Assessing the effects of elevated ozone on physiology, growth, yield and quality of soybean in the past 40 years: A meta-analysis.

Soybean (Glycine max) production is seriously threatened by ground-level ozone (O3) pollution. The goal of our study is to summarize the impacts of O3 on physiology, growth, yield, and quality of soybean, as well as root parameters. We performed meta-analysis on the collated 48 peer-reviewed papers published between 1980 and 2019 to quantitatively summarize the response of soybean to elevated O3 concentrations ([O3]). Relative to charcoal-filtered air (CF), elevated [O3] significantly accelerated chlorophyll degradation, enhanced foliar injury, and inhibited growth of soybean, evidenced by great reductions in leaf area (-20.8%), biomass of leaves (-13.8%), shoot (-22.8%), and root (-16.9%). Shoot of soybean was more sensitive to O3 than root in case of biomass. Chronic ozone exposure of about 75.5 ppb posed pronounced decrease in seed yield of soybean (-28.3%). In addition, root environment in pot contributes to higher reduction in shoot biomass and yield of soybean. Negative linear relationships were observed between yield loss and intensity of O3 treatment, AOT40. The larger loss in seed yield was significantly associated with higher reduction in shoot biomass and other yield component. This meta-analysis demonstrates the effects of elevated O3 on soybean were pronounced, suggesting that O3 pollution is still a soaring threat to the productivity of soybean in regions with high ozone levels.

Dietary Curcumin Prevented Astrocytosis, Microgliosis, and Apoptosis Caused by Acute and Chronic Exposure to Ozone.

Ozone is the most oxidant tropospheric pollutant gas, causing damage through the formation of reactive oxygen and nitrogen species. Reactive species induce the nuclear factor-kappa B (NF-κB) activation leading to neuroinflammation characterized by astrocytosis, microgliosis, and apoptotic cell death. There is interest in evaluating the pharmacological activity of natural antioxidants to confer neuroprotection against the damage caused by ozone in highly polluted cities. Curcumin has been proven to exert a protective action in the central nervous system (CNS) of diverse experimental models, with no side effects. The aim of this work is to evaluate the effect of curcumin in a preventive and therapeutic manner against the astrocytosis, microgliosis, and apoptosis induced by ozone in rat hippocampus. Fifty Wistar rats were distributed into five experimental groups: The intact control, curcumin fed control, ozone-exposed group, and the preventive and therapeutic groups receiving the curcumin supplementation while exposed to ozone. Ozone caused astrocytosis and microgliosis, as well as apoptosis in the hippocampus. Meanwhile, curcumin was able to decrease the activation of microglia and astrocytes, and apoptotic cell death in both periods of exposure. Therefore, we propose that curcumin could be used as a molecule capable of counteracting the damage caused by ozone in the CNS.

Long-Term Exposure to Ozone and Cause-Specific Mortality Risk in the United States.

Rationale: Many studies have linked short-term exposure to ozone (O3) with morbidity and mortality, but epidemiologic evidence of associations between long-term O3 exposure and mortality is more limited.Objectives: To investigate associations of long-term (annual or warm season average of daily 8-h maximum concentrations) O3 exposure with all-cause and cause-specific mortality in the NIH-AARP Diet and Health Study, a large prospective cohort of U.S. adults with 17 years of follow-up from 1995 to 2011.Methods: The cohort (n = 548,780) was linked to census tract-level estimates for O3. Associations between long-term O3 exposure (averaged values from 2002 to 2010) and multiple causes of death were evaluated using multivariate Cox proportional hazards models, adjusted for individual- and census tract-level covariates, and potentially confounding copollutants and temperature.Measurements and Main Results: Long-term annual average exposure to O3 was significantly associated with deaths caused by cardiovascular disease (per 10 ppb; hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.01-1.06), ischemic heart disease (HR, 1.06; 95% CI, 1.02-1.09), respiratory disease (HR, 1.04; 95% CI, 1.00-1.09), and chronic obstructive pulmonary disease (HR, 1.09; 95% CI, 1.03-1.15) in single-pollutant models. The results were robust to alternative models and adjustment for copollutants (fine particulate matter and nitrogen dioxide), although some evidence of confounding by temperature was observed. Significantly elevated respiratory disease mortality risk associated with long-term O3 exposure was found among those living in locations with high temperature (Pinteraction < 0.05).Conclusions: This study found that long-term exposure to O3 is associated with increased risk for multiple causes of mortality, suggesting that establishment of annual and/or seasonal federal O3 standards is needed to more adequately protect public health from ambient O3 exposures.

