The role of air pollution and weather changes in childhood asthma

Eighty asthmatic children were studied for two years. Daily records of various parameters of asthma were correlated with levels of different air pollutants and such climatological factors as bad weather conditions and temperature changes. High levels of ozone and carbon monoxide significantly correlated with the number, duration and the severity of asthmatic attacks. However, all the factors combined played only a minor role in the complex etiology of asthma, accounting for only 5 percent to 15 percent of the total variance.     

Pulmonary effects of sulfur dioxide exposure and ipratropium bromide pretreatment in adults with nonallergic asthma

In this study we examined the potential short-term effect of sulfur dioxide (SO2) on total respiratory resistance and forced expiratory volume in patients with nonallergic asthma. A group of nine adult subjects with nonallergic asthma, 55 years of age or older, were exposed to SO2 at 0, 0.5, and 1.0 ppm for 20 minutes at rest followed by 10 minutes during light-moderate exercise. The measures of pulmonary function assessed were FEV1, specific total respiratory resistance (SRT), and maximal expiratory flow rates at 50% (Vmax50) and 75% (Vmax75) of expired vital capacity. Measurements were made before exposure to SO2 (baseline), postresting exposure, postexercising exposure, and at 30 minutes thereafter (recovery). Repeat measure analysis of variance revealed a statistically significant dose-response effect of SO2 inhalation on FEV1 (p = 0.008), SRT (p = 0.033), Vmax50 (p = 0.017), and Vmax75 (p = 0.048). Eight subjects had repeat exposure to SO2 at 1.0 ppm after treatment with either placebo or ipratropium bromide, 60 micrograms by metered-dose inhaler. Inpratropium bromide treatment, compared to placebo treatment, resulted in a statistically significant improvement in all baseline measures of pulmonary function: FEV1 (p = 0.017), SRT (p = 0.027), Vmax50 (p = 0.018), and Vmax75 (p = 0.035). However, this drug did not significantly alter the proportionate change in pulmonary function caused by SO2 inhalation in these subjects. These findings indicate that adults with nonallergic asthma are sensitive to short-term low-level SO2 exposure and that treatment with 60 micrograms of ipratropium bromide causes significant bronchodilation but does not protect, completely, these patients from the effect of SO2 inhalation.     

The cyclo-copolymerization of diallyl compounds and sulfur dioxide. II. Diallyldimethylammonium chloride and sulfur dioxide

Copolymers of diallyldimethylammonium chloride and sulfur dioxide were prepared. The copolymerization was carried out in dimethylsulfoxide, methanol or acetone using radical initiators. The effect of the polymerization conditions on the yields and the molecular weight was studied. The structure of the water-soluble polysulfones obtained was studied by means of IR spectroscopy and elementary analysis. The properties of the copolymers were investigated.     

The cyclo-copolymerization of diallyl compound and sulfur dioxide. I. Diallylamine hydrochloride and sulfur dioxide

Copolymer of diallylamine hydrochloride and sulfur dioxide was prepared. The copolymerization was carried out in dimethylsulfoxide, dimethylformamide, or methanol using radical initiators. The structure of the obtained water-soluble copolymer has been studied by IR-spectra and elementary analysis. The properties of the copolymer were investigated.     

The cyclo-copolymerization of diallyl compounds and sulfur dioxide, 6. 1,6-Heptadiene and sulfur dioxide

Copolymers from 1,6-heptadiene ( 1 ) and SO₂ with various mole ratios of their units were prepared. Their structures were studied by elemental analyses, IR and ¹H NMR spectroscopy. Structures containing a cyclopentane ring ( 2 ) and such containing a thiane ring ( 3 ) in the main chain are proposed.     

Genetic polymorphisms as biomarkers of sensitivity to inhaled sulfur dioxide in subjects with asthma.

BACKGROUND: Individuals with asthma are sensitive to inhaled sulfur dioxide (SO2); decrements in pulmonary function occur after exposure to low concentrations even for a short duration of time. There is a great amount of interindividual variation in response to SO2. OBJECTIVE: It was our objective to determine whether one of the following polymorphism locations linked with asthma is associated with the bronchial hyperresponsiveness to SO2 observed in some asthmatic patients: the beta2-adrenergic receptor, interleukin-4 (IL-4) receptor alpha subunit, Clara cell secretory protein (CC16), TNF-alpha gene promoter, and first intron of the lymphotoxin alpha (LT-alpha) gene. METHODS: Subjects were volunteers with physician-diagnosed asthma requiring regular asthma medication. Spirometry was performed before and after a 10-minute exposure to 0.5 ppm SO2. Subjects were classified as SO2 responders if forced expiratory volume in 1 second (FEV1) decreased > or = 12%. DNA obtained from buccal cell samples was analyzed for genetic polymorphisms. RESULTS: Of the 62 subjects (21 male and 41 female), 13 had a 12% or greater decrement in FEV1 after SO2 exposure (range + 19% to -49%). Response to SO2 was associated with the wild-type allele of the TNF-alpha promoter polymorphism (12 of 12 SO2 responders versus 28 of 46 nonresponders; P < .05) but with no other polymorphisms. Medication category and atopic status showed no association with SO2 sensitivity. CONCLUSIONS: The wild-type allele of the TNF-alpha promoter polymorphism may be associated with mechanisms of asthmatic sensitivity to inhaled SO2.     

