Air pollution, genetic factors, and chronic rhinosinusitis: A prospective study in the UK Biobank.

BACKGROUND: Chronic rhinosinusitis (CRS) is a prevalent upper respiratory condition that manifests in two primary subtypes: CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). While previous studies indicate a correlation between air pollution and CRS, the role of genetic predisposition in this relationship remains largely unexplored. We hypothesized that higher air pollution exposure would lead to the development of CRS, and that genetic susceptibility might modify this association. METHODS: This cohort study involving 367,298 adult participants from the UK Biobank, followed from March 2006 to October 2021. Air pollution metrics were estimated at residential locations using land-use regression models. Cox proportional hazard models were employed to explore the associations between air pollution exposure and CRS, CRSwNP, and CRSsNP. A polygenic risk score (PRS) was constructed to evaluate the joint effect of air pollution and genetic predisposition on the development of CRS. RESULTS: We found that the risk of CRS increased under long-term exposure to PM2.5 [the hazard ratios (HRs) with 95 % CIs: 1.59 (1.26-2.01)], PM10 [1.64 (1.26-2.12)], NO2 [1.11 (1.04-1.17)], and NOx [1.18 (1.12-1.25)], respectively. These effects were more pronounced among participants with CRSwNP, although the differences were not statistically significant. Additionally, we found that the risks for CRS and CRSwNP increased in a graded manner among participants with higher PRS or higher exposure to PM2.5, PM10, or NOx concentrations. However, no multiplicative or additive interactions were observed. CONCLUSIONS: Long-term exposure to air pollution increases the risk of CRS, particularly CRSwNP underscoring the need to prioritize clean air initiatives and environmental regulations.

A Lung Cancer Mouse Model Database.

Lung cancer, the leading cause of cancer mortality, exhibits diverse histological subtypes and genetic complexities. Numerous preclinical mouse models have been developed to study lung cancer, but data from these models are disparate, siloed, and difficult to compare in a centralized fashion. Here we established the Lung Cancer Mouse Model Database (LCMMDB), an extensive repository of 1,354 samples from 77 transcriptomic datasets covering 974 samples from genetically engineered mouse models (GEMMs), 368 samples from carcinogen-induced models, and 12 samples from a spontaneous model. Meticulous curation and collaboration with data depositors have produced a robust and comprehensive database, enhancing the fidelity of the genetic landscape it depicts. The LCMMDB aligns 859 tumors from GEMMs with human lung cancer mutations, enabling comparative analysis and revealing a pressing need to broaden the diversity of genetic aberrations modeled in GEMMs. Accompanying this resource, we developed a web application that offers researchers intuitive tools for in-depth gene expression analysis. With standardized reprocessing of gene expression data, the LCMMDB serves as a powerful platform for cross-study comparison and lays the groundwork for future research, aiming to bridge the gap between mouse models and human lung cancer for improved translational relevance.

Epigenetic Reprogramming Drives Epithelial Disruption in Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) remains a major public health challenge that contributes greatly to mortality and morbidity worldwide. Although it has long been recognized that the epithelium is altered in COPD, there has been little focus on targeting it to modify the disease course. Therefore, mechanisms that disrupt epithelial cell function in patients with COPD are poorly understood. In this study, we sought to determine whether epigenetic reprogramming of the cell-cell adhesion molecule E-cadherin, encoded by the CDH1 gene, disrupts epithelial integrity. By reducing these epigenetic marks, we can restore epithelial integrity and rescue alveolar airspace destruction. We used differentiated normal and COPD-derived primary human airway epithelial cells, genetically manipulated mouse tracheal epithelial cells, and mouse and human precision-cut lung slices to assess the effects of epigenetic reprogramming. We show that the loss of CDH1 in COPD is due to increased DNA methylation site at the CDH1 enhancer D through the downregulation of the ten-eleven translocase methylcytosine dioxygenase (TET) enzyme TET1. Increased DNA methylation at the enhancer D region decreases the enrichment of RNA polymerase II binding. Remarkably, treatment of human precision-cut slices derived from patients with COPD with the DNA demethylation agent 5-aza-2'-deoxycytidine decreased cell damage and reduced air space enlargement in the diseased tissue. Here, we present a novel mechanism that targets epigenetic modifications to reverse the tissue remodeling in human COPD lungs and serves as a proof of concept for developing a disease-modifying target.

