Fine particulate matter contributes to COPD-like pathophysiology: experimental evidence from rats exposed to diesel exhaust particles.

BACKGROUND: Ambient fine particulate matter (PM2.5) is considered a plausible contributor to the onset of chronic obstructive pulmonary disease (COPD). Mechanistic studies are needed to augment the causality of epidemiologic findings. In this study, we aimed to test the hypothesis that repeated exposure to diesel exhaust particles (DEP), a model PM2.5, causes COPD-like pathophysiologic alterations, consequently leading to the development of specific disease phenotypes. Sprague Dawley rats, representing healthy lungs, were randomly assigned to inhale filtered clean air or DEP at a steady-state concentration of 1.03 mg/m3 (mass concentration), 4 h per day, consecutively for 2, 4, and 8 weeks, respectively. Pulmonary inflammation, morphologies and function were examined. RESULTS: Black carbon (a component of DEP) loading in bronchoalveolar lavage macrophages demonstrated a dose-dependent increase in rats following DEP exposures of different durations, indicating that DEP deposited and accumulated in the peripheral lung. Total wall areas (WAt) of small airways, but not of large airways, were significantly increased following DEP exposures, compared to those following filtered air exposures. Consistently, the expression of α-smooth muscle actin (α-SMA) in peripheral lung was elevated following DEP exposures. Fibrosis areas surrounding the small airways and content of hydroxyproline in lung tissue increased significantly following 4-week and 8-week DEP exposure as compared to the filtered air controls. In addition, goblet cell hyperplasia and mucus hypersecretions were evident in small airways following 4-week and 8-week DEP exposures. Lung resistance and total lung capacity were significantly increased following DEP exposures. Serum levels of two oxidative stress biomarkers (MDA and 8-OHdG) were significantly increased. A dramatical recruitment of eosinophils (14.0-fold increase over the control) and macrophages (3.2-fold increase) to the submucosa area of small airways was observed following DEP exposures. CONCLUSIONS: DEP exposures over the courses of 2 to 8 weeks induced COPD-like pathophysiology in rats, with characteristic small airway remodeling, mucus hypersecretion, and eosinophilic inflammation. The results provide insights on the pathophysiologic mechanisms by which PM2.5 exposures cause COPD especially the eosinophilic phenotype.

Nasal oxidative stress mediating the effects of colder temperature exposure on pediatric asthma symptoms.

BACKGROUND: Colder temperature exposure is a known trigger for pediatric asthma exacerbation. The induction of oxidative stress is a known pathophysiologic pathway for asthma exacerbation. However, the role of oxidative stress in linking colder temperature exposure and worsened pediatric asthma symptoms is poorly understood. METHODS: In a panel study involving 43 children with asthma, aged 5-13 years old, each child was visited 4 times with a 2-week interval. At each visit, nasal fluid, urine, and saliva samples were obtained and measured for biomarkers of oxidative stress in the nasal cavity (nasal malondialdehyde [MDA]), the circulatory system (urinary MDA), and the oral cavity (salivary MDA). Childhood Asthma-Control Test (CACT) was used to assess asthma symptoms. RESULTS: When ambient daily-average temperature ranged from 7 to 18 °C, a 2 °C decrement in personal temperature exposures were significantly associated with higher nasal MDA and urinary MDA concentrations by 47-77% and 6-14%, respectively. We estimated that, of the decrease in child-reported CACT scores (indicating worsened asthma symptoms and asthma control) associated with colder temperature exposure, 14-57% were mediated by nasal MDA. CONCLUSION: These results suggest a plausible pathway that colder temperature exposure worsens pediatric asthma symptoms partly via inducing nasal oxidative stress. IMPACT: The role of oxidative stress in linking colder temperature exposure and worsened asthma symptoms is still poorly understood. Lower temperature exposure in a colder season was associated with higher nasal and systemic oxidative stress in children with asthma. Nasal MDA, a biomarker of nasal oxidative stress, mediated the associations between colder temperature exposures and pediatric asthma symptoms. The results firstly suggest a plausible pathway that colder temperature exposure worsens pediatric asthma symptoms partly via inducing oxidative stress in the nasal cavity.

Effects of ambient temperature on pediatric incident seizure: A case-crossover analysis using distributed lag non-linear models.

