Characterization of risks and pathogenesis of respiratory diseases caused by rural atmospheric PM2.5.

Forty-six percent of the world's population resides in rural areas, the majority of whom belong to vulnerable groups. They mainly use cheap solid fuels for cooking and heating, which release a large amount of PM2.5 and cause adverse effects to human health. PM2.5 exhibits urban-rural differences in its health risk to the respiratory system. However, the majority of research on this issue has focused on respiratory diseases induced by atmospheric PM2.5 in urban areas, while rural areas have been ignored for a long time, especially the pathogenesis of respiratory diseases. This is not helpful for promoting environmental equity to aid vulnerable groups under PM2.5 pollution. Thus, this study focuses on rural atmospheric PM2.5 in terms of its chemical components, toxicological effects, respiratory disease types, and pathogenesis, represented by PM2.5 from rural areas in the Sichuan Basin, China (Rural SC-PM2.5). In this study, organic carbon is the most significant component of Rural SC-PM2.5. Rural SC-PM2.5 significantly induces cytotoxicity, oxidative stress, and inflammatory response. Based on multiomics, bioinformatics, and molecular biology, Rural SC-PM2.5 inhibits ribonucleotide reductase regulatory subunit M2 (RRM2) to disrupt the cell cycle, impede DNA replication, and ultimately inhibit lung cell proliferation. Furthermore, this study supplements and supports the epidemic investigation. Through an analysis of the transcriptome and human disease database, it is found that Rural SC-PM2.5 may mainly involve pulmonary hypertension, sarcoidosis, and interstitial lung diseases; in particular, congenital diseases may be ignored by epidemiological surveys in rural areas, including tracheoesophageal fistula, submucous cleft of the hard palate, and congenital hypoplasia of the lung. This study contributes to a greater scientific understanding of the health risks posed by rural PM2.5, elucidates the pathogenesis of respiratory diseases, clarifies the types of respiratory diseases, and promotes environmental equity.

Effect of ambient air pollution on hospital admission for respiratory diseases in Hanoi children during 2007-2019.

Air pollution poses a threat to children's respiratory health. This study aims to quantify the association between short-term air pollution exposure and respiratory hospital admissions among children in Hanoi, Vietnam, and estimate the population-attributable burden using local data. A case-crossover analysis was conducted based on the individual records where each case is their own control. The health data was obtained from 13 hospitals in Hanoi and air pollution data was collected from four monitoring stations from 2007 to 2019. We used conditional logistic regression to estimate Percentage Change (PC) and 95% Confidence Interval (CI) in odd of hospital admissions per 10 µg/m3 increase in daily average particulate matter (e.g. PM1, PM2.5, PM10), Sulfur Dioxide (SO2), Nitrogen Dioxide (NO2), 8-h maximum Ozone and per 1000 µg/m3 increase in daily mean of Carbon Monoxide (CO). We also calculated the number and fraction of admissions attributed to air pollution in Hanoi by using the coefficient at lag 0. A 10 µg/m3 increase in the concentration of PM10, PM2.5, PM1, SO2, NO2, O3 8-h maximum and 1000 µg/m3 increase in CO concentration was associated with 0.6%, 1.2%, 1.4%, 0.8%, 1.6%, 0.3%, and 1.7% increase in odd of admission for all respiratory diseases among children under 16 years at lag 0-2. All PM metrics and NO2 are associated with childhood admission for pneumonia and bronchitis. Admissions due to asthma and upper respiratory diseases are related to increments in NO2 and CO. For attributable cases, PM2.5 concentrations in Hanoi exceeding the World Health Organization Air Quality Guidelines accounted for 1619 respiratory hospital admissions in Hanoi children in 2019. Our findings show that air pollution has a detrimental impact on the respiratory health of Hanoi children and there will be important health benefits from improved air quality management planning to reduce air pollution in Vietnam.

Long-term residential exposure to air pollution and risk of chronic respiratory diseases in Italy: The BIGEPI study.

