The relationship between the severity of inflammatory bowel diseases and expirium air carbon monoxide levels.

INTRODUCTION: We investigated the relationship between expirium air carbon monoxide (E-CO) levels and disease severity in patients with ulcerative colitis (UC) and Crohn's disease (CD). METHODS: After their first follow-ups, the E-CO levels of 162 patients with UC and 100 with CD were measured for four consecutive weeks. Blood samples were collected from all the patients, and their clinical severity was determined 1 month after their initial presentation. The clinical severity of CD was determined using the Harvey Bradshaw index (HBI), while the patients with UC completed the SEO clinical activity index (SEOI). The relationships between the disease severity and the means of these four E-CO readings were then compared. RESULTS: The mean age of the participants was 42.28 ± 14.9 years, and 158 (60.3%) were men. In addition, 27.2% of the UC group and 44% of the CD group were smokers. The mean SEOI score was 145.7 ± 42.0 (min = 90, max = 227), and the mean HBI score was 5.75 ± 3.3 (min = 1, max = 15). Increased CO ppm (OR = -9.047 to 7.654 95% CI) and the number of cigarettes smoked per day (OR = -0.161 to 1.157 95% CI) emerged as independent risk factors for lower SEO scores in the linear regression models (p < 0.001), while the number of cigarettes smoked per day (OR = 0.271 to 1.182% 95 CI) was a risk factor for higher HBI scores (p = 0.022). CONCLUSION: UC severity decreased with higher E-CO levels and the mean number of cigarettes smoked, while CD severity increased in line with the mean number of cigarettes smoked.

Exposure-response relationships for personal exposure to fine particulate matter (PM2·5), carbon monoxide, and black carbon and birthweight: an observational analysis of the multicountry Household Air Pollution Intervention Network (HAPIN) trial.

BACKGROUND: Household air pollution (HAP) from solid fuel use is associated with adverse birth outcomes, but data for exposure-response relationships are scarce. We examined associations between HAP exposures and birthweight in rural Guatemala, India, Peru, and Rwanda during the Household Air Pollution Intervention Network (HAPIN) trial. METHODS: The HAPIN trial recruited pregnant women (9-<20 weeks of gestation) in rural Guatemala, India, Peru, and Rwanda and randomly allocated them to receive a liquefied petroleum gas stove or not (ie, and continue to use biomass fuel). The primary outcomes were birthweight, length-for-age, severe pneumonia, and maternal systolic blood pressure. In this exposure-response subanalysis, we measured 24-h personal exposures to PM2·5, carbon monoxide, and black carbon once pre-intervention (baseline) and twice post-intervention (at 24-28 weeks and 32-36 weeks of gestation), as well as birthweight within 24 h of birth. We examined the relationship between the average prenatal exposure and birthweight or weight-for-gestational age Z scores using multivariate-regression models, controlling for the mother's age, nulliparity, diet diversity, food insecurity, BMI, the mother's education, neonate sex, haemoglobin, second-hand smoke, and geographical indicator for randomisation strata. FINDINGS: Between March, 2018, and February, 2020, 3200 pregnant women were recruited. An interquartile increase in the average prenatal exposure to PM2·5 (74·5 µg/m3) was associated with a reduction in birthweight and gestational age Z scores (birthweight: -14·8 g [95% CI -28·7 to -0·8]; gestational age Z scores: -0·03 [-0·06 to 0·00]), as was an interquartile increase in black carbon (7·3 µg/m3; -21·9 g [-37·7 to -6·1]; -0·05 [-0·08 to -0·01]). Carbon monoxide exposure was not associated with these outcomes (1·7; -3·1 [-12·1 to 5·8]; -0·003 [-0·023 to 0·017]). INTERPRETATION: Continuing efforts are needed to reduce HAP exposure alongside other drivers of low birthweight in low-income and middle-income countries. FUNDING: US National Institutes of Health (1UM1HL134590) and the Bill & Melinda Gates Foundation (OPP1131279).

Six Air Pollutants Associated With Increased Risk of Thyroid Nodules: A Study of 4.9 Million Chinese Adults.

