work, but that inhalation resistance alone serves as a better predictor of ventilation during respirator wear.

Adolescent↗

Influence of thoracic radiotherapy on exhaled nitric oxide levels in patients with lung cancer.

BACKGROUND: To determine the physiological role of exhaled nitric oxide (NO) in patients with lung cancer. METHODS: We investigated changes in exhaled NO levels in 29 patients undergoing thoracic radiation therapy with or without chemotherapy. The exhaled NO level was assessed using a chemiluminescence analyzer. RESULTS: The level of exhaled NO was higher in patients with lung cancer before treatment than in controls. With radiotherapy, the exhaled NO level decreased for patients undergoing 40 Gy irradiation and post-radiotherapy. However, five patients showed elevated levels of exhaled NO three times or more than that before radiotherapy. Three of these patients showed signs of radiation pneumonitis. However, none of the other patients showed signs of radiation pneumonitis (p = 0.002). CONCLUSION: Radiation therapy can lower exhaled levels of NO and the levels of exhaled NO may be a useful index for the early prediction of radiation pneumonitis.

Aged↗

The determination of radon exhalation rates.

The exhalation of radon from porous materials like mining wastes and building materials can be determined by studying the growth of radon activity in vessels containing samples of the materials. It is demonstrated that the initial part of the activity growth curve determines the total free exhalation rate of the sample used, independently of container leakage and back diffusion. It is furthermore shown that a specific area exhalation rate adequately describes the exhalation process, when the exhalation is restricted to take place in one direction only, and when the dimension in the exhaling direction is greater than approx. 2 times the diffusion length. A determination of the free surface exhalation rate as a function of the sample thickness also yields information on the diffusion length, as well as the radon production rate per unit volume of material. In case of sample dimensions smaller than about half the diffusion length, the total exhalation rate is shown to be proportional to the mass or volume of the sample.

Diffusion↗

Determining the 222Rn exhalation rate of building materials using liquid scintillation counting.

A new method for determining the free 222Rn exhalation rate from building materials is described. The sample is enclosed in a container from which the exhaled Rn is continuously purged by nitrogen gas. After 2-3 h, when the Rn level in the container has reached a steady-state concentration, the outflowing Rn is trapped on silica gel at about -190 degrees C. About 16 h after sampling, the silica gel is analyzed by liquid scintillation counting to determine the area exhalation rate. The method described has a good repeatability and reproducibility with coefficients of variation of 7.8% and 8.3%, respectively, at 5 Bq m-2 h-1. The low limit of detection of 11 mBq 222Rn offers the opportunity to quantify the exhalation rate of almost all kinds of building materials. It was found that the air humidity strongly influences the exhalation rates of building material and, therefore, should be controlled. Two typical building materials were investigated. For gypsum, an increase in the exhalation rate with increasing water vapor pressure was found, whereas for concrete, a linear decrease with increasing water vapor pressure was observed. The 222Rn area exhalation rates of 20 Dutch building materials, including some experimental ones, were determined at 50% RH, 20 degrees C, showing a range of less than 0.02-15.8 Bq m-2 h-1. The lowest values were found for natural gypsum board, the highest for phosphogypsum blocks. Building materials containing fly ash gave area exhalation rates comparable to those of similar materials without fly ash.

Air Pollutants, Radioactive↗

Exhaled nitric oxide in the assessment of asthma.

PURPOSE: Asthma is now defined as a TH2-mediated inflammatory disease involving both large and small airways. However, assessment of airways inflammation is limited by techniques that are time consuming and possibly distressing to the patient. Exhaled nitric oxide, an easily and rapidly obtained noninvasive study, is a potential surrogate for measuring airways inflammation, but its clinical utility remains to be determined. This review examines the role of exhaled nitric oxide in assessing and directing therapy of asthmatic airways inflammation. RECENT FINDINGS: It is well established that exhaled nitric oxide is increased in patients with untreated asthma and decreases with corticosteroid treatment. Exhaled nitric oxide also generally correlates with eosinophilic inflammation in asthmatic patients. Recent studies show that this correlation is especially pronounced in atopic subjects with asthma when compared with nonatopic subgroups. Recent studies also show that exhaled nitric oxide may be useful in identifying subclinical inflammation, assessing the antiinflammatory effects of asthma medications other than inhaled or oral corticosteroids, and heralding an asthma exacerbation. A number of new studies assert the utility of exhaled nitric oxide as a diagnostic tool for asthma. SUMMARY: Exhaled nitric oxide may be a useful parameter for monitoring asthmatic inflammation, adjusting therapy, and diagnosing asthma, although prospective longitudinal trials investigating the correlation between exhaled nitric oxide and clinical outcomes are necessary to determine its utility.