Long-term exposure to air pollution has adverse respiratory health effects. We investigated the cross-sectional relationship between residential exposure to air pollutants and the risk of suffering from chronic respiratory diseases in some Italian cities. In the BIGEPI project, we harmonised questionnaire data from two population-based studies conducted in 2007-2014. By combining self-reported diagnoses, symptoms and medication use, we identified cases of rhinitis (n = 965), asthma (n = 328), chronic bronchitis/chronic obstructive pulmonary disease (CB/COPD, n = 469), and controls (n = 2380) belonging to 13 cohorts from 8 Italian cities (Pavia, Turin, Verona, Terni, Pisa, Ancona, Palermo, Sassari). We derived mean residential concentrations of fine particulate matter (PM10, PM2.5), nitrogen dioxide (NO2), and summer ozone (O3) for the period 2013-2015 using spatiotemporal models at a 1 km resolution. We fitted logistic regression models with controls as reference category, a random-intercept for cohort, and adjusting for sex, age, education, BMI, smoking, and climate. Mean ± SD exposures were 28.7 ± 6.0 µg/m3 (PM10), 20.1 ± 5.6 µg/m3 (PM2.5), 27.2 ± 9.7 µg/m3 (NO2), and 70.8 ± 4.2 µg/m3 (summer O3). The concentrations of PM10, PM2.5, and NO2 were higher in Northern Italian cities. We found associations between PM exposure and rhinitis (PM10: OR 1.62, 95%CI: 1.19-2.20 and PM2.5: OR 1.80, 95%CI: 1.16-2.81, per 10 µg/m3) and between NO2 exposure and CB/COPD (OR 1.22, 95%CI: 1.07-1.38 per 10 µg/m3), whereas asthma was not related to environmental exposures. Results remained consistent using different adjustment sets, including bi-pollutant models, and after excluding subjects who had changed residential address in the last 5 years. We found novel evidence of association between long-term PM exposure and increased risk of rhinitis, the chronic respiratory disease with the highest prevalence in the general population. Exposure to NO2, a pollutant characterised by strong oxidative properties, seems to affect mainly CB/COPD.

Emission of Industrial Air Pollution and Mortality Due to Respiratory Diseases: A Birth Cohort Study in Poland.

BACKGROUND: Air pollution is a major risk factor for public health worldwide, but evidence linking this environmental problem with the mortality of children in Central Europe is limited. OBJECTIVE: To investigate the relationship between air pollution due to the emission of industry-related particulate matter and mortality due to respiratory diseases under one year of age. METHODS: A retrospective birth cohort analysis of the dataset including 2,277,585 children from all Polish counties was conducted, and the dataset was matched with 248 deaths from respiratory diseases under one year of age. Time to death during the first 365 days of life was used as a dependent variable. Harmful emission was described as total particle pollution (TPP) from industries. The survival analysis was performed using the Cox proportional hazards model for the emission of TPP at the place of residence of the mother and child, adjusted individual characteristics, demographic factors, and socioeconomic status related to the contextual level. RESULTS: Infants born in areas with extremely high emission of TPP had a significantly higher risk of mortality due to respiratory diseases: hazard ratio (HR) = 1.781 [95% confidence interval (CI): 1.175, 2.697], p = 0.006, compared with those born in areas with the lowest emission levels. This effect was persistent when significant factors were adjusted at individual and contextual levels (HR = 1.959 [95% CI: 1.058, 3.628], p = 0.032). The increased risk of mortality was marked between the 50th and 150th days of life, coinciding with the highest exposure to TPP. CONCLUSIONS: The emission of TPP from industries is associated with mortality due to respiratory diseases under one year of age. A considerable proportion of children's deaths could be prevented in Poland, especially in urban areas, if air pollution due to the emission of particle pollution is reduced.

Association of air pollutants and hospital admissions for respiratory diseases in Lanzhou, China, 2014-2019.

