Prenatal and early-life air pollutant exposure and epigenetic aging acceleration.

BACKGROUND: This study investigated the association of prenatal and early childhood exposure to air pollution with epigenetic age acceleration (EAA) at six years of age using the Environment and Development of Children Cohort (EDC Cohort) MATERIALS & METHODS: Air pollution, including particulate matter [< 2.5 µm (PM2.5) and < 10 µm (PM10) in an aerodynamic diameter], nitrogen dioxide (NO2), ozone (O3), carbon monoxide (CO), and sulfur dioxide (SO2) were estimated based on the residential address for two periods: 1) during the whole pregnancy, and 2) for one year before the follow-up in children at six years of age. The methylation levels in whole blood at six years of age were measured, and the methylation clocks, including Horvath's clock, Horvath's skin and blood clock, PedBE, and Wu's clock, were estimated. Multivariate linear regression models were constructed to analyze the association between EAA and air pollutants. RESULTS: A total of 76 children in EDC cohort were enrolled in this study. During the whole pregnancy, interquartile range (IQR) increases in exposure to PM2.5 (4.56 µg/m3) and CO (0.156 ppm) were associated with 0.406 years and 0.799 years of EAA (Horvath's clock), respectively. An IQR increase in PM2.5 (4.76 µg/m3) for one year before the child was six years of age was associated with 0.509 years of EAA (Horvath's clock) and 0.289 years of EAA (Wu's clock). PM10 (4.30 µg/m3) and O3 (0.003 ppm) exposure in the period were also associated with EAA in Horvath's clock (0.280 years) and EAA in Horvath's skin and blood clock (0.163 years), respectively. CONCLUSION: We found that prenatal and childhood exposure to ambient air pollutants is associated with EAA among children. The results suggest that air pollution could induce excess biological aging even in prenatal and early life.

The short-term effects of individual and mixed ambient air pollutants on suicide mortality: A case-crossover study.

It is critical to explore intervenable environmental factors in suicide mortality. Based on 30,688 suicide cases obtained from the Mortality Surveillance System of the Jiangsu Provincial Centre for Disease Control and Prevention, we utilized a case-crossover design, and found that the OR of suicide deaths increased by a maximum of 0.71 % (95 % CI: 0.09 %, 1.32 %), 0.68 % (95 % CI: 0.12 %, 1.25 %), 0.77 % (95 % CI: 0.19 %, 1.37 %), 2.95 % (95 % CI: 1.62 %, 4.29 %), 4.18 % (95 % CI: 1.55 %, 6.88 %), and 0.93 % (95 % CI: 0.10 %, 1.77 %), respectively, for per 10 µg/m3 increase in the particulate matter (PM) with diameters ≤ 2.5 µm (PM2.5), PM with diameters ≤ 10 µm (PM10), ozone (O3), nitrogen dioxide (NO2), sulfur dioxide (SO2), and per 0.1 mg/m3 increase in carbon monoxide (CO) concentrations with the conditional logistic regression analysis. People living in county-level cities were more susceptible. Particularly, a significant positive association was found between air pollutant mixture exposure and suicide deaths (OR=1.04,95 % CI: 1.01, 1.06). The excess fraction of suicide deaths due to air pollution reached a maximum of 8.07 %. In conclusion, we found associations between individual and mixed ambient air pollutants and suicide deaths, informing the development of integrated air pollution management and targeted measures for suicide prevention and intervention. ENVIRONMENTAL IMPLICATION: As a major contributor to the global burden of disease, air pollution was confirmed by accumulating studies to have adverse impact on mental health, and potentially lead to suicide deaths. However, systematic studies on the association between air pollution and suicide mortality are lacking. We explored the associations of multiple air pollutants and pollution mixtures with suicide deaths and assessed excess suicide mortality due to air pollution, emphasizing the importance of air pollution control on suicide prevention. Our study provides evidence to support mechanistic studies on the association between air pollution and suicide, and informs comprehensive air pollution management.

Investigation of Cerebral Mitochondrial Injury in a Porcine Survivor Model of Carbon Monoxide Poisoning.

