Fractional exhaled nitric oxide (FE NO ) levels are increased in children and adults with asthma, whereas low levels have been found in cystic fibrosis and primary ciliary dyskinesia. The aim of this study was to investigate whether FE NO measurements could distinguish between children below the age of 2 with different airway diseases. FE NO measurements were performed in 118 infants aged between 4.6 and 25.2 mo: 74 infants with recurrent wheezing (RW), 24 with bronchopulmonary dysplasia (BPD), and 20 with cystic fibrosis (CF). FE NO was measured also in 100 healthy controls aged between 1.1 and 7.7 mo. Geometric mean (95% confidence interval) FE NO values were 10.4 (9.1-12.0) parts per billion (ppb) in healthy infants, 18.6 (15.6 -22.2) ppb in wheezy infants, 11.7 (8.2-16.8) ppb in BPD infants and 5.9 (3.4 -10.1) ppb in CF infants. FE NO in wheezers was higher than in controls, BPD, and CF (p ϭ 0.009, p ϭ 0.038, and p Ͻ 0.001, respectively). Atopic wheezers showed higher FE NO than nonatopic wheezers (p ϭ 0.04). CF infants had lower FE NO than healthy controls and BPD infants (p ϭ 0.003 and p ϭ 0.043, respectively). FE NO values in BPD and control infants were not different. We conclude that FE NO is helpful to differentiate various airway diseases already in the first 2 y of life. T he fractional concentration of nitric oxide in exhaled air (FE NO ) has been suggested as a marker of bronchial eosinophilic inflammation. Increased FE NO levels have been found in asthmatic adults (1) and children with symptoms of asthma and atopy (2). Guidelines for the measurement of FE NO are available for both adults and children (3,4), and normal values for healthy children between 4 and 17 y of age have been recently published (5). Although in the last decade there has been a growing interest in measuring FE NO in noncooperative young children as well, few studies have investigated FE NO as a marker of bronchial inflammation in children below the age of 2 y. It has been shown that infants with recurrent wheeze have elevated levels of FE NO during exacerbations that rapidly decrease after steroid therapy (6), suggesting that eosinophilic airway inflammation is present in early childhood wheeze. Low FE NO levels have been found in infants with CF (7), primary ciliary dyskinesia (8) and rhinorrhea (9). A recent study by Baraldi and co-workers (10) showed that school-age children with BPD and airflow limitation had lower FE NO levels than healthy matched controls and asthmatic children, suggesting that airflow limitation in children with BPD might not be related to ongoing inflammation as is the case in asthma. It is well known that infants with BPD have an early inflammatory response followed by chronic inflammation and airways remodeling (11-13). Only one study previously reported high FE NO levels in infants with chronic lung disease (14).The aim of the present study was to measure FE NO in infants below the age of 2 y and to evaluate whether FE NO could be used to differentiate airways diseases in the first 2 y of ...

Guidelines for the measurement of fractional exhaled nitric oxide (FE(NO)) recommend refraining from lung function tests (LFT) and certain foods and beverages before performing FE(NO) measurements, as they may lead to transiently altered FE(NO) levels. Little is known of such factors in infants. The aim of the present study was to evaluate whether forced expiratory maneuvers, sedation, nasal contamination, and breastfeeding affect FE(NO) values in infants. FE(NO) was measured off-line during tidal breathing by means of a facemask covering nose and mouth. FE(NO) measurements were performed in 45 sedated infants (mean age 12.1 months) who underwent LFT because of airway diseases and in 83 unsedated healthy infants (mean age 4.3 months). In infants with airway diseases, no difference was found in FE(NO) values before and 5 min after LFT (n = 19 infants, p = 0.7) and FE(NO) values before sedation did not differ from FE(NO) values during sedation (n = 10 infants, p = 0.2). Oral FE(NO) values were significantly lower than mixed (nasal + oral) FE(NO) (n = 42 infants, p < 0.001). FE(NO) values before and 5 min after breastfeeding were not different (n = 11 healthy infants, p = 0.57). The short-term reproducibility in healthy infants (n = 54) was satisfactory (intraclass correlation coefficient = 0.94). We conclude that, in infants with airway diseases, LFT prior to FE(NO) measurement did not influence FE(NO) values and FE(NO) values did not change after sedation. Oral FE(NO) values were significantly lower than mixed (oral + nasal) FE(NO), and breastfeeding did not influence FE(NO). Short-term reproducibility in awake healthy infants was good.

The role of inhaled corticosteroids in the treatment of recurrent or persistent wheeze in infancy remains unclear. We evaluated the effect of 3 months of treatment with inhaled fluticasone propionate, 200 microg daily (FP200), on lung function and symptom scores in wheezy infants. Moreover, we evaluated whether infants with atopy and/or eczema respond better to FP200 as compared with non-atopic infants. Forced expiratory flow (Vmax(FRC)) was measured at baseline and after treatment. Sixty-five infants were randomized to receive FP200 or placebo, and 62 infants (mean age, 11.3 months) completed the study. Mean Vmax(FRC), expressed as a Z score, was significantly below normal at baseline and after treatment in both groups. The change from baseline of Vmax(FRC) was not different between the two treatment arms. After 6 weeks of treatment, and not after 13 weeks, the FP200 group had a significantly higher percentage of symptom-free days and a significant reduction in mean daily cough score compared with placebo. Separate analysis of treatment effect in infants with atopy or eczema showed no effect modification. We conclude that in wheezy infants, after 3 months of treatment with fluticasone, there was no improvement in lung function and no reduction in respiratory symptoms compared with placebo.

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