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The relation between respiratory illness in primary schoolchildren and the use of gas for cooking--II. Factors affecting nitrogen dioxide levels in the home.

The study was designed to determine whether there was an association between indoor levels of nitrogen dioxide (NO2) and respiratory illness and lung function in schoolchildren. NO2 was measured for one week in the winter outside and inside the homes of children aged 6-7 years living and attending primary schools in a defined 4 square km area in Middlesbrough, Cleveland, UK. Outdoor levels of NO2 measured at 75 points within the area ranged from 14-24 ppb weekly average. Measurements were also made in 428 kitchens with gas cookers, range 5-317 ppb, mean 112.2 ppb, and in 87 kitchens with electric cookers, range 6-188 ppb, mean 18.0 ppb. In a random subsample of homes the range of NO2 levels in 107 children's bedrooms in homes where gas was used for cooking was 4-169 ppb, mean 30.5 ppb, in 18 bedrooms in electric cooking homes the range was 3-37 ppb, mean 13.9 ppb. NO2 levels in the gas cooking kitchens were positively related to the presence of pilot lights, use of gas fires for main heating, number of regular smokers, and the number of people in the home. Information from 29 homes with the highest kitchen NO2 levels paired with 29 low NO2 gas cooking homes showed that the daily number of meals eaten and the frequency with which the cooker was used for heating and drying clothes were significantly greater in the high NO2 homes.

Air Pollutants

Nitrogen dioxide inhalation and human blood biochemistry.

Blood from ten young adult male humans, exposed to 1 ppm or 2 ppm nitrogen dioxide (NO2) for 2.5--3.0 hr, was examined for evidence of biochemical changes. The experiments lasted three days. The subjects entered an environmental chamber, performed mild exercise, and completed a series of measurements of pulmonary physiology while breathing filtered air. Blood samples were then taken and analyzed. This regimen was repeated on the second and third day, except that the chamber atmosphere now contained 1 ppm or 2 ppm NO2. Paired group analyses were performed on the data. A statistically significant decrease was observed in the activity of the erythrocyte membrane enzyme acetylcholinesterase at both NO2 levels. Levels of peroxidized red blood cell lipids showed statistically significant elevations after inhalation of 2 ppm NO2 but not 1 ppm. Glucose-6-phosphate dehydrogenase was significantly elevated only after the second 2-ppm NO2 exposure. Small but statistically significant decreases were observed in both hemoglobin and hematocrit values after exposure to both NO2 levels. The experiment was repeated with NO2, (i.e., three days of filtered air) to detect possible effects of the experimental procedure. Decreases were again seen in hemoglobin and hematocrit, and acetyecholinesterase, although of smaller magnitude than when NO2 was inhaled. Other data showed random variations that were not additive over the three-day sham exposure period. It was concluded that significant blood biochemical changes resulted from NO2 inhalation, although the three-day experimental regimen independently produced changes that account for some of the apparent response.

Acetylcholinesterase

Influence of 0.5 ppm nitrogen dioxide exposure of mice of macrophage congregation in the lungs.

The lungs of 12 mice, half of which were exposed to continuous 0.5 ppm nitrogen dioxide for 3 weeks, were explanted in culture, and the instances of macrophage congregation were quantitated according to numbers of target cells involved, categories of congregation from three to 11 or more, numbers of macrophages participating in each category for the total cultures, and the influence of delaying explantation for 24 and 96 hr. A total of 9042 macrophages and 2140 epithelial and spindle target cells were counted in the outgrowths from 306 explants. The incidence of macrophage congregation (or numbers of target cells) was greater for the cultures from the NO2-exposed animals, both with respect to total incidences between groups (p leads to) and the 0-hr (p less than 0.001) and 24-hr (p less than 0.01) culture subgroups. In addition, the values for T3 to T6 macrophage congregation were individually and consistently greater for the exposed animal group. Postmortem interval stress at 96 hr appeared to result in large colonies, but they were reduced greatly in number. Also the incidence of macrophage congregation fell by 28% as compared to 0-hr and 24-hr subgroups.