INTRODUCTION: Carbon monoxide (CO) is a colorless and odorless gas that is a leading cause of environmental poisoning in the USA with substantial mortality and morbidity. The mechanism of CO poisoning is complex and includes hypoxia, inflammation, and leukocyte sequestration in brain microvessel segments leading to increased reactive oxygen species. Another important pathway is the effects of CO on the mitochondria, specifically at cytochrome c oxidase, also known as Complex IV (CIV). One of the glaring gaps is the lack of rigorous experimental models that may recapitulate survivors of acute CO poisoning in the early phase. The primary objective of this preliminary study is to use our advanced swine platform of acute CO poisoning to develop a clinically relevant survivor model to perform behavioral assessment and MRI imaging that will allow future development of biomarkers and therapeutics. METHODS: Four swine (10 kg) were divided into two groups: control (n = 2) and CO (n = 2). The CO group received CO at 2000 ppm for over 120 min followed by 30 min of re-oxygenation at room air for one swine and 150 min followed by 30 min of re-oxygenation for another swine. The two swine in the sham group received room air for 150 min. Cerebral microdialysis was performed to obtain semi real-time measurements of cerebral metabolic status. Following exposures, all surviving animals were observed for a 24-h period with neurobehavioral assessment and imaging. At the end of the 24-h period, fresh brain tissue (cortical and hippocampal) was immediately harvested to measure mitochondrial respiration. RESULTS: While a preliminary ongoing study, animals in the CO group showed alterations in cerebral metabolism and cellular function in the acute exposure phase with possible sustained mitochondrial changes 24 h after the CO exposure ended. CONCLUSIONS: This preliminary research further establishes a large animal swine model investigating survivors of CO poisoning to measure translational metrics relevant to clinical medicine that includes a basic neurobehavioral assessment and post exposure cellular measures.

The role of carbon monoxide in aerotoxic syndrome.

Chronic low-level exposure to toxic compounds in airplane cabin air may result in Aerotoxic Syndrome (AS). Aetiologic agents are organophosphates and numerous volatile organic hydrocarbons originating from leaks of engine oil and hydraulic fluids. Despite a documented history spanning decades, the role of carbon monoxide remains controversial. What evidence exists that carbon monoxide (CO), present in the cocktail of toxic compounds in bleed air, contributes to the AS? We selected 22 publications encompassing 888 flights with 18 different aircraft types. In one study of 100 flights, fume events were confirmed in 38. Four studies were initialized after air quality incidents. The cabin CO concentrations could be categorized in three levels, 1) low (<5 ppm), without health implications, 2) moderate (5-10 ppm) with probably health implications in case of chronic exposure, and 3) high > 10 ppm, with health effects in case of acute and chronic exposure. These levels were recorded in 12, 6 and 4 studies respectively. In the six studies in category 2, max CO concentrations ranged from 5.8-9.4 ppm. The four studies with CO > 10 ppm comprised 376 of the 888 flights (42%) with six aircraft types. Toxic CO levels ranging between 13-60 ppm were identified in at least 129 of 888 (14.5%) flights. In one study with high CO levels four flight attendants were diagnosed with CO poisoning with elevated HbCO levels. Max CO levels in aviation are either the same or higher than current occupational exposure limits (OEL) for ground-based workplace exposures or levels for urban street transport environments. Specific aspects of aviation should be taken into consideration: the effect of low(er) air pressure at high altitudes increasing the toxicity of CO, and the binding of CO to CYP enzymes, leading to impaired organophosphate detoxification. We conclude that CO must be considered an important factor in the lubrication derived cocktail of airborne toxic compounds causing AS. In line with the WHO advice, a reduction of the OEL to 5 ppm over 8 hr time weighted average (TWA) for aircrew is strongly recommended. And we advocate continuous monitoring during all phases of flight and installation of CO detectors in the air supply ducts to the aircraft cabin.

Effects and possible mechanisms of combined exposure to noise and carbon monoxide on male reproductive system in rats.

