| 1. |
- Högman, Marieann, et al.
(författare)
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Extended NO analysis in a healthy subgroup of a random sample from a Swedish population
- 2009
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Ingår i: Clinical Physiology and Functional Imaging. - 1475-0961 .- 1475-097X. ; 29:1, s. 18-23
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: There is an interest in modelling exhaled nitric oxide (NO). Studies have shown that flow-independent NO parameters i.e. NO of the alveolar region (C(A)NO), airway wall (C(aw)NO), diffusing capacity (D(aw)NO) and flux (J(aw)NO), are altered in several disease states such as asthma, cystic fibrosis, alveolitis and chronic obsmuctive pulmonary disease (COPD). However, values from a healthy population are missing. OBJECTIVES: To calculate NO parameters in a healthy population by collecting NO values at different exhalation flow rates. METHODS: A random sample from the ECRHS II study was investigated. Among the 281 subjects that had performed a bronchial hyperreactivity (BHR)-test, FEV(1.0), IgE and NO-analyses 89 were found to be healthy. RESULTS: There were no differences in F(E)NO(0.05) or NO parameters between men and women. There were weak correlations between height and both F(E)NO(0.05) (r = 0.23, P = 0.03) and C(aw)NO (r = 0.22, P = 0.04). There was also a correlation between age and C(A)NO (r = 0.28, P = 0.007). When controlled for gender, this correlation was more powerful in women (r = 0.51, P = 0.001) but did not remain for male subjects. CONCLUSION: Extended NO analysis is a simple non-invasive tool that gives by far more information than F(E)NO(0.05). Based on our results, we suggest that the values for healthy subjects should be considered to fall between the following ranges: F(E)NO(0.05), 10-30 ppb; C(aw)NO, 50-250 ppb; D(aw)NO, 5-15 ml s(-1); J(aw)NO, 0.8-1.6 nl s(-1); and C(A)NO, 0-4 ppb. Values outside these intervals indicate the need for further investigation to exclude a state of disease.
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| 2. |
- Malinovschi, Andrei, et al.
(författare)
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Basal and induced NO formation in the pharyngo-oral tract influences estimates of alveolar NO levels
- 2009
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Ingår i: Journal of applied physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 106:2, s. 513-519
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Tidskriftsartikel (refereegranskat)abstract
- The present study analyzed how models currently used to distinguish alveolar from bronchial contribution to exhaled nitric oxide (NO) are affected by manipulation of NO formation in the pharyngo-oral tract. Exhaled NO was measured at multiple flow rates in 15 healthy subjects in two experiments: 1) measurements at baseline and 5 min after chlorhexidine (CHX) mouthwash and 2) measurements at baseline, 60 min after ingestion of 10 mg NaNO3/kg body wt, and 5 min after CHX mouthwash. Alveolar NO concentration (CalvNO) and bronchial flux (J′awNO) were calculated by using the slope-intercept model with or without adjustment for trumpet shape of airways and axial diffusion (TMAD). Salivary nitrate and nitrite were measured in the second experiment. CalvNO [median (range)] was reduced from 1.16 ppb (0.77, 1.96) at baseline to 0.84 ppb (0.57, 1.48) 5 min after CHX mouthwash (P < 0.001). The TMAD-adjusted CalvNO value after CHX mouthwash was 0.50 ppb (0, 0.85). The nitrate load increased J′awNO from 32.2 nl/min (12.2, 60.3) to 57.1 nl/min (22.0, 119) in all subjects and CalvNO from 1.47 ppb (0.73, 1.95) to 1.87 ppb (10.85, 7.20) in subjects with high nitrate turnover (>10-fold increase of salivary nitrite after nitrate load). CHX mouthwash reduced CalvNO levels to 1.15 ppb (0.72, 2.07) in these subjects with high nitrate turnover. All these results remained consistent after TMAD adjustment. We conclude that estimated alveolar NO concentration is affected by pharyngo-oral tract production of NO in healthy subjects, with a decrease after CHX mouthwash. Moreover, unknown ingestion of dietary nitrate could significantly increase estimated alveolar NO in subjects with high nitrate turnover, and this might be falsely interpreted as a sign of peripheral inflammation. These findings were robust for TMAD.
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| 3. |
- Malinovschi, Andrei, et al.