Animals

Nitrogen dioxide and the erythrocyte redox state.

Normal human erythrocytes were exposed for two hours at 38 C to an atmosphere of air containing variable concentrations of nitrogen dioxide, in order to detect any primary cytoplasmic effect of NO2 on the calculated oxidation-reduction (redox) ratio ([NAD+]/[NADH]) of a mitochondria-free cell. Substantial increases in the redox ratio were noted only when NO2 concentrations exceeded 15 ppm. In the range of 15 to 500 ppm NO2, the increase in the redox ratio significantly correlated with the NO2 concentration (r=.71; p less than .01). Intracellular to extracellular anion distribution ratios for chloride, lactate, and pyruvate were similar in NO2 and non-NO2 exposed cells, suggesting absence of a substantial hemolytic effect. These data identify a direct cytoplasmic NO2-induced biochemical change that may be mediated by a mechanism other than lipid peroxidation. Alteration of hemoglobin or NAD-NADH-dependent enzyme activity is suggested.

Cell Fractionation

Proliferation of lung and airway cells induced by nitrogen dioxide.

Proliferation of lung cells of Chinese hamsters was examined in several regions of the lung parenchyma and ciliated airway epithelium after a 24-h exposure to 28.2 mg/m3 (15 ppm) nitrogen dioxide (NO2). Label was retained 3 wk after the injection of [3H]thymidine, and autoradiographic methods were used to localize the site of retention. By 24 h after administration of [3H]thymidine, parenchymal areas, exclusive of airways, showed an increased labeling index, indicative of cell death and replacement. This increase in the number of labeled cells persisted for 3 wk. Type II cells were labeled twice as frequently in regions of the terminal bronchiole than in other alveolar areas. Type II cell cycle time was reduced from 26 to 3 d after NO2 exposure. Alveolar macrophages were significantly labeled in the alveolar areas during the thymidine pulse at the end of the exposure episode and retained label for 3 wk. Airway epithelia showed no labeling in the trachea and progressively greater labeling in increasingly small er airways. Epithelial cells lining the small airways and alveoli showed greater susceptibility to NO2 injury than cells lining the bronchi or trachea. Nonciliated or basal cells serve as a precursor of ciliated cells in the epithelium of small airways (0.35 mm) and bronchi.

Animals

The relation between respiratory illness in primary schoolchildren and the use of gas for cooking--III. Nitrogen dioxide, respiratory illness and lung infection.

We examined the relation between lung function and respiratory illness in a population of 808 primary school children aged 6-7 years and the levels of nitrogen dioxide (NO2) in the kitchens and bedrooms in their homes. Complete data were collected on about 66% of the population. The children lived in a defined 4 square km area in Middlesbrough, Cleveland, UK. One week average outdoor levels of NO2 varied little over the area (14-24 ppb); The prevalence of respiratory illness was higher in children from gas than electric cooking homes (p approximately or equal to 0.1). Although prevalence was not related to kitchen NO2 levels (range 5-317 ppb) it increased with increasing levels of NO2 in the children's bedrooms in gas cooking homes (range 4-169 ppb, p approximately or equal to 0.1). Symptoms in siblings and parents were not related to kitchen NO2 levels. Lung function was not related to NO2 levels in the kitchen or bedroom. Because of the very low levels of NO2 at which an association with illness was observed and the inconsistency between our results in the UK and those from several studies in the US, it is possible that the NO2 levels were a proxy for some other factor more directly related to respiratory disease such as temperature or humidity.

Air Pollutants

Collagen breakdown and nitrogen dioxide inhalation.

Measurements of urinary hydroxylysine glycosides indicate that considerable collagen degradation occurred during the reentry into the earth's atmosphere of the American astronauts of the Apollo-Soyuz mission. Since the crew accidentally inhaled nitrogen dioxide, a recognized pulmonary irritant, and showed clinical and roentgenographic signs of diffuse chemical pneumonitis, it is likely that collagen degradation occurred in the pulmonary parenchyma.

Collagen