Background: Thyroid nodules has become a significant public health issue worldwide with a rapidly increasing prevalence. However, its association with outdoor air pollution remains poorly understood. We aim to investigate the relationship between six outdoor air pollutants (PM2.5, PM10, NO2, SO2, CO, and O3) and the risk of thyroid nodules. Methods: We utilized a database including 4,920,536 participants who attended the annual physical examinations in the Meinian HealthCare Screening Center in 157 Chinese cities in 2017. City-specific concentrations of six pollutants (PM2.5, PM10, NO2, SO2, CO, and O3) from 2015 to 2017 were estimated based on the China's National Urban Air Quality Real Time Publishing Platform. Thyroid nodule was measured with ultrasound. Multivariable Logistic regression was used to examine the associations between air pollutants and thyroid nodules with adjustment for age, sex, education, smoking, body mass index, fasting blood glucose, triglyceride, low density lipoprotein cholesterol, high density lipoprotein cholesterol, urine iodine, gross domestic product, and thyroid stimulating hormone. We conducted stratified analyses to investigate potential effect modification by sex, age, and urine iodine groups. Results: Approximately 38% of the participants (1,869,742) were diagnosed with thyroid nodules. Each of the six air pollutants was significantly and linearly associated with the risk for thyroid nodules. The adjusted odds ratios [95% CI] for every increase of 10 µg/m3 for PM2.5, PM10, NO2, SO2, and O3 were 1.062 [1.061, 1.064], 1.04 [1.03, 1.04], 1.10 [1.09, 1.10], 1.11 [1.11, 1.12], and 1.151 [1.149, 1.154], respectively; The odds ratio for each increase of 1 mg/m3 for CO was 1.50 [1.49 to 1.52]. Furthermore, these associations were significantly higher in the participants who were men, younger, or having lower urine iodine level (p <0.001). Conclusion: The six air pollutants may contribute to the high prevalence of thyroid nodules in China.

Carbon Monoxide Regulates Macrophage Differentiation and Polarization toward the M2 Phenotype through Upregulation of Heme Oxygenase 1.

Carbon monoxide (CO) is generated by heme oxygenase (HO), and HO-1 is highly induced in monocytes and macrophages upon stimulation. Monocytes differentiate into macrophages, including pro-inflammatory (M1) and anti-inflammatory (M2) cells, in response to environmental signals. The present study investigated whether CO modulates macrophage differentiation and polarization, by applying the CO-releasing molecule-3 (CORM-3). Results showed that murine bone marrow cells are differentiated into macrophages by CORM-3 in the presence of macrophage colony-stimulating factor. CORM-3 increases expressions of macrophage markers, including F4/80 and CD11b, and alters the cell morphology into elongated spindle-shaped cells, which is a typical morphology of M2 cells. CORM-3 upregulates the expressions of genes and molecules involved in M2 polarization and M2 phenotype markers, such as STAT6, PPARγ, Ym1, Fizz1, arginase-1, and IL-10. However, exposure to CORM-3 inhibits the iNOS expression, suggesting that CO enhances macrophage differentiation and polarization toward M2. Increased HO-1 expression is observed in differentiated macrophages, and CORM-3 further increases this expression. Hemin, an HO-1 inducer, results in increased macrophage differentiation, whereas the HO-1 inhibitor zinc protoporphyrin IX inhibits differentiation. In addition, CORM-3 increases the proportion of macrophages in peritoneal exudate cells and enhances the expression of HO-1 and arginase-1 but inhibits iNOS. Taken together, these results suggest that the abundantly produced CO in activated macrophages enhances proliferation, differentiation, and polarization toward M2. It will probably help clear apoptotic cells, resolve inflammation, and promote wound healing and tissue remodeling.

Ambient carbon monoxide exposure and elevated risk of mortality in the glioblastoma patients: A double-cohort retrospective observational study.