OBJECTIVE: Emerging evidence supports that brain dysfunction may be attributable to environmental factors. This study aims to examine associations of ambient temperature and temperature variability (TV) with seizure incidence in children, which has not been explored. MATERIAL AND METHODS: Data on 2718 outpatient visits due to seizure were collected in Shanghai, China, from 2018 to 2023. Exposure to ambient temperature was estimated at children's residential addresses using spatial-temporal models. A time-stratified case-crossover design with a distributed lag non-linear model (DLNM) was conducted to assess the association between seizure incidence and daily average of ambient temperature over a period of 21 days prior to a case date of disease onset. For a given case date, we selected all dates falling on the same day of the week within the same month as control dates. We calculated a composite index of intra-day and inter-day TV, which was the standard deviation of the daily minimum and maximum temperatures, respectively, over 7 days preceding a case date. We then assessed the association between TV and seizure incidence. Stratified analyses were conducted by age (73.51% < 5 years old and 26.49 % ≥ 5 years old), sex (41.83% female), presence of fever (69.72%), and diagnosis of epilepsy (27.63%). RESULTS: We observed inversed J-shaped temperature-response curves. Lower temperatures had a significant and prolonged effect than higher temperatures. Using 20 °C (with the minimum effect) as the reference, the cumulative odds ratios (ORs) for over 0-21 days preceding the onset at the 5th percentile of the temperature (3 °C) and at the 95th percentile (29 °C) were 3.17 (95% CI: 1.77, 5.68) and 1.54 (95% CI: 0.97, 2.44), respectively. In addition, per 1 °C increases in TV0-7 was associated with OR of 1.08 (95% CI: 1.01, 1.15). Older children and those experiencing seizure with fever exhibited a higher risk of seizure onset at both lower and higher ambient temperatures. CONCLUSION: Both low and high temperatures can contribute to the morbidity related to pediatric seizure. Lower temperatures, however, exerted a longer period of effect prior to seizure onset than higher temperatures. An increased risk for incident seizure was significantly associated with temperature variability during preceding 7 days.

Radon decay product particle radioactivity and oxidative stress biomarkers in patients with COPD.

Radon decay products include α-radiation emitting radionuclides that attach to airborne particles that have potential to promote oxidative tissue damage after inhalation. To assess associations between α-particle radioactivity (α-PR) with urinary biomarkers of oxidative tissue damage, 140 patients with chronic obstructive pulmonary disease (COPD) had up to four 1-week seasonal assessments (N = 413) of indoor (home) and ambient (central site) PM2.5 and black carbon (BC). Following environmental sampling, urine samples were analyzed for total and free malondialdehyde (MDA), biomarkers of lipid oxidation, and 8-hydroxyl-2'-deoxyguanosine (8-OHdG), a biomarker of DNA oxidative damage. Particle radioactivity was measured as α-activity on PM2.5 filter samples. Linear mixed-effects regression models adjusted for urinary creatinine and other personal characteristics were used to assess associations. Indoor α-PR was associated with an increase in 8-OhdG (8.53%; 95% CI: 3.12, 14.23); total MDA (5.59%; 95% CI: 0.20, 11.71); and free MDA (2.17%; 95% CI: 2.75, 7.35) per interquartile range (IQR) of α-PR [median 1.25 mBq/m3; IQR 0.64], similar adjusting for PM2.5 or BC. The ratio of indoor/ambient α-PR was positively associated with each biomarker and associations with ambient α-PR were positive but weaker than with indoor concentrations. These findings are consistent with a contribution of radon decay products as measured by α-PR to oxidative stress in patients with COPD, with a greater contribution of indoor radon decay products.

Bi-directional association between outdoor or social activities and cognitive function: do the PM2.5 exposure catalyze the detrimental inactivity-poor cognition cycle?

BACKGROUND: Previous research has shown that lack of leisure activities, either outdoor or social activities, impedes cognitive function. However, the interrelationship between poor cognition and deficient activities is understudied. In addition, whether exposure to air pollution, such as PM2.5, can accelerate the detrimental 'inactivity-poor cognition' cycle, is worthy of investigation. METHODS: We used data from the 2008, 2011, 2014, and 2018 waves of the Chinese Longitudinal Healthy Longevity Survey (CLHLS). We assessed the frequency of outdoor or social activities at each wave. The cognitive function was examined using a China-Modified Mini-mental State Examination. We estimated the residential exposure to fine particular matter (PM2.5) via a satellite-based model. We applied cross-lagged panel (CLP) model to examine the bi-directional relationship between outdoor or social activities and cognitive function. We then examined the effect of PM2.5 exposure with sequent cognitive function and activities using generalized estimation equation (GEE) model. FINDINGS: Overall, we observed significant bi-directional associations between outdoor or social activities and cognitive function. Participants with better cognitive function in the last wave were more likely to engage in outdoor or social activities in the following wave (outdoor activities: ß = 0.37, 95% CI [0.27,0.48], P < 0.01; social activities: ß = 0.05, 95% CI [0.02,0.09] P < 0.01). Meanwhile, higher engagement in outdoor or social activities in the last wave was associated with more favorable cognitive function in the following wave (outdoor activities: ß = 0.06, 95% CI [0.03,0.09], P < 0.01; social activities: ß = 0.10, 95% CI [0.03,0.18], P < 0.01). Notably, an increase in PM2.5 exposure during the preceding year was significantly associated with a declining cognitive function (ß = -0.05, 95% CI [-0.08,-0.03], P < 0.01), outdoor activities (ß = -0.02, 95% CI [-0.04, -0.01], P < 0.01) and social activities (ß = -0.02, 95% CI [-0.02, -0.01], P < 0.01) in the current year; the lagged effects of the PM2.5 exposure in the past year of the last wave on activities and cognitive function of the following wave were also observed. INTERPRETATION: Our findings not only indicate the bi-directional links between the frequency of outdoor or social activities and cognitive function, but also report that PM2.5 exposure plays a role in catalyzing the detrimental inactivity-poor cognition cycle. Future research should investigate whether the policy-driven interventions, such as clean air policies, can break the unfavorable activity-cognition cycle, and thereby promoting health from the dual gains in leisure activities and cognition.

