Comparison of total suspended particulate concentration-response relationships for respiratory symptoms between Chinese children with a different susceptibility status.

Few studies have explored concentration-response (C-R) relationships between levels of particulate matter (PM) and respiratory morbidity in terms of the susceptibility of children to respiratory diseases. We sought to determine whether the shapes of C-R curves for comparing total suspended particle (TSP) concentration versus the adjusted prevalence of bronchitis (persistent cough or phlegm) and asthma (current wheeze or asthma) symptoms between children with a different susceptibility status. We used the restricted cubic spline (RCS) function to characterize the C-R relationships between TSP and the adjusted prevalence rates of four respiratory symptoms, after controlling for possible confounding by SO(2) and NO(2) levels, in 11,860 children selected from 18 districts of six cities in Liaoning province. Susceptible children exhibited a 2- to 3-fold elevation in the prevalence of all four respiratory symptoms across the entire TSP range (188-689µg/m(3)). Significant differences in the shapes of C-R curves were evident in children with symptoms of bronchitis (ballistic "S"-shaped curves) and asthma (flattened "U"-shaped curves), as well as between the low and high TSP ranges of such curves, when children were grouped by susceptibility status. A significant linear association between TSP levels and current asthma prevalence was found only among susceptible children exposed to high levels of TSP. The shapes and properties of the TSP-morbidity C-R curves differed significantly by type of respiratory symptom, susceptibility status, and TSP range. More work is required to characterize CR relationships in terms of susceptibility status in countries with different PM levels.

Air pollution and children's respiratory symptoms in six cities of Northern China.

OBJECTIVE: The associations between air pollution and children's respiratory health in the high pollution range have not yet been clearly characterized. We evaluated the effects of outdoor air pollution on respiratory morbidity in children selected from multiple sites in a heavy industrial province of northeastern China. METHODS: The study included 11,860 children aged 3-12 years, selected from 18 districts of 6 cities in Liaoning province, the participation rate is 89.9%. Informed consent and written responses to surveys about children's historic and current health status, personal and household characteristics, and other information were obtained from parents. A two-stage regression approach was applied in data analyses. RESULTS: There were wide gradients for TSP (188-689 µg/m(3)), SO(2) (14-140 µg/m(3) and NO(2) (29-94 µg/m(3)) across the 18 districts of 6 cities. The three air pollutants significantly increased the prevalence of persistent cough (21-28%), persistent phlegm (21-30%) and current asthma (39-56%) for each interquartile range increment (172 µg/m(3) for TSP, 69 µg/m(3) for SO(2), 30 µg/m(3) for NO(2)), showing larger between-city effects than within-city. Rates of respiratory symptoms were significantly higher for children with younger age, atopy, respiratory disease in early age, family history of asthma or chronic bronchitis, and tobacco smoke exposure. CONCLUSION: The high levels of outdoor air pollution in north China are positively associated with children's respiratory symptoms, the associations with TSP appear to be stronger than SO(2) and NO(2).

Effect of aldosterone on isolated human penile corpus cavernosum tissue.

OBJECTIVE: To clarify the physiological effects of aldosterone on human penile corpus cavernosum (hPCC) tissue, as aldosterone has a wider physiological action than just the maintenance of electrolyte balance, and there are mineralocorticoid receptors, i.e. aldosterone receptors, in hPCC tissue. MATERIALS AND METHODS: Specimens of hPCC were obtained from 10 patients (mean age 38 years, range 21-75), with informed consent and approval by the local ethics committee. One patient had a penectomy because of penile cancer, and nine had a penile biopsy because of erectile dysfunction. Patients with diabetes mellitus, hypertension or ischaemic heart disease were excluded. In a pharmacological study we evaluated the effect of aldosterone on the isolated hPCC tissues. RESULTS: Aldosterone caused no significant change in resting tension and did not affect the nitric oxide-dependent relaxation reaction. However, the dose-response curve of noradrenaline was shifted to the left when the strip preparation was treated with aldosterone (1 x 10(-5)M) for 20 min before administering noradrenaline. Moreover, the shift to the left was completely blocked when spironolactone (anti-aldosterone agent) was added as a pre-treatment. Pre-treatment with aldosterone also significantly extended the mean (SEM) time required to reach 50% relaxation of a noradrenaline-induced contraction, of 9.3 (1.5) min, vs the control, of 5.2 (1.0) min (P = 0.002). CONCLUSION: Aldosterone has no direct contractile action or a relaxant action on human penile cavernous tissue, but acts to significantly enhance the noradrenaline-induced contraction. The effect on the noradrenaline-induced contraction is probably caused by aldosterone enhancing the affinity of the alpha-receptors for noradrenaline in hPCC. We suggest that aldosterone acts to enhance contraction of hPCC tissue, and is one of the restraining factors for human penile erection.

