Time Series Analysis of Climate and Air Pollution Factors Associated with Atmospheric Nitrogen Dioxide Concentration in Japan.

Nitrogen dioxide (NO2) is an air pollutant discharged from combustion of human activities. Nitrous acid (HONO), measured as NO2, is thought to impact respiratory function more than NO2. HONO and NO2 have an equilibrium relationship, and their reaction is affected by climate conditions. This study was conducted to discuss the extent of HONO contained in NO2, depending on the level of urbanization. Whether climate conditions that promote HONO production enhanced the level of NO2 measured was investigated using time series analysis. Climate and outdoor air pollution data measured in April 2009-March 2017 in urban (Tokyo, Osaka, and Aichi) and rural (Yamanashi) areas in Japan were used for the analysis. Air temperature had a trend of negative associations with NO2, which might indicate the decomposition of HONO in the equilibrium between HONO and NO2. The associations of relative humidity with NO2 did not have consistent trends by prefecture: humidity only in Yamanashi was positively associated with NO2. In high relative humidity conditions, the equilibrium goes towards HONO production, which was observed in Yamanashi, suggesting the proportion of HONO in NO2 might be low/high in urban/rural areas.

Lowest observed adverse effect level of pulmonary pathological alterations due to nitrous acid exposure in guinea pigs.

BACKGROUND: We previously demonstrated that continuous exposure to nitrous acid gas (HONO) for 4 weeks, at a concentration of 3.6 parts per million (ppm), induced pulmonary emphysema-like alterations in guinea pigs. In addition, we found that HONO affected asthma symptoms, based on the measurement of respiratory function in rats exposed to 5.8 ppm HONO. This study aimed to investigate the dose-response effects of HONO exposure on the histopathological alterations in the respiratory tract of guinea pigs to determine the lowest observed adverse effect level (LOAEL) of HONO. METHODS: We continuously exposed male Hartley guinea pigs (n = 5) to four different concentrations of HONO (0.0, 0.1, 0.4, and 1.7 ppm) for 4 weeks (24 h/day). We performed histopathological analysis by observing lung tissue samples. We examined samples from three guinea pigs in each group under a light microscope and measured the alveolar mean linear intercept (Lm) and the thickness of the bronchial smooth muscle layer. We further examined samples from two guinea pigs in each group under a scanning electron microscope (SEM) and a transmission electron microscope (TEM). RESULTS: We observed the following dose-dependent changes: pulmonary emphysema-like alterations in the centriacinar regions of alveolar ducts, significant increase in Lm in the 1.7 ppm HONO-exposure group, tendency for hyperplasia and pseudostratification of bronchial epithelial cells, and extension of the bronchial epithelial cells and smooth muscle cells in the alveolar duct regions. CONCLUSIONS: These histopathological findings suggest that the LOAEL of HONO is < 0.1 ppm.

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.

Effects of nitrous acid exposure on baseline pulmonary resistance and Muc5ac in rats.

We examined the baseline pulmonary resistance (RLung), baseline dynamic lung compliance (Cdyn), cytokine inductions, and histological alterations in rats exposed to nitrous acid (HONO) with secondary products of nitrogen dioxide (NO2) and nitric oxide (NO) to assess its biological effects. We exposed three groups of nine male F344 rats to different doses of HONO for six weeks (24 h/day). The cumulative values of HONO concentration were measured twice. The average concentrations of nitrogen oxide for each group were 5.8 parts per million (ppm) HONO with secondary products of 0.7 ppm NO2 and 2.3 ppm NO, 4.1 ppm HONO with 0.1 ppm NO2 and 0.6 ppm NO, and a clean air control. We measured baseline RLung and baseline Cdyn using tracheal cannulation. A tracheal tube was inserted into the trachea by tracheostomy, and lung function measurements (baseline RLung and baseline Cdyn) were conducted in mechanically ventilated rats. We measured mRNA levels of Cxcl-1, TNF-α, and Muc5ac in the right lung using quantitative RT-PCR, and observed histological alterations and the alveolar mean linear intercept (Lm) on the left lung. Our results demonstrated that HONO exposure significantly increased baseline RLung, Lm and Muc5ac expression, but did not affect baseline Cdyn or expression of Cxcl-1 and TNF-α. Further, we identified bronchial smooth muscle hypertrophy, pulmonary emphysema-like alterations in the alveolar duct centriacinar regions, and increased goblet cells in HONO-exposed rats. The present results suggest that HONO (with secondary products) adversely affects respiratory function, but that these pathologies may be unrelated to inflammation.

Comparing the role of silica particle size with mineral fiber geometry in the release of superoxide from rat alveolar macrophages.

Particulate air pollutants and mineral fibers activate inflammatory cells to release oxidants, which contribute to inflammation and injury in the lower respiratory tract. Our aim was to compare the role of silica particle size with mineral fiber length and width in the ability to induce superoxide release from rat alveolar macrophages. We estimated the ability of four types of silica particle samples, with different mode diameter, and three types of mineral fiber samples, with different geometric mean lengths and widths, to induce lucigenin-dependent chemiluminescence (CL) from the cells per number of dust particles (i.e., silica particles and mineral fibers). A close positive correlation was observed between dust size and the ability to induce CL in silica as well as mineral fiber samples. Moreover, the ability of silica samples to induce CL was weaker than that of long mineral fiber sample. This ability increased at a larger rate in small silica particle and thin mineral fiber samples than in large silica particle and thick mineral fiber samples at the initial stage of administration. These results suggest that the kinetics of the induction superoxide release from macrophages is similar between silica particles and mineral fibers; moreover, this depends on silica particle size and mineral fiber geometry. Finally, large silica particles were more active than small ones.