Longitudinal effects of air pollution on exhaled nitric oxide: the Children's Health Study

Abstract

OBJECTIVES To assess the effects of long-term variations in ambient air pollutants on longitudinal changes in exhaled nitric oxide (FeNO), a potentially useful biomarker of eosinophilic airway inflammation, based on data from the southern California Children’s Health Study. METHODS Based on a cohort of 1,211 schoolchildren from 8 Southern California communities with FeNO measurements in 2006/07 and 2007/08, regression models adjusted for short-term effects of air pollution were fitted to assess the association between changes in annual long-term exposures and changes in FeNO. RESULTS Increases in annual average concentrations of 24-hr average NO2 and PM2.5 (scaled to the interquartile range (IQR) of 1.8 ppb and 2.4 μg/m3, respectively) were associated with a 2.29 ppb (CI=[0.36,4.21]; p =0.02) and a 4.94 ppb (CI=[1.44,8.47]; p = 0.005) increase in FeNO, respectively, after adjustments for short term effects of the respective pollutants. In contrast, changes in annual averages of PM10 and O3 were not significantly associated with changes in FeNO. These findings did not differ significantly by asthma status. CONCLUSIONS Changes in annual average exposure to current levels of ambient air pollutants are significantly associated with changes in FeNO levels in children, independent of short-term exposures and asthma status. Use of this biomarker in population-based epidemiologic research has great potential for assessing the impact of changing real world mixtures of ambient air pollutants on children’s respiratory health.

Exhaled NO: Determinants and Clinical Application in Children With Allergic Airway Disease

“…26 Additionally, data from the Southern California Children's Health Study have shown that increases in annual average exposure to ambient air pollutants, such as NO2 and PM2.5, are significantly associated with increased FeNO in children, independent of short-term exposure to ambient air pollution and asthma status. 27 FeNO levels have been correlated with personal and ambient air pollution in children with asthma. 28 In 2 pollutant models, FeNO levels were strongly positively associated with personal and ambient elemental carbon and NO2, and with personal, but not with ambient PM2.5.…”

“…There are some inconsistent results with regard to the study population (i.e., atopic vs nonatopic and asthmatic vs nonasthmatic), treatment (i.e., naïve asthma vs after corticosteroid treatment), asthma condition (i.e., asthma controlled vs uncontrolled and stable asthma vs during asthma exacerbation), and various levels of exposure (i.e., personal vs ambient exposure, level of exposure, and short term vs long term exposure). 27 Therefore, further research on the usefulness of FeNO to identify the adverse respiratory effects of the exposure to pollutants in children is needed.…”

“…30,35,36 Some studies have not found a significant effect of passive smoking on FeNO in children, 30,36 whereas others suggested that environmental tobacco smoke lowers FeNO levels (Table). 27,35 According to the type of smoke exposure, acute exposure may induce a marked, but transient reduction in FeNO levels related to a negative feedback of iNOS activity, since tobacco smoke contains high concentrations of NO. 27 The mechanism for the effect of daily exposure to tobacco smoke could be hypothesized as a progressive negative feedback leading to the inhibition of iNOS gene expression.…”

“…Ultimately, high levels of NO are produced from epithelial Emerging evidence indicates that air pollution is associated with FeNO. 26,27 Therefore, FeNO could be used as an indirect biomarker of airway inflammation in population-based epidemiological research to assess the impact of ambient air pollution on children's respiratory health. Short-term increases in ambient air pollutants, such as PM2.5, PM10, and O3, have been associated with higher levels of FeNO in children, independent of asthma and allergic status (Table).…”

Air Pollution Exposure

“…Th ough not specifi c for air pollution exposure, biomarkers with the potential for future clinical application include exhaled nitric oxide, micronuclei frequency in buccal mucosa cells, microRNA in induced sputum samples, malondialdehyde in exhaled breath condensate, and serum IL-6 levels. 37,[55][56][57][58] Of the ILDs, IPF, in particular, is age-related, raising the possibility that lifetime cumulative environmental exposures may relate to the advanced cellular senescence seen in this disease. 23,59 Comprehensively characterizing the environmental contributors to fi brogenesis (either directly or through gene and environment interactions) may be an essential step in understanding the complex pathobiology of IPF.…”