An increasing number of studies indicate air pollutants infiltrate into the brain. We aimed to find the association of cumulative air pollution exposure in the main body of primary brain tumor: glioblastoma (GBM). In this double-cohort, retrospective analysis study with a protocol, we compared the health effect of air pollution on the GBM patients from the SEER (Surveillance, Epidemiology, and End Results Program) in 27 U.S. counties from 10 states and GBM patients of Severance cohort of Korea. From 2000 to 2015, 10621 GBM patients of the SEER were individually evaluated for the cumulative average exposure for each pollutant, and 9444 (88.9%) mortality events were reported. From 2011 to 2018, 398 GBM patients of the Severance with the same protocol showed 259 (65.1%) mortality events. The multi-pollutant models show that the association level of risk with CO is increased in the SEER (HR 1.252; 95% CI 1.141-1.373) with an increasing linear trend of relative death rate in the spline curve. The Severance GBM data showed such a statistically significant result of the health impact of CO on GBM patients. The overall survival gain of the less exposure group against CO was 2 and 3 months in the two cohorts. Perioperative exposure to CO may increase the risk of shorter survival of GBM patients of the SEER and the Severance cohort.

Continuous exposure to ambient air pollution and chronic diseases: prevalence, burden, and economic costs.

Studies that assess the connection between the prevalence of chronic diseases and continuous exposure to air pollution are scarce in developing countries, mainly due to data limitations. Largely overcoming data limitations, this study aimed to investigate the association between the likelihood of reporting a set of chronic diseases (diabetes, cancer, stroke and myocardial infarction, asthma, and hypertension) and continuous exposure to carbon monoxide (CO), nitrogen dioxide (NO2), ozone (O3), and coarse particulate matter (PM10). Using the estimated associations, the disease burden and economic costs of continuous exposure to air pollutants were also approximated. A 2011 Health Equity Assessment and Response Tool survey from Tehran, Iran, was used in the main analyses. A sample of 67,049 individuals who had not changed their place of residence for at least 2 years before the survey and reported all relevant socioeconomic information was selected. The individuals were assigned with the average monthly air pollutant levels of the nearest of 16 air quality monitors during the 2 years leading to the survey. Both single- and multi-pollutant analyses were conducted. The country's annual household surveys from 2002 to 2011 were used to calculate the associated economic losses. The single-pollutant analysis showed that a one-unit increase in monthly CO (ppm), NO2 (ppb), O3 (ppb), and PM10 (µg/m3) during the 2 years was associated with 751 [confidence interval (CI): 512-990], 18 (CI: 12-24), 46 (CI: -27-120), and 24 (CI: 13-35) more reported chronic diseases in 100,000, respectively. The disease-specific analyses showed that a unit change in average monthly CO was associated with 329, 321, 232, and 129 more reported cases of diabetes, hypertension, stroke and myocardial infarction, and asthma in 100,000, respectively. The measured associations were greater in samples with older individuals. Also, a unit change in average monthly O3 was associated with 21 (in 100,000) more reported cases of asthma. The multi-pollutant analyses confirmed the results from single-pollutant analyses. The supplementary analyses showed that a one-unit decrease in monthly CO level could have been associated with about 208 (CI: 147-275) years of life gained or 15.195 (CI: 10.296-20.094) thousand US dollars (USD) in life-time labor market income gained per 100,000 30-plus-year-old Tehranis.

Acute Effects of Air Pollution on Hospital Admissions for Asthma, COPD, and Bronchiectasis in Ahvaz, Iran.

Background and Aim: Although air pollution is a serious problem in Ahvaz, the association between air pollution and respiratory diseases has not been studied enough in this area. The aim of this study was to determine the relation between short-term exposure to air pollutants and the risk of hospital admissions due to asthma, COPD, and bronchiectasis in Ahvaz. Methods: Hospital admissions data and air pollutants including O3, NO, NO2, SO2, CO, PM10, and PM2.5 were obtained from 2008 to 2018. Adjusted Quasi-Poisson regression with a distributed lag model, controlled for trend, seasonality, weather, weekdays, and holidays was used for data analysis. Results: The results showed a significant increase in hospital admissions for asthma (RR=1.004, 95% CI: 1.002-1.007) and COPD (RR=1.003, 95% CI: 1.001-1.005) associated with PM2.5. PM10 was associated with increased hospital admissions due to bronchiectasis in both genders (Men: RR=1.003, 95% CI: 1.001-1.006) (Female: RR=1.003, 95% CI: 1.000-1.006). NO2 was also associated with an increased risk of hospital admissions for asthma (RR=1.040, 95% CI: 1.008-1.074) and COPD (RR=1.049, 95% CI: 1.010-1.090). SO2 was associated with the risk of hospital admissions of asthma (RR=1.069, 95% CI: 1.017-1.124) and bronchiectasis (RR=1.030, 95% CI: 1.005-1.056). Finally, CO was associated with COPD (RR=1.643, 95% CI: 1.233-2.191) and bronchiectasis (RR=1.542, 95% CI: 1.035-2.298) hospital admissions. Conclusion: Short-term exposure to air pollutants significantly increases the risk of hospital admissions for asthma, COPD, and bronchiectasis in the adult and elderly population.