A chronic stress-induced microbiome perturbation, highly enriched in Ruminococcaceae_UCG-014, promotes colorectal cancer growth and metastasis.

Purpose: Mounting evidence indicates that psychological stress adversely affects cancer progression including tumor growth and metastasis. The aim of this study was to investigate the role of chronic stress-induced microbiome perturbation in colorectal cancer (CRC) progression. Methods: Chronic restraint stress (CRS) was used to establish the chronic stress mouse model, behavioral tests were used for the CRS model evaluation. Subcutaneous xenograft model and lung metastasis model were established to investigate the growth and metastasis of CRC promoted by CRS exposure. 16S rRNA gene sequencing and liquid chromatograph-mass spectrometer (LC-MS) were applied to observe the effects of CRS exposure on the alteration of the gut microbiome and microbial metabolites. Bioinformatics analysis and correlation analyses were applied to analyse the changes in the frequency of body mass, tumor volume, inflammatory factors, neuroendocrine hormones and metabolites of the gut microbiota. Results: In this study, we identifed that CRS exposure model was appropriately constructed by achieving expected increases in disease activity index and enhanced depressive-like behaviors. CRS exposure can promote growth and metastasis of CRC. Besides, the data indicated that CRS exposure not only increased the neuro- and immune-inflammation, but also weakened the gut mucosal immunological function. The 16s rRNA gene sequencing data showed that CRS exposure increased the abundance of g_Ruminococcaceae_UCG_014. Furthermore, the LC-MS data indicated that with only 2 exceptions of carpaine and DG (15:0/20:4(5Z,8Z,11Z,14Z)/0:0), the majority of these 24 metabolites were less abundant in CRS-exposed mice. Bioinformatics analysis and correlation analyses indicated that only Ruminoscoccaceae-UCG-014 was significantly associated with inflammation (IL-6), neurotransmission (5-HT), and microbial metabolism (PS). Conclusion: CRS exposure altered diversity, composition and metabolites of the gut microbiome, with Ruminococcaceae_UCG-014 perturbation consistently correlated to inflammatory responses, suggesting a particular role of this bacterial genus in CRC growth and metastasis.

Gestational age modifies the association between exposure to fine particles and fetal death: findings from a nationwide epidemiological study in the contiguous United States.

BACKGROUNDS: The vulnerability of fetuses differs at different developmental stages, in response to environmental stressors such as fine particulate matter (PM2.5), a ubiquitous air pollutant. Whether gestational age (GA) modifies the association between prenatal fine particulate matter (PM2.5) exposure and fetal death remains unclear. METHODS: We selected approximately 47.8 million eligible United States (US) livebirth and fetal death (defined as a termination at a GA of 20-43 weeks) records from 1989 to 2004. For each record, we took the level of prenatal exposure to PM2.5 as the average concentration in the mother's residential county during the entire gestational period, or a specific trimester (i.e., GA-specific exposure), according to well-established estimates of monthly levels across the contiguous US. First, we evaluated the associations between PM2.5 exposure and fetal death at a specific GA (i.e., GA-specific outcome) using five different logit models (unadjusted, covariate-adjusted, propensity-score, double robust, and diagnostic-score models). Double robust model was selected as the main model due to its advantages in causal inference. Then, we conducted meta-analyses to pool the estimated GA-specific associations, and explored how the pooled estimates varied with GA. RESULTS: According to the meta-analysis, all models suggested gestational PM2.5 exposure was associated with fetal death. However, there was slight heterogeneity in the estimated effects, as different models revealed a range of 3.6-10.7% increase in the odds of fetal death per 5-µg/m3 increment of PM2.5. Each 5-µg/m3 increase in PM2.5 exposure during the entire gestation period significantly increased the odds of fetal death, by 8.1% (95% confidence interval [CI]: 5.1-11.2%). In terms of GA-specific outcomes, the odds of fetal death at a GA of 20-27, 28-36, or ≥ 37 weeks increased by 11.0% (5.9-16.4%), 5.2% (0.4-10.1%), and 8.3% (2.5-14.5%), respectively. In terms of GA-specific exposure, the odds of fetal death increased by 6.0% (3.9-8.2%), 4.1% (3.9-8.2%), and 4.3% (0.5-8.2%) with 5-µg/m3 increases in PM2.5 exposure during the first, second, and third trimester, respectively. The association had the largest effect size (odds ratio = 1.098, 95% CI: 1.061-1.137) between PM2.5 exposure during early gestation (i.e., first trimester) and early fetal death (i.e., 20-27 weeks). CONCLUSIONS: Prenatal exposure to PM2.5 was significantly associated with an increased risk of fetal death. The association was varied by gestational-age-specific exposures or outcomes, suggesting gestation age as a potential modifier on the effect of PM2.5. The fetus was most vulnerable during the early stage of development to death associated with PM2.5 exposure.

