Exhaled nitric oxide in asthmatic and non‐asthmatic children: Influence of type of allergen sensitization and exposure to tobacco smoke

Abstract

Asthmatic bronchial inflammation is associated with increased nitric oxide concentrations in exhaled air (eNO). Recent data suggest that this effect arises from atopy. Our aim in this study was to find out whether atopy and sensitization to particular allergens influences eNO levels. A total of 213 subjects (41 asthmatics and 172 controls) (96 boys and 117 girls, 7.3-14 years of age) were studied. Parents completed a questionnaire that sought information on their children's respiratory symptoms and exposure to tobacco smoke. Subjects underwent skin-prick tests for the following common allergens: Dermatophagoides pteronyssinus (Dpt), cat fur, Aspergillus fumigatus, Alternaria tenuis, mixed grass, mixed tree pollen, Parietaria officinalis, egg, and cow's milk. eNO was collected in 1-l mylar bags (exhaled pressure 10 cmH2O, flow 58 ml/s) and analyzed by using chemiluminescence. Atopic and non-atopic children without a history of chronic respiratory symptoms had a similar geometric mean eNO (atopics, n = 28, 11.2 p.p.b.; non-atopics, n = 96, 10.0 p.p.b.; mean ratio 1.1, 95% confidence interval [CI]: 0.7-1.6). Conversely, atopic asthmatic subjects had significantly higher eNO values than non-atopic asthmatic subjects (atopics, n = 25, 24.8 p.p.b.; non-atopics, n = 16, 11.4 p.p.b.; mean ratio 2.2, 95% CI: 1.2-3.9, p= 0.000). In children with rhinitis alone (n = 15) and those with lower respiratory symptoms other than asthma (n = 33), eNO increased slightly, but not significantly, with atopy. eNO levels correlated significantly with Dpt wheal size (r = 0.51) as well with the wheal size for cat, mixed grass, and Parietaria officinalis (r = 0.30-0.29), and with the sum of all wheals (r = 0.47) (p= 0.000). Subjects sensitized only for Dpt (but not those subjects sensitized only for grass pollen or other allergens) showed significantly higher eNO levels than non-atopic subjects (16.4 p.p.b. vs. 10.2 p.p.b., mean ratio 1.6, 95% CI: 1.1-2.3, p= 0.002). In asthmatic subjects, Dpt sensitization markedly increased eNO levels (Dpt-sensitized subjects: 28.0 p.p.b.; Dpt-unsensitized subjects: 12.2 p.p.b.; mean ratio 2.3, 95% CI: 1.5-3.5, p= 0.000). Non-asthmatic Dpt-sensitized subjects also had significantly higher eNO values than non-asthmatic, non-Dpt-sensitized subjects (14.2 p.p.b. vs. 10.1 p.p.b.; mean ratio 1.4, 95% CI: 1.1-1.9, p= 0.008). No difference was found between eNO levels in asthmatic subjects and control subjects exposed or unexposed to tobacco smoke. In conclusion, eNO concentrations are high in atopic asthmatic children and particularly high in atopic asthmatics who are sensitized to house-dust mite allergen.

Interrelationships among asthma, atopy, rhinitis and exhaled nitric oxide in a population‐based sample of children

“…there was a substantial increase in eNO level in atopic asthmatics, whereas non-atopic asthmatics had a low eNO, similar to that of the control group. This result was also consistent with previous findings [16,21]. This difference between the two subgroups raises the question of whether the pathophysiological mechanisms of atopic asthma and non-atopic asthma are different.…”

“…As previously noted in adults [16] and in children [21], we found a low level of eNO that did not vary depending on the subjects' atopic or non-atopic status in the control group. This result was consistent with studies [22,23] that found no inflammatory modification of the bronchoalveolar lining in atopic or non-atopic healthy subjects.…”

Factors that influence exhaled nitric oxide in Italian schoolchildren

“…Similarly, Leuppi et al 23 showed that in atopic children, an increased eNO level is associated with sensitization to perennial allergens but not with seasonal allergens. In addition, Barreto et al 19 reported no difference in eNO levels between nonatopic and atopic children sensitized to grass pollen. Thus, sensitization to indoor perennial allergens appears to affect eNO production in the respiratory tract, possibly through longlasting inflammatory stimuli, regardless of clinical respiratory manifestations.…”

“…Nevertheless, controversial results exist on the relation between sex and eNO levels; in fact, in some studies no association was found between sex and eNO. 18,19 In the study by Malmberg et al, 18 the authors demonstrated that height was a strong predictor of increased eNO in healthy children. The latter association was not found in our study.…”

Seasonal variation and environmental predictors of exhaled nitric oxide in children with asthma

“…19,20 The association of environmental tobacco smoke exposure and FeNO in children, however, is mixed, with no relationship in some studies and an inverse association in others. 21,22 Environmental exposures and asthma symptoms can vary by season, and these exposures affect asthma control. 23 One study, demonstrated that mean FeNO levels were higher in the winter than the spring, but only winter and spring FeNO levels were examined.…”