Levels and Determinants of Fine Particulate Matter and Carbon Monoxide in Kitchens Using Biomass and Non-Biomass Fuel for Cooking.

To assist interpretation of a study in rural Pakistan on the use of biomass for cooking and the risk of coronary heart disease, we continuously monitored airborne concentrations of fine particulate matter (PM2.5) and carbon monoxide (CO) for up to 48 h in the kitchens of households randomly selected from the parent study. Satisfactory data on PM2.5 and CO respectively were obtained for 16 and 17 households using biomass, and 19 and 17 using natural gas. Linear regression analysis indicated that in comparison with kitchens using natural gas, daily average PM2.5 concentrations were substantially higher in kitchens that used biomass in either a chimney stove (mean difference 611, 95% CI: 359, 863 µg/m3) or traditional three-stone stove (mean difference 389, 95% CI: 231, 548 µg/m3). Daily average concentrations of CO were significantly increased when biomass was used in a traditional stove (mean difference from natural gas 3.7, 95% CI: 0.8, 6.7 ppm), but not when it was used in a chimney stove (mean difference -0.8, 95% CI: -4.8, 3.2 ppm). Any impact of smoking by household members was smaller than that of using biomass, and not clearly discernible. In the population studied, cooking with biomass as compared with natural gas should serve as a good proxy for higher personal exposure to PM2.5.

Concurrent Alcohol Use and Waterpipe Tobacco Smoking: Smoking Topography, Toxicant Exposure, and Abuse Liability.

INTRODUCTION: Relative to non-waterpipe (WP) smokers, WP smokers are more than twice as likely to use alcohol and frequently consume alcohol before or during smoking sessions. Co-use of alcohol and WP may result in greater toxicant exposure compared to WP smoking alone. To date, no study systematically has investigated the impact of acute alcohol intoxication on WP smoking topography, exposure to tobacco-related toxicants, or abuse liability. METHODS: Dyads of current WP smokers and drinkers (N = 42; age = 21-32 years) completed two in-laboratory ad libitum smoking sessions (≤2 hours) following 12-hour nicotine abstinence in a double-blind, randomized crossover design in which they consumed a placebo versus active drink (sustained breath alcohol concentration = .08). Exhaled carbon monoxide (eCO) and plasma nicotine concentration were assessed. Questionnaires assessed smoking experience and smoking urge. Smoking topography was measured continuously throughout each smoking session. RESULTS: The alcohol session was associated with increased inhaled volume, flow rate, and WP session duration compared to placebo. Compared to placebo, participants reported a more positive overall smoking experience following the alcohol session and greater smoking urges pre- and post-smoking session. Although both sessions resulted in significant increases in eCO and plasma nicotine, no significant differences emerged in eCO or nicotine exposure between the active and placebo sessions. CONCLUSIONS: Co-use of alcohol and WP may contribute to the maintenance of WP smoking through enhanced smoking experiences, increased urge to smoke, and significant exposure to addictive nicotine. Regulations may be necessary to limit the sale of alcohol in WP smoking lounges and reduce exposure to secondhand smoke. IMPLICATIONS: The findings suggest co-use of alcohol and WP tobacco likely maintain WP use and dependence by enhancing the smoking experience and increasing urges to smoke. These findings have implications for regulations aimed at limiting co-use of alcohol and WP tobacco in WP lounges and limiting exposure to secondhand smoke. CLINICAL TRIALS REGISTRATION: NCT03096860.

