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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.

Nitric oxide (NO) can be detected in human exhaled air, and its endogenous production is increased in patients with asthma. It may provide a noninvasive means for measuring airway inflammation. The aim of this study was to establish reference values for exhaled NO concentrations in a large number of healthy school-age children. We measured exhaled NO levels in 159 white healthy children (88 girls, 71 boys, age range 6-15 years) recruited from two public schools of Padua, Italy. Exhaled NO levels in exhaled gas were measured by a tidal breathing method with a chemiluminescence analyzer, and NO steady-state levels were recorded. Nasal NO levels were measured by direct sampling from the nose during mouth breathing. The mean concentration of endogenous NO in orally exhaled gas was 8.7 parts per billion (ppb) (95% confidence interval (C.I.), 8.1-9.2 ppb) and sampled data followed a log-normal distribution (Kolmogorov-Smirnov d = 0.77, P > 0.2). No difference was found between boys (mean value, 8.4 ppb; 95% C.I., 7.3-9.4 ppb) and girls (mean value, 8.9 ppb; 95% C.I., 7.9-9.9 ppb). No significant correlation was found between age, height, or spirometric data and exhaled NO levels (r < 0.2). The mean value of nasal NO concentrations was 216 ppb (95% C.I., 204-228 ppb). There was no correlation between exhaled and nasal NO values (r = 0.16, P = ns). In conclusion, this study establishes a reference range for exhaled NO values measured by a tidal breathing method in children between age 6-15 years. The observed levels are independent of age, gender, and lung function, and can be used to monitor airway inflammation in asthmatic children.

The measurement of exhaled nitric oxide concentrations [NO] may provide a simple, noninvasive means for measuring airway inflammation. However, several measurement conditions may influence exhaled NO levels, and ambient NO may be one of these. We measured exhaled NO levels in 47 stable asthmatic children age 5 to 17 years and in 47 healthy children, gender and age matched. Exhaled [NO] in expired air was measured by a tidal breathing method with a chemiluminescence analyzer, sampling at the expiratory side of the mouthpiece. NO steady-state levels were recorded. In order to keep the soft palate closed and avoid nasal contamination, the breathing circuit had a restrictor providing an expiratory pressure of 3-4 cm H2O at the mouthpiece. To evaluate the effect of [NO] in ambient air, measurements were randomly performed by breathing ambient air or NO-free air from a closed circuit. Breathing NO-free air, exhaled [NO] in asthmatics (mean +/- SEM) was 23.7 +/- 1.4 ppb, significantly higher (P < 0.001) than in healthy controls (8.7 +/- 0.4 ppb). Exhaled NO concentrations measured during ambient air breathing were higher (49 +/- 4.6 ppb, P < 0.001) than when breathing NO-free air (23.7 +/- 1.4 ppb) and were significantly correlated (r = 0.89, P < 0.001) with atmospheric concentrations of NO (range 3-430 ppb). These findings show that 1) exhaled [NO] values of asthmatic children are significantly higher than in healthy controls, and 2) atmospheric NO levels critically influence the measurement of exhaled [NO]. Therefore, using a tidal breathing method the inhalation of NO-free air during the test is recommended.

It has been hypothesized that concentrations of exhaled nitric oxide (NO) may be related to the extent of cytokine-mediated airway inflammation. Recent findings indicate the nasal airways as an important site of NO production. Our objective was to evaluate whether children with allergic rhinitis show different nasal NO levels when compared with normal healthy subjects and the effect of topical steroids and anti-histamine therapy. We have measured the concentration of NO drawn from the nose of 21 children (5-17 years old) affected by perennial allergic rhinitis (house dust mite) out of therapy for at least 3 weeks. Thirteen children were then treated with nasal beclomethasone dipropionate (BDP) (400 micrograms daily) and eight subjects with nasal anti-histamine levocabastine (200 micrograms daily). Measurements were performed before and after 10 days of treatment. As a control group we evaluated 21 healthy children aged 5-15 years. To measure NO we used a chemiluminescence analyser. Before treatment the whole group of children with allergic rhinitis showed a mean (+/- SEM) nasal NO concentration of 267 +/- 18 ppb, significantly higher (P < 0.01) than the control group (186 +/- 15 ppb). The group of children treated with BDP showed, after 10 days of therapy, a significant (P < 0.05) decrease of nasal NO concentration (271 +/- 21 ppb vs. 212 +/- 20 ppb). Indeed, in the group treated with levocabastine, nasal NO concentrations did not present a significant difference (P not significant) compared with baseline (261 +/- 33 ppb and 252 +/- 31 ppb, respectively). These data suggest that (1) children with allergic rhinitis have higher levels of nasal NO than non-atopic controls and (2) intranasal steroid therapy significantly reduces nasal NO production in children with allergic rhinitis. We speculate that the allergic inflammatory response may influence the nasal NO levels and that NO measurements may be a useful marker of nasal inflammation.