Identifying critical windows of air pollution exposure during preconception and gestational period on birthweight: a prospective cohort study.

BACKGROUND: Few studies have assessed air pollution exposure association with birthweight during both preconception and gestational periods. METHODS: Leveraging a preconception cohort consisting of 14220 pregnant women and newborn children in Shanghai, China during 2016-2018, we aim to assess associations of NO2 and PM2.5 exposure, derived from high-resolution spatial-temporal models, during preconception and gestational periods with outcomes including term birthweight, birthweight Z-score, small-for-gestational age (SGA) and large-for-gestational age (LGA). Linear and logistic regressions were used to estimate 3-month preconception and trimester-averaged air pollution exposure associations; and distributed lag models (DLM) were used to identify critical exposure windows at the weekly resolution from preconception to delivery. Two-pollutant models and children's sex-specific associations were explored. RESULTS: After controlling for covariates, one standard deviation (SD) (11.5 µg/m3, equivalent to 6.1 ppb) increase in NO2 exposure during the second and the third trimester was associated with 13% (95% confidence interval: 2 - 26%) and 14% (95% CI: 1 - 29%) increase in SGA, respectively; and one SD (9.6 µg/m3) increase in PM2.5 exposure during the third trimester was associated with 15% (95% CI: 1 - 31%) increase in SGA. No association have been found for outcomes of birthweight, birthweight Z-score and LGA. DLM found that gestational weeks 22-32 were a critical window, when NO2 exposure had strongest associations with SGA. The associations of air pollution exposure tended to be stronger in female newborns than in male newborns. However, no significant associations of air pollution exposure during preconception period on birthweight outcomes were found. CONCLUSION: Consistent with previous studies, we found that air pollution exposure during mid-to-late pregnancy was associated with adverse birthweight outcomes.

Inhibition of TRPA1 reduces airway inflammation and hyperresponsiveness in mice with allergic rhinitis.

This study was conducted to investigate whether a transient receptor potential ankyrin 1 (TRPA1) antagonist (HC-030031) can reduce airway inflammation and hyperresponsiveness in a murine allergic rhinitis (AR) model. BALB/c mice were sensitized and challenged by ovalbumin (OVA) to induce AR. HC-030031 or vehicle was administrated to mice via intraperitoneal injection prior to OVA challenges. Nose-scratching events, histopathologic alterations of the airways, and bronchial hyperresponsiveness (BHR) were assessed. Differential cells and proinflammatory cytokines in the nasal lavage (NAL) and bronchoalveolar lavage (BAL) fluid were measured. Expressions of TRPA1 in nasal mucosa were examined by immunohistochemistry. TRPA1-expressing vagal neurons were labeled by immunofluorescent staining. HC-030031-treated AR mice had markedly reduced type-2 inflammation in nasal mucosa and ameliorated-nose-scratching events than AR mice received vehicle. HC-030031 treatment also dramatically reduced leucocyte numbers and IL-8 level in the BAL fluid, inhibited lower airway remodeling and fibrosis, and nearly abolished BHR. HC-0300031 treatment significantly inhibited the upregulated number of TRPA1 expressing nasal epithelial cells and TRPA1 expressing sensory neurons, leading to downregulation of SP in both upper and lower airways. Targeting TRPA1 may represent a promising strategy for treating AR and AR-related asthma.

Tobacco Retail Outlets, Neighborhood Deprivation and the Risk of Prenatal Smoke Exposure.