Low-level carbon monoxide exposure affects BOLD fMRI response.

Blood oxygen level dependent (BOLD) fMRI is a common technique for measuring brain activation that could be affected by low-level carbon monoxide (CO) exposure from, e.g. smoking. This study aimed to probe the vulnerability of BOLD fMRI to CO and determine whether it may constitute a significant neuroimaging confound. Low-level (6 ppm exhaled) CO effects on BOLD response were assessed in 12 healthy never-smokers on two separate experimental days (CO and air control). fMRI tasks were breath-holds (hypercapnia), visual stimulation and fingertapping. BOLD fMRI response was lower during breath holds, visual stimulation and fingertapping in the CO protocol compared to the air control protocol. Behavioural and physiological measures remained unchanged. We conclude that BOLD fMRI might be vulnerable to changes in baseline CO, and suggest exercising caution when imaging populations exposed to elevated CO levels. Further work is required to fully elucidate the impact on CO on fMRI and its underlying mechanisms.

Carboxyhemoglobin in umbilical cord blood and maternal smoking.

Background Smoking during pregnancy still exists in daily life but the effect on the newborn in the early stage of life is still unclear. This study investigates the normal reference range of carboxyhemoglobin (HbCO) in umbilical cord blood gas (UBG). Methods A single center retrospective cross-sectional cohort study was performed with 1172 cases. We analyzed HbCO values in umbilical cord blood, maternal smoking, birth weight percentiles, duration of amenorrhea and maternal admission duration prior to delivery. Results HbCO levels in newborns range from 0 to 7.7% with a mean of 0.6% (standard deviation 0.6). Newborns from women who smoked during pregnancy have a significant higher HbCO value compared to newborns from women who did not smoke. Birth weight is negatively correlated with HbCO (P = 0.001). Conclusion Our results show the normal reference range in this study is 0-1.2% for HbCO in the umbilical blood of newborns. Smoking prior to delivery leads to a higher HbCO value in the UBG sample of the newborn, a lower birth weight and may be potential harmful.

Carbon monoxide releasing molecule-2 protects against particulate matter-induced lung inflammation by inhibiting TLR2 and 4/ROS/NLRP3 inflammasome activation.

Exposure to airborne particulate matter (PM) not only causes lung inflammation and chronic respiratory diseases, but also increases the incidence and mortality of cardiopulmonary diseases. The nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome activation has been shown to play a critical role in the formation of many chronic disorders. On the other hand, carbon monoxide (CO) has been shown to possess anti-inflammatory and antioxidant effects in many tissues and organs. Here, we investigated the effects and mechanisms of carbon monoxide releasing molecule-2 (CORM-2) on PM-induced inflammatory responses in human pulmonary alveolar epithelial cells (HPAEpiCs). We found that PM induced C-reactive protein (CRP) expression, NLRP3 inflammasome activation, IL-1ß secretion, and caspase-1 activation, which were inhibited by pretreatment with CORM-2. In addition, transfection with siRNA of Toll-like receptor 2 (TLR2) or TLR4 and pretreatment with an antioxidant (N-acetyl-cysteine, NAC), the inhibitor of NADPH oxidase (diphenyleneiodonium, DPI), or a mitochondria-specific superoxide scavenger (MitoTEMPO) reduced PM-induced inflammatory responses. CORM-2 also inhibited PM-induced NADPH oxidase activity and NADPH oxidase- and mitochondria-derived ROS generation. However, pretreatment with inactivate CORM-2 (iCORM-2) had no effects on PM-induced inflammatory responses. Finally, we showed that CORM-2 inhibited PM-induced CRP, NLRP3 inflammasome, and ASC protein expression in the lung tissues of mice and IL-1ß levels in the serum of mice. PM-enhanced leukocyte count in bronchoalveolar lavage fluid in mice was reduced by CORM-2. The results of this study suggested a protective role of CORM-2 in PM-induced lung inflammation by inhibiting the TLR2 and TLR4/ROS-NLRP3 inflammasome-CRP axial.

Pharmacological treatment of inhalation injury after nuclear or radiological incidents: The Chinese and German approach.