Subchronic exposure to ambient PM 2.5 impairs novelty recognition and spatial memory.

Air pollution remains a great challenge for public health, with the detrimental effects of air pollution on cardiovascular, rhinosinusitis, and pulmonary health increasingly well understood. Recent epidemiological associations point to the adverse effects of air pollution on cognitive decline and neurodegenerative diseases. Mouse models of subchronic exposure to PM 2.5 (ambient air particulate matter < 2.5 µm) provide an opportunity to demonstrate the causality of target diseases. Here, we subchronically exposed mice to concentrated ambient PM 2.5 for 7 weeks (5 days/week; 8h/day) and assessed its effect on behavior using standard tests measuring cognition or anxiety-like behaviors. Average daily PM 2.5 concentration was 200 µg/m 3 in the PM 2.5 group and 10 µg/m 3 in the filtered air group. The novel object recognition (NOR) test was used to assess the effect of PM 2.5 exposure on recognition memory. The increase in exploration time for a novel object versus a familiarized object was lower for PM 2.5 -exposed mice (42% increase) compared to the filtered air (FA) control group (110% increase). In addition, the calculated discrimination index for novel object recognition was significantly higher in FA mice (67 %) compared to PM 2.5 exposed mice (57.3%). The object location test (OLT) was used to examine the effect of PM 2.5 exposure on spatial memory. In contrast to the FA-exposed control mice, the PM 2.5 exposed mice exhibited no significant increase in their exploration time between novel location versus familiarized location indicating their deficit in spatial memory. Furthermore, the discrimination index for novel location was significantly higher in FA mice (62.6%) compared to PM 2.5 exposed mice (51%). Overall, our results demonstrate that subchronic exposure to higher levels of PM 2.5 in mice causes impairment of novelty recognition and spatial memory.

SARS-CoV-2 infection alters mitochondrial and cytoskeletal function in human respiratory epithelial cells mediated by expression of spike protein.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, SCV2), which has resulted in higher morbidity and mortality rate than other respiratory viral infections, such as Influenza A virus (IAV) infection. Investigating the molecular mechanisms of SCV2-host infection vs IAV is vital in exploring antiviral drug targets against SCV2. We assessed differential gene expression in human nasal cells upon SCV2 or IAV infection using RNA sequencing. Compared to IAV, we observed alterations in both metabolic and cytoskeletal pathways suggestive of epithelial remodeling in the SCV2-infected cells, reminiscent of pathways activated as a response to chronic injury. We found that spike protein interaction with the epithelium was sufficient to instigate these epithelial responses using a SCV2 spike pseudovirus. Specifically, we found downregulation of the mitochondrial markers SIRT3 and TOMM22. Moreover, SCV2 spike infection increased extracellular acidification and decreased oxygen consumption rate in the epithelium. In addition, we observed cytoskeletal rearrangements with a reduction in the actin-severing protein cofilin-1 and an increase in polymerized actin, indicating epithelial cytoskeletal rearrangements. This study revealed distinct epithelial responses to SCV2 infection, with early mitochondrial dysfunction in the host cells and evidence of cytoskeletal remodeling that could contribute to the worsened outcome in COVID-19 patients compared to IAV patients. These changes in cell structure and energetics could contribute to cellular resilience early during infection, allowing for prolonged cell survival and potentially paving the way for more chronic symptoms. IMPORTANCE COVID-19 has caused a global pandemic affecting millions of people worldwide, resulting in a higher mortality rate and concerns of more persistent symptoms compared to influenza A. To study this, we compare lung epithelial responses to both viruses. Interestingly, we found that in response to SARS-CoV-2 infection, the cellular energetics changed and there were cell structural rearrangements. These changes in cell structure could lead to prolonged epithelial cell survival, even in the face of not working well, potentially contributing to the development of chronic symptoms. In summary, these findings represent strategies utilized by the cell to survive the infection but result in a fundamental shift in the epithelial phenotype, with potential long-term consequences, which could set the stage for the development of chronic lung disease or long COVID-19.

Examining the association of habitual e-cigarette use with inflammation and endothelial dysfunction in young adults: The VAPORS-Endothelial function study.

