Association between indoor nitrous acid, outdoor nitrogen dioxide, and asthma attacks: results of a pilot study.

The association between nitrogen dioxide (NO2) and asthma has been investigated. However, conventional NO2 assays measure nitrous acid (HONO) as NO2. In this pilot epidemiological observational study, we assessed exposure to indoor HONO and some air pollutants in pediatric asthma patients and examined possible association between exposure and asthma symptoms. Indoor HONO and nitric oxide (NO), which are primarily generated by the combustion of certain substances, were significantly associated with asthma attacks in 2010. In 2010, indoor HONO was closely correlated with indoor NO than with outdoor NO2. Conversely, in 2012, indoor HONO was closely correlated with outdoor NO2 and NO than with indoor NO2 and NO. Outdoor NO2 was significantly associated with asthma attacks in 2012. Our results highlight the need for further epidemiological studies of the association between indoor HONO and asthma symptoms using multivariate analyses to examine the role of NO2 in asthma symptoms. Abbreviations: CXCL1: the chemokine (C-X-C motif) ligand 1; EP: the entire study period; FP: the first half of study period; HONO: nitrous acid; NO: nitric oxide; NO2: nitrogen dioxide; OH radical: hydroxyl radical; SP: the second half of study period; TNF-α: tumor necrosis factor-α; US EPA: United States Environmental Protection Agency; WHO: World Health Organization.

Background factors of chemical intolerance and parent-child relationships.

BACKGROUND: Chemical intolerance is a widespread public health problem characterized by symptoms that reportedly result from low-level exposure to chemicals. Although several studies have reported factors related to chemical intolerance in adults, the impact of family members has not been reported. In the present study, we investigated the background factors related to chemical intolerance in family members and parent-child relationships. METHODS: We distributed a self-reported questionnaire to 4325 mothers who were invited to visit the Kishiwada Health Center in Kishiwada City, Osaka, between January 2006 and December 2007 for the regular health checkup of their three-and-a-half-year-old children. RESULTS: The prevalence of chemical intolerance in the 3-year-old children was almost one eighteenth of that reported by their mothers. Multiple logistic regression analyses revealed that cold sensitivity [odds ratio (OR), 1.89; 95% confidence interval (CI), 1.04-3.44], past bronchial asthma (OR, 2.84; 95% CI, 1.46-5.53), and any past allergies (OR, 2.21; 95% CI, 1.36-3.60) were significantly associated with chemical intolerance in the mother. The presence of indoor cat during childhood (OR, 1.99; 95% CI, 1.08-3.69) was significantly associated with chemical intolerance in the mother; however, the association was weak compared with cold sensitivity and past asthma and allergies. The current chemical intolerance of the mother was significantly associated with allergic rhinitis (OR, 2.32; 95% CI, 1.19-4.53), bronchial asthma (OR, 3.66; 95% CI, 2.00-6.69), and chronic bronchitis (OR, 3.69; 95% CI, 1.04-13.03) in her 3-year-old child. CONCLUSIONS: The results suggest that inherent physical constitution and childhood housing environment are associated with a risk of acquiring chemical intolerance. Children of mothers with chemical intolerance have a possible risk of respiratory hypersensitivity or inflammation. Further investigation is recommended to determine the inherent physical constitution and background environmental factors associated with the risk of acquiring chemical intolerance. The impact of having mothers with chemical intolerance on the health of children also requires further study.

[A strategy for assessing environmental influence on airway allergy using a regression binary tree-based method].