Inhalation injury is often associated with burns and significantly increases morbidity and mortality. The main toxic components of fire smoke are carbon monoxide, hydrogen cyanide, and irritants. In the case of an incident at a nuclear power plant or recycling facility associated with fire, smoke may also contain radioactive material. Medical treatments may vary in different countries, and in this paper, we discuss the similarities and differences in the treatments between China and Germany. Carbon monoxide poisoning is treated by 100% oxygen administration and, if available, hyperbaric oxygenation in China as well as in Germany. In addition, antidotes binding the cyanide ions and relieving the respiratory chain are important. Methemoglobin-forming agents (e.g., nitrites, dimethylaminophenol) or hydroxocobalamin (Vitamin B12) are options. The metabolic elimination of cyanide may be enhanced by sodium thiosulfate. In China, sodium nitrite with sodium thiosulfate is the most common combination. The use of dimethylaminophenol instead of sodium nitrite is typical for Germany, and hydroxocobalamin is considered the antidote of choice if available in cases of cyanide intoxications by fire smoke inhalation as it does not further reduce oxygen transport capacity. Systematic prophylactic use of corticosteroids to prevent toxic pulmonary edema is not recommended in China or Germany. Stable iodine is indicated in the case of radioiodine exposure and must be administered within several hours to be effective. The decorporation of metal radionuclides is possible with Ca (DTPA) or Prussian blue that should be given as soon as possible. These medications are used in both countries, but it seems that Ca (DTPA) is administered at lower dosages in China. Although the details of the treatment of inhalation injury and radionuclide(s) decorporation may vary, the general therapeutic strategy is very similar in China and Germany.

Tar, nicotine and carbon monoxide yield of UK cigarettes and the risk of non-muscle-invasive and muscle-invasive bladder cancer.

Cigarette smoking is a major risk factor for bladder cancer (BC); however, the impact of cigarette content remains unclear. This study aims to investigate tar, nicotine and carbon monoxide (TNCO) yields of different filtered cigarettes in relation to BC risk. From the Bladder Cancer Prognosis Programme 575 non-muscle-invasive bladder cancer (NMIBC) cases, 139 muscle-invasive bladder cancer (MIBC) cases and 130 BC-free controls with retrospective data on smoking behaviour and cigarette brand were identified. Independently measured TNCO yields of cigarettes sold in the UK were obtained through the UK Department of Health and merged with the Bladder Cancer Prognosis Programme dataset to estimate the daily intake of TNCO. BC risk increased by TNCO intake category for NMIBC cases (P <0.050 in all multivariate models), but only for the daily intake of tar for MIBC cases (P=0.046) in multivariate models. No difference in risk was observed between smokers of low-tar/low-nicotine and high-tar/high-nicotine cigarettes compared with never smokers, either for NMIBC (P=0.544) or MIBC (P=0.449). High daily intake of TNCO additionally increases the risk of both NMIBC and MIBC compared with low daily intake. However, as there is no difference in BC risk between low-tar/low-nicotine and high-tar/high-nicotine cigarette smokers, it remains unclear whether smoking behaviour or TNCO yield of cigarettes explains this association.

Cardiovascular Effects of Hookah Smoking: Potential Implications for Cardiovascular Risk.