INTRODUCTION: Acute exposure to e-cigarette aerosol has been shown to have potentially deleterious effects on the cardiovascular system. However, the cardiovascular effects of habitual e-cigarette use have not been fully elucidated. Therefore, we aimed to assess the association of habitual e-cigarette use with endothelial dysfunction and inflammation - subclinical markers known to be associated with increased cardiovascular risk. METHODS: In this cross-sectional study, we analyzed data from 46 participants (23 exclusive e-cigarette users; 23 non-users) enrolled in the VAPORS-Endothelial function study. E-cigarette users had used e-cigarettes for ≥6 consecutive months. Non-users had used e-cigarettes <5 times and had a negative urine cotinine test (<30 ng/mL). Flow-mediated dilation (FMD) and reactive hyperemia index (RHI) were used to assess endothelial dysfunction, and we assayed high-sensitivity C-reactive protein, interleukin-6, fibrinogen, p-selectin, and myeloperoxidase as serum measures of inflammation. We used multivariable linear regression to assess the association of e-cigarette use with the markers of endothelial dysfunction and inflammation. RESULTS: Of the 46 participants with mean age of 24.3 ± 4.0 years, the majority were males (78%), non-Hispanic (89%), and White (59%). Among non-users, 6 had cotinine levels <10 ng/mL while 17 had levels 10-30 ng/mL. Conversely, among e-cigarette users, the majority (14 of 23) had cotinine ≥500 ng/mL. At baseline, the systolic blood pressure was higher among e-cigarette users than non-users (p=0.011). The mean FMD was slightly lower among e-cigarette users (6.32%) compared to non-users (6.53%). However, in the adjusted analysis, current e-cigarette users did not differ significantly from non-users in their mean FMD (Coefficient=2.05; 95% CI: -2.52-6.63) or RHI (Coefficient= -0.20; 95% CI: -0.88-0.49). Similarly, the levels of inflammatory markers were generally low and did not differ between e-cigarette users and non-users. CONCLUSIONS: Our findings suggest that e-cigarette use may not be significantly associated with endothelial dysfunction and systemic inflammation in relatively young and healthy individuals. Longer term studies with larger sample sizes are needed to validate these findings.

The mediating roles of the oral microbiome in saliva and subgingival sites between e-cigarette smoking and gingival inflammation.

BACKGROUND: Electronic cigarettes (ECs) have been widely used by young individuals in the U.S. while being considered less harmful than conventional tobacco cigarettes. However, ECs have increasingly been regarded as a health risk, producing detrimental chemicals that may cause, combined with poor oral hygiene, substantial inflammation in gingival and subgingival sites. In this paper, we first report that EC smoking significantly increases the odds of gingival inflammation. Then, through mediation analysis, we seek to identify and explain the mechanism that underlies the relationship between EC smoking and gingival inflammation via the oral microbiome. METHODS: We collected saliva and subgingival samples from 75 EC users and 75 non-users between 18 and 34 years in age and profiled their microbial compositions via 16S rRNA amplicon sequencing. We conducted raw sequence data processing, denoising and taxonomic annotations using QIIME2 based on the expanded human oral microbiome database (eHOMD). We then created functional annotations (i.e., KEGG pathways) using PICRUSt2. RESULTS: We found significant increases in α-diversity for EC users and disparities in ß-diversity between EC users and non-users. We also found significant disparities between EC users and non-users in the relative abundance of 36 microbial taxa in the saliva site and 71 microbial taxa in the subgingival site. Finally, we found that 1 microbial taxon in the saliva site and 18 microbial taxa in the subgingival site significantly mediated the effects of EC smoking on gingival inflammation. The mediators on the genus level, for example, include Actinomyces, Rothia, Neisseria, and Enterococcus in the subgingival site. In addition, we report significant disparities between EC users and non-users in the relative abundance of 71 KEGG pathways in the subgingival site. CONCLUSIONS: These findings reveal that continued EC use can further increase microbial dysbiosis that may lead to periodontal disease. Our findings also suggest that continued surveillance for the effect of ECs on the oral microbiome and its transmission to oral diseases is needed.

Socioeconomic disparity in the association between fine particulate matter exposure and papillary thyroid cancer.