OBJECTIVE: To clarify the living environment factors that increase the risk of allergic sensitization to house dust mites, we applied a regression binary tree-based method (CART, Classification & Regression Trees) to an epidemiological study on airway allergy. The utility of the tree map in personal sanitary guidance for preventing allergic sensitization was examined with respect to feasibility and validity. SUBJECTS AND METHODS: A questionnaire was given to 386 healthy adult women, asking them about their individual living environments. Also, blood samples were collected to measure Dermatophagoides pteronyssinus (Dp)-specific IgE, the presence/absence of Dp-sensitization being expressed as positive/negative. The questionnaire consisted of nine items on (1) home ventilation by keeping windows open, (2) personal or family smoking habits, (3) use of air conditioners in hot weather, (4) type of flooring (tatami/wooden/carpet) in the living room, (5) visible mold proliferation in the kitchen, (6) type of housing (concrete/wooden), (7) residential area (heavy or light traffic area) (8) heating system (use of unventilated combustion appliances), and (9) frequency of cleaning (every day or less often). There also were queries on the past history of airway allergic diseases, such as bronchial asthma and allergic rhinitis. CART and a multivariate logistic regression analysis (MLRA) were performed. The subjects were first classified into two groups, with and without a history of airway allergic diseases (Groups WPH and WOPH). In each group, the involvement of living environment factors in Dp-sensitization was examined using CART and MLRA. RESULTS: In the MLRA study, individual living environment factors showed promotional or suppressive effects on Dp-sensitization with differences between the two groups. With respect to the CART results, the two groups were first split by the factor that had the most significant odds ratio for MLRA. In Group WPH, which had a Dp-sensitization risk of 19.5%, the first split was by the factor of visible mold proliferation in the kitchen into the factor-present group with a risk value of 45.5% and the factor-absent group with 13.5%. The mold proliferation group was split with reference to frequent cleaning, and the risk rose to 75% in the factor-absent group and to 100% when family smoking habits were reported. Group WOPH (the risk: 10.8%) was first split into two groups according to the use of air conditioners in hot weather for more than 6 hours a day or less, which showed risk values of 16.7% and 6.9%, respectively. The risk of the group that intensively used air conditioners fell to 8.3% with tatami as flooring in the living room, and, if others, rose to 20.8%. The risk of the factor-lacking group fell to 4.0% without wooden flooring. CONCLUSIONS: CART analysis enables us to express complex relationships between living environment factors and Dp-sensitization simply by a binary regression tree, pointing to preventive strategies that can be flexibly changed according to the individual living environments of the subjects.

[Potential risk factors aggravating airway allergy--aspects of involvement of airtight housing and passive smoking].

OBJECTIVES: The involvement of tightly insulated housing conditions and passive smoking in atopic sensitization, a major risk factor for airway allergy, was examined with nonsmoking adult women and school-age children. SUBJECTS AND METHODS: The subjects were 382 nonsmoking healthy adult women (housewives) who underwent medical examinations for prevention of adult diseases conducted in a district of Osaka from 1995 to 1997, and 214 elementary school-children 9-12 years old living in an urban district of Osaka who underwent medical examinations at a health center in April, 2000 to prevent allergic diseases. We also examined the correlation between tightly insulated housing conditions and the amount of passive smoking based on family smoking habits with 170 children under 12 years old who had been under the care of a hospital pediatrics department between December, 1993 and May, 1994. A questionnaire was administered to all subjects to survey the housing structure (concrete/wooden housing), family smoking habits and visible mold proliferation in the kitchen in relation to airtight housing conditions, passive smoking and exposure to inhalant allergens. Atopic sensitization was assessed by positivity for serum house dust mite-specific IgE, and passive smoking was defined as a urinary cotinine level of more than 6 ng/mgCr. RESULTS: 1. Among the three factors, indoor mold proliferation and family smoking habits were positively and synergistically related with atopic sensitization to house dust mites. 2. Airtight conditions of concrete housing showed a promotional effect on passive smoking for housewives, but a suppressive effect for school-age children. 3. Taking into account the above results, the promotional effects of passive smoking on atopic sensitization appeared predominantly in the concrete housing-residence group of housewives and the wooden housing-residence group of school-age children. 4. Effects of visible mold proliferation in the kitchen on atopic sensitization appeared predominantly in wooden housing-residence group of housewives. CONCLUSIONS: The results suggest that involvement of the three factors in atopic sensitization is due to increased exposure to indoor inhalant allergens or enhanced IgE-antibody production (adjuvant effects of tobacco smoke) and the extent of their inpact varies depending on the individual life styles of the housewives and school-age children.

Tissue-specific induction of cytochromes P450 1A1 and 1B1 by polycyclic aromatic hydrocarbons and polychlorinated biphenyls in engineered C57BL/6J mice of arylhydrocarbon receptor gene.

