<b>Background: </b>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. <b>Aims: </b>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). <b>Methods: </b>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. <b>Results: </b>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. <b>Conclusion: </b>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.

Background: According to recent studies in children, IgE sensitization not only against perennial allergens, but also against food allergens, is related to asthma risk and increased airway inflammation. During the last decade, a new technique for IgE determination based on allergen components has become available, but its use in epidemiological studies has been limited. Aims: To investigate the relationship between the pattern of IgE sensitization to allergen components and the prevalence of asthma, airway inflammation and hyperresponsiveness in a population-based setting. To examine the relationship of IgE sensitization to allergen extract, and airway inflammation, airway hyperresponsiveness and blood eosinophilia in asthmatics. To examine the natural history of IgE sensitization to food allergens in adults. To compare extract-based and component-based IgE measurements in relation with new-onset respiratory disease and airway inflammation and hyperresponsiveness. Methods: The present thesis is based on cross-sectional and longitudinal analyses of the adult, the population-based study ECRHS (European Community Health Survey) and a cross-sectional, observational study of young subjects with asthma. IgE sensitization was examined by means of both extract-based and component-based tests. Airway inflammation was assessed by exhaled NO and airway hyperresponsiveness with methacholine test. Results: IgE sensitization to food allergens independently related to increased airway inflammation in both a population-based study and a study of asthmatics. Furthermore, a relation was found with increased blood eosinophils in asthmatics. The decrease in prevalence of IgE sensitization against food allergens during a 9-year follow-up was larger than the decrease of aeroallergens. Subjects with IgE sensitization to both cat extract and components showed more frequent airway inflammation, greater bronchial responsiveness and higher likelihood of developing asthma and rhinitis than subjects with IgE sensitization only to cat extract. Conclusions: The presence of IgE antibodies against food allergens was independently associated with airway and systemic inflammation. Both aeroallergens and food allergens should be examined in order to understand the signaling of local and systemic inflammation in asthma. Prevalence of IgE sensitization to food decreased in adults to a larger extent than IgE sensitization against aeroallergens. Measurement of IgE sensitization to cat allergen components appears to have a higher clinical value than extract-based measurement