The aim of this study was to assess the effects of air pollutants on hospital admissions for respiratory disease (RD) by using distributed lag nonlinear model (DLNM) in Lanzhou during 2014-2019. In this study, the dataset of air pollutants, meteorological, and daily hospital admissions for RD in Lanzhou, from January 1st, 2014 to December 31st, 2019, were collected from three national environmental monitoring stations, China meteorological data service center, and three large general hospitals, respectively. A time-series analysis with DLNM was used to estimate the associations between air pollutants and hospital admissions for RD including the stratified analysis of age, gender, and season. The key findings were expressed as the relative risk (RR) with a 95% confidence interval (CI) for single-day and cumulative lag effects (0-7). A total of 90, 942 RD hospitalization cases were identified during the study period. The highest association (RR, 95% CI) of hospital admissions for RD and PM2.5 (1.030, 1.012-1.049), and PM10 (1.009, 1.001-1.015), and NO2 (1.047, 1.024-1.071) were observed at lag 07 for an increase of 10 µg/m3 in the concentrations, and CO at lag07 (1.140, 1.052-1.236) for an increase of 1 mg/m3 in the concentration. We observed that the RR estimates for gaseous pollutants (e.g., CO and NO2) were larger than those of particulate matter (e.g., PM2.5 and PM10). The harmful effects of PM2.5, PM10, NO2, and CO were greater in male, people aged 0-14 group and in the cold season. However, no significant association was observed for SO2, O38h, and total hospital admissions for RD. Therefore, some effective intervention strategies should be taken to strengthen the treatment of the ambient air pollutants, especially gaseous pollutants (e.g., CO and NO2), thereby, reducing the burden of respiratory diseases.

The effects of sugammadex vs. neostigmine on postoperative respiratory complications and advanced healthcare utilisation: a multicentre retrospective cohort study.

Reversing neuromuscular blockade with sugammadex can eliminate residual paralysis, which has been associated with postoperative respiratory complications. There are equivocal data on whether sugammadex reduces these when compared with neostigmine. We investigated the association of the choice of reversal drug with postoperative respiratory complications and advanced healthcare utilisation. We included adult patients who underwent surgery and received general anaesthesia with sugammadex or neostigmine reversal at two academic healthcare networks between January 2016 and June 2021. The primary outcome was postoperative respiratory complications, defined as post-extubation oxygen saturation < 90%, respiratory failure requiring non-invasive ventilation, or tracheal re-intubation within 7 days. Our main secondary outcome was advanced healthcare utilisation, a composite outcome including: 7-day unplanned intensive care unit admission; 30-day hospital readmission; or non-home discharge. In total, 5746 (6.9%) of 83,250 included patients experienced postoperative respiratory complications. This was not associated with the reversal drug (adjusted OR (95%CI) 1.01 (0.94-1.08); p = 0.76). After excluding patients admitted from skilled nursing facilities, 8372 (10.5%) patients required advanced healthcare utilisation, which was not associated with the choice of reversal (adjusted OR (95%CI) 0.95 (0.89-1.01); p = 0.11). Equivalence testing supported an equivalent effect size of sugammadex and neostigmine on both outcomes, and neostigmine was non-inferior to sugammadex with regard to postoperative respiratory complications or advanced healthcare utilisation. Finally, there was no association between the reversal drug and major adverse cardiovascular events (adjusted OR 1.07 (0.94-1.21); p = 0.32). Compared with neostigmine, reversal of neuromuscular blockade with sugammadex was not associated with a reduction in postoperative respiratory complications or post-procedural advanced healthcare utilisation.

Short-term air pollution exposure and hospital admissions for cardiorespiratory diseases in Brazil: A nationwide time-series study between 2008 and 2018.

The established evidence associating air pollution with health is limited to populations from specific regions. Further large-scale studies in several regions worldwide are needed to support the literature to date and encourage national governments to act. Brazil is an example of these regions where little research has been performed on a large scale. To address this gap, we conducted a study looking at the relationship between daily PM2.5, NO2, and O3, and hospital admissions for circulatory and respiratory diseases across Brazil between 2008 and 2018. A time-series analytic approach was applied with a distributed lag modeling framework. We used a generalized conditional quasi-Poisson regression model to estimate relative risks (RRs) of the association of each air pollutant with the hospitalization for circulatory and respiratory diseases by sex, age group, and Brazilian regions. Our study population includes 23, 791, 093 hospital admissions for cardiorespiratory diseases in Brazil between 2008 and 2018. Among those, 53.1% are respiratory diseases, and 46.9% are circulatory diseases. Our findings suggest significant associations of ambient air pollution (PM2.5, NO2, and O3) with respiratory and circulatory hospital admissions in Brazil. The national meta-analysis for the whole population showed that for every increase of PM2.5 by 10 µg/m3, there is a 3.28% (95%CI: 2.61; 3.94) increase in the risk of hospital admission for respiratory diseases. For O3, we found positive associations only for some sub-group analyses by age and sex. For NO2, our findings suggest that a 10 ppb increase in this pollutant, there was a 35.26% (95%CI: 24.07; 46.44) increase in the risk of hospital admission for respiratory diseases. This study may better support policymakers to improve the air quality and public health in Brazil.