Multifocal Stroke From Ozone Gas Emboli.

A 34-year-old man with chronic neck pain was treated with regular cervical paravertebral ozone injections. After his last injection, he experienced a syncopal episode and, upon awakening, was found to have ataxia, aphasia, hemiparesis, and left sixth nerve palsy. Computed tomographic angiography demonstrated intra-arterial gas in the right vertebral artery; multiple posterior circulation infarcts were seen on brain MRI. This case illustrates the potential dangers of paravertebral injections of ozone.

Ambient ozone pollution is associated with decreased semen quality: longitudinal analysis of 8945 semen samples from 2015 to 2018 and during pollution-control period in Beijing, China.

Previous studies suggest that air pollution has a negative effect on semen quality. However, most studies are cross-sectional and the results are controversial. This study investigated the associations between air pollutants (PM2.5, PM10, SO2, NO2, CO, and O3) and semen quality among sperm donation candidates, especially when the air pollution was artificially controlled in Beijing, China. We analyzed 8945 semen samples in the human sperm bank of Peking University Third Hospital (Beijing, China) from October 2015 to May 2018. Air pollution data during the entire period (0-90 days prior) and key stages (0-9, 10-14, and 70-90 days prior) of sperm development were collected from the China National Environmental Monitoring Centre. The association between air pollutants and semen parameters (sperm concentration and progressive motility) was analyzed by a mixed model adjusted for age, abstinence duration, month, and average ambient temperature. Only O3during key stages of 0-9 days and 10-14 days and the entire period was negatively associated with sperm concentration between 2015 and 2018 (P < 0.01). During the period of air pollution control from November 2017 to January 2018, except for the increase in O3concentration, other five pollutants' concentrations decreased compared to those in previous years. In this period, the sperm concentration decreased (P < 0.001). During the pollution-control period, O3exposure 10-14 days prior was negatively associated with sperm concentration (95% CI: -0.399--0.111; P < 0.001). No significant association was found between the other five pollutants and semen quality during that period. Our study suggested that only O3exposure was harmful to semen quality. Therefore, O3should not be neglected during pollution control operation.

The effects of ex vivo ozone treatment on human erythrocyte carbonic anhydrase enzyme.

Ozone autohemotherapy is used in the treatment of some diseases. Carbonic anhydrases (CAs, EC 4.2.1.1) are metalloenzymes and play a role in homeostatic mechanisms. The aim of this study was to investigate the effects of ozone on human red blood cell CA (hCA) enzyme activity. Blood samples were treated with different doses of ozone (10, 20, 30 µg/ml) and the erythrocyte total CA activities were determined. Also, purified hCAI and hCAII isozymes were treated with the same doses of ozone and the enzyme activities were measured. About 30 µg/ml ozone treatment decreased the purified hCAI and hCAII activity and increased the total CA activity compared to the control. Because the implication of CAs on many physiological and biochemical processes is linked to pathologies, it can be suggested that the ozone at a concentration of 30 µg/ml is safely used by autohaemotherapy in a well-designed clinical trial.

Nitrogen dioxide exposure in school classrooms of inner-city children with asthma.

BACKGROUND: Ambient and home exposure to nitrogen dioxide (NO2) causes asthma symptoms and decreased lung function in children with asthma. Little is known about the health effects of school classroom pollution exposure. OBJECTIVE: We aimed to determine the effect of indoor classroom NO2 on lung function and symptoms in inner-city school children with asthma. METHODS: Children enrolled in the School Inner-City Asthma Study were followed for 1 academic year. Subjects performed spirometry and had fraction of exhaled nitric oxide values measured twice during the school year at school. Classroom NO2 was collected by means of passive sampling for 1-week periods twice per year, coinciding with lung function testing. Generalized estimating equation models assessed lung function and symptom relationships with the temporally nearest classroom NO2 level. RESULTS: The mean NO2 value was 11.1 ppb (range, 4.3-29.7 ppb). In total, exposure data were available for 296 subjects, 188 of whom had complete spirometric data. At greater than a threshold of 8 ppb of NO2 and after adjusting for race and season (spirometry standardized by age, height, and sex), NO2 levels were associated highly with airflow obstruction, such that each 10-ppb increase in NO2 level was associated with a 5% decrease in FEV1/forced vital capacity ratio (ß = -0.05; 95% CI, -0.08 to -0.02; P = .01). Percent predicted forced expiratory flow between the 25th and 75th percentile of forced vital capacity was also inversely associated with higher NO2 exposure (ß = -22.8; 95% CI, -36.0 to -9.7; P = .01). There was no significant association of NO2 levels with percent predicted FEV1, fraction of exhaled nitric oxide, or asthma symptoms. Additionally, there was no effect modification of atopy on lung function or symptom outcomes. CONCLUSION: In children with asthma, indoor classroom NO2 levels can be associated with increased airflow obstruction.