Environmental hazards are an increasing concern due to the rapid pace of industrialization. Among these hazards, noise and carbon monoxide (CO) are common risk factors and have been shown to cause serious health problems. However, existing studies focused on the individual effects of noise and CO exposure and the combined effects of these two factors remain poorly understood. Our study aimed to examine the combined effects of noise and CO exposure on testicular function by constructing individual and combined exposure models. Our findings indicated that combined exposure to noise and CO was associated with a higher risk of testicular damage and male reproductive damage when compared to exposure alone. This was evidenced by poorer semen quality and more severe pathological damage to the testis. This combined exposure led to higher levels of oxidative stress and apoptosis in the testes, with bioinformatics analyses suggesting the signaling pathways involved in these responses. Specifically, activation of the P53 signaling pathway was found to contribute to the testicular damage caused by the combined exposure. Encouragingly, pterostilbene (PTE), a novel phytochemical, alleviated combined exposure-induced testicular damage by reducing oxidative stress and germ cell apoptosis. Overall, we identified joint reproductive toxicity resulting from the exposure to noise and CO, and found that PTE is a promising potential treatment for injuries caused by these factors. The cover image is based on the Research Article Effects and possible mechanisms of combined exposure to noise and carbon monoxide on male reproductive system in rats by Yingqing Li et al., https://doi.org/10.1002/tox.23927.

Ambient carbon monoxide and the risk of cardiovascular disease emergency room visits: a time-series study in Lanzhou, China.

Until now, the epidemiological evidence on the association between short-term exposure to ambient carbon monoxide (CO) and cardiovascular diseases (CVDs) is relatively lacking and controversial. This study aims to examine the relationship between ambient CO and daily emergency room visits (ERVs) for total and cause-specific CVD in Lanzhou, China. A distributed lag nonlinear model was used to examine the association. For every 1 mg/m3 increase in the CO concentration, the relative risks of daily ERVs were 1.041 (95% CI: 1.017, 1.065) for total CVD, 1.065 (95% CI: 1.018, 1.114) for ischemic heart disease (IHD), 1.083 (95% CI: 1.020, 1.149) for heart rhythm disturbances (HRD), 1.062 (95% CI: 1.011, 1.115) for heart failure (HF), and 1.057 (95% CI: 1.017, 1.098) for cerebrovascular diseases (CD). For the two different gender subgroups, the short-term impact of CO on total CVD, IHD, and CD was relatively stronger for the females than for the males, while the opposite was true for HRD and HF. In the age subgroup analyses, the effect of ambient CO on total CVD and IHD appeared to be greater for the age ≥ 65 years group, while the opposite was true for HRD, HF, and CD. The associations for all disease categories were stronger in cold seasons than in warm seasons. We also observed a nearly linear correlation between CO and CVD ERVs. In conclusion, the study showed that exposure to ambient CO may increase the risks of ERVs for total and cause-specific CVD. Besides, CO-ERVs associations may vary by gender and age.

An artificial intelligence algorithm for analyzing globus pallidus necrosis after carbon monoxide intoxication.

Globus pallidus necrosis (GPN) is one of typical neurological imaging features in patients with carbon monoxide (CO) poisoning. Current clinical guideline recommends neurological imaging examination for CO-intoxicated patients with conscious disturbance rather than routine screening, which may lead to undiagnosed GPN. We aimed to develop an artificial intelligence algorithm for predicting GPN in CO intoxication patients. We included CO intoxication patients with neurological images between 2000 and 2019 in Chang Gung Memorial Hospital. We collected 41 clinical and laboratory parameters on the first day of admission for algorithm development. We used fivefold cross validation and applied several machine learning algorithms. Random forest classifier (RFC) provided the best predictive performance in our cohort. Among the 261 patients with CO intoxication, 52 patients presented with GPN. The artificial intelligence algorithm using the RFC-based AI model achieved an accuracy = 79.2 ± 2.6%, sensitivity = 77.7%, precision score = 81.9 ± 3.4%, and F1 score = 73.2 ± 1.8%. The area under receiver operating characteristic was approximately 0.64. Top five weighted variables were Platelet count, carboxyhemoglobin, Glasgow Coma scale, creatinine, and hemoglobin. Our RFC-based algorithm is the first to predict GPN in patients with CO intoxication and provides fair predictive ability. Further studies are needed to validate our findings.

Effect of plasma carboxyhemoglobin level on gonadal hormone levels.