Animals↗

Contribution from upper and lower airways to exhaled endogenous nitric oxide in humans.

Endogenous nitric oxide (NO) is thought to regulate many biological functions, including pulmonary circulation and bronchomotion, and it has been found in exhaled air. Our aim was to study the excretion of NO in different parts of the respiratory system. Exhaled concentrations of NO were measured by chemiluminescence in chronic tracheostomy outpatients (group 1), in patients admitted for minor abdominal surgery (group 2), and in patients with acute respiratory failure (ARF) during mechanical ventilation (group 3). In awake volunteers (group 4), 0.57 L/min gas was aspirated through the nasal cavity into the chemiluminescence device. In group 1 (tracheostomy, n = 5) we detected 16 +/- 2 (mean +/- s.e. mean) parts per billion (ppb) NO when exhaling through the mouth, and a lower (P < 0.05) value of 4.6 +/- 0.8 ppb NO when exhaling through the tracheostomy. Before anaesthesia, group 2 (n = 11) exhibited 18 +/- 2.4 ppb NO in orally exhaled gas, increasing considerably during exhalation through the nose. Upon endotracheal intubation exhaled NO concentration dropped to 1.3 +/- 0.2 ppb (P < 0.05). In group 3 (ARF, n = 7) tracheal NO concentrations were 0.8 +/- 0.2 ppb. In group 4 (volunteers, n = 6) 394 +/- 23 ppb NO was recorded in air from the nasal cavity. In both healthy subjects and patients with respiratory failure a significant NO excretion occurs in the lower airways and lungs. The upper airways, especially the nose, contribute the largest amount of NO (> 90%) to exhaled air. The physiological implications of an upper airway source of NO remain to be defined.

Adolescent↗

Dispersion of exhaled droplet nuclei in a two-bed hospital ward with three different ventilation systems.

UNLABELLED: Effective ventilation in general hospital wards is important for controlling the airborne transmission of infectious respiratory diseases. Experiments have been carried out to increase our understanding of the interaction of the breathing flows of two individuals in a full-scale experimental hospital ward with three ventilation systems, i.e. mixing, downward and displacement ventilation. Two life-size breathing thermal manikins were used to simulate a source patient and a receiving patient. The exhalation jet from a bed-lying manikin was visualized using smoke. N2O was used as tracer gas to simulate the droplet nuclei exhaled by patients; and the spatial distribution of its concentrations was measured. Our experimental results show that for both mixing and downward ventilation, the exhaled jet penetrates a short distance and is diluted quickly by ventilation air. The exhaled droplet nuclei are well mixed in the ward. Bed distance does not affect the personal exposure of the receiving patient. For displacement ventilation, the exhaled jet can penetrate a long distance. A high concentration layer of exhaled droplet nuclei because of thermal stratification locking has also been observed with displacement ventilation. This work is useful for identifying an appropriate ventilation method that can remove droplet nuclei more effectively and minimize the risk of cross-infections in a hospital ward environment. PRACTICAL IMPLICATIONS: As one of the major potential sources for infectious droplet nuclei in a hospital environment, exhalation flows of an infected patient can interact with the respiratory activities of other close individuals and with the room ventilation systems. Our latest results provide information on the penetration of exhalation jets into the ambient environment in different ventilation systems. This work is useful in identifying an appropriate and effective ventilation method for removing droplet nuclei more effectively, and thus minimizing the risk of cross-infections in hospital wards with multiple beds.

Air Movements↗

Relationship between exhaled nitric oxide and mucosal eosinophilic inflammation in mild to moderately severe asthma.

