Additive effect of eosinophilia and atopy on exhaled nitric oxide levels in children with or without a history of respiratory symptoms

Abstract

Although atopy and blood eosinophilia both influence exhaled nitric oxide (eNO) measurements, no study has quantified their single or combined effect. We assessed the combined effect of atopy and blood eosinophilia on eNO in unselected schoolchildren. In 356 schoolchildren (boys/girls: 168/188) aged 9.0-11.5 yr, we determined eNO, total serum IgE, blood eosinophil counts and did skin prick tests (SPT) and spirometry. Parents completed a questionnaire on their children's current or past respiratory symptoms. Atopy was defined by a SPT >3 mm and eosinophilia by a blood cell count above the 80th percentile (>310 cells/ml). eNO levels were about twofold higher in atopic-eosinophilic subjects than in atopic subjects with low blood eosinophils [24.3 p.p.b. (parts per billion) vs. 14.1 p.p.b.] and than non-atopic subjects with high or low blood eosinophils (24.3 p.p.b. vs. 12.2 p.p.b. and 10.9 p.p.b.) (p <0.001 for both comparisons). The additive effect of atopy and high eosinophil count on eNO levels remained unchanged when subjects were analyzed separately by sex or by a positive history of wheeze (n=60), respiratory symptoms other than wheeze (n=107) or without respiratory symptoms (n=189). The frequency of sensitization to Dermatophagoides (Dpt or Dpf) was similar in atopic children with and without eosinophilia (66.2% and 67.4%, respectively); eosinophilia significantly increased eNO levels in Dp-sensitized children as well in children sensitized to other allergens. In a multiple linear regression analysis, eNO levels were mainly explained by the sum of positive SPT wheals and a high blood eosinophil count (t=4.8 and 4.3, p=0.000), but also by the presence of respiratory symptoms (especially wheeze) and male sex (t=2.6 and 2.0, p=0.009 and 0.045, respectively). Measuring eNO could be a simple, non-invasive method for identifying subjects at risk of asthma in unselected school populations.

Factors that influence exhaled nitric oxide in Italian schoolchildren

“…This result is in agreement with the works of Barreto et al 4 and Wong et al, 16 who recently demonstrated a sex difference in eNO levels in schoolchildren. Similarly, Nordvall et al, 17 in a large population sample, found a significantly higher eNO in boys than in girls.…”

“…Similar results were previously reported in both adults 13,14 and children. [2][3][4] However, other studies did not find a relation between atopy and eNO levels in children. 1,5,15 In particular, Latzin et al 15 failed to demonstrate a relation between atopy and eNO levels in 4-to 18-year-old healthy children.…”

“…This result is consistent with previous studies demonstrating the effect of the number of positive skin test results on the level of eNO. 1,2,4,7,22 In particular, Franklin et al 2 found that in healthy children eNO levels were higher in those with a positive skin prick test result and even higher in children with more than 1 positive skin test result, suggesting that allergen sensitization may play a significant role in elevating eNO production in the respiratory tract.…”

“…Increased levels of eNO have been found in asthmatic children 1 and in asymptomatic atopic children. [2][3][4] Consequently, it has been suggested that the relation between asthma and increased eNO levels may be mediated by atopy itself. 5 This suggestion emphasizes the key role of atopic inflammation in determining an increase in eNO production for allergic diseases such as asthma and rhinitis.…”

“…1,8 Conversely, other studies demonstrated a linear or dose-response relation between the degree of skin test positivity and eNO levels. 2,4,7 The relative weight of some factors (atopy, clinical disease, number of positive skin test results) remains to be determined. The aim of the present study was to identify the determinants of high eNO levels in a sample of schoolchildren with and without respiratory disease.…”