Exhaled nitric oxide (NO) reflects inflammation in the lower airways and is well adapted for use in children. The aims of this study were to investigate the distribution of the fraction of expired NO (FENO) in school children and to compare FENO and spirometry in relation to the International Study of Asthma and Allergies in Childhood questionnaire. The study was performed in 959 randomly selected 13-14-year-old school children in Uppsala, Sweden. Exhaled NO was measured at an inhalation rate of 0.1 l/s (FENO0.1) and a spirometric test was performed and data from these measurements were related to questionnaire data. Exhaled NO was measured according to American Thoracic Society recommendations, except the use of a mouth wash and an exhalation flow rate of 0.1 l/s. The distribution of the mean FENO0.1 values was skewed, with a preponderance of very low levels and a widespread tail of values ranging up to 102 parts per billion (ppb). Boys exhibited significantly higher mean FENO0.1 values than girls, 5.2 (4.7-5.7) vs 4.4 (4.0-4.8) ppb (geometric mean and 95% CI), P <0.01). Children who reported wheezing in the last year had higher FENO0.1 values than children that had not, 8.5 (7.1-10.2) vs 4.3 (4.0-4.6) ppb, P <0.001). The same association was found to most symptoms indicating hay fever and eczema. In contrast to this, only weak or inconsistent associations were found between asthma and spirometric indices. Exhaled NO levels were found to be independently related to male gender, wheeze and rhinoconjuctivitis but not to current eczema. In conclusion, exhaled NO was closely associated with reported asthma and allergy symptoms whereas spirometric indices such as percent predicted forced expiratory volume in 1 s were not. As most asthma cases in a population are mild, the findings suggest that exhaled NO is a sensitive marker of asthma and allergy.

This study indicates the importance of distinguishing between subtypes of asthma when assessing the effect of different risk factors. While the risk of both allergic and non-allergic asthma increased with increasing BMI, associations between early-life and current environmental exposure were primarily found in relation to non-allergic asthma.

Allergen exposure seems to be the most important determinant for exhaled NO levels in IgE-sensitised children whereas in non-sensitised children NO levels were associated with respiratory infections and home window pane condensation.

EBC nitrite mainly originates in the pharyngo-oral tract and its increase in CF is possibly explained by a regional change in bacterial activity. The limited lower airway contribution supports the view of a genuinely impaired formation and metabolism of NO in CF, rather than poor diffusion of the molecule.

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. SummaryBackground: Studies using mouse models have revealed that mast cell progenitors are recruited from the blood circulation to the lung during acute allergic airway inflammation. The discovery of a corresponding human mast cell progenitor population in the blood has enabled to study the relation of circulating mast cell progenitors in clinical settings. Objectives:To explore the possible association between the frequency of mast cell progenitors in the blood circulation and allergic asthma, we assessed the relation of this recently identified cell population with asthma outcomes and inflammatory mediators in allergic asthmatic patients and controls.Methods: Blood samples were obtained, and spirometry was performed on 38 wellcontrolled allergic asthmatic patients and 29 controls. The frequency of blood mast cell progenitors, total serum IgE and 180 inflammation-and immune-related plasma proteins were quantified.Results: Allergic asthmatic patients and controls had a similar mean frequency of blood mast cell progenitors, but the frequency was higher in allergic asthmatic patients with reduced FEV 1 and PEF (% of predicted) as well as in women. The level of fibroblast growth factor 21 (FGF-21) correlated positively with the frequency of mast cell progenitors, independent of age and gender, and negatively with lung function.The expression of FcεRI on mast cell progenitors was higher in allergic asthmatic patients and correlated positively with the level of total IgE in the controls but not in the asthmatic patients. Conclusion: Elevated levels of circulating mast cell progenitors are related to reduced lung function, female gender and high levels of FGF-21 in young adults with allergic asthma. K E Y W O R D S allergic asthma, asthma, lung function, mast cell progenitors, mast cells | 875 SALOMONSSON et AL. S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section at the end of the article. How to cite this article: Salomonsson M, Malinovschi A, Kalm-Stephens P, et al. Circulating mast cell progenitors correlate with reduced lung function in allergic asthma. Clin