Effects of Multiday Exposure to Ozone on Airway Inflammation as Determined Using Sputum Induction

Single short-term exposures to ozone are known to cause acute changes in pulmonary function and neutrophilic airway inflammation. The respiratory health effects of repeated exposures are not as well studied. Pulmonary function decrements are known to attenuate, but it is less clear how injury and inflammation are affected. Using sputum induction (SI) to sample respiratory tract lining fluid after single- and multiday exposures, we designed a study to test the hypothesis that neutrophils would increase after multiday exposure compared with single-day exposure. In a randomized, crossover design, 15 normal healthy subjects were exposed to O(3) (0.2 ppm) under two conditions: for 4 hr for 1 day (1D) and for 4 hr for 4 consecutive days (4D). Pulmonary function testing was performed immediately before and after each 4-hr exposure. The SI was performed 18 hr after the end of the 1D and 4D conditions. The symptom and pulmonary function data followed a pattern seen in other multiday O(3) exposure studies, with the greatest changes occurring on the second day. In contrast to previous studies using bronchoalveolar lavage, however, there was a significant increase in the percentage of neutrophils and a significant decrease in the percentage of macrophages after the 4D condition compared with the 1D condition. Given that SI likely samples proximal airways better than distal lung, these results add to the body of evidence that differential airway compartmental responses to O(3) occur in humans and other species

Estimation of infectious risks in residential populations exposed to airborne pathogens during center pivot irrigation of dairy wastewaters

In the western United States where dairy wastewaters are commonly land applied, there are concerns over individuals being exposed to airborne pathogens. In response, a quantitative microbial risk assessment (QMRA) was performed to estimate infectious risks after inhalation exposure of pathogens aerosolized during center pivot irrigation of diluted dairy wastewaters. The dispersion of pathogens (Campylobacter jejuni, Escherichia coli O157:H7, non-O157 E. coli, Listeria monocytogenes, and Salmonella spp.) was modeled using the atmospheric dispersion model, AERMOD. Pathogen concentrations at downwind receptors were used to calculate infectious risks during one-time (1, 8, and 24 h) and multi-day (7 d at 1 h/d) exposure events using a Beta-Poisson dose-response model. This assessment considered risk of infection in residential populations that were 1 to 10 km from a center pivot operation. In the simulations, infectious risks were estimated to be the greatest in individuals closest to the center pivot, as a result of a higher pathogen dose. Based on the results from this QMRA, it is recommended that wastewaters only be applied during daylight hours when inactivation and dilution of airborne pathogens is highest. Further refinement of the dispersion and dose-response models should be considered to increase the utility of this QMRA

Is there adaptation in the ozone mortality relationship: A multi-city case-crossover analysis

<p>Abstract</p> <p>Background</p> <p>Ozone has been associated with daily mortality, mainly in the summer period. Despite the ample literature on adaptation of inflammatory and pulmonary responses to ozone, and the link, in cohort studies, between lung function and mortality risk there has been little done to date to examine the question of adaptation in the acute mortality risk associated with ambient ozone.</p> <p>Methods</p> <p>We applied a case-crossover design in 48 US cities to examine the ozone effect by season, by month and by age groups, particularly focusing on whether there was an adaptation effect.</p> <p>Results</p> <p>We found that the same day ozone effect was highest in summer with a 0.5% (95% CI: 0.38, 0.62) increase in total mortality for 10 ppb increase in 8-hr ozone, whilst the effect decrease to null in autumn and winter. We found higher effects in the months May- July with a 0.46% (95% CI: 0.24, 0.68) increase in total mortality for 10 ppb increase in ozone in June, and a 0.65% (95% CI: 0.47, 0.82) increase in mortality during July. The effect decreased in August and became null in September. We found similar effects from the age group 51–60 up to age 80 and a lower effect in 80 years and older.</p> <p>Conclusion</p> <p>The mortality effects of ozone appear diminished later in the ozone season, reaching the null effect previously reported in winter by September. More work should address this issue and examine the biological mechanism of adaptation.</p

Neural effects of elevated CO2 in fish may be amplified by a vicious cycle

Maladaptive behavioural disturbances have been reported in some fishes and aquatic invertebrates exposed to projected future CO2 levels. These disturbances have been linked to altered ion gradients and neurotransmitter function in the brain. Still, it seems surprising that the relatively small ionic changes induced by near-future CO2 levels can have such profound neural effects. Based on recent transcriptomics data, we propose that a vicious cycle can be triggered that amplifies the initial disturbance, explaining howsmall pH regulatory adjustments in response to ocean acidification can lead to major behavioural alterations in fish and other water-breathing animals. The proposed cycle is initiated by a reversal of the function of some inhibitory GABA(A) receptors in the direction of neural excitation and then amplified by adjustments in gene expression aimed at suppressing the excitation but in reality increasing it. In addition, the increased metabolic production of CO2 by overexcited neurons will feed into the cycle by elevating intracellular bicarbonate levels that will lead to increased excitatory ion fluxes through GABA(A) receptors. We also discuss the possibility that an initiation of a vicious cycle could be one of the several factors underlying the differences in neural sensitivity to elevated CO2 displayed by fishes