Tissue-specific induction of mRNA of cytochrome P450 (P450 or CYP) 1A1 and 1B1 by polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) was investigated in wild and arylhydrocarbon receptor (AhR)-deficient C57BL/6J mice. Ratios of mRNA expression of CYP1A1 or CYP1B1 over beta-actin were determined and used to compare levels of expression and induction of these P450s by PAHs and PCBs in various organs. CYP1A1 mRNA was detected in control mice at very low levels in liver, lung, heart, kidney, intestine, thymus, testis, uterus, ovary, and brain and was highly induced in these organs by benzo[a]pyrene and 3,4,3',4'-tetrachlorobiphenyl in AhR(+/+) mice. In AhR(+/+) and AhR(-/-) mice, CYP1B1 mRNA was found to be constitutively expressed at significant levels in heart (the ratio of mRNAs of CYP1B1 to beta-actin was approximately 0.6), kidney ( approximately 0.8), intestine ( approximately 0.3), testis ( approximately 0.9), thymus ( approximately 0.4), uterus ( approximately 0.3), ovary ( approximately 1.4), and brain ( approximately 0.4), whereas it was low in liver and lung (the mRNA ratio to beta-actin was <0.2 in these cases). CYP1B1 in the latter two organs was highly induced by PAHs and 3,4,3',4'-tetrachlorobiphenyl in AhR(+/+) mice. The induction of CYP1B1 by PAHs and PCBs was more extensive in organs in which the constitutive expression of CYP1B1 was low. For example, CYP1B1 was induced 9-fold and 10-fold by benzo[a]pyrene and 3,4,3',4'-tetrachlorobiphenyl in livers of male and female mice, respectively, whereas in testis and ovary, the fold induction of CYP1B1 by two inducers was only 1.1 and 1.4, respectively. Liver microsomal xenobiotic oxidation activities were induced by these PAHs and PCBs in male and female AhR(+/+) mice. These results suggest that CYP1A1 and CYP1B1 are differentially regulated in their expression in extrahepatic organs of mice and could be induced by PAHs and PCBs with different extents of induction depending on the inducers used and the organs examined in AhR(+/+) mice. The findings of significant levels of constitutive expression of CYP1B1 in AhR(-/-) mice as well as AhR(+/+) mice in several organs including heart, kidney, thymus, testis, ovary, and brain in AhR(-/-) mice as well as AhR(+/+) mice are of importance in understanding the basis of toxicity and carcinogenesis by chemicals that are metabolized by CYP1B1.

Arylhydrocarbon receptor-dependent induction of liver and lung cytochromes P450 1A1, 1A2, and 1B1 by polycyclic aromatic hydrocarbons and polychlorinated biphenyls in genetically engineered C57BL/6J mice.

Arylhydrocarbon receptor knock-out, AhR(-/-), mice have recently been shown to be rather resistant to benzo[a]pyrene (B[a]P)-induced tumor formation, probably reflecting the inability of these mice to express significant levels of cytochrome P450 (P450 or CYP) 1A1 that activates B[a]P to reactive metabolites (Y. Shimizu, Y. Nakatsuru, M. Ichinose, Y. Takahashi, H. Kume, J. Mimura, Y. Fujii-Kuriyama and T. Ishikawa (2000) PROC: Natl Acad. Sci. USA, 97, 779-782). However, it is not precisely determined whether CYP1B1, another enzyme that is also active in activating B[a]P, plays a role in the B[a]P carcinogenesis in mice. To understand the basis of roles of CYP1A1 and CYP1B1 in the activation of chemical carcinogens, we compared levels of induction of liver and lung CYP1A1, 1A2, and 1B1 by various polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls in AhR(+/+) and AhR(-/-) mice. Liver and lung CYP1A1 and 1B1 mRNAs were highly induced in AhR(+/+) mice by a single intraperitoneal injection of each of the carcinogenic PAHs, such as B[a]P, 7,12-dimethylbenz[a]anthracene, dibenz[a,l]pyrene, 3-methylcholanthrene, 1,2,5,6-dibenzanthracene, benzo[b]fluoranthene, and benzo[a]anthracene and by a co-planar PCB congener 3,4,3',4'-tetrachlorobiphenyl. We also found that 6-aminochrysene, chrysene, benzo[e]pyrene, and 1-nitropyrene weakly induced the mRNA expression of CYP1A1 and 1B1, whereas anthracene, pyrene, and fluoranthene that have been reported to be non-carcinogenic in rodents, were very low or inactive in inducing these P450s. The extents of induction of liver CYP1A2 by these chemicals were less than those of CYP1A1 and 1B1 in AhR(+/-/+/-) mice. In AhR(-/-) mice, there was no induction of these P450s by PAHs and polychlorinated biphenyls. Liver microsomal activities of 7-ethoxyresorufin and 7-ethoxycoumarin O-deethylations and of mutagenic activation of (+/-)-trans-7,8-dihydroxy-7,8-dihydro-B[a]P to DNA-damaging products were found to correlate with levels of CYP1A1 and 1B1 mRNAs in the liver. Our results suggest that carcinogenicity potencies of PAHs may relate to the potencies of these compounds to induce CYP1A1 and 1B1 through AhR-dependent manner and that these induced P450s participate in the activation of B[a]P and related carcinogens causing initiation of cancers in mice.