BACKGROUND: Limited data exists suggesting that cumulative exposure to air pollution in the form of fine particulate matter (aerodynamic diameter ≤ 2.5 µm [PM2.5]) may be associated with papillary thyroid carcinoma (PTC), although this relationship has not been widely established. This study aims to evaluate the association between PM2.5 and PTC and determine the subgroups of patients who are at the highest risk of PTC diagnosis. METHODS: Under IRB approval, we conducted a case-control study of adult patients (age ≥ 18) newly diagnosed with PTC between 1/2013-12/2016 across a single health care system were identified using electronic medical records. These patients were compared to a control group of patients without any evidence of thyroid disease. Cumulative PM2.5 exposure was calculated for each patient using a deep learning neural networks model, which incorporated meteorological and satellite-based measurements at the patients' residential zip code. Adjusted multivariate logistic regression was used to quantify the association between cumulative PM2.5 exposure and PTC diagnosis. We tested whether this association differed by gender, race, BMI, smoking history, current alcohol use, and median household income. RESULTS: A cohort of 1990 patients with PTC and a control group of 6919 patients without thyroid disease were identified. Compared to the control group, patients with PTC were more likely to be older (51.2 vs. 48.8 years), female (75.5% vs 46.8%), White (75.2% vs. 61.6%), and never smokers (71.1% vs. 58.4%) (p < 0.001). After adjusting for age, sex, race, BMI, current alcohol use, median household income, current smoking status, hypertension, diabetes, COPD, and asthma, 3-year cumulative PM2.5 exposure was associated with a 1.41-fold increased odds of PTC diagnosis (95%CI: 1.23-1.62). This association varied by median household income (p-interaction =0.03). Compared to those with a median annual household income <$50,000, patients with a median annual household income between $50,000 and < $100,000 had a 43% increased risk of PTC diagnosis (aOR = 1.43, 95%CI: 1.19-1.72), and patients with median household income ≥$100,000 had a 77% increased risk of PTC diagnosis (aOR = 1.77, 95%CI: 1.37-2.29). CONCLUSIONS: Cumulative exposure to PM2.5 over 3 years was significantly associated with the diagnosis of PTC. This association was most pronounced in those with a high median household income, suggesting a difference in access to care among socioeconomic groups.

Association between temperature variability and global meningitis incidence.

BACKGROUND: Meningitis can cause devastating epidemics and is susceptible to climate change. It is unclear how temperature variability, an indicator of climate change, is associated with meningitis incidence. METHODS: We used global meningitis incidence data along with meteorological and demographic data over 1990-2019 to identify the association between temperature variability and meningitis. We also employed future (2020-2100) climate data to predict meningitis incidence under different emission levels (SSPs: Shared Socioeconomic Pathways). RESULTS: We found that the mean temperature variability increased by almost 3 folds in the past 30 years. The largest changes occurred in Australasia, Tropical Latin America, and Central Sub-Saharan Africa. With a logarithmic unit increase in temperature variability, the overall global meningitis risk increases by 4.8 %. Australasia, Central Sub-Saharan Africa, and High-income North America are the most at-risk regions. Higher statistical differences were identified in males, children, and the elderly population. Compared to high-emission (SSP585) scenario, we predicted a median reduction of 85.8 % in meningitis incidence globally under the low-emission (SSP126) climate change scenario by 2100. CONCLUSION: Our study provides evidence for temperature variability being in association with meningitis incidence, which suggests that global actions are urgently needed to address climate change and to prevent meningitis occurrence.

Loss of E-cadherin is causal to pathologic changes in chronic lung disease.

Epithelial cells line the lung mucosal surface and are the first line of defense against toxic exposures to environmental insults, and their integrity is critical to lung health. An early finding in the lung epithelium of patients with chronic obstructive pulmonary disease (COPD) is the loss of a key component of the adherens junction protein called E-cadherin. The cause of this decrease is not known and could be due to luminal insults or structural changes in the small airways. Irrespective, it is unknown whether the loss of E-cadherin is a marker or a driver of disease. Here we report that loss of E-cadherin is causal to the development of chronic lung disease. Using cell-type-specific promoters, we find that knockout of E-cadherin in alveolar epithelial type II but not type 1 cells in adult mouse models results in airspace enlargement. Furthermore, the knockout of E-cadherin in airway ciliated cells, but not club cells, increase airway hyperreactivity. We demonstrate that strategies to upregulate E-cadherin rescue monolayer integrity and serve as a potential therapeutic target.

The Association Between E-Cigarette Use and Prediabetes: Results From the Behavioral Risk Factor Surveillance System, 2016-2018.

