RBM thickening and the eosinophilic inflammation characteristic of asthma in older children and adults are not present in symptomatic infants with reversible airflow obstruction, even in the presence of atopy.

Exhaled nitric oxide (FENO) was proposed as a marker of airway inflammation, but data about FENO in healthy children measured with standardized methods are so far limited. In order to assess the determinants of FENO in healthy children, we investigated a population-based sample of school-age children (n = 276) with a questionnaire, skin-prick tests, spirometry, and the measurement of FENO. The FENO of 114 nonatopic and nonsmoking children considered healthy were analyzed with stepwise multiple regression analysis, which showed significant associations with age, standing height, weight, and body surface area, but not with gender. Height was found to be the best independent variable for the regression equation for FENO, which on average showed an increase in the height range of 120-180 cm from 7 to 14 ppb. In the random sample of children, increased FENO was associated with atopy (odds ratio, 9.0; 95% confidence interval, 3.9-21.1; P < 0.0001), and significantly with allergic rhinitis and atopic dermatitis, but not with asthma. Respiratory symptom-free children with skin-prick test positivity had significantly higher FENO than healthy nonatopic subjects. We conclude that height is the best determinant of FENO in healthy children. Due to the strong effect of atopy, FENO data should not be interpreted without knowing the atopic status of the child. The present reference values of FENO may serve in clinical assessments for measuring airway inflammation in children.

Background: Respiratory function and airway inflammation can be evaluated in preschool children with special techniques, but their relative power in identifying young children with asthma has not been studied. This study was undertaken to compare the value of exhaled nitric oxide (FE NO ), baseline lung function, and bronchodilator responsiveness in identifying children with newly detected probable asthma. Methods: Ninety six preschool children (age 3.8-7.5 years) with asthmatic symptoms or history and 62 age matched healthy non-atopic controls were studied. FE NO was measured with the standard online single exhalation technique, and baseline lung function and bronchodilator responsiveness were measured using impulse oscillometry (IOS). Results: Children with probable asthma (n=21), characterised by recent recurrent wheeze, had a significantly higher mean (SE) concentration of FE NO than controls (22.1 (3.4) ppb v 5.3 (0.4) ppb; mean difference 16.8 ppb, 95% CI 12.0 to 21.5) and also had higher baseline respiratory resistance, lower reactance, and larger bronchodilator responses expressed as the change in resistance after inhalation of salbutamol. Children with chronic cough only (n=46) also had significantly raised mean FE NO (9.2 (1.5) ppb; mean difference 3.9 ppb, 95% CI 0.8 to 7.0) but their lung function was not significantly reduced. Children on inhaled steroids due to previously diagnosed asthma (n=29) differed from the controls only in their baseline lung function. The analysis of receiver operating characteristics (ROC) showed that FE NO provided the best power for discriminating between children with probable asthma and healthy controls, with a sensitivity of 86% and specificity of 92% at the cut off level of 1.5 SD above predicted. Conclusions: FE NO is superior to baseline respiratory function and bronchodilator responsiveness in identifying preschool children with probable asthma. The results emphasise the presence of airway inflammation in the early stages of asthma, even in young children.

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In order to study the determinants of respiratory system impedance and bronchodilator response in preschool children, a sample (n = 109) of healthy children (age 2.1-7.0 years) attending kindergarten was measured by using the impulse oscillometry. Their selection was based on a standardized questionnaire, negative skin prick test results and clinical examination, and sufficient cooperation. Triple measurements of respiratory resistance (Rrs) and reactance (Xrs) at 5, 10, 15 and 20 Hz, total respiratory impedance (Zrs), the resonance frequency (Fr) and the frequency dependence of resistance (dRrs/df) were performed, to determine individual mean values. Measurements were repeated after inhalation of 300 microg salbutamol (n = 89) or placebo (n = 19). At the baseline, Zrs and Rrs5-20 showed negative, and Xrs5-20, Fr and dRrs/df positive correlations with age, height and weight. However, logarithmic transformed height was the best independent variable for the regression equations of all the oscillometric variables. After inhalation of placebo, none of the oscillometric variables changed significantly. In the salbutamol group, the mean (SD) change in Rrs5 was -0.187 (0.124) kPa l(-1) s(-1) and -19.2 (10.2)%, corresponding to a lower reference limit of -36.9%. Both the within-test and between-test repeatabilities for the measurement of respiratory resistance were acceptable, for Rrs5 the coefficients of variation being 6.2 and 6.1%, respectively. As the overall success rate in our sample was high (89%), the forced oscillation technique seems to be a useful method in assessing respiratory function and bronchial lability in preschool children.