While it is known that exhaled nitric oxide (ENO) is increased in adults and school children with asthma exacerbation probably as an expression of disease activity, no studies have investigated whether this phenomenon also occurs in infants and young children with recurrent wheeze exacerbation. We measured ENO in 13 young children (mean age 20.2 mo) with recurrent wheeze (Group 1) during an acute episode and after 5 d of oral prednisone therapy. ENO was measured also in nine healthy control subjects (Group 2) (mean age 16.9 mo) and in six children with a first-time viral wheezy episode (Group 3) (mean age 11 mo). To measure ENO, infants inhaled NO-free air via a face mask from a reservoir and, through a nonrebreathing valve, exhaled in a collecting bag that was analyzed by chemiluminescence. To address the question of whether the levels of ENO collected in the bag are a reflection of the pulmonary airway, ENO determinations were performed in two healthy infants before and after tracheal intubation for elective surgery. During the acute episode of wheezing the mean (+/- SEM) value of ENO in children with recurrent wheeze (Group 1) was 14.1 +/- 1.8 ppb, almost threefold higher than in healthy control subjects (5.6 +/- 0.5 ppb, p < 0.001). After steroid therapy we found a mean fall of 52% in ENO (5.9 +/- 0.7 ppb, p < 0.01) compared with baseline values. ENO values measured before and after intubation in two infants were 6 ppb and 5 ppb in one child and 7 ppb and 6 ppb in the other one. The mean value of ENO of children with first-time wheeze (Group 3) was 8.3 +/- 1.3 ppb, significantly lower (p < 0.05) than the value of children with recurrent wheeze (Group 1). In conclusion, we describe a method to measure ENO in young children and show that infants with recurrent wheeze have elevated levels of ENO during exacerbation that rapidly decrease after steroid therapy. This suggests that, in these children, airway inflammation could be present at a very early stage.

It is known that exhaled nitric oxide (ENO) is increased in asthmatic individuals, probably as an expression of airway inflammation, but no studies have been reported of ENO and exercise-induced bronchoconstriction (EIB). We assessed the effect of a treadmill exercise challenge on ENO concentration in 24 asthmatic children aged 11.2 +/- 0.4 yr (mean +/- SEM). According to the presence or absence of EIB, the children were divided into an EIB group (n = 10) and a non-EIB group (n = 14). ENO was measured with a single-breath reservoir technique. FEV(1), ENO, and heart rate were measured at baseline and 1, 6, 12, and 18 min after the end of exercise. We also measured ENO in 18 healthy control children aged 10.8 +/- 0.6 yr, of whom nine underwent an exercise challenge identical to that of the asthmatic children. After the exercise test, the mean decrease in FEV(1) was 34% in the EIB group and 5% in the non-EIB group. The EIB group had higher baseline ENO values (12.3 +/- 1.6 ppb) than the healthy children (6.1 +/- 0.2 ppb) (p < 0.01). The time course of ENO was similar in the EIB, non-EIB, and control groups, with no significant changes after exercise (p = NS). In the overall group of asthmatic children there was a significant correlation (r = 0.61, p < 0.01) between baseline (preexercise) ENO and magnitude of the maximal decrease in FEV(1) after exercise. In conclusion, our study shows that ENO levels do not change during acute airway obstruction induced by exercise challenge in asthmatic children. In addition, baseline ENO values correlate with the magnitude of postexercise bronchoconstriction, suggesting that NO may be a predictor of airway hyperresponsiveness to exercise.

Exhaled nitiric oxide (NO) is increased in exhaled breath of asthmatic patients. The aim of this study was to investigate the longitudinal changes of exhaled NO outside and during the pollen season in pollen-allergic asthmatic children. Twenty-one children (age 6 to 16 yr), with a seasonal allergic asthma sensitive to grass pollen, underwent measurements of exhaled NO and pulmonary function before (March), during (May), and after (November) the pollen season. Exhaled NO was measured by a tidal breathing method with a chemiluminescence analyzer and NO steady-state levels were recorded. The timing of the measurements during the pollen season was based on the atmospheric pollen count. Exhaled NO values of asthmatic children were compared with those of 21 sex- and age-matched healthy children. Pulmonary function and symptoms of asthma were also evaluated at each visit. The mean value of exhaled NO before the grass season was 12.7 +/- 5.1 ppb (mean +/- SD), significantly higher when compared with controls (7.8 +/- 2.7 ppb, p < 0.001). In the pollen season there was a significant (p < 0.001) twofold increase in exhaled NO (21.4 +/- 7.6 ppb) that, after the season, returned to values similar (12.8 +/- 5.8 ppb, p = NS) to those found before the season. There were no significant changes in FEV1 before and during the season (98.6% predicted versus 101% predicted, p = NS). We conclude that natural allergen exposure is related to an increase of exhaled NO in asthmatic grass pollen-allergic children even in absence of significant changes in airways function. We speculate that measurement of exhaled NO could be a sensitive noninvasive marker of asthma disease activity.

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