INTRODUCTION: Smoking is a major cause of cardiovascular morbidity and mortality worldwide. Hookah (ie, waterpipe) smoking is a centuries-old revived yet understudied global epidemic of tobacco use. Because of the traditional set-up of a hookah-pipe, in addition to inhaling tobacco-combustion products, smokers are also exposed to large amounts of charcoal combustion products from the burning charcoal briquettes used to heat the hookah flavored tobacco. Despite being heavily advertised and actively glamorized in the mass media as a healthier tobacco alternative, the toxicological constituents of hookah smoke-including nicotine, carbon monoxide, particulates, oxidants, heavy metals, phenols and flavorants-indicate the potential to cause adverse cardiovascular events. METHODS: Herein, we review evidence on hookah smoke toxicological constituents, cardiovascular effects and potential mechanisms by which hookah smoke aerosol could cause cardiovascular disease. RESULTS: The evidence reviewed here indicates that contrary to the widespread popular belief that hookah is a healthier tobacco alternative, the constituents of hookah smoke aerosol contains similar chemicals compared to cigarette smoke, many of which are known to be harmful to cardiovascular health and mediated by similar pathophysiologic processes. Because the burning charcoal briquettes are a unique source of toxicant emissions specific to hookah smoking, some constituents differ in their quantities from cigarettes with some of their cardiovascular effects unknown. CONCLUSIONS: To date, much more is known about the constituents and their toxicology than about the effects of hookah smoking on human cardiovascular health. Further research on long-term consequences of hookah use is needed. IMPLICATIONS: This review provides an overview on the potential impact of hookah smoking on cardiovascular health. Readers will gain an insight into evidence on its toxicological constituents, human health effects, and pathophysiological mechanisms by which hookah smoking might cause cardiovascular disease. The review also highlights current research gaps regarding the cardiovascular consequences of hookah smoking, specifically the long-term consequences in the United States and Europe among flavored-hookah tobacco users.

Noncommunicable Respiratory Disease and Air Pollution Exposure in Malawi (CAPS). A Cross-Sectional Study.

RATIONALE: Noncommunicable respiratory diseases and exposure to air pollution are thought to be important contributors to morbidity and mortality in sub-Saharan African adults. OBJECTIVES: We set out to explore the prevalence and determinants of noncommunicable respiratory disease among adults living in Chikhwawa District, Malawi. METHODS: We performed a cross-sectional study among adults in communities participating in a randomized controlled trial of a cleaner-burning biomass-fueled cookstove intervention (CAPS [Cooking and Pneumonia Study]) in rural Malawi. We assessed chronic respiratory symptoms, spirometric abnormalities, and personal exposure to air pollution (particulate matter <2.5 µm in aerodynamic diameter [PM2.5] and carbon monoxide [CO]). Weighted prevalence estimates were calculated; multivariable and intention-to-treat analyses were done. MEASUREMENTS AND MAIN RESULTS: One thousand four hundred eighty-one participants (mean [SD] age, 43.8 [17.8] yr; 57% female) were recruited. The prevalence of chronic respiratory symptoms, spirometric obstruction, and restriction were 13.6% (95% confidence interval [CI], 11.9-15.4), 8.7% (95% CI, 7.0-10.7), and 34.8% (95% CI, 31.7-38.0), respectively. Median 48-hour personal PM2.5 and CO exposures were 71.0 µg/m3 (interquartile range [IQR], 44.6-119.2) and 1.23 ppm (IQR, 0.79-1.93), respectively. Chronic respiratory symptoms were associated with current/ex-smoking (odds ratio [OR], 1.59; 95% CI, 1.05-2.39), previous tuberculosis (OR, 2.50; 95% CI, 1.04-15.58), and CO exposure (OR, 1.46; 95% CI, 1.04-2.05). Exposure to PM2.5 was not associated with any demographic, clinical, or spirometric characteristics. There was no effect of the CAPS intervention on any of the secondary trial outcomes. CONCLUSIONS: The burden of chronic respiratory symptoms, abnormal spirometry, and air pollution exposures in adults in rural Malawi is of considerable potential public health importance. We found little evidence that air pollution exposures were associated with chronic respiratory symptoms or spirometric abnormalities and no evidence that the CAPS intervention had effects on the secondary trial outcomes. More effective prevention and control strategies for noncommunicable respiratory disease in sub-Saharan Africa are needed. Clinical trial registered with www.isrctn.com (ISRCTN 59448623).