INTRODUCTION: Smoking and smoke exposure among pregnant women remain persistent public health issues. Recent estimates suggest that approximately one out of four nonsmokers have measurable levels of cotinine, a marker indicating regular exposure to secondhand smoke. Epidemiological research has attempted to pinpoint individual-level and neighborhood-level factors for smoking during pregnancy. However, most of these studies have relied upon self-reported measures of smoking. AIMS AND METHODS: To more accurately assess smoke exposure resulting from both smoking and secondhand exposure in mothers during pregnancy, we used Bayesian regression models to estimate the association of cotinine levels with tobacco retail outlet (TRO) exposure and a neighborhood deprivation index (NDI) in six counties in North Carolina centered on Durham County. RESULTS: Results showed a significant positive association between TRO exposure (ß = 0.008, 95% credible interval (CI) = [0.003, 0.013]) and log cotinine after adjusting for individual covariates (eg, age, race/ethnicity, education, marital status). TRO exposure was not significant after including the NDI, which was significantly associated with log cotinine (ß = 0.143, 95% CI = [0.030, 0.267]). However, in a low cotinine stratum (indicating secondhand smoke exposure), TRO exposure was significantly associated with log cotinine (ß = 0.005, 95% CI = [0.001, 0.009]), while in a high cotinine stratum (indicating active smoking), the NDI was significantly associated with log cotinine (ß = 0.176, 95% CI = [0.005, 0.372]). CONCLUSIONS: In summary, our findings add to the evidence that contextual factors are important for active smoking during pregnancy. IMPLICATIONS: In this study, we found several significant associations that suggest a more nuanced understanding of the potential influence of environmental- and individual-level factors for levels of prenatal smoke exposure. Results suggested a significant positive association between TRO exposure and cotinine levels, after adjusting for the individual factors such as race, education, and marital status. Individually, NDI was similarly positively associated with cotinine levels as well. However, when combining TRO exposure alongside NDI in the same model, TROs were no longer significantly associated with overall cotinine levels.

Arachidonic acid metabolism and inflammatory biomarkers associated with exposure to polycyclic aromatic hydrocarbons.

Exposure to polycyclic aromatic hydrocarbons (PAHs) has been associated with systemic inflammation, yet what mechanisms regulate PAHs' inflammatory effects are less understood. This study evaluated the change of arachidonic acid (ARA) metabolites and inflammatory biomarkers in response to increased exposure to PAHs among 26 non-smoking healthy travelers from Los Angeles to Beijing. Traveling from Los Angeles to Beijing significantly increased urinary metabolites of dibenzofuran (800%), fluorene (568%), phenanthrene (277%), and pyrene (176%), accompanied with increased C-reactive protein, fibrinogen, IL-8, and IL-10, and decreased MCP-1, sCD40L, and sCD62P levels in the blood. Meanwhile, the travel increased the levels of ARA lipoxygenase metabolites that were positively associated with a panel of pro-inflammatory biomarkers. Concentrations of cytochrome P450 metabolite were also increased in Beijing and were negatively associated with sCD62P levels. In contrast, concentrations of ARA cyclooxygenase metabolites were decreased in Beijing and were negatively associated with anti-inflammatory IL-10 levels. Changes in both inflammatory biomarkers and ARA metabolites were reversed 4-7 weeks after participants returned to Los Angeles and were associated with urinary PAH metabolites, but not with other exposures such as secondhand smoke, stress, or diet. These results suggested possible roles of ARA metabolic alteration in PAHs-associated inflammatory effects.

Association between outdoor artificial light at night and sleep duration among older adults in China: A cross-sectional study.

BACKGROUND: Light after dusk disrupts the circadian rhythms and shifts the timing of sleep later; but it is unknown whether outdoor artificial light at night (ALAN) affects sleep quality. This study aimed to explore the association between residential outdoor ALAN and sleep duration in a nationally representative sample of Chinese older adults. METHODS: We examined the cross-sectional associations of outdoor ALAN with self-reported sleep duration in 13,474 older adults participating in the 2017-2018 wave of the Chinese Longitudinal Healthy Longevity Survey (CLHLS). Outdoor ALAN exposure was estimated at the residence level using satellite images. We applied generalized linear mixed models to investigate the association between ALAN exposure and sleep duration. We performed stratified analyses by age, sex, education, and household income levels. Moreover, we used multi-level logistic regression models to investigate the effects of ALAN on the short sleep duration (≤6 h) and the long sleep duration (>8 h), respectively, in reference to sleep for >6-8 h per day. RESULTS: We found a significant association between outdoor ALAN intensity and sleep duration. The highest quartile of ALAN was associated with 17.04 (95% CI: 9.42-24.78) fewer minutes of sleep as compared to the lowest quartile. The reductions in sleep duration per quartile change in ALAN were greater in the young old (≥65-85 years) and in those with higher levels of education, and those with higher household income, respectively. We did not detect a sex difference. In addition, those in the highest quartile of ALAN were more likely to report a 25% (95% CI: 10%-42%) increase in short sleep (<6 h), and a 21% (95% CI: 9%-31%) decrease in long sleep (>8 h). CONCLUSIONS: Increasing outdoor nighttime light intensity surrounding residences was associated with shorter sleep duration in older residents in China. This finding implies the importance of urban outdoor artificial light management as a potential means to lower the public health burden of sleep disorders.

