A selective inhibitor of inducible nitric oxide synthase inhibits exhaled breath nitric oxide in healthy volunteers and asthmatics

Hansel, Trevor T.; Kharitonov, Sergei A.; Donnelly, Louise E.; Erin, Edward M.; Currie, Mark G.; Moore, William M.; Manning, Pamela T.; Recker, David P.; Barnes, Peter J.

doi:10.1096/fj.02-0633fje

Cited by 190 publications

(118 citation statements)

References 58 publications

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“…Therefore, it is likely that genetic factors may account for the ''missing variability'' of FeNO. Given that inducible NO synthase in squamous and respiratory epithelia produces the vast majority of the NO detected in exhaled breath in normal subjects [25], it can be speculated that ethnic differences in the genetic regulation of NO synthase pathway may explain the differences of FeNO levels between Asian and Caucasian children. In addition, the observation that Asian children in both the current population and in a previous study [26] have relatively low spirometry values has led to speculation regarding differences in lung function to explain FeNO differences between Asian and Caucasian children.…”

Section: Exhaled Biomarkers T-c Yao Et Almentioning

confidence: 99%

Reference values of exhaled nitric oxide in healthy Asian children aged 5 to 18 years

Yao

Wi²,

Ls³

et al. 2011

European Respiratory Journal

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This study was undertaken to establish reference values of exhaled nitric oxide fraction (FeNO) and its determinants in healthy Asian children.693 healthy Asian children aged 5-18 yrs were assessed using a single-breath online FeNO measurement (exhaled flow 50 mL?s -1 ), questionnaires, anthropometric measurements, spirometry and total and specific immunoglobulin (Ig) E.Geometric mean FeNO and the upper 95% CI were 13.7 ppb and 49.7 ppb, respectively, for healthy children, and 11.2 ppb and 30.2 ppb, respectively, for those without allergic sensitisation. FeNO was positively associated with age, allergic sensitisation, total IgE, ambient nitric oxide, measurement in the afternoon, and drinking water within 1 h before testing, and was negatively associated with weight. In healthy children without allergic sensitisation, age was the single best explanatory variable. The FeNO predicted values were 1-2 ppb higher in Asian than in Caucasian children in earlier studies, while the upper 95% CI were 9-10 ppb higher.In conclusion, the upper limits of normal FeNO in Asian children depend on age, from 21 ppb in young children to 39 ppb in adolescents. Ethnicity, age, allergic sensitisation, total IgE, ambient nitric oxide, time of testing, drinking water and weight are important determinants.

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Section: Exhaled Biomarkers T-c Yao Et Almentioning

confidence: 99%

Reference values of exhaled nitric oxide in healthy Asian children aged 5 to 18 years

Yao

Wi²,

Ls³

et al. 2011

European Respiratory Journal

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“…New and more effective antioxidants are in development [116], and selective inducible nitric oxide synthase inhibitors are already in clinical trials [117].…”

Section: Reversal Of Corticosteroid Resistancementioning

confidence: 99%

Corticosteroid effects on cell signalling

Barnes¹

2006

Eur Respir J

360

245

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Corticosteroids are the most effective anti-inflammatory therapy for asthma. Inflammation in asthma is characterised by the increased expression of multiple inflammatory genes regulated by pro-inflammatory transcription factors, such as nuclear factor-kB and activator protein-1, which bind to and activate coactivator molecules that acetylate core histones and switch on gene transcription. Corticosteroids suppress the multiple inflammatory genes that are activated in asthmatic airways, mainly by reversing histone acetylation of activated inflammatory genes through binding of glucocorticoid receptors to coactivators and recruitment of histone deacetylase 2 to the activated transcription complex.Activated glucocorticoid receptors also bind to recognition sites in the promoters of certain genes in order to activate their transcription, resulting in secretion of anti-inflammatory proteins, such as mitogen-activated protein kinase phosphatase-1, which inhibits mitogen-activated protein kinase signalling pathways. Glucocorticoid receptors may also interact with other recognition sites to inhibit transcription, for example of several genes linked to their side-effects.In some patients with steroid-resistant asthma, there are abnormalities in glucocorticoid receptor signalling pathways. In chronic obstructive pulmonary disease patients and asthmatic patients who smoke, histone deacetylase 2 is markedly impaired as a result of oxidative/nitrative stress, and so inflammation is resistant to the anti-inflammatory effects of corticosteroids.The therapeutic implications of these new findings are discussed.

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“…They include sex and sexual hormones, body weight and age, circadian changes of respiratory function in health and disease, caffeine and alcohol, meals rich in nitrate, genetic background for some enzymes, upper respiratory tract infection, exercise, drugs (including inhibitors of NO synthases) and of course smoking [46,[54][55][56][57][58][59][60][61][62][63][64][65][66][67][68][69][70][71][72][73]. Moreover, FeNO levels in healthy subjects are influenced by atopy, i.e.…”

Section: Exhaled Nitric Oxidementioning

confidence: 99%

Bronchoalveolar lavage, sputum and exhaled clinically relevant inflammatory markers: values in healthy adults

et al. 2007

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Bronchoalveolar lavage (BAL), induced sputum and exhaled breath markers (exhaled nitric oxide and exhaled breath condensate) can each provide biological insights into the pathogenesis of respiratory disorders. Some of their biomarkers are also employed in the clinical management of patients with various respiratory diseases. In the clinical context, however, defining normal values and cut-off points is crucial. The aim of the present review is to investigate to what extent the issue of defining normal values in healthy adults has been pursued for the biomarkers with clinical value.The current authors reviewed data from literature that specifically addressed the issue of normal values from healthy adults for the four methodologies.Most studies have been performed for BAL (n59), sputum (n53) and nitric oxide (n53). There are no published studies for breath condensate, none of whose markers yet has clinical value. In healthy adult nonsmokers the cut-off points (mean+2SD) for biomarkers with clinical value were as follows. BAL: 16.7% lymphocytes, 2.3% neutrophils and 1.9% eosinophils; sputum: 7.7610 6 ?mL -1 total cell count and 2.2% eosinophils; nitric oxide: 20.2 ppb. The methodologies differ concerning the quantity and characteristics of available reference data. Studies focusing on obtaining reference values from healthy individuals are still required, more evidently for the new, noninvasive methodologies.

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A selective inhibitor of inducible nitric oxide synthase inhibits exhaled breath nitric oxide in healthy volunteers and asthmatics

Cited by 190 publications

References 58 publications

Reference values of exhaled nitric oxide in healthy Asian children aged 5 to 18 years

Reference values of exhaled nitric oxide in healthy Asian children aged 5 to 18 years

Corticosteroid effects on cell signalling

Bronchoalveolar lavage, sputum and exhaled clinically relevant inflammatory markers: values in healthy adults

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