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PubMed2006

[Exhaled nitric oxide in patients with obstructive sleep apnea syndrome].

UNLABELLED: Exhaled nitric oxide has been extensively investigated as a non-invasive marker of airway inflammation. Some authors have suggested that morning FE(NO) in obstructive sleep apnea syndrome (OSAS) patients is elevated due to inflammation of upper airways, while others have not found any differences between patients and healthy subjects. The purpose of this study was to analyze concentration of exhaled nitric oxide (FE(NO)) in OSAS patients. METHODS: 119 (99 M, 20 F) consecutive patients of sleep laboratory participated in this study. Standard overnight sleep studies with polysomnography or portable screening device were carried out in the whole group: OSAS was diagnosed in 66 patients and 53 no-OSAS served as controls. FE(NO) was measured on-line with a flow rate kept at 0.045 - 0.055 l/s, according to the recommendations of ATS using a chemiluminescence analyzer twice: before the sleep study (8-10 p.m.) and after termination of data collection (6 - 8 a.m.). There were no differences in age between patients and controls. Respiratory disturbance index (RDI) was 40.3+/-24.9 in patients and 3.7+/-2.8 in controls (p<0.001). In OSAS patients both evening and morning FE(NO) was significantly higher compared to controls (23.1+/-14.8 ppb vs. 16.8+/-9.8 ppb and 22.4+/-13.2 ppb vs. 15.3+/-8.1 ppb respectively, p<0.05). Weak but statistically significant correlations for the whole group between morning FE(NO) and mean and minimum arterial oxygen saturation (SaO2) during sleep and number of study minutes with SaO2<90% were observed. Lower evening FE(NO) in OSAS patients with coexisting arterial hypertension when compared to normotensive OSAS patients was also noticed (19.1+/-10.8 ppb vs. 27.1+/-19.1 ppb; p<0.05). CONCLUSIONS: The increase in FE(NO) in OSAS patents may be caused by repetitive apneas and hypoxemia during sleep.

Adult↗

PubMed2006

[Influence of bronchoscopy on nitric oxide in exhaled air].

UNLABELLED: Nitric oxide has been extensively studied as a noninvasive marker of airway inflammation, especially in asthma. Assuming, bronchoscopy can produced not only systemic but also local inflammatory response we hypothesized that bronchofiberoscopy can be responsible for an increase in nitric oxide synthesis with resulting increase in fractional concentration of exhaled nitric oxide (FE(NO)). Seventeen subjects (10 M, 7 F), at mean age of 53.8+/-14.1 yrs undergoing diagnostic bronchoscopy participated in the study. The indications for bronchoscopy were as follows: lung cancer (n=5; 29%), interstitial lung diseases (n=3; 18%), slowly resolving pneumonia (n=3; 18%), hemoptysis (n=3; 18%), differential diagnosis of asthma/ dyspnea (n=3; 18%). During bronchoscopy bronchial washing (n=7) and bronchoalveolar lavage (BAL) (n=10) has been performed. FE(NO) has been analyzed on-line with chemiluminescence analyzer (NIOX, Aerocrine, Sweden) according to American Thoracic Society guidelines, before and at 1, 2, 3 and 24 hours after bronchoscopy. Mean FE(NO) before bronchoscopy was 19.7+/-4.5 ppb (mean +/- SEM), post - bronchoscopy a decrease with a nadir at second hour (12.1+/-1.5 ppb, p<0.05) was observed, FE(NO) 24 hours after bronchoscopy was not different than baseline (18.4+/-2.5 ppb). There were no differences in the FE(NO) profile in BAL patients when compared to those in whom only the bronchial washing has been performed. CONCLUSIONS: Bronchoscopy leads to a significant decrease in exhaled nitric oxide. The underlying mechanisms are unclear. Future studies including analysis of other inflammatory markers are needed to explain these changes.

Asthma↗

PubMedDate not supplied

[Effect of long-term anti-orthostatic hypokinesia on the composition of volatile metabolites in the exhaled air].