Oral cavity response to air pollutant exposure and association with pulmonary inflammation and symptoms in asthmatic children.

Exposure to fine particulate matter (PM2.5) and ozone (O3) may lead to inflammation and oxidative damage in the oral cavity, which is hypothesized to contribute to the worsening of airway inflammation and asthma symptoms. In this panel study of 43 asthmatic children aged 5-13 years old, each child had 4 clinic visits with a 2-week interval between two consecutive visits. At each visit, saliva samples were collected and subsequently analyzed for interleukin 6 (IL-6) and eosinophil cationic protein (ECP) as biomarkers of inflammation and malondialdehyde (MDA) as a biomarker of oxidative stress in the oral cavity. At each visit, children were measured for fractional exhaled nitric oxide (FeNO) as a marker of pulmonary inflammation. Asthma symptoms of these children were measured using the Childhood Asthma Control Test (C-ACT). We found that an interquartile range (IQR) increase in 24-h average personal exposure to PM2.5 measured 1 and 2 days prior was associated with increased salivary IL-6 concentration by 3.0% (95%CI: 0.2%-6.0%) and 4.2% (0.7%-8.0%), respectively. However, we did not find a clear association between personal O3 exposure and any of the salivary biomarkers, except for a negative association between salivary MDA and O3 exposure measured 1 day prior. An IQR increase in salivary IL-6 concentration was associated with significantly increased FeNO by 28.8% (4.3%-53.4%). In addition, we found that increasing salivary IL-6 concentrations were associated with decreased individual and total C-ACT scores, indicating the worsening of asthma symptoms. We estimated that 13.2%-22.2% of the associations of PM2.5 exposure measured 1 day prior with FeNO and C-ACT scores were mediated by salivary IL-6. These findings suggest that the induction of inflammation in the oral cavity may have played a role in linking air pollution exposure with the worsening of airway inflammation and asthma symptoms.

NO2 and PM2.5 air pollution co-exposure and temperature effect modification on pre-mature mortality in advanced age: a longitudinal cohort study in China.

BACKGROUND: There is a discourse on whether air pollution mixture or air pollutant components are causally linked to increased mortality. In particular, there is uncertainty on whether the association of NO2 with mortality is independent of fine particulate matter (PM2.5). Furthermore, effect modification by temperature on air pollution-related mortality also needs more evidence. METHODS: We used the Chinese Longitudinal Healthy Longevity Study (CLHLS), a prospective cohort with geographical and socio-economic diversity in China. The participants were enrolled in 2008 or 2009 and followed up in 2011-2012, 2014, and 2017-2018. We used remote sensing and ground monitors to measure nitrogen dioxide (NO2), fine particulate matter (PM2.5) , and temperature. We used the Cox-proportional hazards model to examine the association between component and composite air pollution and all-cause mortality, adjusted for demographic characteristics, lifestyle, geographical attributes, and temperature. We used the restricted cubic spline to visualize the concentration-response curve. RESULTS: Our study included 11 835 individuals with an average age of 86.9 (SD: 11.4) at baseline. Over 55 606 person-years of follow-up, we observed 8 216 mortality events. The average NO2 exposure was 19.1 µg/m3 (SD: 14.1); the average PM2.5 exposure was 52.8 µg/m3 (SD: 15.9). In the single pollutant models, the mortality HRs (95% CI) for 10 µg/m3 increase in annual average NO2 or PM2.5 was 1.114 (1.085, 1.143) and 1.244 (1.221, 1.268), respectively. In the multi-pollutant model co-adjusting for NO2 and PM2.5, the HR for NO2 turned insignificant: 0.978 (0.950, 1.008), but HR for PM2.5 was not altered: 1.252 (1.227, 1.279). PM2.5 and higher mortality association was robust, regardless of NO2. When acccounting for particulate matter, NO2 exposure appeared to be harmful in places of colder climates and higher seasonal temperature variation. CONCLUSIONS: We see a robust relationship of PM2.5 exposure and premature mortality in advance aged individuals, however, NO2 exposure and mortality was only harmful in places of colder climate such as northeast China, indicating evidence of effect modification by temperature. Analysis of NO2 without accounting for its collinearity with PM2.5, may lead to overestimation.

Nitrated Polycyclic Aromatic Hydrocarbons and Arachidonic Acid Metabolisms Relevant to Cardiovascular Pathophysiology: Findings from a Panel Study in Healthy Adults.