Long-term study of urinary bisphenol A in elementary school children.

OBJECTIVES: Due to its industrial application and frequent use as a coating material for food containers, bisphenol A (4,4'-isopropylidenediphenol, BPA) is present in abundance in our environment. Data on intake levels of BPA are limited in preadolescent children in Japan. This study was designed to help us better understand the current state of BPA exposure in children in Japan. METHODS: We followed first graders (n = 104) attending school in a Tokyo suburb from 1998 until the sixth grade (2003), during which time we collected a total of three morning urine samples. Urinary BPA was analyzed using high-performance liquid chromatography isotope-dilution tandem mass spectrometry. RESULTS: Ninety-four children were followed for 5 years. Median urinary BPA level was 2.66 ng/mg creatinine (CRE) (range 0.9-38.9) at first grade (1998), 1.52 ng/mg CRE (0.4-11.8) at third grade (2000), and 0.66 ng/mg CRE (0.2-8.5) at sixth grade (2003), showing a significant decrease in urinary BPA levels over a 5-year follow-up study (p < 0.001). No significant difference was seen between boys and girls at each grade. CONCLUSIONS: Urinary levels of BPA were relatively low throughout the study period; however, as the study progressed, we observed a significant decline in levels, the reason behind which is not yet clear.

DNA-adduct formation in lungs, nasal mucosa, and livers of rats exposed to urban roadside air in Kawasaki City, Japan.

The potency of ambient air for DNA-adduct formation was estimated using Wistar rats. The animals were maintained in a small-animal facility located beside a main highway intersection in Kawasaki City, Japan, for up to 60 weeks and were exposed to roadside air contaminated mainly with automobile emission (exposure group, EG) or to clean air (control group, CG). Compared to CG, the relative adduct levels (RAL) were increased significantly in EG lungs (17.1-fold (P<0.05)), nasal mucosa, and livers after exposure for 4 weeks. However, there were no significant differences in RAL between EG and CG after exposure for 12 weeks, but they were elevated again in EG after exposure for 48 or 60 weeks. These results suggest that roadside air in this region can cause the generation of DNA adducts. This activity of ambient roadside air can be estimated using experimental animals, indicating that biological monitoring of DNA-adduct formation may be a powerful tool to assess the effect of ambient air on human health.

Morphological effects in rat lungs exposed to urban roadside air.

We examined the effect of polluted roadside air on the pathogenesis of chronic respiratory diseases, by exposing rats directly to roadside air in Kawasaki City. Five-week-old Wistar rats were assigned to be exposed to either roadside air (containing 55.7 ppb NO2 and 62.7 microg/m(3) suspended particulate matter [SPM]; roadside-air group) or filtered air (containing 5.1 ppb NO2 and 14.3 microg/m(3) SPM; filtered-air group), prepared by eliminating dust and emission gas from the polluted roadside air, for a period of 60 consecutive wk. The morphological changes over time in the respiratory tissue of these animals were observed by light microscopy and electron microscopy at 24, 48, and 60 wk of exposure. In addition to the general microscopic findings, other features observed for included the proliferation of goblet cells producing mucus in the airways, acidification of neutral mucous granules in these goblet cells, the behavior of inflammatory cells such as alveolar macrophages, mast cells, and plasma cells, and the number of alveolar holes, known to be a primary indicator of early alveolar destruction. Focal anthracosis, acidified mucus in the goblet cells, and infiltration to the submucosa by inflammatory cells were observed in the lungs of the animals after 60 wk of exposure to polluted roadside air. However, these inflammatory changes were weak. No remarkable differences in the number of alveolar holes were noted between the two experimental groups. These findings suggest that the effects of roadside air on the respiratory tissue in rats may not be as severe as would be expected under these experimental conditions.

Chronic diesel exhaust exposures of rats demonstrate concentration and time-dependent effects on pulmonary inflammation.