BACKGROUND: Exhaled levels of nitric oxide (NO) are raised in asthma but the relationship between exhaled NO levels and a direct measure of airway inflammation has not been investigated in asthmatic patients treated with inhaled steroids. METHODS: The relationship between exhaled NO levels, clinical measures of asthma control, and direct markers of airway inflammation were studied in patients with asthma treated with and without inhaled corticosteroids. Thirty two asthmatic patients (16 not using inhaled steroids and 16 using inhaled beclomethasone dipropionate, 400-1000 microg/day) were monitored with respect to measures of asthma control including lung function, symptom scores, medication usage, and variability of peak expiratory flow (PEF) for one month. Measurements of exhaled NO and fibreoptic bronchoscopy were performed at the end of the monitoring period. Bronchial mucosal biopsy specimens were stained with an anti-MBP antibody for quantification of eosinophils. RESULTS: There was no significant difference in lung function, symptom scores, or medication usage between the two groups, but there was a significant difference in PEF variability (8.7 (1.2)% in steroid naive patients versus 13.6 (1.9)% in steroid treated patients, p<0.05) and exhaled NO levels (9.9 (3.5) ppb in steroid naive patients versus 13.6 (2.0) ppb in steroid treated patients, p<0.05). There was no correlation between exhaled NO and mucosal eosinophils, or between NO and conventional measures of asthma control. There was a significant correlation between mucosal eosinophils and lung function (r = -0.43, p<0.05). CONCLUSIONS: Exhaled NO levels do not reflect airway mucosal eosinophilia and these markers reflect different aspects of airway inflammation. The clinical usefulness of exhaled NO needs to be determined in prospective longitudinal studies.

Adult↗

Effect of measurement conditions on measured levels of peak exhaled nitric oxide.

BACKGROUND: It is possible to measure nitric oxide (NO) levels in exhaled air. The absolute concentrations of exhaled NO obtained by separate workers in similar patient groups and normal subjects with apparently similar techniques have been very different. A study was undertaken to determine whether changes in measurement conditions alter the concentration of exhaled NO. METHOD: NO concentrations measured by a chemiluminescence analyser (Dasibi Environmental Corporation) and carbon dioxide (CO2) measured by a Morgan capnograph were analysed in single exhalations from total lung capacity in healthy volunteers (mean age 35.9 years). Ten subjects performed five exhalations at four different expiratory flow rates, at four different expiratory mouth pressures, and before and after drinking hot (n = 5) or cold (n = 5) water. Three subjects performed five exhalations on a day of high background NO (mean NO level 134 ppb) before and after a set of five exhalations made while both the subject and analysers were sampling from a low NO/NO-free reservoir system. RESULTS: The mean peak concentration of NO decreased by 35 ppb (95% CI 25.7 to 43.4) from a mean (SE) of 79.0 (15.5) ppb at an expiratory flow rate of 250 ml/min to 54.1 (10.7) ppb at 1100 ml/min. The mean peak concentration of NO did not change significantly with change in mouth pressure. The mean (SE) peak NO concentration decreased from 94.4 (20.8) ppb to 70.8 (16.5) ppb (p = 0.002, 95% CI 12.9 to 33.1) with water consumption. The mean NO concentration with machine and subject sampling from the low NO reservoir was 123.1 (19.4) ppb, an increase from results obtained before (81.9 (10.2) ppb, p = 0.001, 95% CI -19.9 to -62.7) and after (94.2 (18.3) ppb, p = 0.017, 95% CI 6.0 to 51.8) sampling with high ambient NO. CONCLUSIONS: The measurement of exhaled NO must be performed in a carefully standardised manner to enable different teams of investigators to compare results.

Adolescent↗

Elevation of exhaled ethane concentration in asthma.

Ethane is a product of lipid peroxidation as a result of oxidative stress and can be detected in the exhaled air. Oxidative stress plays a role in the pathogenesis of asthma. We measured exhaled ethane in 26 asthmatic subjects (mean age +/- SEM, 38 +/- 8 yr; 15 male, FEV(1) 60 +/- 4%) and compared it with exhaled nitric oxide (NO) measured by chemiluminescence, a noninvasive marker of oxidative stress and inflammation. Exhaled ethane was collected during a flow- and pressure-controlled exhalation into a reservoir discarding dead space air contaminated with ambient air. A sample of the expired air was analyzed by chromatography. Exhaled ethane levels were elevated in asthma patients not receiving steroid (n = 12, 2.06 +/- 0.30 ppb) compared with steroid-treated patients (n = 14, 0.79 +/- 0.10 ppb, p < 0.01) and to 14 nonsmoking control subjects (0.88 +/- 0.09 ppb, p < 0.05). In patients not receiving steroid treatment there was a positive correlation between exhaled ethane and NO (r = 0.55, p < 0.05) and air trapping assessed by the ratio of residual volume to total lung capacity (RV/ TLC) (r = 0.60, p < 0.05). In addition, untreated patients with FEV(1) < 60% predicted value had higher concentrations of ethane (2.86 +/- 0.37 ppb) compared with less obstructed patients (FEV(1) > 60%, 1.26 +/- 0.12 ppb, p < 0.05). NO concentrations were higher in patients not on steroid treatment (14.7 +/- 1.7 ppb) than in steroid-treated patients (8.6 +/- 0.5 ppb, p < 0.05). Exhaled ethane is elevated in asthma, reduced in steroid-treated patients, and correlates with NO and airway obstruction. It may be a useful noninvasive marker of oxidative stress.