BACKGROUND: In emergency departments, carbon monoxide (CO) is a common cause of toxic poisoning. We aimed to determine the relationship between plasma carboxyhemoglobin (COHb) levels and late post-treatment gonadal hormone changes in CO poisoning. METHODS: The study included 237 patients older than 18 who presented to the Emergency Department due to CO intoxication between January 2008 and December 2016. Patients with a COHb level of less than 30% were classified as having mild-to-moderate disease, while those with a COHb level of more than 30% were classified as having severe disease. RESULTS: Of 41 (17%) patients with gonadal hormone change (GHC), 19 (46.3%) were females. In cases with GHC, the exposure time was 5.76±1.64 hours (P=0.001). COHb level was 50.46±4.43% in the severe group (P=0.001), while hormone levels were normal in women and men before CO poisoning. GHC within one month and two years after poisoning was significantly higher (P=0.001). There were 138 (58.2%) patients in the mild-to-moderate group, and 99 (41.8%) patients in the severe group. Of the gonadal hormones, LH2 (luteinizing hormone) was 13.54±3.40 mIU/mL, FSH2 (follicle-stimulating hormone) 16.69±4.35 mIU/mL, PRL2 (prolactin) 16.23±4.73 ng/mL, and TTN2 (testosterone) 644.06±120.40 (P=0.001). In addition, COHb was found to be 42.68±8.42% (P=0.001). In univariate and multivariate Cox regression analysis, gender, LH1, LH2, PRL2, TTN2 and COHb values were found to be prognostic signs in terms of endocrine gonadal hormone change (P<0.05). In the correlation of COHb level with GHC, positive moderate-strong correlation was found between LH2, FSH2, PRL2, TTN2 (P=0.001). CONCLUSIONS: In patients admitted to the emergency services due to CO poisoning, elevated COHb may help predict the risk for late gonadal hormone levels.

Reduced Diffusing Capacity in Humidifier Disinfectant-Associated Asthma Versus Typical Asthma: A Retrospective Case Control Study.

BACKGROUND: Humidifier disinfectant-related lung injury (HDLI) is a severe form of toxic inhalational pulmonary parenchymal damage found in residents of South Korea previously exposed to specific guanidine-based compounds present in humidifier disinfectants (HD). HD-associated asthma (HDA), which is similar to irritant-induced asthma, has been recognized in victims with asthma-like symptoms and is probably caused by airway injury. In this study, diffusing capacity of the lung for carbon monoxide (DLCO) in individuals with HDA was compared to that in individuals with pre-existing asthma without HD exposure. METHODS: We retrospectively compared data, including DLCO values, of 70 patients with HDA with that of 79 patients having pre-existing asthma without any known exposure to HD (controls). Multiple linear regression analysis and logistic regression analysis were performed to confirm the association between HD exposure and DLCO after controlling for confounding factors. The correlation between DLCO and several indicators related to HD exposure was evaluated in patients with HDA. RESULT: The mean DLCO was significantly lower in the HDA group than in the control group (81.9% vs. 88.6%; P = 0.021). The mean DLCO of asthma patients with definite HD exposure was significantly lower than that of asthma patients with lesser exposure (P for trend = 0.002). In multivariable regression models, DLCO in the HDA group decreased by 5.8%, and patients with HDA were 2.1-fold more likely to have a lower DLCO than the controls. Pathway analysis showed that exposure to HD directly affected DLCO values and indirectly affected its measurement through a decrease in the forced vital capacity (FVC). Correlation analysis indicated a significant inverse correlation between DLCO% and cumulative HD exposure time. CONCLUSION: DLCO was lower in patients with HDA than in asthma patients without HD exposure, and decreased FVC partially mediated this effect. Therefore, monitoring the DLCO may be useful for early diagnosis of HDA in patients with asthma symptoms and history of HD exposure.

Influence of the COVID-19 pandemic on causes for the development of carbon monoxide intoxications.