(författare)
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Both allergic and nonallergic asthma are associated with increased FENO levels, but only in never-smokers
- 2009
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538 .- 1398-9995. ; 64:1, s. 55-61
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Tidskriftsartikel (refereegranskat)abstract
- Allergic asthma is consistently associated with increased FENO levels whereas divergence exists regarding the use of exhaled nitric oxide (NO) as marker of inflammation in nonallergic asthma and in asthmatic smokers. The aim of this study is to analyze the effect of having allergic or nonallergic asthma on exhaled nitric oxide levels, with special regard to smoking history. Exhaled NO measurements were performed in 695 subjects from Turin (Italy), Gothenburg and Uppsala (both Sweden). Current asthma was defined as self-reported physician-diagnosed asthma with at least one asthma symptom or attack recorded during the last year. Allergic status was defined by using measurements of specific immunoglobulin E (IgE). Smoking history was questionnaire-assessed. Allergic asthma was associated with 91 (60, 128) % [mean (95% CI)] increase of FENO while no significant association was found for nonallergic asthma [6 (-17, 35) %] in univariate analysis, when compared to nonatopic healthy subjects. In a multivariate analysis for never-smokers, subjects with allergic asthma had 77 (27, 145) % higher FENO levels than atopic healthy subjects while subjects with nonallergic asthma had 97 (46, 166) % higher FENO levels than nonatopic healthy subjects. No significant asthma-related FENO increases were noted for ex- and current smokers in multivariate analysis. Both allergic and nonallergic asthma are related to increased FENO levels, but only in never-smoking subjects. The limited value of FENO to detect subjects with asthma among ex- and current smokers suggests the predominance of a noneosinophilic inflammatory phenotype of asthma among ever-smokers.
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| 4. |
- Malinovschi, Andrei, et al.
(författare)
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Effect of smoking on exhaled nitric oxide and flow-independent nitric oxide exchange parameters
- 2006
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 28:2, s. 339-345
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Tidskriftsartikel (refereegranskat)abstract
- It is a well-known fact that smoking is associated with a reduction in exhaled nitric oxide (NO) levels. There is, however, limited knowledge relating to the smoking-induced changes in production or exchange of NO in different compartments of the airways. This study comprised 221 adult subjects from the European Community Respiratory Health Survey 11, who were investigated in terms of their exhaled NO, lung function, immunoglobulin E sensitisation and smoking habits. The following parameters were determined using extended NO analysis: airway tissue nitric oxide concentration (Caw,NO), airway transfer factor (or diffusing capacity) for nitric oxide (Daw,NO), alveolar nitric oxide concentration (CA,No) and fractional exhaled nitric oxide concentration at a flow rate of 50 mL(.)s(-1) (FeNO,0.05). Maximum total airway nitric oxide flux (J'aw,NO) was calculated from Daw,NO(Caw,NO-CA,NO). Current smokers (n=35) exhibited lower (geometric mean) FeNO,0.05 (14.0 versus 22.8 ppb), Caw,NO (79.0 versus 126 ppb) and J'aw,NO (688 versus 1,153 pL(.)s(-1)) than never-smokers (n=111). Ex-smokers (n=75) were characterised by lower FeNO,0.05 (17.7 versus 22.8 ppb) and Jaw,NO (858 versus 1,153 pL-s(-1)) than never-smokers. These relationships were maintained after adjusting for potential confounders (sex, age, height, immunoglobulin E sensitisation and forced expiratory volume in one second), and, in this analysis, a negative association was found between current smoking and CA,NO. Snus (oral moist snuff) consumption (n=21) in ex-smokers was associated with an increase in Daw,NO and a reduction in Caw,No, after adjusting for potential confounders. Passive smoking was associated with a higher CA,NO. Using extended nitric oxide analysis, it was possible to attribute the reduction in exhaled nitric oxide levels seen in ex- and current smokers to 6 lower total airway nitric oxide flux in ex-smokers and reduced airway and alveolar nitric oxide concentrations in current smokers. The association between snus (oral tobacco) use and reduced nitric oxide concentrations in the airways and increased nitric oxide transfer from the airways warrants further studies.
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| 5. |
- Malinovschi, Andrei, et al.