Outdoor and indoor ozone level--A potential impact on human health.

BACKGROUND/AIM: Air pollution outside and inside is still one of the most sensitive issues. The aim of this study was to assess the ozone level in ambient air and working premises in terms of its possible influence on human health. METHODS: The study was based on the results obtained in Lithuanian conditions. Continuous ozone measurement data from the rural monitoring station in Preila over the period 1995-2011 were analyzed. More than 180,000 hourly values were examined according to the requirements in the Directive 2008/50/EC. The World Health Organization (WHO) and European Union indicators the Sum of Ozone Means Over 35 ppb (SOMO 35), the maximum daily 8-hour mean concentration of ozone higher than 100 and 120 microg/m3 were estimated. Indoor ozone concentrations in copying and welding rooms were evaluated. The ozone concentration was measured with the ozone analyzer 0341M. RESULTS: The frequency distribution of ozone hourly concentrations at the Preila station showed that less than 1% of the data were higher than 120 microg/m3 and 6% of them higher than 100 microg/m3, that could have the adverse effect on human health, during 1995-2011. The investigations made in working premises showed that near a copying machine the ozone concentration can reach 330 +/- microg/m3, however in the room, i.e., 0.5 m from the machine, the average ozone concentration during automatic copying was 165 microg/m3 and during manual copying it was 50 microg/m3. Measurements in a welding room showed that the ozone concentration was in the range of 380-1850 microg/m3 at the distance of 25 cm from the electrode and at the distance of 1 m from the source the ozone concentration decreased 2.5 times. Conclusion. The danger of the ambient ozone level to human health practically was not observed in Lithuanian conditions. However, almost 6% of the data exceed the new WHO guideline of 100 microg/m3 during the measurement time. Indoor ozone during welding reached a higher level than during, copying that can cause human health problems.

ROCK insufficiency attenuates ozone-induced airway hyperresponsiveness in mice.

Ozone causes airway hyperresponsiveness (AHR) and pulmonary inflammation. Rho kinase (ROCK) is a key regulator of smooth muscle cell contraction and inflammatory cell migration. To determine the contribution of the two ROCK isoforms ROCK1 and ROCK2 to ozone-induced AHR, we exposed wild-type, ROCK1(+/-), and ROCK2(+/-) mice to air or ozone (2 ppm for 3 h) and evaluated mice 24 h later. ROCK1 or ROCK2 haploinsufficiency did not affect airway responsiveness in air-exposed mice but significantly reduced ozone-induced AHR, with a greater reduction in ROCK2(+/-) mice despite increased bronchoalveolar lavage (BAL) inflammatory cells in ROCK2(+/-) mice. Compared with wild-type mice, ozone-induced increases in BAL hyaluronan, a matrix protein implicated in ozone-induced AHR, were lower in ROCK1(+/-) but not ROCK2(+/-) mice. Ozone-induced increases in other inflammatory moieties reported to contribute to ozone-induced AHR (IL-17A, osteopontin, TNFα) were not different in wild-type vs. ROCK1(+/-) or ROCK2(+/-) mice. We also observed a dose-dependent reduction in ozone-induced AHR after treatment with the ROCK1/ROCK2 inhibitor fasudil, even though fasudil was administered after induction of inflammation. Ozone increased pulmonary expression of ROCK2 but not ROCK1 or RhoA. A ROCK2 inhibitor, SR3677, reduced contractile forces in primary human airway smooth muscle cells, confirming a role for ROCK2 in airway smooth muscle contraction. Our results demonstrate that ozone-induced AHR requires ROCK. Whereas ROCK1-dependent changes in hyaluronan may contribute to ROCK1's role in O3-induced AHR, the role of ROCK2 is downstream of inflammation, likely at the level of airway smooth muscle contraction.