Introduction: Several causes can lead to carbon monoxide (CO) intoxication. A first-line treatment option for such intoxications is hyperbaric oxygenation (HBO2) therapy. The COVID-19 pandemic has been changing everyday life in Germany since March 2020, mainly caused by statutory provisions. Our aim was to review whether these changes have an influence on the causes and frequency for the development of CO intoxication. Methods: We retrospectively analyzed the data of patients who were treated for CO intoxication in our institution between April 2019 and March 2021. Besides demographic data, we compared the overall number and documented causes for each CO intoxication in the period of April 2020 to March 2021 with the period between April 2019 and March 2020. Results: After applying inclusion and exclusion criteria, 139 patients were included. We found a significant decrease in the overall number of patients who needed treatment since the beginning of the COVID-19 pandemic. However, the share of CO intoxication caused by the indoor use of coal stoves, coal barbecue, or suicide attempts increased. In contrast, the share of cases caused by apartment or house fire, smoking waterpipe, or gas stoves decreased. Conclusion: The COVID-19 pandemic and the associated restrictions lead to a significant reduction in the number of patients in need for HBO2 therapy due to CO-Intoxication. The causes leading to CO intoxication also changed since the beginning of the COVID-19 pandemic. We observed a shift toward causes related to the indoor use of coal-fired stoves and barbecues as well as suicide attempts.

Development of an Integrated Platform to Assess the Physicochemical and Toxicological Properties of Wood Combustion Particulate Matter.

Wood burning contributes to indoor and ambient particulate matter (PM) pollution and has been associated with increased morbidity and mortality. Here, we present an integrated methodology that allows to generate, sample, and characterize wood smoke derived from different moisture contents and representative combustion conditions using pine wood as a model. Flaming, smoldering, and incomplete combustion were assessed for low-moisture pine, whereas both low-moisture pine and high-moisture pine were investigated under flaming conditions. Real-time monitoring of carbon monoxide, volatile organic compounds, and aerosol number concentration/size in wood smoke was performed. The PM was size-fractionated, sampled, and characterized for elemental/organic carbon, organic functional groups, and inorganic elements. Bioactivity of PM was assessed by measuring the sterile alpha motif (SAM) pointed domain containing ETS (E-twenty-six) transcription factor (SPDEF) gene promoter activity in human embryonic kidney 293 (HEK-293T) cells, a biomarker for mucin gene expression. Findings showed that moisture content and combustion condition significantly affected the organic and inorganic elemental composition of PM0.1 as well as its bioactivity. Also, for a given moisture and combustion scenario, PM chemistry and bioactivity differed considerably with PM size. Importantly, PM0.1 from flaming combustion of low-moisture pine contained the highest abundance of the oxygenated saturated aliphatic functional group [H-C-O] and was also biologically most potent in stimulating SPDEF promoter activity, suggesting the role of organic compounds such as carbohydrates and sugar alcohols (that contain [H-C-O]) in driving mucus-related respiratory outcomes. Our platform enables further well-controlled parametric studies using a combination of in vitro and in vivo approaches to link wood burning parameters with acute and chronic inhalation health effects of wood smoke.

A novel source of carbon monoxide for suicide attempt.

Carbon monoxide (CO) inhalation is a common method of suicide. The combination of formic acid with sulfuric acid creates carbon monoxide. This novel method is described in readily accessible internet-based resources. We present the case of a 35-year-old woman who developed CO toxicity by using this method. It is important for hyperbaric medicine physicians to be aware of this source of CO toxicity.

The impact of air pollution on COVID-19 incidence, severity, and mortality: A systematic review of studies in Europe and North America.

BACKGROUND: Air pollution is speculated to increase the risks of COVID-19 spread, severity, and mortality. OBJECTIVES: We systematically reviewed studies investigating the relationship between air pollution and COVID-19 cases, non-fatal severity, and mortality in North America and Europe. METHODS: We searched PubMed, Web of Science, and Scopus for studies investigating the effects of harmful pollutants, including particulate matter with diameter ≤2.5 or 10 µm (PM2.5 or PM10), ozone (O3), nitrogen dioxide (NO2), sulfur dioxide (SO2) and carbon monoxide (CO), on COVID-19 cases, severity, and deaths in Europe and North America through to June 19, 2021. Articles were included if they quantitatively measured the relationship between exposure to air pollution and COVID-19 health outcomes. RESULTS: From 2,482 articles screened, we included 116 studies reporting 355 separate pollutant-COVID-19 estimates. Approximately half of all evaluations on incidence were positive and significant associations (52.7%); for mortality the corresponding figure was similar (48.1%), while for non-fatal severity this figure was lower (41.2%). Longer-term exposure to pollutants appeared more likely to be positively associated with COVID-19 incidence (63.8%). PM2.5, PM10, O3, NO2, and CO were most strongly positively associated with COVID-19 incidence, while PM2.5 and NO2 with COVID-19 deaths. All studies were observational and most exhibited high risk of confounding and outcome measurement bias. DISCUSSION: Air pollution may be associated with worse COVID-19 outcomes. Future research is needed to better test the air pollution-COVID-19 hypothesis, particularly using more robust study designs and COVID-19 measures that are less prone to measurement error and by considering co-pollutant interactions.

