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 ...

The effect of pre-and post-natal smoke exposure on exhaled nitric oxide fraction (FeNO) in infants was evaluated and the association between respiratory symptoms and FeNO in the first 2 months of life was investigated. The Generation R study is a population-based, prenatally recruited birth cohort.Exposures were assessed by means of questionnaires prospectively administered during pregnancy and after birth. Successful off-line FeNO measurements during tidal breathing were obtained in 187 infants (median age 6.9 weeks). The association between possible determinants and log FeNO was investigated with multiple linear regression analysis.Infants exposed pre-and post-natally to smoke showed lower FeNO than infants exposed only after birth (geometric mean difference (95% confidence interval) 1.5 (1.0-2.1) ppb) and never-exposed infants (1.4 (1.0-1.8) ppb). FeNO was reduced in infants with severe upper respiratory symptoms compared with infants with nonsevere symptoms (1.6 (1.0-2.4) ppb). Infants with symptoms of the lower respiratory tract had lower FeNO than asymptomatic infants (1.2 (1.0-1.50) ppb).In conclusion, the nature of the association between smoke exposure and exhaled nitric oxide fraction is dependent on timing and intensity of exposure. The occurrence and the severity of respiratory symptoms in the first 2 months of life are associated with lower exhaled nitric oxide fraction.

American Thoracic Society (ATS) guidelines recommend to refrain from spirometry or exercise before measuring fractional exhaled nitric oxide (FENO) because forced breathing maneuvers might influence FENO values. However the few studies already reported in children have given conflicting results. The aim of the study was to observe to what extent spirometry or exercise could affect FENO in asthmatic children. Twenty-four asthmatic children (mean age 12.8 yr) were enrolled. Measurements of FENO were performed before and 5, 15, 30, 45 and 60 min after spirometry or a 6-min walk test, on two separate days in random order. Geometric mean FENO at baseline was 25.6 parts per billion (ppb) before spirometry and 23.5 ppb before exercise. A small drop of FENO to 24.2 and 23.7 ppb was found 5 and 15 min after spirometry (both p = 0.04). After exercise, FENO values showed a larger drop to 18.5 ppb after 5 min and 20.7 ppb after 15 min (p < 0.001; p = 0.004 respectively). Changes in FENO occurred after exercise irrespective of baseline FENO and values returned to baseline within 30 min. We conclude that both spirometry and exercise affect FENO in asthmatic children. As the changes after exercise may lead to erroneous interpretations, children should refrain from physical exercise during at least 30 min before FENO measurements.

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.

BackgroundAir pollution is associated with asthma exacerbations. We examined the associations of exposure to ambient particulate matter (PM10) and nitrogen dioxide (NO2) with the risk of wheezing in preschool children, and assessed whether these associations were modified by tobacco smoke exposure.MethodsThis study was embedded in the Generation R Study, a population-based prospective cohort study among 4,634 children. PM10 and NO2 levels were estimated for the home addresses using dispersion modeling. Annual parental reports of wheezing until the age of 3 years and fetal and infant tobacco smoke exposure was obtained by questionnaires.ResultsAverage annual PM10 or NO2 exposure levels per year were not associated with wheezing in the same year. Longitudinal analyses revealed non-significant tendencies towards positive associations of PM10 or NO2 exposure levels with wheezing during the first 3 years of life (overall odds ratios (95% confidence interval): 1.21 (0.79, 1.87) and 1.06 (0.92, 1.22)) per 10 μg/m3 increase PM10 and NO2, respectively). Stratified analyses showed that the associations were stronger and only significant among children who were exposed to both fetal and infant tobacco smoke (overall odds ratios 4.54 (1.17, 17.65) and 1.85 (1.15, 2.96)) per 10 μg/m3 increase PM10 and NO2, respectively (p-value for interactions <0.05).ConclusionsOur results suggest that long term exposure to traffic-related air pollutants is associated with increased risks of wheezing in children exposed to tobacco smoke in fetal life and infancy. Smoke exposure in early life might lead to increased vulnerability of the lungs to air pollution.