Association between air pollution exposure and exhaled nitric oxide in an elderly population

Abstract

Background: Animal models suggest that the cardiovascular effects of air pollution result in part from inflammation caused by proinflammatory mediators originating in the lung. In a human study of the cardiovascular effects of air pollution, we aimed to evaluate the potential association between air pollution levels and the fraction of exhaled nitric oxide (FE NO ), a non-invasive measure of airway inflammation. Methods: Breath samples were collected weekly between September and December 2000 in a community based group of elderly subjects (median age 70.7 years) in Steubenville, Ohio. The samples were analysed for NO. Air pollution levels were measured concurrently at a central site monitor. Results: An increase in the 24 hour average PM 2.5 concentration of 17.7 mg/m 3 was associated with an increase in FE NO of 1.45 ppb (95% CI 0.33 to 2.57) in models adjusted for subject, week of study, day of the week, hour of the day, ambient barometric pressure, temperature, and relative humidity. This represents a change of approximately 15% compared with the mean FE NO in the cohort (9.9 ppb). A significant association was also observed for a 24 hour moving average of ambient NO (0.83 ppb increase, 95% CI 0.26 to 1.40). In two-pollutant models, the magnitude and precision of the PM 2.5 effect was not reduced and the ambient NO effect was no longer significant. The associations between FE NO and PM 2.5 were significantly higher in subjects with a doctor's diagnosis of COPD (p value for interaction = 0.03). Conclusions: Ambient pollution may lead to airway inflammation as measured by FE NO . These subclinical inflammatory changes may be an important step in the pathogenesis of the cardiopulmonary effects induced by exposure to air pollution.

Inflammatory and Oxidative Stress Responses of Healthy Young Adults to Changes in Air Quality during the Beijing Olympics

“…This finding supports an association between lowered whole-body oxidative stress and improved air quality. Although there has been a considerable literature reporting associations between ambient PM and oxidative stress in children and adults with asthma or other cardiorespiratory diseases (20,36,(53)(54)(55), our study provides evidence in healthy and young adults, with both respiratory tract and whole-body biomarkers, to support the oxidative stress mechanism.…”

“…Increased air pollution levels have been associated with increased levels of fractional exhaled nitric oxide (FE NO ), reflecting pulmonary inflammation, in children and the elderly (12)(13)(14)(15)(19)(20)(21)(22). Traffic pollution exposure has been associated with increased airway acidity (lowered EBC pH) in persons with asthma (16), reflecting inhibition of local epithelial proton pumps during airway inflammation (23).…”

Bias and confounding in longitudinal measures of exhaled monoxides

“…Possible mechanisms by which inhaled NO and CO influence exhaled monoxide concentrations include: (1) deadspace (some fraction of the exhaled monoxides are from residual inhaled air in the airway); (2) failure to maintain subject adherence with breath collection protocols (incomplete mouth seal during inhalation); (3) leaks within the collection device, its connection to the balloon, or via microperformations in the balloons; (4) inhaled monoxides cause increases in eCO and eNO (Steerenberg et al, 1999), perhaps by upregulating HO-1 and iNOS respectively); (5) confounding by air pollutants such as particulate matter, or other nitrogen-containing compounds such as nitrogen dioxide or nitrous/nitric acid (Adamkiewicz et al, 2004), which may upregulate HO-1 or iNOS. Confounding by PM did not explain the eNO-iNO association, since even in models that included PM 10 or PM 2.5 , iNO remained strongly associated with eNO (data not presented).…”

“…Since inhaled monoxide concentrations are associated both with exhaled concentrations and with copollutant concentrations, the observed associations between exhaled monoxides and PM may be due to confounding by inhaled monoxides. Prior longitudinal studies of eNO and eCO vary considerably in their approaches towards accounting for the influence of inhaled concentrations on exhaled concentrations, with some adjusting for monoxides measured indoors, (Zanconato et al, 2002;Adamkiewicz et al, 2004) outdoors (Koenig et al, 2003Adamkiewicz et al, 2004;Mar et al, 2005), both (Adamkiewicz et al, 2004) or neither Pearson et al, 2005). Furthermore, while some investigations have used NO scrubbers (Adamkiewicz et al, 2004;Jansen et al, 2005), others have not (Koenig et al, 2003Mar et al, 2005), raising the question of whether reported associations between pollutants and eNO may be confounded by inhaled NO concentrations.…”

“…Concentrations of eNO (Baraldi et al, 1997) and eCO (Yamaya et al, 1999(Yamaya et al, , 2001) are higher during exacerbations, and decrease with steroid treatment (Kharitonov et al, 1996), although these observations are more consistent for eNO than for eCO (Kharitonov et al, 2002;Zanconato et al, 2002). Because the measurement of exhaled monoxides permits the non-invasive monitoring of airway inflammation, recent studies of air pollution have included as key outcome measurements concentrations of eNO (Koenig et al, 2003;Adamkiewicz et al, 2004;Jansen et al, 2005;Koenig et al, 2005;Mar et al, 2005) and eCO (Nightingale et al, 2000). Additionally, longitudinal measures of eNO have been used to guide clinical asthma management (Pearson et al, 2005;Pijnenburg et al, 2005;Smith et al, 2005).…”