Hourly Air Pollutants and Acute Coronary Syndrome Onset in 1.29 Million Patients.

BACKGROUND: Short-term exposure to ambient air pollution has been linked with daily hospitalization and mortality from acute coronary syndrome (ACS); however, the associations of subdaily (hourly) levels of criteria air pollutants with the onset of ACS and its subtypes have rarely been evaluated. METHODS: We conducted a time-stratified case-crossover study among 1 292 880 patients with ACS from 2239 hospitals in 318 Chinese cities between January 1, 2015, and September 30, 2020. Hourly concentrations of fine particulate matter (PM2.5), coarse particulate matter (PM2.5-10), nitrogen dioxide (NO2), sulfur dioxide (SO2), carbon monoxide (CO), and ozone (O3) were collected. Hourly onset data of ACS and its subtypes, including ST-segment-elevation myocardial infarction, non-ST-segment-elevation myocardial infarction, and unstable angina, were also obtained. Conditional logistic regressions combined with polynomial distributed lag models were applied. RESULTS: Acute exposures to PM2.5, NO2, SO2, and CO were each associated with the onset of ACS and its subtypes. These associations were strongest in the concurrent hour of exposure and were attenuated thereafter, with the weakest effects observed after 15 to 29 hours. There were no apparent thresholds in the concentration-response curves. An interquartile range increase in concentrations of PM2.5 (36.0 µg/m3), NO2 (29.0 µg/m3), SO2 (9.0 µg/m3), and CO (0.6 mg/m3) over the 0 to 24 hours before onset was significantly associated with 1.32%, 3.89%, 0.67%, and 1.55% higher risks of ACS onset, respectively. For a given pollutant, the associations were comparable in magnitude across different subtypes of ACS. NO2 showed the strongest associations with all 3 subtypes, followed by PM2.5, CO, and SO2. Greater magnitude of associations was observed among patients older than 65 years and in the cold season. Null associations of exposure to either PM2.5-10 or O3 with ACS onset were observed. CONCLUSIONS: The results suggest that transient exposure to the air pollutants PM2.5, NO2, SO2, or CO, but not PM2.5-10 or O3, may trigger the onset of ACS, even at concentrations below the World Health Organization air quality guidelines.

A NIR-emissive probe with a remarkable Stokes shift for CO-releasing molecule-3 detection in cells and in vivo.

Carbon monoxide (CO) is regarded as one of the most important gaseous transmitters, playing a vital role in biological systems; meanwhile, abnormal levels of CO can be correlated with conditions such as lung disease, Alzheimer's disease, and cardiovascular disease. CO-releasing molecules (CORMs) are chemical agents used to release CO as an endogenous, biologically active molecule in order to treat diseases. CO-releasing molecule-3 (CORM-3), as a convenient and safe CO donor and therapeutic drug molecule, has been widely used to release exogenous CO in living cells to study the physiological and pathological roles of CO in living systems. Herein, we designed a NIR-emitting probe (NIR-CORM-3) with a large Stokes shift based on a 4-(dimethylamino)cinnamaldehyde lepidine derived fluorophore. A 4-nitrobenzyl group was selected as the CORM-3 recognizing moiety, and the probe is able to selectively and sensitively respond to CORM-3 (within only 15 min). Upon encountering CORM-3, NIR-CORM-3 releases a fluorophore with a response at 670 nm, and it shows a remarkable Stokes shift (up to 250 nm). In addition, NIR-CORM-3 has low cytotoxicity and exhibits outstanding NIR imaging abilities in living cells and mice.