Ozone and Daily Mortality in Shanghai, China

BACKGROUND: Controversy remains regarding the relationship between ambient ozone and mortality worldwide. In mainland China, the largest developing country, there has been no prior study investigating the acute effect of O(3) on death risk. Given the changes in types of air pollution from conventional coal combustion to the mixed coal combustion/motor vehicle emissions in China’s large cities, it is worthwhile to investigate the acute effect of O(3) on mortality outcomes in the country. OBJECTIVES: We conducted a time-series study to investigate the relation between O(3) and daily mortality in Shanghai using 4 years of daily data (2001–2004). METHODS: We used the generalized additive model with penalized splines to analyze mortality, O(3) pollution, and covariate data in warm and cold seasons. We considered daily counts of all-cause mortality and several cause-specific subcategories (respiratory and cardiovascular). We also examined these associations among several subpopulations based on age and sex. RESULTS: O(3) was significantly associated with total and cardiovascular mortality in the cold season but not in the warm season. In the whole-year analysis, an increase of 10 μg/m(3) of 2-day average (lag01) O(3) corresponds to 0.45% [95% confidence interval (CI), 0.16–0.73%], 0.53% (95% CI, 0.10–0.96%), and 0.35% (95% CI, −0.40 to 1.09%) increase of total nonaccidental, cardiovascular, and respiratory mortality, respectively. In the cold season, the estimates increased to 1.38% (95% CI, 0.68–2.07%), 1.53% (95% CI, 0.54–2.52%), and 0.95% (95% CI, −0.71 to 2.60%), respectively. In the warm season, we did not observe significant associations for both total and cause-specific mortality. The results were generally insensitive to model specifications such as lag structure of O(3) concentrations and degree of freedom for time trend. Multipollutant models indicate that the effect of O(3) was not confounded by particulate matter ≤ 10 μm in diameter (PM(10)) or by sulfur dioxide; however, after adding nitrogen dioxide into the model, the association of O(3) with total and cardiovascular mortality became statistically insignificant. CONCLUSIONS: O(3) pollution has stronger health effects in the cold than in the warm season in Shanghai. Our analyses also strengthen the rationale for further limiting levels of O(3) pollution in outdoor air in the city

The Effects of Components of Fine Particulate Air Pollution on Mortality in California: Results from CALFINE

OBJECTIVE: Several epidemiologic studies provide evidence of an association between daily mortality and particulate matter < 2.5 μm in diameter (PM(2.5)). Little is known, however, about the relative effects of PM(2.5) constituents. We examined associations between 19 PM(2.5) components and daily mortality in six California counties. DESIGN: We obtained daily data from 2000 to 2003 on mortality and PM(2.5) mass and components, including elemental and organic carbon (EC and OC), nitrates, sulfates, and various metals. We examined associations of PM(2.5) and its constituents with daily counts of several mortality categories: all-cause, cardiovascular, respiratory, and mortality age > 65 years. Poisson regressions incorporating natural splines were used to control for time-varying covariates. Effect estimates were determined for each component in each county and then combined using a random-effects model. RESULTS: PM(2.5) mass and several constituents were associated with multiple mortality categories, especially cardiovascular deaths. For example, for a 3-day lag, the latter increased by 1.6, 2.1, 1.6, and 1.5% for PM(2.5), EC, OC, and nitrates based on interquartile ranges of 14.6, 0.8, 4.6, and 5.5 μg/m(3), respectively. Stronger associations were observed between mortality and additional pollutants, including sulfates and several metals, during the cool season. CONCLUSION: This multicounty analysis adds to the growing body of evidence linking PM(2.5) with mortality and indicates that excess risks may vary among specific PM(2.5) components. Therefore, the use of regression coefficients based on PM(2.5) mass may underestimate associations with some PM(2.5) components. Also, our findings support the hypothesis that combustion-associated pollutants are particularly important in California

Quantitative trait analysis of the development of pulmonary tolerance to inhaled zinc oxide in mice

BACKGROUND: Individuals may develop tolerance to the induction of adverse pulmonary effects following repeated exposures to inhaled toxicants. Previously, we demonstrated that genetic background plays an important role in the development of pulmonary tolerance to inhaled zinc oxide (ZnO) in inbred mouse strains, as assessed by polymorphonuclear leukocytes (PMNs), macrophages, and total protein in bronchoalveolar lavage (BAL) phenotypes. The BALB/cByJ (CBy) and DBA/2J (D2) strains were identified as tolerant and non-tolerant, respectively. The present study was designed to identify candidate genes that control the development of pulmonary tolerance to inhaled ZnO. METHODS: Genome-wide linkage analyses were performed on a CByD2F2 mouse cohort phenotyped for BAL protein, PMNs, and macrophages following 5 consecutive days of exposure to 1.0 mg/m(3 )inhaled ZnO for 3 hours/day. A haplotype analysis was carried out to determine the contribution of each quantitative trait locus (QTL) and QTL combination to the overall BAL protein phenotype. Candidate genes were identified within each QTL interval using the positional candidate gene approach. RESULTS: A significant quantitative trait locus (QTL) on chromosome 1, as well as suggestive QTLs on chromosomes 4 and 5, for the BAL protein phenotype, was established. Suggestive QTLs for the BAL PMN and macrophage phenotypes were also identified on chromosomes 1 and 5, respectively. Analysis of specific haplotypes supports the combined effect of three QTLs in the overall protein phenotype. Toll-like receptor 5 (Tlr5) was identified as an interesting candidate gene within the significant QTL for BAL protein on chromosome 1. Wild-derived Tlr5-mutant MOLF/Ei mice were tolerant to BAL protein following repeated ZnO exposure. CONCLUSION: Genetic background is an important influence in the acquisition of pulmonary tolerance to BAL protein, PMNs, and macrophages following ZnO exposure. Promising candidate genes exist within the identified QTL intervals that would be good targets for additional studies, including Tlr5. The implications of tolerance to health risks in humans are numerous, and this study furthers the understanding of gene-environment interactions that are likely to be important factors from person-to-person in regulating the development of pulmonary tolerance to inhaled toxicants