J.G.C. van Amsterdam

Relationship between exhaled NO, respiratory symptoms, lung function, bronchial hyperresponsiveness, and blood eosinophilia in school children

Background: Exhaled nitric oxide (eNO) may serve as a non-invasive marker of airway inflammation but its relationship with other commonly used measures has not been evaluated. Methods: Levels of eNO in a sample of 450 children aged 7–12 years out of a total sample of 2504 school children living in different urban areas near motorways were determined. The aim of this cross-sectional study was to explore the relationship between eNO, impairment of lung function (PEF, FVC, FEV1 and MMEF), bronchial hyperresponsiveness (BHR), and blood eosinophilia in children with and without atopy as assessed by skin prick testing. Results: Regression analysis showed that wheezing and nasal discharge and conjunctivitis that had occurred during the previous 12 months were positively associated with eNO levels in atopic children (relative increase of 1.48 and 1.41, respectively; p<0.05) but not in non-atopic children. Similarly, BHR and the number of blood eosinophils per ml were positively associated with eNO levels in atopic children (relative increase of 1.55 and 2.29, respectively; p<0.05) but not in non-atopic children. The lung function indices PEF, FVC, FEV1 and MMEF were not associated with eNO levels. Conclusions: In addition to conventional lung function tests and symptom questionnaires, eNO is a suitable measure of airway inflammation and its application may reinforce the power of epidemiological surveys on respiratory health.

The relationship between exhaled nitric oxide and allergic sensitization in a random sample of school children

Background Exhaled nitric oxide (NO) has been proposed as novel a non‐invasive marker of airway inflammation.

Nitric oxide metabolites in nasal lavage fluid of patients with house dust mite allergy.

BACKGROUND--The role of nitric oxide in the early and late phase of the allergic process was investigated in patients with allergic rhinitis against house dust mite and the effect of fluticasone propionate aqueous nasal spray was determined. METHODS--Production of nitric oxide (measured as nitrite+nitrate) in vivo in nasal mucosa was examined in 24 patients with rhinitis allergic to the house dust mite. In a double blind placebo controlled crossover study fluticasone propionate 200 micrograms aqueous nasal spray was administered twice daily for two weeks. In response to provocation with house dust mite extract (after four basal nasal lavages) nasal lavages were performed every hour for 9.5 hours by washing the nose with saline. In addition, a similar lavage protocol was performed in healthy volunteers with or without challenge with phosphate buffered saline. RESULTS--Nitric oxide is present in nasal lavage fluid in detectable amounts (range 10-50 microM), the level gradually increasing with time in both patients and controls after a decrease during the four basal lavages. Treatment with fluticasone propionate aqueous nasal spray did not affect initial basal production of nitric oxide nor production following provocation with house dust mite extract. CONCLUSIONS--Production of nitric oxide in nasal mucosa determined in sequential nasal washings is not affected by therapeutic doses of intranasal steroids.

Acute Effect of Air Pollution on Respiratory Complaints, Exhaled NO and Biomarkers in Nasal Lavages of Allergic Children during the Pollen Season

During 2 months of the pollen season, the acute and putative adjuvant effect of traffic-related air pollution on respiratory health was investigated in children sensitised to grass pollen or house dust mite (HDM). Respiratory complaints were objectified via measurement of exhaled NO and inflammatory mediators in nasal lavage (NAL). During the study children, skin prick negative (n = 31) or positive to grass pollen (n = 22), HDM (n = 34) or grass pollen + HDM (n = 32), kept a daily diary on respiratory symptoms, and NAL and exhaled air was sampled twice a week. The level of air pollutants and pollen was monitored continuously. Like children sensitised to HDM, those sensitised to pollen reported respiratory complaints (shortness of breath, itchy eyes or blocked nose) more frequently than non-sensitised children during (but not before) the pollen season; the respiratory complaints of sensitised children were independent of the pollen level. In addition, exposure to increased levels of PM10 induces ‘shortness of breath’ in pollen- and HDM-sensitised children, whereas ozone induces a blocked nose in HDM-sensitised children. Combined exposure to PM10 + pollen and O3 + pollen induces a blocked nose in both HDM-sensitised children and children sensitised to pollen + HDM. Significant positive associations were found between eNO and the levels of NO2, CO, PM2.5 and pollen in both sensitised and non-sensitised children. At the start of the pollen season, the NAL concentration of eosinophils and ECP in pollen-sensitised children was increased compared to winter, but their levels were not further affected by increased exposure to pollen or air pollution. In conclusion, during the pollen season, sensitised children continuously report a high prevalence of respiratory complaints which coincides with increased levels of upper and lower airway inflammatory markers. No additional pro-inflammatory effect of air pollution was observed, which indicates that air pollution does not facilitate allergen-induced inflammatory responses.

The Prevalence of Allergic Sensitisation in Immigrant Children in the Netherlands

Background: Differences in the prevalence of allergic sensitisation have been reported in immigrant children living in the same urban environment. The purpose of this study is to investigate the prevalence of allergic sensitisation in school children of Dutch, Turkish and Moroccan origin. Methods: The prevalence of sensitisation to aero-allergens was assessed using the skin prick test in a non-selected sample of 512 children (response rate 54%) living in the same inner city district of Utrecht. In addition, exhaled nitric oxide (FeNO) was determined. Results: The prevalence of allergic sensitisation was dependent on the ethnic origin. As compared with Dutch children (19.1%), a higher prevalence of allergic sensitisation was observed in immigrant children for whom both parents were born in Turkey (23.6%, not significant) or Morocco (30.6%, p < 0.05). The prevalence of allergic sensitisation in Dutch children was nearly 2 times lower than the reported prevalence in German children. In all sensitised children, the mean FeNO value was significantly (p < 0.05) higher than in non-sensitised children, and the mean FeNO level was highest in Moroccan children sensitised to indoor allergens. Conclusion: In the Netherlands, immigrant children show a higher prevalence of allergic sensitisation as compared to Dutch children.

Flow dependency and off‐line measurement of exhaled NO in children

Levels of exhaled nitric oxide (eNO) are flow‐dependent, and the choice of an optimal flow rate for off‐line and on‐line eNO measurement has raised much debate. Recently, a flow rate of 50 ml/s was recommended, but children younger than 5–6 years are not capable of stabilizing their expiratory flow at low flow rates. The power of off‐line eNO values to discriminate between normal and atopic children was therefore evaluated at different exhalation flow rates. At flow rates of both 8.3 ml/s and of 350 ml/s, children (8–12 years) sensitive to house dust mite have two‐fold higher eNO values (p < 0.001) as compared with children lacking such a sensitivity. The power of eNO to discriminate between normal and atopic subjects was similar at the two flow rates (no difference in AUC of receiver operation curves, p = 0.89). All children from 4.5 to 5 years of age (n = 29) could perform a single off‐line exhalation manoeuvre at high (>350 ml/s) but not at low (8.3 ml/s) flow rates. At high exhalation flow rate, eNO was 7.1 ± 2.4 (mean ± SD) median, 6.5 p.p.b. with a mean variation coefficient of 5.5%. Depending on their developmental level, about half of the younger children (35–46 months of age) could perform an off‐line exhalation manoeuvre at high flow rate with good reproducibility (mean variation coefficient of 6.6%). It is concluded that an exhalation flow rate of 350 ml/s is feasible to determine off‐line eNO‐values in children from 3.5 years of age, and that this high flow rate does not compromise the power of eNO to detect allergic disease.