Associations between ozone and preterm birth in women who develop gestational diabetes.

Prenatal exposure to ambient air pollutants might cause adverse birth outcomes; however, there have been few studies in which the association between air pollution and preterm birth was examined after stratifying by pregnancy complications. We conducted a population-based case-control study of 1,510,064 singleton births from the Taiwanese birth registry during 2001-2007. Of the total of 1,510,064 births, we designated all 86,224 preterm births as the case group and then randomly selected an additional 344,896 from the remaining births (equivalent to 4 full-term births for every 1 preterm birth) as the control sample. We used an inverse distance weighting approach to calculate an average exposure parameter for air pollutants. The adjusted odds ratio for preterm birth per 10-ppb increase in ozone was 1.12 (95% confidence interval: 1.01, 1.23) for women with gestational diabetes mellitus who were exposed in the third trimester and 1.02 (95% confidence interval: 1.01, 1.03) for women without gestational diabetes (P for interaction <0.001). These findings suggest that exposure to ozone in pregnancy is associated with an increased risk of preterm birth, particularly for women who have gestational diabetes mellitus.

Ozone therapy in the management and prevention of caries.

The purpose of this article was to assess the effectiveness of ozone therapy in the management and prevention of caries, reviewing clinical and in vitro studies. Ozone has proven to be effective against gram-negative and gram-positive bacteria, viruses, and fungi. In dentistry, most of the published articles are based on ozone's antimicrobial effects and the treatment of caries. Most of the clinical studies reported ozone to be a promising alternative to conventional methods for caries management. However, a few studies have shown ozone to be insufficient for preventing caries and reducing microorganisms in open occlusal carious lesions. Ozone might be a useful tool to reduce and control oral infectious microorganisms in dental plaque and dental cavity. However, the results of in vitro studies are controversial; while some researchers reported that ozone therapy had a minimal or no effect on the viability of microorganisms, others suggested ozone to be highly effective in killing both gram-positive and gram-negative oral microorganisms. Therefore, more evidence is required before ozone can be accepted as an alternative to present methods for the management and prevention of caries.

Inhibitory effect of hydrogen sulfide on ozone-induced airway inflammation, oxidative stress, and bronchial hyperresponsiveness.

Exposure to ozone has been associated with airway inflammation, oxidative stress, and bronchial hyperresponsiveness. The goal of this study was to examine whether these adverse effects of ozone could be prevented or reversed by hydrogen sulfide (H2S) as a reducing agent. The H2S donor sodium (NaHS) (2 mg/kg) or vehicle (PBS) was intraperitoneally injected into mice 1 hour before and after 3-hour ozone (2.5 ppm) or air exposure, and the mice were studied 24 hours later. Preventive and therapeutic treatment with NaHS reduced the ozone-induced increases in the total cells, including neutrophils and macrophages; this treatment also reduced levels of cytokines, including TNF-α, chemokine (C-X-C motif) ligand 1, IL-6, and IL-1ß levels in bronchial alveolar lavage fluid; inhibited bronchial hyperresponsiveness; and attenuated ozone-induced increases in total malondialdehyde in bronchoalveolar lavage fluid and decreases in the ratio of reduced glutathione/oxidized glutathione in the lung. Ozone exposure led to decreases in the H2S production rate and in mRNA and protein levels of cystathionine-ß-synthetase and cystathionine-γ-lyase in the lung. These effects were prevented and reversed by NaHS treatment. Furthermore, NaHS prevented and reversed the phosphorylation of p38 mitogen-activated protein kinase and heat shock protein 27. H2S may have preventive and therapeutic value in the treatment of airway diseases that have an oxidative stress basis.

Cost of near-roadway and regional air pollution-attributable childhood asthma in Los Angeles County.