Glutathione S-transferase P1 gene polymorphism and air pollution as interactive risk factors for childhood asthma

BACKGROUND: Polymorphisms at the glutathione S-transferase (GST) P1 locus were associated with asthma-related phenotypes and bronchial hyper-responsiveness. OBJECTIVE: This study investigated whether GSTP1 genotypes and outdoor air pollution were interactive risk factors on childhood asthma. METHODS: Four hundred and thirty-six subjects were recruited for oral mucosa samplings from 2853 fourth- to ninth-grade schoolchildren from three districts with different air pollution levels in southern Taiwan. PCR-based assays were performed by oral mucosa DNA to determine GSTP1 genotypes. We also conducted a nested case-control study comprising 61 asthmatic children and 95 controls confirmed by International Study of Asthma and Allergies in Childhood questionnaire results and methacholine challenge test. Multiple logistic regression was used to adjust for potential confounding factors. RESULTS: All participants were homozygous at the Ala-114 locus. Although only a marginally significant association existed between the frequency of homozygosity at the Ile-105 locus and asthma when air pollution was not considered, we found a significant gene-environmental interaction between GSTP1-105 alleles and air pollution after adjusting for confounders (P=0.035). Specifically, we found that compared with participants carrying any Val-105 allele in low air pollution, those who are Ile-105 homozygotes in high air pollution district had a significantly increased risk of asthma (adjusted odds ratio (AOR)=5.52, 95% confidence interval (CI)=1.64-21.25). Compared with participants carrying any Val-105 allele, in high air pollution district, children with Ile-105 homozygotes had a significantly increased risk of asthma (AOR=3.79, 95% CI=1.01-17.08), but those who carried two Ile-105 alleles in low or moderate air pollution districts did not show similar tendencies. The risk of asthma also revealed a clear dose-response relationship with outdoor air pollution in children with Ile-105 homozygotes. CONCLUSION: Our result suggests a gene-environmental interaction between GSTP1-105 genotypes and outdoor air pollution on childhood asthma.     

Passive smoking and childhood asthma

Passive exposure to tobacco smoke was assessed in children with asthma (age 3-15) and in referents. There was statistically significantly (P less than 0.0005) higher excretion of the nicotine metabolite, cotinine, in the urine of 49 children with asthma (geometric mean 10 ng/ml) compared with 77 referents (4.8 ng/ml). Maternal smoking was statistically significantly more prevalent among the asthmatics than among the referents (relative risk = RR = 2.6, 95% C1 = 1.2-5.3). In conclusion, the exposure to environmental tobacco smoke in asthmatic children was higher than among healthy children, indicating that passive smoking may be a predisposing and/or aggravating factor for childhood asthma.     

Alternating copolymerization of cyclohexene oxide and sulfur dioxide

Copolymerization of cyclohexene oxide (CHO) and sulfur dioxide (SO₂) was conducted at 80°C by using a variety of catalysts both in the presence and absence of solvent. Aromatic tertiary amines such as pyridine gave an alternating copolymer of CHO and SO₂ in the presence of solvents such as 1,2-dimethoxyethane. The alternating copolymer obtained was a white thermoplastic which could readily be thermoformed. It was soluble in acetone and chloroform but insoluble in water and hexane. From the reaction of the equimolar mixture of CHO, SO₂ and pyridine at 20°C, an 1 : 1 : 1 adduct of CHO, SO₂ and pyridine (see formula 2 ) could be isolated. This adduct was confirmed to be the active species for the present copolymerization.     

Bronchoconstrictor responses to sulfur dioxide or sulfur dioxide plus sodium chloride droplets in allergic,nonasthmatic adolescents

Eight atopic adolescent subjects without diagnosis of clinical asthma but with signs of hyperactive airways were studied. The subjects were exposed for 30 min at rest followed by 10 min during moderate exercise on a treadmill to the following: (1) filtered air, (2) 1 mg/m³ NaCl droplet aerosol, (3) 1 ppm SO₂ and NaCl droplet aerosol, or (4) 1 ppm SO₂. All exposures were at 75% relative humidity and 22 °C. Exposures to either SO₂ mode produced statistically significant changes in pulmonary function, whereas sham exposures to air on NaCl did not. These results are similar to those seen earlier in a group of extrinsic asthmatic adolescent subjects and are three to 22 times greater than changes we saw in a group of normal adolescent subjects. The changes seen after inhalation of SO₂ were not statistically different from those seen after inhalation of SO₂ and NaCl droplet aerosol. Our results indicate that inhalation of 1 ppm SO₂ by a group of atopic adolescents can produce exercise-induced bronchospasm at a level of exercise that has no effect by itself.     

GSTP1 is a hub gene for gene–air pollution interactions on childhood asthma

There is growing evidence that multiple genes and air pollutants are associated with asthma. By identifying the effect of air pollution on the general population, the effects of air pollution on childhood asthma can be better understood. We conducted the Taiwan Children Health Study (TCHS) to investigate the influence of gene–air pollution interactions on childhood asthma. Complete monitoring data for the ambient air pollutants were collected from Taiwan Environmental Protection Agency air monitoring stations. Our results show a significant two‐way gene–air pollution interaction between glutathione S‐transferase P (GSTP1) and PM₁₀ on the risk of childhood asthma. Interactions between GSTP1 and different types of air pollutants have a higher information gain than other gene–air pollutant combinations. Our study suggests that interaction between GSTP1 and PM₁₀ is the most influential gene–air pollution interaction model on childhood asthma. The different types of air pollution combined with the GSTP1 gene may alter the susceptibility to childhood asthma. It implies that GSTP1 is an important hub gene in the anti‐oxidative pathway that buffers the harmful effects of air pollution.