Concerns on nitrated polycyclic aromatic hydrocarbons (nitro-PAHs) in the environment have mainly arisen from their mutagenic and carcinogenic effects. The objective of this study is to investigate whether nitro-PAH exposures are associated with biomarkers of cardiovascular pathophysiology. In a panel study design, urines and blood samples were collected up to four times with a 2-week interval from 89 healthy adults. We measured 1-naphthylamine, 2-naphthylamine, 9-aminophenanthrene, 2-aminofluorene, and 1-aminopyrene as biomarkers of nitro-PAH exposures. We measured three urinary metabolites of arachidonic acid (AA) including 20-hydroxyeicosatetraenoic acid (20-HETE) from the cytochrome P450 (CYP) pathway, 8-isoprostane from the nonenzymatic pathway, and 11-dehydro-thromboxane B2 (11-dhTXB2) from the cyclooxygenase (COX) pathway. Urinary malondialdehyde, 8-hydroxy-2'-deoxyguanosine (8-OHdG), and 6-sulfatoxymelatonin (aMT6s) were measured to reflect systemic oxidative stress. Plasma concentrations of the soluble P-selectin and von Willebrand factor (vWF) were measured as biomarkers of platelet activation and endothelial dysfunction. We found that increased urinary concentrations of amino-PAHs were significantly associated with increased 20-HETE, 11-dhTXB2, and 8-OHdG and with decreased 8-isoprostane and aMT6s. Increased amino-PAHs were positively associated with P-selectin and vWF, respectively. These results suggest that exposure to nitro-PAHs increases systemic oxidative stress and alters AA metabolism toward CYP and COX pathways, leading to an increased cardiovascular disease risk.

Personal Exposure to PM2.5 Oxidative Potential in Association with Pulmonary Pathophysiologic Outcomes in Children with Asthma.

Fine particulate matter (PM2.5) with a higher oxidative potential has been thought to be more detrimental to pulmonary health. We aim to investigate the associations between personal exposure to PM2.5 oxidative potential and pulmonary outcomes in asthmatic children. We measured each of the 43 asthmatic children 4 times for airway mechanics, lung function, airway inflammation, and asthma symptom scores. Coupling measured indoor and outdoor concentrations of PM2.5 mass, constituents, and oxidative potential with individual time-activity data, we calculated 24 h average personal exposures 0-3 days prior to a health outcome measurement. We found that increases in daily personal exposure to PM2.5 oxidative potential were significantly associated with increased small, large, and total airway resistance, increased airway impedance, decreased lung function, and worsened scores of individual asthma symptoms and the total symptom score. Among the PM2.5 constituents, organic matters largely of indoor origin contributed the greatest to PM2.5 oxidative potential. Given that the variability in PM2.5 oxidative potential was a stronger driver than PM2.5 mass for the variability in the respiratory health outcomes, it is suggested to reduce PM2.5 oxidative potential, particularly by reducing the organic matter constituent of indoor PM2.5, as a targeted source control strategy in asthma management.

Identifying the Best Questions for Rapid Screening of Secondhand Smoke Exposure Among Children.

INTRODUCTION: Many children suffer from secondhand smoke exposure (SHSe), which leads to a variety of negative health consequences. However, there is no consensus on how clinicians can best query parents for possible SHSe among children. We employed a data-driven approach to create an efficient screening tool for clinicians to quickly and correctly identify children at risk for SHSe. METHODS: Survey data from mothers and biospecimens from children were ascertained from the Neurodevelopment and Improving Children's Health following Environmental Tobacco Smoke Exposure (NICHES) study. Included were mothers and their children whose saliva were assayed for cotinine (n = 351 pairs, mean child age = 5.6 years). Elastic net regression predicting SHSe, as indicated from cotinine concentration, was conducted on available smoking-related questions and cross-validated with 2015-2016 National Health and Nutrition Examination Survey (NHANES) data to select the most predictive items of SHSe among children (n = 1670, mean child age = 8.4 years). RESULTS: Answering positively to at least one of the two final items ("During the past 30 days, did you smoke cigarettes at all?" and "Has anyone, including yourself, smoked tobacco in your home in the past 7 days?") showed area under the curve = .82, and good specificity (.88) and sensitivity (.74). These results were validated with similar items in the nationally representative NHANES sample, area under the curve = .82, specificity = .78, and sensitivity = .77. CONCLUSIONS: Our data-driven approach identified and validated two items that may be useful as a screening tool for a speedy and accurate assessment of SHSe among children. IMPLICATIONS: The current study used a rigorous data-driven approach to identify questions that could reliably predict SHSe among children. Using saliva cotinine concentration levels as a gold standard for determining SHSe, our analysis employing elastic net regression identified two questions that served as good classifier for distinguishing children who might be at risk for SHSe. The two items that we validated in the current study can be readily used by clinicians, such as pediatricians, as part of screening procedures to quickly identify whether children might be at risk for SHSe.