BACKGROUND: Emerging evidence suggests that near-roadway air pollution (NRP) exposure causes childhood asthma. The associated costs are not well documented. OBJECTIVE: We estimated the cost of childhood asthma attributable to residential NRP exposure and regional ozone (O3) and nitrogen dioxide (NO2) levels in Los Angeles County. We developed a novel approach to apportion the costs between these exposures under different pollution scenarios. METHODS: We integrated results from a study of willingness to pay to reduce the burden of asthma with results from studies of health care use and charges to estimate the costs of an asthma case and exacerbation. We applied those costs to the number of asthma cases and exacerbations caused by regional pollution in 2007 and to hypothetical scenarios of a 20% reduction in regional pollution in combination with a 20% reduction or increase in the proportion of the total population living within 75 m of a major roadway. RESULTS: Cost of air pollution-related asthma in Los Angeles County in 2007 was $441 million for O3 and $202 million for NO2 in 2010 dollars. Cost of routine care (care in absence of exacerbation) accounted for 18% of the combined NRP and O3 cost and 39% of the combined NRP and NO2 cost; these costs were not recognized in previous analyses. NRP-attributable asthma accounted for 43% (O3) to 51% (NO2) of the total annual cost of exacerbations and routine care associated with pollution. Hypothetical scenarios showed that costs from increased NRP exposure might offset savings from reduced regional pollution. CONCLUSIONS: Our model disaggregates the costs of regional pollution and NRP exposure and illustrates how they might vary under alternative exposure scenarios. The cost of air pollution is a substantial burden on families and an economic loss for society.

Ozone-induced airway epithelial cell death, the neurokinin-1 receptor pathway, and the postnatal developing lung.

Children are uniquely susceptible to ozone because airway and lung growth continue for an extensive period after birth. Early-life exposure of the rhesus monkey to repeated ozone cycles results in region-specific disrupted airway/lung growth, but the mediators and mechanisms are poorly understood. Substance P (SP), neurokinin-1 receptor (NK-1R); and nuclear receptor Nur77 (NR4A1) are signaling pathway components involved in ozone-induced cell death. We hypothesize that acute ozone (AO) exposure during postnatal airway development disrupts SP/NK-1R/Nur77 pathway expression and that these changes correlate with increased ozone-induced cell death. Our objectives were to 1) spatially define the normal development of the SP/NK-1R/Nur77 pathway in conducting airways; 2) compare how postnatal age modulates responses to AO exposure; and 3) determine how concomitant, episodic ozone exposure modifies age-specific acute responses. Male infant rhesus monkeys were assigned at age 1 mo to two age groups, 2 or 6 mo, and then to one of three exposure subgroups: filtered air (FA), FA+AO (AO: 8 h/day × 2 days), or episodic biweekly ozone exposure cycles (EAO: 8 h/day × 5 days/14-day cycle+AO). O3 = 0.5 ppm. We found that 1) ozone increases SP/NK-1R/Nur77 pathway expression in conducting airways, 2) an ozone exposure cycle (5 days/cycle) delivered early at age 2 mo resulted in an airway that was hypersensitive to AO exposure at the end of 2 mo, and 3) continued episodic exposure (11 cycles) resulted in an airway that was hyposensitive to AO exposure at 6 mo. These observations collectively associate with greater overall inflammation and epithelial cell death, particularly in early postnatal (2 mo), distal airways.

Age-related increases in ozone-induced injury and altered pulmonary mechanics in mice with progressive lung inflammation.

In these studies we determined whether progressive pulmonary inflammation associated with aging in surfactant protein D (Sftpd)-/- mice leads to an exacerbated response to ozone. In Sftpd-/- mice, but not wild-type (WT) mice, age-related increases in numbers of enlarged vacuolated macrophages were observed in the lung, along with alveolar wall rupture, type 2 cell hyperplasia, and increased bronchoalveolar lavage protein and cell content. Numbers of heme oxygenase+ macrophages also increased with age in Sftpd-/- mice, together with classically (iNOS+) and alternatively (mannose receptor+, YM-1+, or galectin-3+) activated macrophages. In both WT and Sftpd-/- mice, increasing age from 8 to 27 wk was associated with reduced lung stiffness, as reflected by decreases in resistance and elastance spectra; however, this response was reversed in 80-wk-old Sftpd-/- mice. Ozone exposure (0.8 ppm, 3 h) caused increases in lung pathology, alveolar epithelial barrier dysfunction, and numbers of iNOS+ macrophages in 8- and 27-wk-old Sftpd-/-, but not WT mice at 72 h postexposure. Conversely, increases in alternatively activated macrophages were observed in 8-wk-old WT mice following ozone exposure, but not in Sftpd-/- mice. Ozone also caused alterations in both airway and tissue mechanics in Sftpd-/- mice at 8 and 27 wk, but not at 80 wk. These data demonstrate that mild to moderate pulmonary inflammation results in increased sensitivity to ozone; however, in senescent mice, these responses are overwhelmed by the larger effects of age-related increases in baseline inflammation and lung injury.

