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Notes: 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.

Notes: Epidemiological information on symptoms affecting extra-respiratory organs and apparatuses in asthmatic children is scarce. The aim of this study therefore was to evaluate, at a population level, if and what extra-respiratory symptoms are associated with asthma. Two questionnaire-based, cross-sectional surveys were carried out on 1,262 students (651 males; mean age 9.57 years, age-range 6–14 years) in 1992 and on 1,210 students (639 males; mean age 9.02 years, age-range 6–14 years) in 1998, from two elementary and two junior high schools in Rome, Italy. Questionnaires included queries about asthma and its risk factors and extra-respiratory symptoms (headache, restlessness, sleep disturbances, urticaria, itching, and abdominal pain). Of responders, 11.9% (279/2,342) had a history of asthma. After adjustment for gender, family history of atopic disease, low birth weight, early respiratory problems, and damp house, asthma was significantly associated with recurrent abdominal pain (odds ratio [OR] 1.90; 95% confidence interval [CI]: 1.04, 3.16), itching (OR 3.15; 95% CI: 1.75, 5.68), and urticaria (OR 2.52; 95% CI: 1.02, 6.20). Asthma was reported by 10.2% (201/1,962) of children unaffected by this triad, by 20.1% (56/279; OR 2.20) with one of the symptoms, and by 31.6% (12/38; OR 4.04) with two or more symptoms. An emerging characteristic of pediatric asthma in our setting appears to be its association with certain extra-respiratory symptoms (abdominal pain, itching, and urticaria). A global, internistic approach to asthmatic children is increasingly required both in the clinical setting and in future epidemiological studies.

Notes: 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.

Notes: Several studies have shown a higher prevalence of positive skin-prick tests to airborne allergens in Western than in Eastern European countries. We have recently reported that skin histamine reactivity significantly increased in Italy over the past 15 years. Population differences in skin histamine reactivity could, at least in part, explain the reported differences in positive allergen skin tests. To test this hypothesis we compared histamine skin reactivity and the prevalence of allergen positive skin-prick tests in a sample of Italian and Polish schoolchildren. A total of 336 unselected 9-year-old-schoolchildren (198 in Italy and 138 in Poland) underwent skin-prick tests with three different histamine concentrations (10, 1 and 0.2 mg/ml) and with a panel of common airborne allergens according to the ISAAC protocol, phase two. Mean wheals elicited by skin-prick tests with the three serial concentrations of histamine were significantly larger (p 〈 0.001) and shifted more toward higher values (p 〈 0.001) in Italian than in Polish children. The differences were greater for the intermediate histamine concentration tested (1 mg/ml) than for the highest concentration (10 mg/ml). Skin-prick tests for airborne allergens were more frequently positive in Italian children: wheals ≥ 3 mm induced by any allergen [odds ratio (OR) 1.69; confidence interval (CI) 0.98–2.92] by Dermatophagoides pteronyssinus (OR 1.92; CI 0.97–3.80) and by D. farinae (OR 3.15; CI 1.16–8.63). Labeling as positive allergen wheal reactions half the size of the 10 mg/ml histamine wheal or larger reduced but did not abolish the Italian–Polish differences. The significantly higher skin histamine reactivity observed in Italian children could help to explain why allergen skin-test reactions differ in the East and West European populations. Moreover, differences in nonallergen-specific factors among populations should be considered in the interpretation of skin test results (e.g. cut-off points). To obtain meaningful results, epidemiological studies of allergies should include serial histamine dilutions.

Notes: Despite numerous studies demonstrating an association between asthma and many other chronic conditions and signs of Chlamydia pneumoniae (Cp) infection, the role of Cp in the pathogenesis of these illness remain still unclear. We investigated the prevalence of Cp antigen in the upper airways and the prevalence of detectable Cp serum antibodies in an unselected population of 207 9-yr-old schoolchildren. We also sought the presence of asthma, chronic or recurrent respiratory symptoms by means of questionnaire completed by the parents. Nasal aspirate, blood sampling and allergen skin prick tests were also performed. None of the children had obvious signs of acute infection at physical examination. Cp DNA was detected in nasal aspirates from 20 of the 207 children tested and serum IgG antibodies for Cp in 68 children. No association was found between atopy or history of atopic illness and the presence of Cp DNA or antibody production. This finding is explained by the fact that our study was conducted in an unselected childhood population, inherently including few children with asthma. A strong association between the status of antigen carrier and the presence of detectable Cp serum immunoglobulin (Ig)G or IgM suggests that subjects with detectable Cp antibodies have an impaired ability to eliminate this pathogen when infected. Because Cp eradication requires a strong Th1 lymphocyte response, the previously proven association between Cp and asthma, might reflect the known association of asthma with Th2-oriented lymphocytic activity.