This paper presents measurements of volatile metabolites in the air exhaled by test subjects exposed to year-long antiorthostatic hypokinesia (-5 degrees). The test subjects were subdivided into two groups (Group A and Group B), which used different countermeasures. It was found that during the first 30 days of exposure exhalation of volatile metabolites reached a new and higher level. During test days 1 through 240 the content of volatile metabolites increased significantly in both groups; however the increase in Group B was less expressed than in Group A. At the final stage of the experiment, i.e. from day 240 through 370, the difference between the two groups was levelled off.

Acetaldehyde↗

PubMedDate not supplied

[Composition of exhaled air, gas and energy metabolism and bio- chemical indicators of the blood and urine in humans after long- term exposure to hypercapnia and hypoxia].

Four volunteers were enclosed for 40 days in a hypercapnic environment. Their average age was 41-59 years, body weight, 66-90 kg, and height 173-182 cm. During the study the ambient temperature was 19-23 degrees C, relative humidity, 50 +/- 20%; pO2, 19-19.5%; and pCO2, 1.3%. On test days 21-22 and 38-39 pCO2 was increased to 4% and pO2 was decreased to 17%. The time, within which pCO2 was increased to 4% on test days 38-39 when compared to test days 21-22, grew 1.5-fold and amounted to 40 hours. The subjects had three meals a day, consuming canned foodstuffs, the caloric value of which was 2982 kcal/day. In the study the following parameters were measured: malonic dialdehyde in venous blood; catalase, lactate, pyruvate, urea, acid-base content, gases in capillary blood; total nitrogen, ammonia, urea, creatinine and uric acid in 24-hour urine samples. Nitrogen balance and protein nutrition index were calculated. Results were processed using Student's t-test. During exposure lipid peroxidation increased and catalase decreased; malonic dialdehyde in blood increased, being correlated with lower hydrocarbons in exhaled air; gas and energy turnover during hypercapnic intervals enhanced. The above changes in the exhaled air composition, gas and energy turnover, biochemical blood and urine parameters remained within adaptation norm. By the second week of the recovery period the above parameters, except for nitrogen metabolism which remained slightly inhibited, returned to the normal.

Adult↗

PubMed1986

Consumption of pentane by hepatic microsomes and consequences on pentane measurement in exhaled gases.

Pentane measurement in exhaled gases was proposed as a safe method to evaluate the importance of lipoperoxidation in vivo, in man and in animals. However we have observed that pentane, which arises from lipoperoxide decomposition, is significantly consumed by cytochrome P-450-rich liver microsomes. This pentane consumption is completely inhibited after heating the microsomes at 100 degrees C, and is considerably reduced by metyrapone, a cytochrome P-450 inhibitor. Hepatic metabolism of pentane, particularly after cytochrome P-450 induction, constitutes a risk of error, when pentane exhalation is taken as an index of lipoperoxidation in vivo.

Animals↗

PubMedDate not supplied

[Effect of space flight on the levels of volatile metabolites in the exhaled air of astronauts].

The rate of expiration of volatile metabolites as a function of environmental factors is discussed. Concentrations of anthropotoxins in the air exhaled by cosmonauts before and after space flight as well as by test subjects exposed to prolonged antiorthostatic hypokinesia are presented. These observations show that after short-term and particularly after long-term space flights the concentrations of volatile metabolites in the exhaled air increased significantly. This suggests that space flight factors induce changes in the metabolic rate which has been to a certain extent confirmed by bed rest studies.

Aerospace Medicine↗

PubMed1982

Acceleration of 7-[methoxy-14C]coumarin-derived carbon dioxide exhalation by cobalt pretreatment in mice.