Real-time measurements of PM2.5 and ozone to assess the effectiveness of residential indoor air filtration in Shanghai homes.

Portable air cleaners are increasingly used in polluted areas in an attempt to reduce human exposure; however, there has been limited work characterizing their effectiveness at reducing exposure. With this in mind, we recruited forty-three children with asthma from suburban Shanghai and deployed air cleaners (with HEPA and activated carbon filters) in their bedrooms. During both 2-week filtration and non-filtration periods, low-cost PM2.5 and O3 air monitors were used to measure pollutants indoors, outdoors, and for personal exposure. Indoor PM2.5 concentrations were reduced substantially with the use of air cleaners, from 34 ± 17 to 10 ± 8 µg/m3 , with roughly 80% of indoor PM2.5 estimated to come from outdoor sources. Personal exposure to PM2.5 was reduced from 40 ± 17 to 25 ± 14 µg/m3 . The more modest reductions in personal exposure and high contribution of outdoor PM2.5 to indoor concentrations highlight the need to reduce outdoor PM2.5 and/or to clean indoor air in multiple locations. Indoor O3 concentrations were generally low (mean = 8±4 ppb), and no significant difference was seen by filtration status. The concentrations of pollutants and the air cleaner effectiveness were highly variable over time and across homes, highlighting the usefulness of real-time air monitors for understanding individual exposure reduction strategies.

Negative ions offset cardiorespiratory benefits of PM2.5 reduction from residential use of negative ion air purifiers.

Negative ion air purifiers (NIAPs), as a less costly alternative to the HEPA filtration, have been increasingly deployed in China and potentially elsewhere. While reducing indoor concentrations of fine particulate matter (PM2.5 ), NIAPs generate massive amounts of negative ions that may be of health concern. We performed week-long interventions with NIAPs in the dormitories of 56 healthy college students living in Beijing. In a randomized order, each student underwent a true and a sham NIAP session. Cardiorespiratory outcomes were measured before and after each session. The use of true NIAPs reduced indoor PM2.5 concentrations significantly, while notably increased negative ion levels. Increases in PM2.5 and negative ion (NI) exposure were independently associated with increased urinary concentration of malondialdehyde, a biomarker of systemic oxidative stress, resulting in a null net effect of NIAP on malondialdehyde. Likewise, no significant net effects of NIAPs were observed for other outcomes indicative of lung function, vascular tone, arterial stiffness, and inflammation. Our findings suggest that negative ions, possibly along with their reaction products with the room air constituents, adversely affect health. The downsides do not support the use of NIAPs as a health-based mitigation strategy to reduce PM2.5 exposure, especially in residences with PM2.5 concentrations that are not extremely high.

Malondialdehyde in Nasal Fluid: A Biomarker for Monitoring Asthma Control in Relation to Air Pollution Exposure.

Fine particulate matter (PM2.5) and ozone (O3) may exert oxidative damage in the nose, which is hypothesized to be associated with worsened asthma symptoms. This study, hence, is to explore whether an oxidative stress biomarker, malondialdehyde (MDA) in the nasal fluid, has the potential to aid personalized asthma control. In a panel study of 43 asthmatic children, 5-13 years old, each child was measured 4 times with a 2-week interval between consecutive clinic visits. At each visit, nasal fluid and urine samples were collected, and fractional exhaled nitric oxide (FeNO) was measured as a biomarker of pulmonary inflammation. In addition to nasal MDA, urinary MDA and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were measured as biomarkers of systemic oxidative stress. We also assessed asthma symptoms using the Childhood Asthma-Control Test (C-ACT). We found that interquartile range (IQR) increases in 24 h average personal PM2.5 exposure (22.2-33.5 µg/m3), estimated 0 to 5 days prior to a clinic visit, were associated with increased nasal MDA concentrations by 38.6-54.9%. Similarly, IQR increases in 24 h average personal O3 exposure (7.7-8.2 ppb) estimated 2 to 4 days prior were associated with increased nasal MDA by 22.1-69.4%. Only increased PM2.5 exposure was associated with increased FeNO. Increased nasal MDA concentration was associated with decreased total and individual C-ACT scores, indicating worsening of asthma symptoms. However, no significant associations were observed between urinary MDA or 8-OHdG and C-ACT scores. The results confirm that oxidative stress plays an important role in linking air pollution exposure and adverse respiratory health effects. These findings support that MDA in the nasal fluid may serve as a useful biomarker for monitoring asthma status, especially in relation to PM2.5 and O3 exposures, two known risk factors of asthma exacerbation.