Long-term, repeated exposure to particles in air pollution increases the risk for chronic respiratory diseases and cardiorespiratory mortality. The biological linkages remain poorly understood in chronic exposure to particle matter. To elucidate and verify these linkages, we investigated long-term exposure to diesel emission with respect to dose dependence and the effect of components without particles from diesel emission in rats. Wistar rats were exposed to filtered air (C group), diesel exhaust at low (L group), medium (M group), and high level (H group), or at a medium concentration diesel exhaust without particulate matter (MG group), for 16 h/day, 6 days/wk, for 6, 12, 18, or 24 mo. Anesthetized animals were sacrificed and bronchoalveolar lavage (BAL) fluid from the lung and blood from the right ventricle were collected. Various biomarkers of inflammation and components of mucus and surfactant were determined. Changes in total cell counts and cell differentiation, total protein, mucus and surfactant components, and prostaglandin E(2) in BAL fluid, but not biomarkers in plasma, showed statistical differences among the C, L, M, and H groups during the experimental period. The changes in these biomarkers in the H group were greater than those in the M group, whereas those in the L group showed no significant changes compared with those in the C group during the experimental period. The onset of significant changes in inflammatory cells and these biomarkers in BAL fluid for the M and H groups was at 6 to 12 mo of exposure. The maximum level was reached at 12 to 18 mo of exposure. Although BAL prostaglandin E(2) decreased significantly at 6 mo of exposure in the M and H groups, this trend was not observed in the C and L groups. Animals exposed to a medium level of diesel exhaust without particulate matter showed significantly less inflammatory cells and various biomarkers in BAL fluid than animals exposed to the same level of diesel exhaust with particulate matter during the experimental period. These findings suggest that biological response to inhaled particles is aggravated during chronic exposure to diesel exhaust dose-dependently. Inflammation and overproduction of mucus and surfactant components reached a plateau at 12 or 18 mo of exposure during a 24-mo experimental period. No adverse effect of particles (less than 1.0 mg particles/m(3) of diesel emission) was observed in these rats. However, our data suggest that particulate matter plays an important role during development of chronic lung injury induced by diesel emission exhaust.

Health effects of diesel exhaust emissions--a mixture of air pollutants of worldwide concern.

Diesel exhaust is a mixture of particles and gases. It contains more than several hundred different organic and inorganic components, including many chemicals that have been designated as toxic air pollutants. Because mutagens and carcinogens are present in both the gaseous and particulate components, lung cancer has been the focus of attention as a health risk in animal and human research. Moreover, since the epidemiologic data suggest carcinogenicity in humans, and the diesel exhaust exposure data in evaluations in rats by NIOSH, IARC, WHO, and the California EPA, are said to demonstrate or support carcinogenicity, agencies have designated them as latent occupational carcinogens (NIOSH) or toxic air pollutants (California EPA). In regard to their non-carcinogenic effects, a contribution to airway inflammation and allergies, and in relation to disease, the possibility of contracting asthma and chronic bronchitis, have been investigated both experimentally and epidemiologically, and concern has increased about their health effects, particularly in children.

Dose-response assessment and effect of particles in guinea pigs exposed chronically to diesel exhaust: analysis of various biological markers in pulmonary alveolar lavage fluid and circulating blood.