Pretreatment of rats with cobaltous chloride has been shown previously to reduce the content of cytochrome P-450 in the hepatic microsomal protein. This is accompanied by a corresponding decrease in substrate oxidation, e.g. ethyl morphine demethylation, in vitro. The present paper shows that pretreatment of C57BL/6J Han mice with 40 mg of CoCl2/kg/day for 2 days results in a decrease of cytochrome P-450 to 60% of its original value. This is accompanied by a corresponding decrease in overall rate of [14C]methacetin demethylation as measured by 14CO2 exhalation. However, when 7-[methoxy-14C]coumarin is the substrate, cobalt-pretreated animals exhale twice as much 14CO2 than normal animals. Considering the decrease in cytochrome P-450 (and assuming linear relationship between metabolic activity and cytochrome P-450 content), this observation suggested a 2.5-fold increase in the specific activity of the remaining cytochrome P-450. This was found to be true in vitro. It is concluded that cobalt pretreatment of mice leads to an enhanced in vivo demethylation rate of 7-[methoxy-14C]coumarin which is explained by a considerably higher molecular monooxygenase activity toward this substrate that is found in vitro.

Animals↗

PubMedDate not supplied

[Effect of a sugar diet on the exhalation of 14CO2 by rats after the administration of citric acid-3-14C].

In rats of three age groups (one month-old rattlings, young 3-month old and adult rats not younger than 5 months) receiving the usual vivarium food the exhalation of C14O2 substantially decreased with the age and the maximum radioactivity of the air following intraperitoneal introduction of citric acid-3-C14 was greatly delayed. Upon putting for 2 months on a cariogenic diet with 54 per cent of saccharose of one month old and 3-month old animals there was noted a significantly accelerated appearance in the expired air of C14O2 and a quicker reaching the maximum radioactivity of the expired air than in controls. It seems that in an accelerated exhalation of C14O2 a definite role is played by the transormation of citric acid in the muscles and blood with the animals kept on a saccharose diet.

Age Factors↗

PubMedDate not supplied

[Pressure-regulated pulmonary ventilation with an inverse ratio of the duration of the inhalation and exhalation phases].

Clinical and physiological effects of pressure-regulated ventilation of the lungs using the inverse rate of inhalation to exhalation (PCV-IR) were studied in two groups of patients. No appreciable advantages of this mode of pulmonary ventilation in comparison with common ("volumic") method were observed in group 1 patients (following open-heart surgery) with moderately expressed respiratory disorders (PaO2/FIO2 = 340c13 and index of lung comprometation 0.7c0.04). At the same time, the level of the peak inhalation pressure in the airways at PCV-IR was reliably lower than during common artificial ventilation of the lungs (AVL). In patients with grave respiratory disturbances (PaO2/FIO2 = 93c10 and index of lung comprometation 6.88c0.56) application of this scheme brought about an improvement of pulmonary biomechanics and gas exchange, but the hemodynamics was virtually the same. It is noteworthy that the process of PCV-IR adaptation required a thorough preliminary "adjustment" of the ventilation parameters and took rather a long time in the majority of patients. Positive effects of PCV-IR may be due to several mechanisms: a slowing down (ramp-like) flow, limitation of the upper pressure during inhalation, prolongation of exhalation in comparison with inhalation, and a regulated level of internal positive end expiratory pressure. PCV-IR is recommended as a variant of respiratory support in the treatment of patients with severe involvement of the lungs, when the potentialities of common AVL are exhausted.

Adolescent↗

PubMed1996

[Kallikrein-kinin indices and biological composition of exhaled condensate in acute bronchitis patients with varying disease course].

Parameters of blood kallikrein-kinin system (KKS) and biochemical composition of humor condensated from the exhaled air have been evaluated in 87 patients with acute bronchitis (36 cases with lingering course and 31 with recurrent). The progression of acute bronchitis is associated with elevated blood concentrations of acute-phase proteins, KKS activation in the blood and high serotonin and lactic acid content in the humor condensated from the exhaled air. Lingering and recurrent course of the disease are characterized by more pronounced reduction in inhibitory activity of kallikrein, in activity of angiotensin-converting enzyme and emergence of noradrenalin in high concentration.

Acute Disease↗

PubMed1998

[Prenatal diagnosis of fetal hypoxia based on lipid peroxidation values in exhaled air condensate].