Adult↗

Exhaled nitric oxide in specific challenge tests to assess occupational asthma.

Exhaled nitric oxide (NO) is a marker of eosinophilic inflammation of the airway mucosa accompanying changes in the clinical condition of asthma. Allergen exposure has been associated with delayed elevation of exhaled NO. The aim of this study was to assess the asthmatic airway inflammation with exhaled NO measurements during specific bronchial challenge tests with occupational agents. Forty patients with suspected occupational asthma were investigated. Specific bronchial challenge tests were performed with forced expiratory volume in one second or peak expiratory flow follow-up, supplemented by exhaled NO measurements before and 24 h after challenge tests. In active challenges, which induced bronchoconstriction, a significant mean increase of exhaled NO concentration was noted. In patients with a normal or slightly increased (<14.5 parts per billion (ppb)) basal NO level and a late bronchoconstriction, a significant increase in exhaled NO was seen. Patients with a high basal NO level (>14.5 ppb) and a significant bronchoconstriction did not show a significant NO elevation. Challenge tests without bronchoconstriction were not associated with a significant elevation of exhaled NO. Exhaled nitric oxide measurements can be used to indicate the development of airway inflammation accompanying late asthmatic reaction after bronchial challenge tests in patients with a normal or slightly increased basal nitric oxide concentration.

Asthma↗

Increased inflammatory markers in the exhaled breath condensate of cigarette smokers.

Cigarette smoking induces an inflammatory response in the airways that may play a key role in the pathogenesis of chronic obstructive pulmonary disease. Noninvasive markers of inflammation may, therefore, be useful in monitoring the airways of smokers as well as in the screening of subjects at high risk of developing airway obstruction. The aim of the present study was to determine whether the concentrations of the pro-inflammatory cytokine, interleukin (IL)-6, is increased in the exhaled breath condensate of smokers and whether the number of cigarettes smoked has any influence on the exhaled concentrations. The possibility that exhaled IL-6 levels are related to exhaled carbon monoxide (CO) and lung function has also been explored. Another inflammatory marker, leukotriene (LT), was also measured. Twenty-one smokers (39+/-7 yrs, 13 male) and 14 nonsmokers (45+/-6 yrs, eight male) were recruited. IL-6 and LTB4 levels in the breath condensate were measured with an immunoassay kit and exhaled CO examined by means of a modified electrochemical sensor. Higher IL-6 and exhaled CO concentrations were found in current smokers (5.6+/-1.4 pg x mL(-1) and 16.7+/-5.5 parts per million (ppm)) than in nonsmokers (2.6+/-0.2 pg x mL(-1) and 2.1+/-0.6 ppm). Elevated concentrations of LTB4 were also observed in smokers compared to nonsmokers (9.4+/-0.4 pg x mL(-1) versus 6.1+/-0.3 pg x mL(-1)). In addition, there was a correlation between IL-6 concentrations, the number of cigarettes smoked per day, exhaled CO, LTB4 and lung function. Exhaled interleukin-6 and leukotriene B4 levels may be useful noninvasive markers of airway inflammation in cigarette smokers.

Adult↗

Primarily nasal origin of exhaled nitric oxide and absence in Kartagener's syndrome.

The exact origin of nitric oxide (NO) in exhaled air is not known. We wanted to further investigate at what site exhaled NO is produced and to determine whether children with Kartagener's syndrome exhibited altered levels of exhaled NO. NO was measured by chemiluminescence technique in air sampled directly from the nose and in normally exhaled air of four children (2.5-13 years old) with Kartagener's syndrome, 20 healthy children, four healthy adults, and four conscious tracheostomized adults. NO was almost absent (98% reduced) in air sampled directly from the nose in four children with Kartagener's syndrome (4 +/- 1 parts per billion (ppb)), compared to age-matched controls (221 +/- 14 (ppb)). Tracheostomized adult subjects had considerably higher NO values in nasally (22 +/- 3 ppb) and orally (14 +/- 2 ppb) exhaled air, compared to levels in air exhaled through the tracheostomy (2 +/- 0 ppb). Treatment with intranasal corticosteroids for 14 days, or with antibiotics for 1 week, did not affect exhaled NO. These results clearly show that, basically, all NO in exhaled air of healthy subjects originates from the upper respiratory tract, with only a minor contribution from the lower airways. Furthermore, the absence of nasal NO in children with Kartagener's syndrome could be of use as a simple noninvasive diagnostic test.