Application of machine learning approaches to predict the impact of ambient air pollution on outpatient visits for acute respiratory infections.

With a remarkable increase in industrialization among fast-developing countries, air pollution is rising at an alarming rate and has become a public health concern. The study aims to examine the effect of air pollution on patient's hospital visits for respiratory diseases, particularly Acute Respiratory Infections (ARI). Outpatient hospital visits, air pollution and meteorological parameters were collected from March 2018 to October 2021. Eight machine learning algorithms (Random Forest model, K-Nearest Neighbors regression model, Linear regression model, LASSO regression model, Decision Tree Regressor, Support Vector Regression, X.G. Boost and Deep Neural Network with 5-layers) were applied for the analysis of daily air pollutants and outpatient visits for ARI. The evaluation was done by using 5-cross-fold confirmations. The data was randomly divided into test and training data sets at a scale of 1:2, respectively. Results show that among the studied eight machine learning models, the Random Forest model has given the best performance with R2 = 0.606, 0.608 without lag and 1-day lag respectively on ARI patients and R2 = 0.872, 0.871 without lag and 1-day lag respectively on total patients. All eight models did not perform well with the lag effect on the ARI patient dataset but performed better on the total patient dataset. Thus, the study did not find any significant association between ARI patients and ambient air pollution due to the intermittent availability of data during the COVID-19 period. This study gives insight into developing machine learning programs for risk prediction that can be used to predict analytics for several other diseases apart from ARI, such as heart disease and other respiratory diseases.

Association between out-patient visits and air pollution in Chiang Mai, Thailand: Lessons from a unique situation involving a large data set showing high seasonal levels of air pollution.

Chiang Mai is one of the most known cities of Northern Thailand, representative for various cities in the East and South-East Asian region exhibiting seasonal smog crises. While a few studies have attempted to address smog crises effects on human health in that geographic region, research in this regard is still in its infancy. We exploited a unique situation based on two factors: large pollutant concentration variations due to the Chiang Mai smog crises and a relatively large sample of out-patient visits. About 216,000 out-patient visits in the area of Chiang Mai during the period of 2011 to 2014 for upper (J30-J39) and lower (J44) respiratory tract diseases were evaluated with respect to associations with particulate matter (PM10), ozone (O3), and nitrogen dioxide (NO2) concentrations using single-pollutant and multiple-pollutants Poisson regression models. All three pollutants were found to be associated with visits due to upper respiratory tract diseases (with relative risks RR = 1.023 at cumulative lag 05, 95% CI: 1.021-1.025, per 10 µg/m3 PM10 increase, RR = 1.123 at lag 05, 95% CI: 1.118-1.129, per 10 ppb O3 increase, and RR = 1.110 at lag 05, 95% CI: 1.102-1.119, per 10 ppb NO2 increase). Likewise, all three pollutants were found to be associated with visits due to lower respiratory tract diseases (with RR = 1.016 at lag 06, 95% CI: 1.015-1.017, per 10 µg/m3 PM10 increase, RR = 1.073 at lag 06, 95% CI: 1.070-1.076, per 10 ppb O3 increase, and RR = 1.046 at lag 06, 95% CI: 1.040-1.051, per 10 ppb NO2 increase). Multi-pollutants modeling analysis identified O3 as a relatively independent risk factor and PM10-NO2 pollutants models as promising two-pollutants models. Overall, these results demonstrate the adverse effects of all three air pollutants on respiratory morbidity and call for air pollution reduction and control.

The involvement of copper, circular RNAs, and inflammatory cytokines in chronic respiratory disease.