Lipid peroxidation values were measured in the serum and expired air of pregnant women. The levels of diene conjugates, secondary intermediates of free-radical processes, and malonic dialdehyde were increased in exhaled air condensate of pregnant women who gave birth to babies with grave hypoxia, as against women with healthy babies or babies with slight hypoxia. All the studied values were more demonstrative in the expirate than in the serum. Hence, grave fetal and neonatal hypoxia can be diagnosed before delivery by examining the exhaled air condensate of pregnant women.

Apgar Score↗

PubMed1976

[Diagnostics of lactose-malabsorption: value of tolerance tests and 14CO2 exhalation test in patients with and without lactase deficiency (author's transl)].

Lactose-tolerance-test (LTT), ethanol-lactose-tolerance-test (ELTT), 14CO2 breath test and 14C-glucose determination were simultaneously performed in 27 healthy subjects, 16 patients with a Billroth II gastrectomy and 6 patients with a malabsorption syndrome. Intestinal mucosal lactase was absent or significant diminished in 5 of the B II cases and in all patients with malabsorption. In the lactase deficient patients a diminished serum glucose rise after ingestion of 50 g lactose was observed in LTT as well as in ELTT. False positive results in LTT could not be prevented by performing the ELTT. Furthermore the ELTT is not suitable for ambulant investigations because of the required high ethanol load of 0.5 g/kg. Most reliable results were obtained by determination of 14C-serum-glucose after oral application of about 15 muCi of 14C lactose. In respect to lactase level neither false positive nor false negative results were observed. For clinical investigations the procedure of isolation and measurement of 14C-glucose is too laborious however. 14CO2-exhalation test cannot be recommended because of many false positive and false negative results. Moreover 14CO2-exhalation seemed to be insensible and predominant depending on factors other than lactose absorption.

Blood Glucose↗

PubMed2024

Effects of particulate air pollution on BPDE-DNA adducts, telomere length, and mitochondrial DNA copy number in human exhaled breath condensate and BEAS-2B cells.

Traffic-related particulate matter (PM) and polycyclic aromatic hydrocarbons (PAHs) have been linked to respiratory diseases and cancer risk in humans. Genomic damage, including benzo[a]pyrene diolepoxide (BPDE)-DNA adducts as well as alterations in telomere length (TL) and mitochondrial DNA copy number (mtDNA-CN) are associated with respiratory diseases. This study aimed to investigate the association between exposure to traffic-related particulate pollutants and genomic damage in exhaled breath condensate (EBC) in human subjects and a bronchial epithelial cell line (BEAS-2B). Among the 60 healthy recruited subjects, residents living in high-traffic-congested areas were exposed to higher concentrations of PM2.5 (1.66-fold, p < 0.01), UFPs (1.79-fold, p < 0.01), PM2.5-PAHs (1.50-fold, p < 0.01), and UFPs-PAHs (1.35-fold, p < 0.05), than those in low-traffic-congested areas. In line with increased exposure to particulate air pollution, the high-traffic-exposed group had significantly increased BPDE-DNA adducts (1.40-fold, p < 0.05), TL shortening (1.24-fold, p < 0.05), and lower mtDNA-CN (1.38-fold, p < 0.05) in EBC. The observations in the human study linking exposure to PM2.5, UFPs, PM2.5-PAHs, and UFPs-PAHs with the aforementioned biological effects were confirmed by an in vitro cell-based study, in which BEAS-2B cells were treated with diesel exhaust particulate matter (DEP) containing fine and ultrafine PM and PAHs. Increased BPDE-DNA adducts levels, shortened TL, and decreased mtDNA-CN were also found in treated BEAS-2B cells. The shortened TL and decreased mtDNA-CN were in part mediated by decreased transcript levels of hTERT, and SIRT1, which are involved in telomerase activity and mitochondrial biogenesis, respectively. These results suggest that exposure to traffic-related particulate pollutants can cause genomic instability in respiratory cells, which may increase the health risk of respiratory diseases and the development of cancer.