Adolescent↗

Changes in exhaled carbon monoxide and nitric oxide levels following allergen challenge in patients with asthma.

Carbon monoxide is a product of haem degradation by haem oxygenase (HO), activated by inflammatory cytokines and oxidants. This study examined whether allergen challenge can increase exhaled CO levels, as a reflection of HO activation. Exhaled CO and nitric oxide, an expired gas also thought to reflect cytokine-induced airway inflammation, were measured in 15 atopic steroid-naive nonsmoking patients with asthma (13 males, aged 30+/-2 yrs) before and for up to 20 h after allergen challenge. Baseline CO (4.4+/-0.3 parts per million (ppm)) and NO (20.6+/-1.2 parts per billion (ppb)) levels were elevated in asthmatic as compared with nonsmoking normal volunteers (n = 37, 2.1+/-0.2 ppm and 7.0+/-0.1 ppb, respectively, p<0.05). In 10 patients with a dual response in the forced expiratory volume in one second (FEV1) there was a maximal increase in exhaled CO at 1 h (343+/-7.1%) and at 6 h (69+/-12%, p<0.01), followed by a maximal fall in FEV1 (28+/-9%, p<0.05) at 9 h, whereas the maximal NO increase was observed at 10 h (50.2+/-11.8%). The maximal increase in exhaled CO in single response patients (n = 5) was 30+/-2% during the early asthmatic reaction and 46.3+/-9.2% between 4 and 10 h, followed by a fall in FEV1 (9+/-3%, p>0.05) at 9 h, whereas exhaled NO was not significantly changed. In five patients exhaled CO was not attenuated by inhalation of increasing concentrations of histamine causing a 20% fall in FEV1 (PC20) or its subsequent relief by beta2-agonists. In conclusion, exhaled carbon monoxide is increased during the early and late asthmatic reactions independently of the change in airway calibre, while exhaled nitric oxide is increased only during the late reaction and follows the increase in carbon monoxide and fall in the forced expiratory volume in one second in time.

Adult↗

Prostaglandins mediate bradykinin-induced reduction of exhaled nitric oxide in asthma.

Bradykinin (BK) is a mediator of inflammation in asthma with potent bronchoconstrictor actions. Endogenous release of nitric oxide may inhibit BK-induced bronchoconstriction. This study investigated whether bradykinin inhalation could modulate exhaled NO levels in normal and asthmatic subjects, and whether the bradykinin-induced effects were mediated through the production of cyclo-oxygenase products in patients with asthma, by studying the effect of the cyclo-oxygenase inhibitor, L-acetylsalicylic acid (L-ASA). Exhaled NO concentration and forced expiratory volume in one second (FEV1) were measured by chemiluminescence following inhalation of increasing concentrations of BK. In asthmatics (n=11), BK induced a dose-dependent decrease in exhaled NO concentration from 21.3+/-1.6 to 6.+/-0.5 parts per billion (ppb) (p<0.01) at the highest concentration, associated with a significant fall in FEV1. In normal subjects (n=10), the exhaled NO concentration fell from 7.2+/-0.13 to 4.3+/-0.51 ppb (p<0.001) 15 min, after a single inhalation of BK, but without a significant change in FEV1. In asthmatic subjects, pretreatment with inhaled L-ASA (90 x mg x mL(-1), 4 mL) did not alter exhaled NO levels, but prevented a BK-induced fall in exhaled NO concentration, as indicated by a significant increase in exhaled NO levels at the provocative concentration of BK causing a 20% fall in FEV1, (5.7 +/- 0.94 ppb after placebo and 12.0 +/- 1.8 ppb after L-ASA; p<0.05). L-ASA significantly reduced bronchial responsiveness to BK 3.9-fold (p<0.01). Inhaled bradykinin induced bronchoconstriction and a reduction in exhaled nitric oxide levels in asthmatic subjects, an effect that is partly mediated by cyclo-oxygenase products.

