Title: Ambient combustion by-product exposures and exhaled biomarkers of airway inflammation and oxidative stress
Description: Introduction: Numerous studies have found associations between exposure to airborne particulate matter and respiratory morbidity and mortality. However, the varying composition, dependant on the different sources of particulate matter, and its effect on processes of inflammation and oxidative stress in the airways has not been completely elucidated. The use of airway biomarkers, fractional exhaled nitric oxide (FENO) and exhaled breath condensate (EBC), can provide valuable insight into processes of inflammation and oxidative stress in the airways. In these studies we sought to characterize the associations between airborne pollutant exposures and their sources and airway biomarkers. Methods:The study population of interest for Chapters III-V is a subset of children currently enrolled in a birth cohort under the Columbia Children's Center for Environmental Health. Chapter III refers to the validation in this population of a method for partitioning FENO contributions from the proximal and distal airways.

Chapters IV and V refer to the implementation of this method in the study of ambient metals and residential proximity to relevant sources of particulate matter (PM) and black carbon (BC). Briefly, the children of African-American and Dominican mothers living in low-income NYC neighborhoods had FENO samples collected offline at constant flow rates of 50, 83 and 100 mL/sec at ages 9 and/or 11. Surrogate measures for bronchial flux NO (JNO) and alveolar (Calv) NO concentrations were estimated using a previously validated mathematical model. Wheeze in the last 12 months was assessed by the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. Seroatopy was determined by specific IgE at age 9. For Chapter IV, in order to examine the associations between metal fractions of particulate matter and airway inflammation, ambient measures of Ni, V, Zn and Fe were obtained from a local central monitoring site and averaged over nine days based on three 24 hour measures every third day.

Seroatopy was determined by specific IgE at age 7. For Chapter V, residential distance to a major road, truck route and bus stop density, area covered by major roads, stationary point sources (SPS), toxic release inventory sites (TRIS) and commercial buildings, and number of buildings burning residual oil within 250-meters of each child's home were determined. These variables were selected a priori as potential important sources or airborne PM and BC. For Chapter VI, the study population was comprised of seven- and eight-year-old children enrolled in an asthma case-control study in New York City. Seven day averages of domestic levels of particulate matter <2.5 microns (PM2.5), BC and environmental tobacco smoke (ETS) were measured. Urea and 8-isoprostane were measured by liquid chromatography tandem mass spectrometry (LC/MS/MS) in EBC collected during home visits. All data were analyzed with SPSS. Results: In our first study, children with seroatopy had significantly higher median JNO p<0.001) when compared to non-seroatopic children; however, median Calv was not significantly different between these two groups (p=0.644).

Children with wheeze in the past year had significantly higher median Calv (p<0.001), but not JNO (295 vs. 165 pL/s, p=0.241) when compared with children without wheeze. In our second study, ambient V and Fe concentrations were associated positively with FENO50 (p=0.018, p=0.027). Ambient Fe was associated positively with JNO (p=0.017). Ambient Ni and V concentrations were associated positively with Calv (p=0.004, p=0.018 respectively). A stronger association of Ni concentrations with Calv was observed among the children with seroatopy. In our third study, there were no significant associations between any of the air pollution indicator variables and FENO parameters in adjusted models. In our final study, PM2.5and BC, but not ETS, were significantly associated with increases in 8-isoprostane (p<0.05 for both) after adjustment for covariates. In a co-pollutant model including PM2.5, BC and ETS, only BC remained a statistically significant predictor of 8-isoprostane. Discussion: Recent exposure to airborne pollutants was associated with increased levels of biomarkers of airway inflammation and oxidative stress measured in exhaled breath.

The metal and BC fractions of PM might be more relevant to the understanding adverse respiratory outcomes related to air pollution exposure.