No abstract

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.

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.

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.

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. Pediatr Pulmonol. 1999; 27:54–58. © 1999 Wiley‐Liss, Inc.