Exposure to high concentrations of copper is associated with pulmonary inflammation and chronic respiratory disease (CRD). Epigenetic modulation of noncoding RNAs contributes to the development of several CRDs. It is unknown whether epigenetic modulation is involved in copper mediated pulmonary inflammation and CRD. We conducted a case-control study of 101 CRD cases and 161 control subjects in Shijiazhuang, China, and evaluated circRNAs and cytokine levels (IL-6 and IL-8) by qPCR and ELISA. Urinary copper concentration was determined by inductively coupled plasma mass spectrometry. Linear mixed models and generalized linear mixed models were used to assess the associations of circRNAs with CRD, urinary copper, and cytokines. We exposed the human bronchial epithelial cell line, 16HBE, to copper and assessed the functional role of a circRNA, circ_0008882, by RNA overexpression. Cellular location of circ_0008882 was assessed by separation of nuclear and cytoplasmic RNAs. Nine circRNAs were associated with an increased risk for CRDs, while the relative expression of circ_0008882 was decreased after copper exposure in vitro and in vivo. Copper exposure stimulated 16HBE cells to release proinflammatory IL-6 and IL-8. The release of the cytokines was inhibited by overexpression of circ_0008882. These results suggest a role for circ_0008882 in the regulation of CRD associated inflammation following copper exposure.

Duration of Exposure to General Endotracheal Anesthesia during Cesarean Deliveries at Term and Perinatal Complications.

OBJECTIVE: To examine whether the duration of time from initiation of general endotracheal anesthesia (GETA) to delivery for cesarean deliveries (CDs) performed is related to perinatal outcomes. STUDY DESIGN: This is a retrospective study of patients with singleton nonanomalous gestations undergoing CD ≥37 weeks of gestation under GETA with reassuring fetal status at a single tertiary care center from 2000 to 2016. Duration from GETA initiation until delivery was calculated as the time interval from GETA induction to delivery (I-D), categorized into tertiles. Outcomes for those in the tertile with the shortest I-D were compared with those in the other two tertiles. The primary perinatal outcome was a composite of complications (continuous positive airway pressure or high-flow nasal cannula for ≥2 consecutive hours, inspired oxygen ≥30% for ≥4 consecutive hours, mechanical ventilation, stillbirth, or neonatal death ≤72 hours after birth). Secondary outcomes were 5-minute Apgar score <7 and a composite of maternal morbidity (bladder injury, bowel injury, and extension of hysterotomy). Bivariable and multivariable analyses were used to compare outcomes. RESULTS: Two hundred eighteen maternal-perinatal dyads were analyzed. They were dichotomized based on I-D ≤4 minutes (those in the tertile with the shortest duration) or >4 minutes. Women with I-D >4 minutes were more likely to have prior abdominal surgery and less likely to have labored prior to CD. I-D >4 minutes was associated with significantly increased frequency of the primary perinatal outcome. This persisted after multivariable adjustment. In bivariable analysis, 5-minute Apgar <7 was more common in the group with I-D >4 minutes, but this did not persist in multivariable analysis. Frequency of maternal morbidity did not differ. CONCLUSION: When CD is performed at term using GETA without evidence of nonreassuring fetal status prior to delivery, I-D interval >4 minutes is associated with increased frequency of perinatal complications. KEY POINTS: · Cesarean delivery under general anesthesia is associated with increased perinatal complications.. · Perinatal complications are increased with increasing duration of exposure to general anesthetics.. · Maternal complications were not increased with shorter duration of exposure to general anesthesia..

Clinical characteristics and aspirin desensitization in Thai patients with a suggestive history of NSAID-exacerbated respiratory disease.