Administration, Inhalation↗

Smoking cessation is associated with an increase in exhaled nitric oxide.

STUDY OBJECTIVES: Nitric oxide (NO), a gas produced by cells lining the respiratory tract, has been reported to be decreased in the exhaled air of cigarette smokers. We hypothesized that smoking cessation would result in an increase in exhaled NO. DESIGN: Comparison of exhaled NO measured from nonsmokers, cigarette smokers, and smokers after smoking cessation. SETTING: University outpatient smoking cessation clinic. PATIENTS OR PARTICIPANTS: Twenty-five cigarette smokers and 23 normal, nonsmokers. INTERVENTIONS: Exhaled NO was measured by three techniques: (1) a peak oral method; (2) a mean oral method; and (3) a nasal method. The smokers were given nicotine patches and instructed to return after 1 and 8 weeks. The exhaled NO determinations were repeated on each visit. MEASUREMENTS AND RESULTS: Compared with nonsmokers, smokers had decreased NO levels measured by all three methods (p<0.05, each comparison). Nineteen smokers returned after 1 week. Fourteen were successfully abstinent from cigarettes and their exhaled NO increased compared with baseline (p<0.01 for each method) but not in the five subjects who had not successfully quit smoking (p>0.05 for each method). Ten subjects returned after 8 weeks. The exhaled NO levels increased further and were not significantly different from the normal nonsmokers for the peak oral and nasal NO methods (p>0.2), but were still lower than the normal nonsmoker mean oral NO (p=0.018). CONCLUSIONS: These data demonstrate that smoking cessation is associated with an increase in exhaled NO.

Administration, Cutaneous↗

Intrathoracic and extrathoracic sources of exhaled nitric oxide in porcine endotoxemic shock.

OBJECTIVES: Nitric oxide (NO), a highly reactive species produced by the activity of NO synthases (NOS), is normally present in the exhaled air of humans and animals. Exhaled NO concentration increases significantly in humans with sepsis and animals, but neither the source nor NOS isoforms responsible for this rise in pulmonary NO production are known. The main objective of this study is to determine the sites and the mechanisms of enhanced NO production in the exhaled air of endotoxemic pigs. DESIGN: Randomized, controlled, animal study. SETTING: University-based animal research facility. SUBJECTS: Thirteen pathogen-free adult female pigs (22 to 27 kg). INTERVENTIONS: Anesthetized pigs were divided into two groups: control and lipopolysaccharides (LPS) (septic) groups. In both groups, extrathoracic (upper airways, nasal, and paranasal) and intrathoracic (bronchi, bronchioles, and alveoli) compartments were ventilated equally with two separate ventilators connected to two tracheal tubes. The LPS group received slow infusion (over 2 h) of Escherichia coli endotoxin (10 microg/kg/h), whereas saline solution was infused into the control group. Expired air of the two compartments was collected throughout the 2-h observation period. The animals were then killed and the lungs were quickly excised and frozen. MEASUREMENTS: Hemodynamic variables were measured in both groups. NO concentration in the exhaled air of both compartments was measured with a chemiluminescence analyser. Pulmonary NOS activity was evaluated by measuring the conversion of L-[2,3H]-arginine to L-[2,3H]-citrulline, and pulmonary expression of NOS was evaluated by immunoblotting. RESULTS: Baseline NO concentration in both groups was significantly higher in the extrathoracic vs intrathoracic compartment (average of 5.2 vs 3.4 parts per billion). Endotoxin infusion elicited a significant and early (after 45 min) rise in exhaled NO concentration in the extrathoracic compartment. Exhaled NO in the intrathoracic compartment also rose significantly but after 90 min of endotoxin infusion. Measurement of lung NOS activity showed a substantial rise in Ca++/calmodulin-dependent activity in the LPS group with no rise in Ca++/calmodulin-independent activity. Immunoblotting of lung tissue samples indicated the absence of the inducible isoform in both groups of animals. Moreover, LPS injection elicited no significant alterations in the pulmonary expression of the endothelial and the neuronal isoforms. CONCLUSIONS: Both extrathoracic and intrathoracic compartments contribute to the rise in exhaled NO production in experimental septic shock. The rise in exhaled NO production is due to increased activity of constitutive NOS isoforms as a result of increased cofactor availability and/or downregulation of the endogenous inhibitors of NOS.

Animals↗