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      Factors affecting exhaled nitric oxide measurements: the effect of sex

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          Abstract

          Background

          Exhaled nitric oxide (F ENO) measurements are used as a surrogate marker for eosinophilic airway inflammation. However, many constitutional and environmental factors affect F ENO, making it difficult to devise reference values. Our aim was to evaluate the relative importance of factors affecting F ENO in a well characterised adult population.

          Methods

          Data were obtained from 895 members of the Dunedin Multidisciplinary Health and Development Study at age 32. The effects of sex, height, weight, lung function indices, smoking, atopy, asthma and rhinitis on F ENO were explored by unadjusted and adjusted linear regression analyses.

          Results

          The effect of sex on F ENO was both statistically and clinically significant, with F ENO levels approximately 25% less in females. Overall, current smoking reduced F ENO up to 50%, but this effect occurred predominantly in those who smoked on the day of the F ENO measurement. Atopy increased F ENO by 60%. The sex-related differences in F ENO remained significant (p < 0.001) after controlling for all other significant factors affecting F ENO.

          Conclusion

          Even after adjustment, F ENO values are significantly different in males and females. The derivation of reference values and the interpretation of F ENO in the clinical setting should be stratified by sex. Other common factors such as current smoking and atopy also require to be taken into account.

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          Most cited references31

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          Use of exhaled nitric oxide measurements to guide treatment in chronic asthma.

          Andrew D. M. Smith, Jan Cowan, Karen Brassett … (2005)
          International guidelines for the treatment of asthma recommend adjusting the dose of inhaled corticosteroids on the basis of symptoms, bronchodilator requirements, and the results of pulmonary-function tests. Measurements of the fraction of exhaled nitric oxide (FE(NO)) constitute a noninvasive marker that may be a useful alternative for the adjustment of inhaled-corticosteroid treatment. In a single-blind, placebo-controlled trial, we randomly assigned 97 patients with asthma who had been regularly receiving treatment with inhaled corticosteroids to have their corticosteroid dose adjusted, in a stepwise fashion, on the basis of either FE(NO) measurements or an algorithm based on conventional guidelines. After the optimal dose was determined (phase 1), patients were followed up for 12 months (phase 2). The primary outcome was the frequency of exacerbations of asthma; the secondary outcome was the mean daily dose of inhaled corticosteroid. Forty-six patients in the FE(NO) group and 48 in the group whose asthma was treated according to conventional guidelines (the control group) completed the study. The final mean daily doses of fluticasone, the inhaled corticosteroid that was used, were 370 microg per day for the FE(NO) group (95 percent confidence interval, 263 to 477) and 641 microg per day for the control group (95 percent confidence interval, 526 to 756; P=0.003), a difference of 270 microg per day (95 percent confidence interval, 112 to 430). The rates of exacerbation were 0.49 episode per patient per year in the FE(NO) group (95 percent confidence interval, 0.20 to 0.78) and 0.90 in the control group (95 percent confidence interval, 0.31 to 1.49), representing a nonsignificant reduction of 45.6 percent (95 percent confidence interval for mean difference, -78.6 percent to 54.5 percent) in the FE(NO) group. There were no significant differences in other markers of asthma control, use of oral prednisone, pulmonary function, or levels of airway inflammation (sputum eosinophils). With the use of FE(NO) measurements, maintenance doses of inhaled corticosteroids may be significantly reduced without compromising asthma control. Copyright 2005 Massachusetts Medical Society.
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            Correlation between exhaled nitric oxide, sputum eosinophils, and methacholine responsiveness in patients with mild asthma.

            S. Barnes, K. Fan Chung, Felix Lim … (1998)
            Eosinophils in induced sputum and exhaled nitric oxide (NO) are currently used as non-invasive markers in the assessment of airway inflammation in asthma. As both sputum eosinophils (%) and exhaled NO are raised in asthmatic subjects not receiving inhaled steroids and decreased following corticosteroid therapy, a relationship between them is plausible. Exhaled NO was measured by chemiluminescence analyser, sputum induction by 3.5% saline inhalation, and bronchial responsiveness was measured as PC20FEV1 methacholine in 35 stable asthmatic patients using beta 2 agonist alone and the correlation between these non-invasive markers of airway inflammation was studied. There were significant correlations between exhaled NO and PC20 (r = -0.64), exhaled NO and sputum eosinophils (%) (r = 0.48), and also between sputum eosinophils (%) and PC20 (r = -0.40). The correlation between exhaled NO and PC20 suggests that exhaled NO or the mechanisms leading to its increase may contribute to airway hyperresponsiveness in asthma. Furthermore, the relationship between sputum eosinophils (%), exhaled NO, and PC20 highlight the potential use of eosinophils (%) in induced sputum and exhaled NO to monitor the severity of asthma.
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              Exhaled nitric oxide measurements: clinical application and interpretation.

              Max F J R Taylor, J N Munck, Thomas A Smith … (2006)
              The use of exhaled nitric oxide measurements (F(E)NO) in clinical practice is now coming of age. There are a number of theoretical and practical factors which have brought this about. Firstly, F(E)NO is a good surrogate marker for eosinophilic airway inflammation. High F(E)NO levels may be used to distinguish eosinophilic from non-eosinophilic pathologies. This information complements conventional pulmonary function testing in the assessment of patients with non-specific respiratory symptoms. Secondly, eosinophilic airway inflammation is steroid responsive. There are now sufficient data to justify the claim that F(E)NO measurements may be used successfully to identify and monitor steroid response as well as steroid requirements in the diagnosis and management of airways disease. F(E)NO measurements are also helpful in identifying patients who do/do not require ongoing treatment with inhaled steroids. Thirdly, portable nitric oxide analysers are now available, making routine testing a practical possibility. However, a number of issues still need to be resolved, including the diagnostic role of F(E)NO in preschool children and the use of reference values versus individual F(E)NO profiles in managing patients with difficult or severe asthma.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Respir Res
                Title: Respiratory Research
                Publisher: BioMed Central
                ISSN (Print): 1465-9921
                ISSN (Electronic): 1465-993X
                Publication date (Print): 2007
                Publication date (Electronic): 15 November 2007
                Volume: 8
                Issue: 1
                Page: 82
                Affiliations
                [1 ]Department of Respiratory Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand
                [2 ]Firestone Institute for Respiratory Health, Department of Medicine, McMaster University, Hamilton, Ontario, Canada
                [3 ]Dunedin Multidisciplinary Health and Development Research Unit, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand
                Article
                Publisher ID: 1465-9921-8-82
                DOI: 10.1186/1465-9921-8-82
                PMC ID: 2231356
                PubMed ID: 18005450
                SO-VID: 9f67081a-2ad5-422d-b79b-408c94e4eb55
                Copyright © Copyright © 2007 Taylor et al; licensee BioMed Central Ltd.
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 2 June 2007
                Date accepted : 15 November 2007
                Categories
                Subject: Research

                ScienceOpen disciplines: Respiratory medicine
                Data availability:
                ScienceOpen disciplines: Respiratory medicine

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