BACKGROUND: Non-steroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (NERD) is characterized by the triad of chronic rhinosinusitis with nasal polyp, asthma, and aspirin (ASA) or NSAID hypersensitivity. Previous study of NERD has rarely been reported in Asian population. OBJECTIVE: To investigate the clinical characteristics and outcomes of aspirin desensitization (ASAD) in Thai NERD. METHODS: This retrospective chart review included patients with a suggestive history of NERD with or without ASAD from the Adult Allergy Clinic of Siriraj Hospital (Bangkok, Thailand) during January 2008 to December 2018. RESULTS: Ten NERD patients were recruited. The median age of onset was 30 years. Comorbid atopic diseases were found in 4 patients. Asthma control level was step 3 of the Global Initiative for Asthma (GINA) guideline or greater in all patients. Five patients had reactions to more than one NSAIDs. Ibuprofen was the most common culprit agent. Reactions frequently involved the respiratory and cutaneous systems. Four patients underwent ASAD followed by ingestion of ASA 300-600 mg daily. One patient discontinued ASA after taking ASA 600 mg daily for 3 months due to severe gastrointestinal side effect. The remaining three patients successfully continued ASA 300 mg daily as maintenance to control sino-nasal inflammation and to prevent recurrence of nasal polyp. None of the 4 patients required sinus surgery revision. CONCLUSIONS: NERD is a difficult-to-treat disease with unique clinical characteristics. ASAD followed by a maintenance dose of ASA 300 mg daily was found to be effective and well-tolerated in most patients.

Vedolizumab-associated pulmonary manifestations in children with ulcerative colitis.

WHAT IS KNOWN AND OBJECTIVE: The off-label use of vedolizumab (VDZ) for inflammatory bowel disease in children is increasing. We report on possibly the first case of VDZ-associated pulmonary manifestations in paediatrics. CASE SUMMARY: This report details the case of a 13-year-old child with ulcerative colitis who was initiated on VDZ due to persistent active disease. After the first three doses, he developed a persistent and productive cough. Microbiological work-up was normal. VDZ discontinuation led to the resolution of symptoms. WHAT IS NEW AND CONCLUSION: To our knowledge, this is the first case report of VDZ-associated pulmonary manifestations in paediatrics. A direct, pro-inflammatory effect of VDZ has been hypothesized, but further studies are warranted.

Fine Particles in Wildfire Smoke and Pediatric Respiratory Health in California.

BACKGROUND AND OBJECTIVES: Exposure to airborne fine particles with diameters ≤2.5 µm (PM2.5) pollution is a well-established cause of respiratory diseases in children; whether wildfire-specific PM2.5 causes more damage, however, remains uncertain. We examine the associations between wildfire-specific PM2.5 and pediatric respiratory health during the period 2011-2017 in San Diego County, California, and compare these results with other sources of PM2.5. METHODS: Visits to emergency and urgent care facilities of Rady's Children Hospital network in San Diego County, California, by individuals (aged ≤19 years) with ≥1 of the following respiratory conditions: difficulty breathing, respiratory distress, wheezing, asthma, or cough were regressed on daily, community-level exposure to wildfire-specific PM2.5 and PM2.5 from ambient sources (eg, traffic emissions). RESULTS: A 10-unit increase in PM2.5 (from nonsmoke sources) was estimated to increase the number of admissions by 3.7% (95% confidence interval: 1.2% to 6.1%). In contrast, the effect of PM2.5 attributable to wildfire was estimated to be a 30.0% (95% confidence interval: 26.6% to 33.4%) increase in visits. CONCLUSIONS: Wildfire-specific PM2.5 was found to be ∼10 times more harmful on children's respiratory health than PM2.5 from other sources, particularly for children aged 0 to 5 years. Even relatively modest wildfires and associated PM2.5 resolved on our record produced major health impacts, particularly for younger children, in comparison with ambient PM2.5.

Differentiation syndrome with lower-intensity treatments for acute myeloid leukemia.

Differentiation Syndrome (DS) has been identified in a subset of patients undergoing treatment with novel classes of differentiating therapies for acute myeloid leukemia (AML) such as IDH and FLT3 inhibitors. While DS is a well-known treatment-related complication in acute promyelocytic leukemia (APL), efforts are still ongoing to standardize diagnostic and treatment parameters for DS in AML. Though the rates of incidence vary, many of the signs and symptoms of DS are common between APL and AML. So, DS can lead to fatal complications in AML, but prompt management is usually effective and rarely necessitates interruption or discontinuation of AML therapy.

PM2.5 and Trace Elements in Underground Shopping Districts in the Seoul Metropolitan Area, Korea.