INTRODUCTION: Both E-cigarette use and the prevalence of prediabetes have risen dramatically in the past decade. It is crucial to understand whether E-cigarette use is associated with the risk of prediabetes. METHODS: Participants who completed the prediabetes and E-cigarette modules of the Behavioral Risk Factor Surveillance System survey (2016-2018) were included in this study. E-cigarette use information was collected by asking: Have you ever used an e-cigarette or other electronic "vaping" product, even just one time, in your entire life? We defined sole E-cigarette users as current E-cigarette users who are never combustible-cigarette users, and dual users were defined as both current E-cigarette and combustible-cigarette users. Participants with prediabetes were identified by asking: Ever been told by a doctor or other health professional that you have prediabetes or borderline diabetes? Multivariable logistic regression was used to determine the association between E-cigarette use and prediabetes. RESULTS: Among the 600,046 respondents, 28.6% of respondents were aged <35 years. The prevalence of prediabetes among current E-cigarette, sole E-cigarette users, and dual users was 9.0% (95% CI=8.6, 9.4), 5.9% (95% CI=5.3, 6.5), and 10.2% (95% CI=9.8, 10.7), respectively. In the fully adjusted model, the ORs for prediabetes were 1.22 (95% CI=1.10, 1.37) for current E-cigarette users and 1.12 (95% CI=1.05, 1.19) for former E-cigarette users compared with that of never E-cigarette users. The ORs for prediabetes were 1.54 (95% CI=1.17, 2.04) for sole E-cigarette users and 1.14 (95% CI=0.97, 1.34) for dual users. CONCLUSIONS: In this representative sample of U.S. adults, E-cigarette use was associated with greater odds of prediabetes. The results were consistent in sole E-cigarette users.

Nrf2 Regulates ß-Cell Mass by Suppressing ß-Cell Death and Promoting ß-Cell Proliferation.

Finding therapies that can protect and expand functional ß-cell mass is a major goal of diabetes research. Here, we generated ß-cell-specific conditional knockout and gain-of-function mouse models and used human islet transplant experiments to examine how manipulating Nrf2 levels affects ß-cell survival, proliferation, and mass. Depletion of Nrf2 in ß-cells results in decreased glucose-stimulated ß-cell proliferation ex vivo and decreased adaptive ß-cell proliferation and ß-cell mass expansion after a high-fat diet in vivo. Nrf2 protects ß-cells from apoptosis after a high-fat diet. Nrf2 loss of function decreases Pdx1 abundance and insulin content. Activating Nrf2 in a ß-cell-specific manner increases ß-cell proliferation and mass and improves glucose tolerance. Human islets transplanted under the kidney capsule of immunocompromised mice and treated systemically with bardoxolone methyl, an Nrf2 activator, display increased ß-cell proliferation. Thus, by managing reactive oxygen species levels, Nrf2 regulates ß-cell mass and is an exciting therapeutic target for expanding and protecting ß-cell mass in diabetes.

Air Pollution Exposure and the Development of Chronic Rhinosinusitis in the Active Duty Population.

INTRODUCTION: It has been shown that combat environment exposure, including burn pits that produce particulate matter 2.5 (PM2.5), is associated with lower respiratory tract disease in the military population with increased hypothetical risk of upper respiratory disease, but no study has been done that examines the effects of non-combat environmental exposures on the development of chronic rhinosinusitis (CRS) in the active duty population. The primary goal of this study is to evaluate how air pollution exposure correlates to the development of CRS in active duty service members in the United States. METHODS: The military electronic medical record was queried for active duty service members diagnosed with CRS by an otolaryngologist between January 2016 and January 2018, who have never deployed, stationed in the United States from 2015 to 2018 (n = 399). For each subject, the 1-year mean exposure of PM2.5, particulate matter 10 (PM10), nitrogen dioxide (NO2), and ozone was calculated. The control group was comprised of the same criteria except these patients were diagnosed with cerumen impaction and matched to the case group by age and gender (n = 399). Pollution exposure was calculated based on the Environmental Protection Agency's data tables for each subject. Values were calculated using chi-square test for categorical variables and the Mann-Whitney U-test for continuous variables. RESULTS: Matched cases and controls (n = 399) with 33.1% male showed a statistically significant odds ratio (OR) of 5.99 (95% CI, 2.55-14.03) for exposure of every 5 µg/m3 of PM2.5 increase and the development of CRS when controlling for age, gender, and diagnosis year. When further adjusting for smoking status, the OR was still statistically significant at 3.15 (95% CI, 1.03-9.68). Particulate matter 10, ozone, and NO2 did not show any statistical significance. Odds ratios remained statistically significant when further adjusting for PM10 and ozone, but not NO2. Dose-dependent curves largely did not show a statistical significance; however, they did trend towards increased exposure of PM2.5 leading to an elevated OR. CONCLUSION: This study showed that PM2.5 exposure is a major independent contributor to the development of CRS. Exposure to elevated levels produced statistically significant odds even among smokers and remained significant when controlling for other measured pollutants. There is still much to be understood about the genesis of CRS. From a pollution exposure perspective, a prospective cohort study would better elucidate the risk of the development of CRS among those exposed to other pollutants.