Humans↗

PubMed2025

Molecular profiling of exhaled breath condensate in respiratory diseases.

BACKGROUND: Respiratory disorders, , continue to pose a major global health burden. Their complexity and heterogeneity challenge accurate diagnosis, effective monitoring, and therapeutic decision-making. Exhaled breath condensate (EBC) provides a reliable, non-invasive means of sampling the molecular environment of the airways. AIM: This review presents the state-of-the-art in EBC-based omics approaches-particularly metabolomics and proteomics-to characterize molecular signatures associated with chronic respiratory (e.g. asthma, chronic obstructive pulmonary disease, and rhinitis) and infectious diseases (e.g. COVID-19). RESULTS: We critically examine findings from studies applying nuclear magnetic resonance (NMR), mass spectrometry (MS), and sensor-based technologies to analyze EBC across various respiratory conditions. NMR, valued for its reproducibility and minimal sample preparation, consistently discriminates among disease phenotypes, identifies distinct metabotypes, and monitors treatment response over time. MS-based approaches afford enhanced sensitivity and specificity, enabling detailed profiling of inflammatory mediators, such as lipid-derived eicosanoids and amino acid derivatives. Proteomic studies reveal protein-level alterations associated with inflammation and tissue remodeling. In COVID-19 and long COVID, metabolomic and volatile compound profiling distinguishes affected individuals from healthy controls suggesting clinical potential. However, inconsistent sample processing and lack of analytical standardization remain limiting factors. CONCLUSIONS: EBC profiling shows clear promise for improving diagnosis, monitoring, and stratification in respiratory medicine. Yet, translation into clinical practice is hindered by limited standardization and validation. Broader, longitudinal studies will be essential to establish robust molecular signatures across disease states. This review underscores the timely need to implement breathomics investigations to gain mechanistic insight into the underlying biology of respiratory diseases.

Humans↗

PubMed2004

Measuring exhaled nitric oxide in infants during tidal breathing: methodological issues.

Exhaled nitric oxide (FENO) may provide a tool for identifying infants at risk of developing allergic disease in childhood. In infants there is no standardized collection technique; however, the easiest method is to measure FENO during tidal breathing. In this study we investigated various methodological issues for tidal breathing (TB) FENO in infants. These included the effect of ambient NO, oral or nasal breathing, sedation, and tidal expiratory flow. Furthermore, we compared TB FENO in 88 infants with and without wheeze. Ambient NO greater than 5 ppb significantly affected FENO. There was no significant difference between NO levels measured during either oral or nasal breathing; however, there was a significant difference between levels collected from infants before and after sedation (P < 0.001). Tidal breathing FENO decreased with increasing tidal flows (P < 0.001) and increased with age (P = 0.002). There was no significant difference in mixed expired NO between healthy and wheezy children, but children with doctor-diagnosed eczema had significantly raised levels (P = 0.014). There seem to be important methodological limitations for measuring FENO in infants during TB.

Breath Tests↗

PubMed2006

Exhaled nitric oxide in healthy nonatopic school-age children: determinants and height-adjusted reference values.

Exhaled nitric oxide (FENO) was proposed as a marker of airway inflammation, but data about FENO in healthy children measured with standardized methods are so far limited. In order to assess the determinants of FENO in healthy children, we investigated a population-based sample of school-age children (n = 276) with a questionnaire, skin-prick tests, spirometry, and the measurement of FENO. The FENO of 114 nonatopic and nonsmoking children considered healthy were analyzed with stepwise multiple regression analysis, which showed significant associations with age, standing height, weight, and body surface area, but not with gender. Height was found to be the best independent variable for the regression equation for FENO, which on average showed an increase in the height range of 120-180 cm from 7 to 14 ppb. In the random sample of children, increased FENO was associated with atopy (odds ratio, 9.0; 95% confidence interval, 3.9-21.1; P < 0.0001), and significantly with allergic rhinitis and atopic dermatitis, but not with asthma. Respiratory symptom-free children with skin-prick test positivity had significantly higher FENO than healthy nonatopic subjects. We conclude that height is the best determinant of FENO in healthy children. Due to the strong effect of atopy, FENO data should not be interpreted without knowing the atopic status of the child. The present reference values of FENO may serve in clinical assessments for measuring airway inflammation in children.