Dual p38/JNK mitogen activated protein kinase inhibitors prevent ozone-induced airway hyperreactivity in guinea pigs.

Ozone exposure causes airway hyperreactivity and increases hospitalizations resulting from pulmonary complications. Ozone reacts with the epithelial lining fluid and airway epithelium to produce reactive oxygen species and lipid peroxidation products, which then activate cell signaling pathways, including the mitogen activated protein kinase (MAPK) pathway. Both p38 and c-Jun NH2 terminal kinase (JNK) are MAPK family members that are activated by cellular stress and inflammation. To test the contribution of both p38 and JNK MAPK to ozone-induced airway hyperreactivity, guinea pigs were pretreated with dual p38 and JNK MAPK inhibitors (30 mg/kg, i.p.) 60 minutes before exposure to 2 ppm ozone or filtered air for 4 hours. One day later airway reactivity was measured in anesthetized animals. Ozone caused airway hyperreactivity one day post-exposure, and blocking p38 and JNK MAPK completely prevented ozone-induced airway hyperreactivity. Blocking p38 and JNK MAPK also suppressed parasympathetic nerve activity in air exposed animals, suggesting p38 and JNK MAPK contribute to acetylcholine release by airway parasympathetic nerves. Ozone inhibited neuronal M2 muscarinic receptors and blocking both p38 and JNK prevented M2 receptor dysfunction. Neutrophil influx into bronchoalveolar lavage was not affected by MAPK inhibitors. Thus p38 and JNK MAPK mediate ozone-induced airway hyperreactivity through multiple mechanisms including prevention of neuronal M2 receptor dysfunction.

El ejercicio físico aumenta el daño pulmonar inducido por la exposición aguda e intermitente a 0, 5 ppm de ozono en ratas juveniles / Physical exercise increases pulmonary damage induced by acute and intermittent exposure to 0.5 ppm of ozone in juvenile rats

El ozono (O3) troposférico es el principal oxidante del esmog fotoquímico. Como es un contaminante aéreo, sus efectos están relacionados con la dosis efectiva = [Concentración] x [tiempo de exposición] x [ventilación minuto]. Objetivo: Determinar si el ejercicio físico -que aumenta la ventilación minuto- puede aumentar el daño pulmonar inducido por la exposición a O3 en ratas en reposo. Material y Métodos: Se usó 4 series de ratas Sprague-Dawley juveniles. Dos series fueron expuestas a 0,5 ppm de O3 (4 h diarias por 2 días) en reposo (n = 13) o durante ejercicio (n = 12). Dos series control respiraron aire filtrado (AF) en reposo (n = 13) o durante sesiones de ejercicio (n = 13), en una rueda vertical giratoria (15 min de ejercicio alternados con 15 min de descanso hasta completar 4 h diarias durante 2 días). Las ratas fueron eutanasiadas y se determinó la razón peso húmedo/peso seco (PH/PS) en el pulmón izquierdo. En el lavado broncoalveolar (LBA) del pulmón derecho, se determinó recuento total de células, proteínas totales y actividad de gamma-glutamiltraspeptidasa (GGT). Resultados: la razón PH/PS y el recuento de células y las proteínas del LBA aumentaron en las ratas en reposo expuestas a O3 comparadas con las ratas en reposo que respiraron AF (p < 0,05 ANOVA & Newman-Keuls). La actividad de GGT en el LBA fue mayor en las ratas que en ejercicio respiraron AF en comparación con las ratas que respiraron AF en reposo (p < 0,05). Hubo aumento de GGT, proteínas y recuento de células en el LBA de la serie [ejercicio + O3] comparada con la serie [reposo + O3] (p < 0,05). Conclusión: El ejercicio físico aumenta el daño pulmonar inducido por la exposición aguda e intermitente a 0,5 ppm de O3 en ratas juveniles.

