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      IgE sensitisation in relation to flow-independent nitric oxide exchange parameters

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          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 (FE NO 0.05) were determined using the extended NO analysis.

          Results

          IgE-sensitised subjects had higher levels (geometric mean) of FE NO 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 FE NO 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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          Most cited references46

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          The European Community Respiratory Health Survey.

          The European Community Respiratory Health Survey (ECRHS) was planned to answer specific questions about the distribution of asthma and health care given for asthma in the European Community. Specifically, the survey is designed to estimate variations in the prevalence of asthma, asthma-like symptoms and airway responsiveness; to estimate variations in exposures to known or suspected risk factors for asthma, and assess to what extent these variations explain the variations in the prevalence of disease; and to estimate differences in the use of medication for asthma. The protocol provides specific instructions on the sampling strategy adopted by the survey teams, as well as providing instructions on the use of questionnaires, the tests for allergy, lung function measurements, tests of airway responsiveness, and blood and urine collection. The principal data collection sheets and questionnaires are provided in the appendices, together with information on coding and quality control. The protocol is published as a reference for those who wish to know more of the methods used in the study, and also to give other groups who wish to collect comparable data access to the detailed methodology.
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            Use of exhaled nitric oxide measurements to guide treatment in chronic asthma.

            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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              Endogenous airway acidification. Implications for asthma pathophysiology.

              Airway concentrations of many reactive nitrogen and oxygen species are high in asthma. The stability and bioactivities of these species are pH-dependent; however, the pH of the airway during acute asthma has not previously been studied. As with gastric and urinary acidification, asthmatic airway acidification could be expected dramatically to alter the concentrations and bioactivities/cytotoxicities of endogenous nitrogen oxides. Here, we demonstrate that the pH of deaerated exhaled airway vapor condensate is over two log orders lower in patients with acute asthma (5.23 +/- 0.21, n = 22) than in control subjects (7.65 +/- 0.20, n = 19, p < 0. 001) and normalizes with corticosteroid therapy. Values are highly reproducible, unaffected by salivary or therapeutic artifact, and identical to samples taken directly from the lower airway. Further, at these low pH values, the endogenous airway compound, nitrite, is converted to nitric oxide (NO) in quantities sufficient largely to account for the concentrations of NO in asthmatic expired air, and eosinophils undergo accelerated necrosis. We speculate that airway pH may be an important determinant of expired NO concentration and airway inflammation, and suggest that regulation of airway pH has a previously unsuspected role in asthma pathophysiology.
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                Author and article information

                Journal
                Respir Res
                Respiratory Research
                BioMed Central
                1465-9921
                1465-993X
                2006
                20 June 2006
                : 7
                : 1
                : 92
                Affiliations
                [1 ]Department of Medical Cell Biology: Integrative Physiology, Uppsala University, Uppsala, Sweden
                [2 ]Asthma and Allergy Research Centre, Uppsala University, Uppsala, Sweden
                [3 ]Department of Medical Sciences: Respiratory Medicine and Allergology, Uppsala University, Uppsala, Sweden
                [4 ]Department of Medical Sciences: Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden
                [5 ]Department of Engineering Physics and Mathematics, Helsinki University of Technology, Helsinki, Finland
                [6 ]Department of Caring Sciences and Sociology; Section of Medical Science, University of Gävle, Gävle, Sweden
                Article
                1465-9921-7-92
                10.1186/1465-9921-7-92
                1553446
                16787532
                be83059e-20e0-459f-aa85-7e4b38b2db20
                Copyright © 2006 Malinovschi et al; licensee BioMed Central Ltd.

                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
                : 21 February 2006
                : 20 June 2006
                Categories
                Research

                Respiratory medicine
                Respiratory medicine

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