Adolescent↗

PubMed2006

Lack of association between NOS2 pentanucleotide repeat polymorphism and asthma phenotypes or exhaled nitric oxide concentration.

Nitric oxide (NO) plays an immunoregulatory role in balancing cellular immunity. The expression of inducible nitric oxide synthase gene (NOS2) is upregulated upon exposure to proinflammatory cytokines and microbial exposure. The (CCTTT)n polymorphism in NOS2 promoter confers protection against infections and immunological disorders including atopy. We investigated the association between (CCTTT)n and asthma traits in Chinese children. Asthmatic children between 5 and 18 years of age and non-allergic controls were recruited. Plasma total and specific IgEs were measured by immunoassays, and exhaled NO concentration was quantified online by chemiluminescence. NOS2 (CCTTT)n was genotyped by GeneScan analysis. The mean (SD) age of 291 asthmatics and 172 controls were 11.1 (3.8) years and 11.6 (4.0) years, respectively (P = 0.259). NOS2 (CCTTT)n followed Hardy-Weinberg equilibrium in both groups, and its uni-modal allele distribution peaks at 12-repeat. Significant interethnic differences in (CCTTT)n alleles were observed, with our Chinese having less 13-repeat (Pc = 0.022) but more 17-repeat (Pc = 0.033) than Caucasians. The frequency of 14-repeat allele was similar in our Chinese as compared to Japanese (Pc = 0.32). Multivariate regression analyses failed to detect any association between this polymorphic marker and asthma diagnosis (P = 0.949), atopy (P = 0.305), IgE sensitization to aeroallergens (P > 0.2 for all), or FeNO (P = 0.847). These findings do not support NOS2 to be a major candidate gene for asthma or IgE-mediated allergic diseases in Chinese children.

Asthma↗

PubMed2006

Exhaled nitric oxide in the management of childhood asthma: a prospective 6-months study.

Fractional exhaled nitric oxide (FeNO) is elevated in asthma and reflects eosinophilic airway inflammation. The aim of this prospective, randomized, single-blind study was to examine whether the inclusion of repeated FeNO measurements into asthma monitoring leads to an improvement in asthma outcome. Forty-seven children with mild to moderate asthma were allocated to a FeNO group (n = 22) and to a control group (n = 25). In the FeNO group therapy was based on symptoms, beta-agonist use, lung function, and FeNO whereas in the control group therapy was based on symptoms, beta-agonist use and lung function only. Patients performed five visits in 6 weeks intervals. Frequency of respiratory symptoms, beta-agonist use, FEV(1)% predicted and the frequency of exacerbations were similar between groups. Patients in the FeNO group received higher doses of inhaled corticosteroids (ICS) (control group: median (interquartile range): 241 microg (26-607 microg); FeNo group: 316 microg (200-500 microg) and had significantly higher MEF(50)% predicted (control group: median (interquartile range): 68.5% (55.8-83.1%); FeNO group: 83.2% (62.9%-98.3%). At a cut-off point of 22.9 ppb FeNO the best predictive value for exacerbations with a sensitivity of 80% and specificity of 60% was found. Significant relationships were observed between FeNO and dose of ICS (beta = -8.77; P < 0.002), beta-agonist use 2 weeks prior to a visit (beta = 0.11; P < 0.05), asthma symptoms (beta = 0.02; P < 0.0001), and bronchial hyperresponsiveness (beta = 0.04; P = 0.02). In conclusion, FeNO was related to important markers of asthma control. A therapy regimen aimed at lowering FeNO in children with asthma improved parameters of small airway function, but was not able to improve clinical markers of asthma control.

Adolescent↗