We measured PM2.5 in 41 underground shopping districts (USDs) in the Seoul metropolitan area from June to November 2017, and associated 18 trace elements to determine the sources and assess the respiratory risks. The PM2.5 concentrations were 18.0 ± 8.0 µg/m3 inside USDs, which were lower than 25.2 ± 10.6 µg/m3 outside. We identified five sources such as indoor miscellanea, soil dust, vehicle exhaust/cooking, coal combustion, and road/subway dust, using factor analysis. Almost 67% of the total trace element concentration resulted from soil dust. Soil dust contribution increased with the number of stores because of fugitive dust emissions due to an increase in passers-by. Vehicle exhaust/cooking contribution was higher when the entrances of the USDs were closed, whereas coal combustion contribution was higher when the entrances of the USDs were open. Although miscellanea and coal combustion contributions were 3.4% and 0.7%, respectively, among five elements with cancer risk, Cr and Ni were included in miscellanea, and Pb, Cd, and As were included in coal combustion. The excess cancer risk (ECR) was the highest at 67 × 10-6 for Cr, and the ECR for Pb was lower than 10-6, a goal of the United States Environmental Protection Agency for hazardous air pollutants.

Repurposing Ophthalmologic Timolol for Dermatologic Use: Caveats and Historical Review of Adverse Events.

Ophthalmic timolol solution is increasingly being repurposed as a topical therapeutic for a variety of dermatologic diseases, including pyogenic granulomas, infantile hemangiomas, and chronic wounds. There are no published guidelines or protocols for use in these indications in adults, and the dermatologic community may not be familiar with adverse events that have been extensively documented relating to its ophthalmic use. We review the evidence available relating to adverse events to topical timolol use to evaluate its safety in dermatologic applications and to alert clinicians to screening and monitoring that is needed when repurposing this drug for dermatologic use. The majority of serious adverse events associated with ophthalmic timolol were reported in the first 7 years of use, between 1978 and 1985, of which most common were cardiovascular and respiratory events, but also included 32 deaths. The available evidence suggests that ophthalmic timolol safety profiling may have been incomplete prior to widespread use. Recent clinical trials for dermatologic indications have focused on documenting efficacy and have not had rigorous monitoring for potential adverse events. Topical timolol may be safe and effective for the treatment of various dermatologic conditions in patients whose medical histories have been carefully reviewed for evidence of pre-existing cardiac or pulmonary disease and are monitored for potential adverse events. Despite the wide use of timolol in ophthalmologic practice, safe dermatologic repurposing requires recognition of the potential for facilitated systemic absorption though the skin and appreciation of its history of adverse events.

Effect of prenatal cigarette smoke exposure on sevoflurane-induced respiratory suppression in neonatal rats and the protective role of hydrogen sulfide.

Prenatal cigarette smoke (CS) exposure causes numerous respiratory health problems in infants. This study aimed to investigate the effect of prenatal CS exposure on sevoflurane-induced respiratory suppression in neonatal rats and the protective role of H2S. We found that at baseline, minute ventilation (V'E), respiratory frequency (fR), and tidal volume (VT) were similar among tested groups, whereas sigh frequency (fS) was lower in CS group than in the Control group. During 3 % sevoflurane anesthesia, V'E was decreased, fR was slowed, VT was increased, and fS was reduced in all groups; however, the decline in fR and increase in VT was greater in CS group than in the Control group. During the recovery, fS remained lower in CS group. The above changes of respiratory response caused by prenatal CS exposure were alleviated by NaHS pretreatment (a donor of H2S, 56 µmol/kg/d, intraperitoneal injection). These results indicated that prenatal CS exposure alters the breathing into a much slower and deeper manner in neonatal rats during sevoflurane anesthesia, and H2S mitigates this respiratory change.

Cross-Sectional Association Between Lifetime Use of Electronic Cigarettes With or Without Marijuana and Self-Reported Past 12-Month Respiratory Symptoms as well as Lifetime Respiratory Diseases in U.S. Adults.