To elucidate dose-response and other effects of diesel particles in guinea pigs chronically exposed to diesel exhaust, various biomarkers for chronic obstructive lung diseases were studied using bronchoalveolar lavage (BAL) fluid and blood specimens. Guinea pigs were exposed 16 h/day, 6 days/wk, for 6, 12, 18, or 24 mo to filtered air (control group, n = 8-10), a low level of diesel exhaust (L group: NO(2) = 0.22 +/- 0.03 ppm; SO(2) = 0.6 +/- 0.19 ppm; particles = 0.21 +/- 0.07 mg/m(3), n = 8-10), medium level of diesel exhaust (M group; NO(2) = 1.07 +/- 0.09 ppm; SO(2) = 2.83 +/- 0.73 ppm; particles = 1.14 +/- 0.26 mg/m(3), n = 8-10), and high level of diesel exhaust (H group: NO(2) = 2.88 +/- 0.29 ppm; SO(2) = 6.49 +/- 1.75 ppm; particles = 2.94 +/- 0.69 mg/m(3), n = 8-10), or at a medium concentration of diesel exhaust without particulate matters (MG group: NO(2) = 1.01 +/- 0.09 ppm;#10; SO(2) = 2.66 +/- 0.64 ppm; particles = 0.01 +/- 0.01 mg/m(3), n = 8-10). Anesthetized animals were sacrificed and BAL fluid from the lung and blood from right ventricle were collected. Various biomarkers of inflammation, components of mucus and surfactant, bronchoconstrictors were determined. Changes of leukotriene C4 in plasma, eosinophil counts, biomarkers of inflammation and cytotoxicity, and mucus and surfactant components in BAL fluid were statistically different among the C, L, M, and H groups after adjustment for the exposure period and group-by-exposure period with respect to their interactions in two-way analysis of variance (ANOVA). The levels of these biomarkers in the H group were higher than those of the M group, whereas those of the L group showed no significant changes compared with those of the C group during experimental period. Onset of significant changes of these biomarkers for the M group was at 18 mo of exposure, whereas that for the H group was at 12 mo of exposure, which resulted in changes in the levels of biomarkers in BAL fluid. Although numbers of eosinophils in BAL fluid increased significantly in the M and H groups at 12 mo, only leukotriene C4 increased at 18 and 24 mo in blood and at 24 mo in BAL fluid. Animals exposed to the medium level of diesel exhaust without particulate matter showed significantly less increase of these biomarkers as compared with animals exposed to the same level of diesel exhaust with particulate matters. These findings indicate that chronic exposure to diesel exhaust induced continuous inflammation, overproduction of mucus, and phospholipids in the lung. Animals exposed to the high dose of diesel exhaust showed a plateau of biological responses at 12 mo of exposure. Particulate matter in diesel exhaust appears to play an important role in development of lung injury by chronic emission exhaust exposure.

Cytochrome P450 1B1 mRNA levels in peripheral blood cells and exposure to polycyclic aromatic hydrocarbons in Chinese coke oven workers.

Cytochrome P450 1B1 (CYP1B1) is induced through the Ah receptor and is involved in the activation of polycyclic aromatic hydrocarbons (PAHs). To determine the validity of a quantitative analysis of CYP1B1 mRNA in peripheral human blood cells for the estimation of PAH exposure, a real-time quantitative polymerase chain reaction method was used to measure the relative levels of CYP1B1 mRNA in 37 Chinese coke oven workers and 13 control workers. A large inter-individual difference in the levels was observed. The average level of the CYP1B1 mRNA in workers at the top work site, where the PAH exposure level from the coke ovens was highest, was significantly higher than in workers at the middle site (P<0.01) or the controls (P=0.02). A non-significant positive correlation was found between the CYP1B1 mRNA levels and urinary 1-hydroxypyrene (R=0.22, P=0.13), and a significant correlation between these mRNA levels and urinary cotinine (R=0.33, P=0.02). It was interesting that a significant positive correlation between CYP1B1 mRNA and 1-hydroxypyrene was observed in subjects with the Leu/Leu type of CYP1B1 Leu432Val polymorphism (R=0.33, P=0.02, n=38) and a non-significant correlation in subjects with the Leu/Val and Val/Val types (R=-0.36, P=0.25, n=12), although the number of subjects in this strata analysis was small. Our preliminary study suggests that PAH exposure in coke ovens and smoking maybe associated with CYP1B1 mRNA levels in peripheral blood cells although mRNA is generally unstable and could be expressed following exposure to other agents.

Relation between cotinine in the urine and indices based on self-declared smoking habits.

OBJECTIVES: The reliability of surveys on smoking habits based on questionnaires was investigated, using the urinary cotinine content as an objective index. METHODS: The subjects tested were 2,849 office workers of middle age, who responded to questions concerning their smoking status, and also their urinary cotinine was measured by the HPLC method. RESULTS: The boundary value between smokers and non-smokers, determined by the histogram independent of the questionnaire, was 63.1 and 79.4 ng/mg of creatinine for males and females, respectively. The rate of misclassification of the non-smokers and former smokers as smokers was 1.3% for males and 1.8% for females, whereas that of current smokers as non-smokers was 6.3% and 2.1%. We also assessed the effect of smoke inhalation on the urinary cotinine value, and found a significant difference for males in the cotinine value by the presence of inhalation and also its depth. CONCLUSIONS: The rate of misclassification in this study was considered to be comparatively low. Several studies have also assessed the reliability of the questionnaire on smoking habits, and found different misclassification rates, indicating the dependence on the race and number of subjects tested. To our knowledge, there were only a few surveys on smoking among large groups, particularly in Japan, such as this one, therefore the results obtained in this study are meaningful.