Association between personal exposure to household air pollution and gestational blood pressure among women using solid cooking fuels in rural Tamil Nadu, India.

BACKGROUND: The Household Air Pollution Intervention Network (HAPIN) trial is an ongoing multi-center randomized controlled trial assessing the impact of a liquified petroleum gas (LPG) cookstove and fuel intervention on health. Given the potential impacts of household air pollution (HAP) exposure from burning solid fuels on cardiovascular health during pregnancy, we sought to determine whether baseline exposures to particulate matter with an aerodynamic diameter ≤2.5 µm (PM2.5), black carbon (BC) and carbon monoxide (CO) were associated with blood pressure among 799 pregnant women in Tamil Nadu, India, one of the HAPIN trial centers. METHODS: Multivariable linear regression models were used to examine the association between 24-h personal exposure to PM2.5/BC/CO and systolic and diastolic blood pressure, controlling for maternal age, body mass index (BMI), mother's education, household wealth, gestational age, and season. At the time of measurement, women were between 9- and 20-weeks of gestation. RESULTS: We found that systolic blood pressure (SBP) and diastolic blood pressure (DBP) were higher in pregnant women exposed to higher levels of HAP, though only the result for CO and DBP reached conventional statistical significance (p < 0.05). We observed a positive association between CO and DBP among the entire study cohort: a 1-log µg/m3 increase in CO exposure was associated with 0.36 mmHg higher DBP (95% confidence interval [CI]: 0.02 to 0.70). The effect was stronger in pregnant women with higher CO exposures (in the 3rd [≥ 0.9 and < 2.1 ppm] and 4th quartiles [≥ 2.1 and ≤ 46.9 ppm]). We also found that pregnant women with PM2.5 exposures in the highest quartile (≥ 129.9 and ≤ 2100 µg/m3) had a borderline significant association (p = 0.054) with DBP compared to those who had PM2.5 exposures in the lowest quartile (≥ 9.4 and < 47.7 µg/m3). No evidence of association was observed for BC exposure and blood pressure. CONCLUSION: This study contributes to limited evidence regarding the relationship between HAP exposure and blood pressure among women during pregnancy, a critical window for both mother and child's life-course health. Results from this cross-sectional study suggest that exposures to PM2.5 and CO from solid fuel use are associated with higher blood pressure in pregnant women during their first or second trimester.

Carbon monoxide exposures reported to the UK National Poisons Information Service: a 4-year study.

BACKGROUND: Unintentional carbon monoxide (CO) poisoning poses a public health challenge. The UK National Poisons Information Service (NPIS) provides advice to healthcare professionals via the online database, TOXBASE®, and a 24-hour telephone line. Our aim was to analyse all CO-related enquiries to the NPIS. METHODS: We analysed enquiries regarding unintentional CO exposure (1st July 2015-30th June 2019). Information on patient demographics, CO source and location, clinical features and poisoning severity was collected from telephone enquiries and TOXBASE accesses. RESULTS: 2970 unintentional non-fire-related CO exposures were reported. Exposures occurred commonly in the home (60%) with faulty boilers frequently implicated (27.4%). Although five fatalities were reported, 68.7% of patients experienced no or minor symptoms only (headache most frequently reported). Despite being the gold standard measurement, blood carboxyhaemoglobin concentration was only recorded in 25.6% patients, with no statistically significant correlation with severity. CONCLUSIONS: Unintentional CO exposures in the UK commonly occur in domestic settings and although are generally of low severity, fatalities continue to occur. Carboxyhaemoglobin measurement is important to confirm exposure but further work is required to assess its validity as a prognostic indicator in CO exposure. Public health policy should continue to focus on raising awareness of the dangers of CO.

Usefulness of a modified poisoning severity score for predicting prognosis in acute carbon monoxide poisoning.