Effects of exposure to fine particulate matter in elderly hospitalizations due to respiratory diseases in the South of the Brazilian Amazon

Exposure to air pollution is an important cause of hospital admissions due to respiratory diseases. Nevertheless, few studies use pollutant concentration data estimated by mathematical models. A time-series ecological study was developed, using data from hospitalizations due to respiratory diseases in people over 60 years of age, residents of Cuiabá, Brazil, during 2012, obtained from the Brazilian Ministry of Health. The independent variables were the concentrations of fine particulate matter (PM2.5) and carbon monoxide (CO) estimated by mathematical modeling, minimum temperature, and relative humidity (obtained from the Brazilian Meteorological Agency), and the number of forest fires. The generalized linear regression model of Poisson was used, with lags of 0 to 7 days. The coefficients obtained were transformed into relative risk of hospitalization, with respective 95% confidence intervals; alpha=5% was adopted. In that year, 591 hospitalizations were evaluated, with a daily average of 1.61 (SD=1.49), the PM2.5 average concentration was 15.7 µg/m3, and the CO average concentration was 144.2 ppb. Significant associations between exposure to these contaminants and hospitalizations in lags 3 and 4 in 2012 were observed. There was a hospitalization risk increase of 31.8%, with an increase of 3.5 µg/m3 of PM2.5 concentrations and an increase of 188 in the total number of hospitalizations, with an expense of more than ≈US$ 96,000 for the Brazilian Public Health System. This study provided information on the cost of air pollution to the health system and the feasibility of using a mathematical model to estimate environmental concentration of air pollutants.

Genetic variation in biotransformation enzymes, air pollution exposures, and risk of spina bifida.

Spina bifida is a birth defect characterized by incomplete closure of the embryonic neural tube. Genetic factors as well as environmental factors have been observed to influence risks for spina bifida. Few studies have investigated possible gene-environment interactions that could contribute to spina bifida risk. The aim of this study is to examine the interaction between gene variants in biotransformation enzyme pathways and ambient air pollution exposures and risk of spina bifida. We evaluated the role of air pollution exposure during pregnancy and gene variants of biotransformation enzymes from bloodspots and buccal cells in a California population-based case-control (86 cases of spina bifida and 208 non-malformed controls) study. We considered race/ethnicity and folic acid vitamin use as potential effect modifiers and adjusted for those factors and smoking. We observed gene-environment interactions between each of the five pollutants and several gene variants: NO (ABCC2), NO2 (ABCC2, SLC01B1), PM10 (ABCC2, CYP1A1, CYP2B6, CYP2C19, CYP2D6, NAT2, SLC01B1, SLC01B3), PM2.5 (CYP1A1 and CYP1A2). These analyses show positive interactions between air pollution exposure during early pregnancy and gene variants associated with metabolizing enzymes. These exploratory results suggest that some individuals based on their genetic background may be more susceptible to the adverse effects of pollution.

A Phase II Clinical Trial of Low-Dose Inhaled Carbon Monoxide in Idiopathic Pulmonary Fibrosis.

BACKGROUND: Preclinical studies have demonstrated that low-dose carbon monoxide (CO) can abrogate experimental lung fibrosis. To test the therapeutic role of inhaled CO, we designed a clinical study in patients with idiopathic pulmonary fibrosis (IPF). METHODS: We conducted a multicenter, phase IIa, double-blinded, sham-controlled, clinical trial. Patients with IPF were randomized to treatment with inhaled CO at 100 to 200 parts per million or to inhaled 21% oxygen for 2 h daily, twice weekly, for 12 weeks. The primary study end point was the difference in change in matrix metalloproteinase-7 (MMP7) serum concentration after 12 weeks of treatment. Secondary end points included pulmonary function test measures, 6-min walk distance, rates of adverse events, acute exacerbation, hospitalization and death, and quality of life measures. RESULTS: Fifty-eight subjects were randomized to treatment with inhaled CO (n = 29) or placebo (n = 29). Despite modest increases in CO blood levels, the change in MMP7 concentrations after 12 weeks of treatment did not significantly differ between the study arms (MMP7 difference at week 12, -0.90 ng/mL; 95% CI, -4.18 to 2.38 ng/mL). No differences were observed in physiologic measures, incidence of acute exacerbations, hospitalization, death, or patient-reported outcomes. Importantly, no differences in distribution of adverse events were noted between the treatment arms. CONCLUSIONS: Inhaled CO is well tolerated and can be safely administered to patients with IPF in the ambulatory setting; however, inhaled CO did not result in significant changes in study end points. Our findings support testing the efficacy of inhaled therapies in future IPF clinical trials. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01214187; URL: www.clinicaltrials.gov.