Tropospheric ozone (O3) is the major oxidant of photochemical smog. Being an air pollutant, its effects are related to effective dose = [Concentration] x [exposure time] x [pulmonary ventilation]. Objective: Determine whether physical exercise -that increases pulmonary ventilation- is able to augment the pulmonary damage induced by O3 exposure in resting rats. Material and Methods: Four series of juvenile Sprague-Dawley rats were used. Two series were exposed to 0.5 ppm O3 (4 hours a day for 2 days) at rest (n=13) or during exercise (n=12). Two control series breathed filtered air (FA) at rest (n=13) or during exercise sessions (n=13), in a vertical rotary wheel (15 min exercise alternated with 15 min resting until to completing 4 hours a day for 2 days). Rats were euthanized and wet weight / dry weight ratio (W/D ratio) was determined in left lung. Total cell counting, total protein content and γ-glutamyltraspeptidase (GGT) activity were determined in the right lung bronchoalveolar lavage fluid (BALF). Results: W/D weight ratio as well as total cell counting and protein content increased in BALF from resting rats exposed to O3 as compared with resting rats breathing FA (p < 0.05 ANOVA & Newman-Keuls test). GGT activity in BALF increased in rats under exercise breathing FA as compared with resting rats breathing FA (p<0.05). GGT, proteins and cells counting increased in BALFfrom series [exercise + O3] as compared to series [resting + O3] (p< 0.05). Conclusion: Physical exercise increases lung damage induced by intermittent and acute 0.5 ppm O3 exposure in juvenile rats.

Endogenous osteopontin promotes ozone-induced neutrophil recruitment to the lungs and airway hyperresponsiveness to methacholine.

Inhalation of ozone (O3), a common environmental pollutant, causes pulmonary injury, pulmonary inflammation, and airway hyperresponsiveness (AHR) in healthy individuals and exacerbates many of these same sequelae in individuals with preexisting lung disease. However, the mechanisms underlying these phenomena are poorly understood. Consequently, we sought to determine the contribution of osteopontin (OPN), a hormone and a pleiotropic cytokine, to the development of O3-induced pulmonary injury, pulmonary inflammation, and AHR. To that end, we examined indices of these aforementioned sequelae in mice genetically deficient in OPN and in wild-type, C57BL/6 mice 24 h following the cessation of an acute (3 h) exposure to filtered room air (air) or O3 (2 parts/million). In wild-type mice, O3 exposure increased bronchoalveolar lavage fluid (BALF) OPN, whereas immunohistochemical analysis demonstrated that there were no differences in the number of OPN-positive alveolar macrophages between air- and O3-exposed wild-type mice. O3 exposure also increased BALF epithelial cells, protein, and neutrophils in wild-type and OPN-deficient mice compared with genotype-matched, air-exposed controls. However, following O3 exposure, BALF neutrophils were significantly reduced in OPN-deficient compared with wild-type mice. When airway responsiveness to inhaled acetyl-ß-methylcholine chloride (methacholine) was assessed using the forced oscillation technique, O3 exposure caused hyperresponsiveness to methacholine in the airways and lung parenchyma of wild-type mice, but not OPN-deficient mice. These results demonstrate that OPN is increased in the air spaces following acute exposure to O3 and functionally contributes to the development of O3-induced pulmonary inflammation and airway and lung parenchymal hyperresponsiveness to methacholine.

Baseline airway inflammation may be a determinant of the response to ozone exposure in asthmatic patients.

CONTEXT: It is well known that ozone exposure decreases lung function and increases airway neutrophilia, but large variability has been observed among asthmatic patients. OBJECTIVE: To find possible predictors of functional and inflammatory airway response to ozone in asthmatic patients. MATERIALS AND METHODS: We studied 120 patients with mild-to-moderate asthma, randomly exposed to either air or ozone (0.3 ppm for 2 h) in a challenge chamber. Symptoms and pulmonary function test (PFT) were measured before and immediately after exposure. Six hours after exposure, induced sputum was collected. Patients were evaluated according to their functional (FEV1 responders) or neutrophilic (neutrophil responders) response to ozone. We considered, as possible predictors of response: age, baseline FEV1, previous treatment with inhaled corticosteroids (ICS), baseline sputum neutrophils, baseline sputum eosinophils, methacholine responsiveness, atopy and smoking habit. RESULTS: FEV1 responders had lower baseline FEV1, and a lower percentage of these had received ICS treatment. Neutrophil responders were younger, with lower baseline sputum inflammation and greater methacholine responsiveness. These results were confirmed by multivariate logistic analysis. DISCUSSION AND CONCLUSION: Patients not previously treated with ICS and patients with lower FEV1 are more prone to functional response to ozone. Lower baseline airway inflammation and greater bronchial hyperresponsiveness may predict neutrophilic airway response to ozone in asthmatic patients. Thus, determinants of functional and inflammatory responses to ozone are different.