INTRODUCTION: The poisoning severity score (PSS) was developed to grade the severity of various types of poisoning. However, in its current form, it requires investigating many variables, some of which have been found not to be associated with carbon monoxide (CO) poisoning severity. Therefore, in this study, we modified the PSS for CO poisoning and compared its usefulness to that of the original PSS, as an early prognostic factor of short-term outcome in CO poisoning patients. METHODS: This was a retrospective observational study conducted in patients with CO poisoning who visited the emergency department between January 2014 and December 2020. Patients' primary outcome was their Cerebral Performance Category (CPC) scale score at discharge, which classified those with CPC 1-2 as having a favorable outcome and those with CPC 3-5 as having a poor outcome. We calculated the patients' PSS and their CO-modified PSS by replacing blood and metabolic balance category in the original PSS with carboxyhemoglobin (COHb) and lactate levels, respectively. RESULTS: This study included 891 patients, of which 852 (95.6%) and 39 (4.4%) were classified into the favorable and poor outcome groups, respectively. Using multivariate analysis, the PSS (odds ratio [OR], 22.961; 95% confidence interval [CI], 10.641-49.546; p < 0.001) and CO-modified PSS (OR, 28.856; 95% CI, 12.874-64.679; p < 0.001) were both found to be associated with poor outcomes at hospital discharge. The areas under the receiver operating characteristic curves for the PSS and CO-modified PSS were 0.874 (95% CI, 0.850-0.895) and 0.881 (95% CI, 0.858-0.901), respectively. CONCLUSION: The CO-modified PSS, with fewer variables than the original PSS, was not inferior to predict poor outcomes, and if COHb level is considered together with other parameters, then it can be used both for predicting prognosis and in diagnosis.

Emerging cellular-based therapies in carbon monoxide poisoning.

Carbon monoxide (CO) is an odorless and colorless gas with multiple sources that include engine exhaust, faulty furnaces, and other sources of incomplete combustion of carbon compounds such as house fires. The most serious complications for survivors of consequential CO exposure are persistent neurological sequelae occurring in up to 50% of patients. CO inhibits mitochondrial respiration by specifically binding to the heme a3 in the active site of CIV-like hydrogen sulfide, cyanide, and phosphides. Although hyperbaric oxygen remains the cornerstone for treatment, it has variable efficacy requiring new approaches to treatment. There is a paucity of cellular-based therapies in the area of CO poisoning, and there have been recent advancements that include antioxidants and a mitochondrial substrate prodrug. The succinate prodrugs derived from chemical modification of succinate are endeavored to enhance delivery of succinate to cells, increasing uptake of succinate into the mitochondria, and providing metabolic support for cells. The therapeutic intervention of succinate prodrugs is thus potentially applicable to patients with CO poisoning via metabolic support for fuel oxidation and possibly improving efficacy of HBO therapy.

Effects of noise and low-concentration carbon monoxide exposure on rat immunity.

OBJECTIVE: To evaluate the immunotoxicity and effects of noise and/or low-concentration carbon monoxide (CO) exposure on immune organs and immune functions in rats. METHODS: Male Wistar rats exposed to 98 dB(A) white noise and/or 100 ppm CO 4 h/d for 30 d were used to determine the pathological changes in the thymus and spleen, and variations in leukocyte counts, inflammatory factors, and immunoglobulin (Ig) concentrations. RESULTS: The boundaries of the cortex and medulla of the thymus were unclear following noise and combined exposure. The pathological changes in spleen after CO and combined exposure included blurred boundaries of red-pulp and white-pulp, disappearance of normal splenic nodules and neutrophil infiltration. After exposure to noise and in combination, leukocyte and lymphocyte counts decreased significantly. After exposure to low-concentration CO and in combination, serum IgM and IgG levels decreased significantly, but the levels of tumor necrosis factor-α and interferon-γ levels increased significantly. Eosinophils and IgA levels decreased significantly following exposure to noise and/or low concentration of CO, while the level of interleukin-1 increased significantly. Monocytes increased significantly only under noise or CO exposure, but not under combined exposure. CONCLUSIONS: Noise and/or low-concentration CO exposure may suppress innate and adaptive immune functions and induce inflammatory responses. Noise exposure mainly affected the innate immune function of rats, whereas low-concentration CO exposure mainly affected adaptive immune functions. Combined exposure presented higher immunotoxicity than noise or CO alone, suggesting that exposure to noise and low-concentration CO in the living and working environments can affect the immune system.