(författare)
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IgE sensitisation in relation to flow-independent nitric oxide exchange parameters
- 2006
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Ingår i: Respiratory Research. - : Springer Science and Business Media LLC. - 1465-9921 .- 1465-993X. ; 7, s. 92-
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Tidskriftsartikel (refereegranskat)abstract
- Background: A positive association between IgE sensitisation and exhaled NO levels has been found in several studies, but there are no reports on the compartment of the lung that is responsible for the increase in exhaled NO levels seen in IgE-sensitised subjects.Methods: The present study comprised 288 adult subjects from the European Community Respiratory Health Survey II who were investigated in terms of lung function, IgE sensitisation ( sum of specific IgE), smoking history and presence of rhinitis and asthma. Mean airway tissue concentration of NO (Caw(NO)), airway transfer factor for NO (Daw(NO)), mean alveolar concentration of NO (Calv(NO)) and fractional exhaled concentration of NO at a flow rate of 50 mL s(-1) ( FENO0.05) were determined using the extended NO analysis.Results: IgE-sensitised subjects had higher levels ( geometric mean) of FENO 0.05 (24.9 vs. 17.3 ppb) ( p < 0.001), Daw(NO) ( 10.5 vs. 8 mL s(-1)) ( p = 0.02) and Caw(NO) (124 vs. 107 ppb) ( p < 0.001) and positive correlations were found between the sum of specific IgE and FENO 0.05, Caw(NO) and Daw(NO) levels ( p < 0.001 for all correlations). Sensitisation to cat allergen was the major determinant of exhaled NO when adjusting for type of sensitisation. Rhinitis and asthma were not associated with the increase in exhaled NO variables after adjusting for the degree of IgE sensitisation.Conclusion: The presence of IgE sensitisation and the degree of allergic sensitisation were related to the increase in airway NO transfer factor and the increase in NO concentration in the airway wall. Sensitisation to cat allergen was related to the highest increases in exhaled NO parameters. Our data suggest that exhaled NO is more a specific marker of allergic inflammation than a marker of asthma or rhinitis.
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| 6. |
- Malinovschi, Andrei, 1978-
(författare)
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Nitric Oxide Exchange in Central and Peripheral Airways : Determinants in Health and Respiratory Disease
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Exhaled nitric oxide (NO) is a marker of eosinophilic steroid-sensitive inflammation in the airways of patients with respiratory disease. Moreover, information about the localization of inflammation in the respiratory tree is obtained by estimates of bronchial and alveolar contributions to exhaled NO.Aims: The main aim of this thesis was to identify the determinants of exhaled NO, as well as determinants of bronchial and alveolar contributions to exhaled NO in health and disease. Smoking history, degree of IgE sensitization and effects of modulating the pharyngo-oral tract production of NO were specifically studied in this context. Other specific aims were to determine the association of exhaled NO with the presence of asthma and pulmonary hypertension (PH).Methods: Both population-based studies and experimental studies have been performed within the frame of the thesis. The population-based studies are based on data from the European Community Respiratory Health Survey II. NO measurements at several exhalation flow rates were performed in order to estimate alveolar and bronchial contributions to exhaled NO.Results: Both current and previous smoking were associated with decreased exhaled NO and bronchial NO flux levels. Alveolar NO concentrations were decreased in current smokers. The degree of IgE sensitization was positively related to the levels of exhaled NO and its bronchial contribution. Exhaled NO appeared to be a more specific marker of allergic inflammation than of rhinitis or asthma. Both allergic and non-allergic asthma were associated with increased exhaled NO levels, but only in never-smoking persons. The estimated alveolar NO increased after ingestion of nitrate in individuals with high nitrate turnover in the pharyngo-oral tract. Pulmonary arterial hypertension, but not other forms of PH, was associated with decreased bronchial NO flux, whereas PH of all etiologies was related to increased alveolar NO concentrations.Conclusion: Smoking history and IgE sensitization, that are known determinants of exhaled NO, affected the bronchial and alveolar contributions to exhaled NO differently. The limitations of the simple NO pulmonary exchange models were highlighted by the paradoxical effects on estimated alveolar NO when modulating the NO production proximally, in the pharyngo-oral tract. Predominance of non-eosinophilic inflammation in ever-smoking patients with asthma could explain the poor association between the presence of asthma and exhaled NO in these patients. Different pathophysiological changes in terms of bronchial NO production and exchange were related to the etiology of pulmonary hypertension.
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