The association of exhaled nitric oxide with air pollutants in young infants of asthmatic mothers

Abstract

Background: Exhaled nitric oxide is a marker of airway inflammation. Air pollution induces airway inflammation and oxidative stress. Little is known about the impact of air pollution on exhaled nitric oxide in young infants.

Methods: The Breathing for Life Trial recruited pregnant women with asthma into a randomised controlled trial comparing usual clinical care versus inflammometry-guided asthma management in pregnancy. Four hundred fifty-seven infants from the Breathing for Life Trial birth cohort were assessed at six weeks of age. Exhaled nitric oxide was measured in unsedated, sleeping infants. Its association with local mean 24-h and mean seven-day concentrations of ozone, nitric oxide, nitrogen dioxide, carbon monoxide, sulfur dioxide, ammonia, particulate matter less than 10 μm (PM10) and less than 2.5 μm (PM2.5) in diameter was investigated. The air pollutant data were sourced from local monitoring sites of the New South Wales Air Quality Monitoring Network. The association was assessed using a 'least absolute shrinkage and selection operator' (LASSO) approach, multivariable regression and Spearman's rank correlation.

Results: A seasonal variation was evident with higher median exhaled nitric oxide levels (13.6 ppb) in warmer months and lower median exhaled nitric oxide levels (11.0 ppb) in cooler months, P = 0.008. LASSO identified positive associations for exhaled nitric oxide with 24-h mean ammonia, seven-day mean ammonia, seven-day mean PM10, seven-day mean PM2.5, and seven-day mean ozone; and negative associations for eNO with seven-day mean carbon monoxide, 24-h mean nitric oxide and 24-h mean sulfur dioxide, with an R-square of 0.25 for the penalized coefficients. These coefficients selected by LASSO (and confounders) were entered in multivariable regression. The achieved R-square was 0.27.

Conclusion: In this cohort of young infants of asthmatic mothers, exhaled nitric oxide showed seasonal variation and an association with local air pollution concentrations.

Keywords: Air pollution; Breathing for Life Trial; Exhaled nitric oxide (eNO); Infant; Season.

Fig. 1

eNO: exhaled nitric oxide; NO: ambient nitric oxide

Fig. 2

eNO50 measured in each infant (transformed to square root) and plotted by month of test through the duration of the study, with sinterm regression line overlayed. eNO50SqR: square root eNO50 (exhaled nitric oxide interpolated to expiratory flow rate 50ml per second); sinterm: parameterized sine model with assumed value of zero at June, peak in March, and trough in September with increasing amplitude for each year

Fig. 3

CO: carbon monoxide; eNO50: exhaled nitric oxide interpolated to expiratory flow rate 50ml per second; PM10: particulate matter less than 10μm; SO2: sulfur dioxide

Fig. 4

Seven-day mean air pollutants on the day of the infant’s clinical assessment, plotted by month of test through the duration of the study, with cosine regression line overlayed. CO: carbon monoxide; cos: cosine; NH3: ammonia; NO: nitric oxide; NO2: nitrogen dioxide; O3: ozone; PM10: particulate matter less than 10μm; PM2.5: particulate matter less than 2.5μm; reg: regression line; SO2: sulfur dioxide

Fig. 5

CO: carbon monoxide; eNO50SqR: square root eNO50 (exhaled nitric oxide interpolated to expiratory flow rate 50ml per second); NH3: ammonia; NO: nitric oxide; NO2: nitrogen dioxide; O3: ozone; PM10: particulate matter less than 10μm; PM2.5: particulate matter less than 2.5μm; sinterm: parameterized sine model with assumed value of zero at June, peak in March, and trough in September with increasing amplitude for each year; SO2: sulfur dioxide

Fig. 6

1: Summer; 2: autumn/fall; 3: winter; 4: spring; CO: carbon monoxide; eNO50SqR: square root eNO50 (exhaled nitric oxide interpolated to expiratory flow rate 50ml per second); NH3: ammonia; NO: nitric oxide; NO2: nitrogen dioxide; O3: ozone; PM10: particulate matter less than 10μm; PM2.5: particulate matter less than 2.5μm; sinterm: parameterized sine model with assumed value of zero at June, peak in March, and trough in September with increasing amplitude for each year; SO2: sulfur dioxide