INTRODUCTION: The use of electronic cigarettes (vaping), especially with marijuana, has become increasingly popular among adults. AIMS AND METHODS: The Population Assessment of Tobacco and Health study Wave 4 data on 33 606 adult participants who indicated ever using electronic cigarettes were included in the study. By controlling for confounding variables (such as age and smoking history), multivariable weighted logistic regression models were used to examine the cross-sectional association between lifetime e-cigarette use with or without marijuana and self-reported past 12-month respiratory symptoms as well as lifetime respiratory diseases. RESULTS: Compared to adults who never vaped, adults who had ever vaped with marijuana had a significantly higher association with self-reported past 12-month respiratory symptoms but not lifetime respiratory diseases. Compared to adults who had ever vaped without marijuana, adults who had ever vaped at least sometimes with marijuana had a significantly greater risk of having wheezing/whistling in the chest (adjusted odds ratio [aOR] = 1.21, 95% confidence interval [CI]: 1.01, 1.44), chest sounded wheezy during or after exercise (aOR = 1.59, 95% CI: 1.31, 1.93), and had a dry cough at night (aOR = 1.35, 95% CI: 1.16, 1.57), while adults who had ever vaped rarely with marijuana had a significantly greater risk of having wheezing/whistling in the chest (aOR = 1.31, 95% CI: 1.06, 1.61), chest sounded wheezy during or after exercise (aOR = 1.24, 95% CI: 1.01, 1.52), and had a dry cough at night (aOR = 1.24, 95% CI: 1.04, 1.47). CONCLUSIONS: Lifetime e-cigarette use with marijuana is associated with self-reported past 12-month respiratory symptoms in adults. IMPLICATIONS: The use of e-cigarettes with marijuana has become prevalent in recent years. Our cross-sectional study suggests that there may be respiratory health symptoms associated with ever vaping with marijuana that is independent of nicotine vaping, which should raise public awareness of potential health risks associated with the use of e-cigarettes with marijuana. Further longitudinal studies on the respiratory health effects of e-cigarette use with marijuana are warranted.

Association of Electronic Cigarette Use With Incident Respiratory Conditions Among US Adults From 2013 to 2018.

Importance: Generating robust and timely evidence about the respiratory health risks of electronic cigarettes (e-cigarettes) is critical for informing state and federal regulatory standards for product safety. Objective: To examine the association of e-cigarette use with incident respiratory conditions, including chronic obstructive pulmonary disease (COPD), emphysema, chronic bronchitis, and asthma. Design, Setting, and Participants: This prospective cohort study used data from the nationally representative cohort of US adults from the Population Assessment of Tobacco and Health (PATH) study, including wave 1 from 2013 to 2014, wave 2 from 2014 to 2015, wave 3 from 2015 to 2016, and wave 4 from 2016 to 2018. Individuals aged 18 years and older at baseline with no prevalent respiratory conditions were included in the analyses. Analyses were conducted from February to July 2020. Exposures: e-Cigarette use was assessed by self-reported current use status (never, former, or current) at baseline. Main Outcomes and Measures: Incident respiratory conditions, including COPD, emphysema, chronic bronchitis, and asthma, as well as a composite respiratory disease encompassing all 4 conditions. Results: Among 21 618 respondents included in the analyses, 11 017 (491%) were men and 12 969 (65.2%) were non-Hispanic White. A total of 14 213 respondents were never e-cigarette users, 5076 respondents (11.6%) were former e-cigarette users, and 2329 respondents (5.2%) were current e-cigarette users. Adjusted for cigarette and other combustible tobacco product use, demographic characteristics, and chronic health conditions, there was an increased risk of respiratory disease among former e-cigarette uses (incidence rate ratio [IRR], 1.28; 95% CI, 1.09-1.50) and current e-cigarette users (IRR, 1.31; 95% CI, 1.08-1.59). Among respondents with good self-rated health, the IRR for former e-cigarette users was 1.21 (95%CI, 1.00-1.46) and the IRR for current e-cigarette users was 1.43 (95% CI, 1.14-1.79). For specific respiratory diseases among current e-cigarette users, the IRR was 1.33 (95% CI, 1.06-1.67) for chronic bronchitis, 1.69 (95% CI, 1.15-2.49) for emphysema, 1.57 (95% CI, 1.15-2.13) for COPD, and 1.31 (95% CI, 1.01-1.71) for asthma. Conclusions and Relevance: This cohort study found that e-cigarette use was associated with an increased risk of developing respiratory disease independent of cigarette smoking. These findings add important evidence on the risk profile of novel tobacco products.