Diesel exhaust modulates ozone-induced lung function decrements in healthy human volunteers

Abstract

The potential effects of combinations of dilute whole diesel exhaust (DE) and ozone (O₃), each a common component of ambient airborne pollutant mixtures, on lung function were examined. Healthy young human volunteers were exposed for 2 hr to pollutants while exercising (~50 L/min) intermittently on two consecutive days. Day 1 exposures were either to filtered air, DE (300 μg/m³), O₃ (0.300 ppm), or the combination of both pollutants. On Day 2 all exposures were to O₃ (0.300 ppm), and Day 3 served as a followup observation day. Lung function was assessed by spirometry just prior to, immediately after, and up to 4 hr post-exposure on each exposure day. Functional pulmonary responses to the pollutants were also characterized based on stratification by glutathione S-transferase mu 1 (GSTM1) genotype. On Day 1, exposure to air or DE did not change FEV1 or FVC in the subject population (n = 15). The co-exposure to O₃ and DE decreased FEV1 (17.6%) to a greater extent than O₃ alone (9.9%). To test for synergistic exposure effects, i.e., in a greater than additive fashion, FEV1 changes post individual O₃ and DE exposures were summed together and compared to the combined DE and O₃ exposure; the p value was 0.057. On Day 2, subjects who received DE exposure on Day 1 had a larger FEV1 decrement (14.7%) immediately after the O₃ exposure than the individuals' matched response following a Day 1 air exposure (10.9%). GSTM1 genotype did not affect the magnitude of lung function changes in a significant fashion. These data suggest that altered respiratory responses to the combination of O₃ and DE exposure can be observed showing a greater than additive manner. In addition, O₃-induced lung function decrements are greater with a prior exposure to DE compared to a prior exposure to filtered air. Based on the joint occurrence of these pollutants in the ambient environment, the potential exists for interactions in more than an additive fashion affecting lung physiological processes.

Trial registration: ClinicalTrials.gov NCT01874834.

Figures

Figure 1

Design of Study. Subjects were exposed to target levels of either filtered air, 0.300 ppm O3, 300 ug/m3 DE, or combined DE (300 ug/m3) and O3 (0.300 ppm) on Day 1 for 2 hr. On Day 2 subjects were exposed to 0. 300 ppm O3 for 2 hr. During exposures on Days 1 and 2 subjects performed four 30 min cycles of rest/exercise at ~ 50 L/min. Day 3 was a follow-up (F/U) day for measurements and no pollutant exposures occurred.

Figure 2

Changes in FEV1 (A) and FVC (B) after Day 1 pollutant exposures. Subjects performed pre-exposure spirometry immediately before a 2 hr exposure (filtered air, O3, DE, or DE + O3). Spirometry was performed immediately post-exposure and every hour post-exposure for 4 hr. FVC Data in (B) derived from the immediately post time point only. Data in the figure are presented as the mean ± SEM of each group at that time point. *p < 0.05 vs air exposed; **p < 0.05 vs O3 exposure alone; ‡ p = 0.057 vs the sum of the O3 plus DE exposure FEV1 changes using Mixed Effects Model testing as described in the materials and methods section.

Figure 3

Day 1 Changes in FEV1 immediately after a Day1 exposure in GSTM1- individuals. Mixed Effects Model testing was used for statistical analysis.

Figure 4

Changes in FEV1 (A) and FVC (B) immediately post Day 2 O3exposure (0. 300 ppm). *p < 0.05 vs air exposed values using Mixed Effects Model testing.

Figure 5

Individual changes (n = 15) in FEV1 immediately after Day 2 O3exposure for individuals exposed to either air or DE on day 1. *p < 0.05 vs air exposure using Mixed Effects Model testing.