Objectives: Nitric oxide (NO) produced in human airways seems to have both homeostatic and proinflammatory actions in the respiratory system. NO production has been shown to be higher in the exhaled air of asthmatic adults than in normal subjects. The aim of this study was to evaluate exhaled NO production during asthma exacerbation in children and the effect of a rescue course of oral steroid therapy., Study Design: We measured NO in the exhaled air of 16 children (8 girls and 8 boys, aged 6 to 13 years) with an acute asthmatic episode before and after 5 days of therapy with prednisone, and in 16 healthy children. To measure NO, children inhaled NO-free air and, breathing at tidal volume, exhaled in a circuit from which a chemiluminescence analyzer sampled continuously. To assess the effect of acute changes in bronchial caliber on exhaled NO levels, we measured NO before and after a positive bronchodilation test result with albuterol in seven children with asthma whose disease was stable., Results: In the group with acute asthma (forced expiratory volume in 1 second 62% +/- 4.4% predicted, mean +/- SEM), NO levels were significantly higher (31.3 +/- 4.2 parts per billion [ppb]) than in healthy children (5.4 +/- 0.4 ppb, p < 0.001). Administration of prednisone (1 mg/kg per day orally) for 5 days resulted in a mean decrease of 46% +/- 4% in exhaled NO concentrations (16.5 +/- 2.3 ppb, p < 0.001) compared with baseline, accompanied by a significant improvement in lung function (forced expiratory volume in 1 second 90.7% +/- 4.3% predicted). However, in patients with asthma exhaled NO levels remained significantly higher than in control children (p < 0.001) after steroid treatment. When exhaled NO was measured before and after a positive result after bronchodilator reversibility testing, we found no difference in exhaled NO levels (24 +/- 3.8 ppb vs 23.8 +/- 3 ppb; difference not significant). This demonstrates that inhaled albuterol and acute changes in bronchial caliber do not affect exhaled NO measurement., Conclusions: These data show that children with asthma exacerbation have high levels of exhaled NO that rapidly decrease with oral steroid therapy. We suggest that measurement of exhaled NO may represent a noninvasive method of monitoring airway inflammation in children with asthma.

Recently, it has been demonstrated that paranasal sinuses are an important site of nitric oxide (NO) production in the upper airways. The aim of this study was to evaluate the NO nasal concentration in children with acute maxillary sinusitis before and after treatment with antibiotic therapy. We performed NO nasal measurements in 16 children 4 to 13 yr of age with acute maxillary sinusitis and compared values with 16 age- and sex-matched healthy control subjects. The diagnosis of acute sinusitis was done by clinical signs and symptoms in addition to radiographic examination. NO nasal concentrations were measured by a chemiluminescence analyzer. Nasal NO steady state during oral breathing was recorded. The mean +/- SEM NO nasal concentration in children with sinusitis was 70 +/- 8.7 parts per billion (ppb) and increased significantly to 220 +/- 15 ppb (p < 0.001) after antibiotic therapy (amoxicillin/clavulanate). NO values after recovery from sinusitis were similar to those of healthy control subjects (245 +/- 15 ppb, p = NS). NO nasal measurements were also performed before and after antibiotic treatment in nine children 4 to 12 yr of age with symptoms of upper respiratory tract infection but no symptoms of sinusitis. In these children NO nasal levels were 249 +/- 32 ppb and did not change (p = NS) after antibiotic therapy. We conclude that during acute maxillary sinusitis the concentration of nasal NO is largely decreased, probably because of an impaired flow of NO from the paranasal sinuses, and that NO returns to normal levels after antibiotic therapy.