Ambient particulate matter air pollution is associated with increased risk of papillary thyroid cancer.

BACKGROUND: The association between exposure to air pollution and papillary thyroid carcinoma is unknown. We sought to estimate the relationship between long-term exposure to the fine (diameter ≤ 2.5 µm) particulate matter component of air pollution and the risk of papillary thyroid cancer. METHODS: Adult (age ≥18) patients with newly diagnosed papillary thyroid carcinoma between January 1, 2013 and December 31, 2016 across a single health system were identified using electronic medical records. Data from 1,990 patients with papillary thyroid carcinoma were compared with 3,980 age- and sex-matched control subjects without any evidence of thyroid disease. Cumulative fine (diameter <2.5 µm) particulate matter exposure was estimated by incorporating patients' residential zip codes into a deep learning neural networks model, which uses both meteorological and satellite-based measurements. Conditional logistic regression was performed to assess for association between papillary thyroid carcinoma and increasing fine (diameter ≤2.5 µm) particulate matter concentrations over 1, 2, and 3 years of cumulative exposure preceding papillary thyroid carcinoma diagnosis. RESULTS: Increased odds of developing papillary thyroid carcinoma was associated with a 5 µg/m3 increase of fine (diameter ≤2.5 µm) particulate matter concentrations over 2 years (adjusted odds ratio = 1.18, 95% confidence interval: 1.00-1.40) and 3 years (adjusted odds ratio = 1.23, 95% confidence interval: 1.05-1.44) of exposure. This risk differed by smoking status (pinteraction = 0.04). Among current smokers (n = 623), the risk of developing papillary thyroid carcinoma was highest (adjusted odds ratio = 1.35, 95% confidence interval: 1.12-1.63). CONCLUSION: Increasing concentration of fine (diameter ≤2.5 µm) particulate matter in air pollution is significantly associated with the incidence of papillary thyroid carcinoma with 2 and 3 years of exposure. Our novel findings provide additional insight into the potential associations between risk factors and papillary thyroid carcinoma and warrant further investigation, specifically in areas with high levels of air pollution both nationally and internationally.

Exposure to Particulate Matter Air Pollution and Anosmia.

Importance: Anosmia, the loss of the sense of smell, has profound implications for patient safety, well-being, and quality of life, and it is a predictor of patient frailty and mortality. Exposure to air pollution may be an olfactory insult that contributes to the development of anosmia. Objective: To investigate the association between long-term exposure to particulate matter (PM) with an aerodynamic diameter of no more than 2.5 µm (PM2.5) with anosmia. Design, Setting, and Participants: This case-control study examined individuals who presented from January 1, 2013, through December 31, 2016, at an academic medical center in Baltimore, Maryland. Case participants were diagnosed with anosmia by board-certified otolaryngologists. Control participants were selected using the nearest neighbor matching strategy for age, sex, race/ethnicity, and date of diagnosis. Data analysis was conducted from September 2020 to March 2021. Exposures: Ambient PM2.5 levels. Main Outcomes and Measures: Novel method to quantify ambient PM2.5 exposure levels in patients diagnosed with anosmia compared with matched control participants. Results: A total of 2690 patients were identified with a mean (SD) age of 55.3 (16.6) years. The case group included 538 patients with anosmia (20%), and the control group included 2152 matched control participants (80%). Most of the individuals in the case and control groups were women, White patients, had overweight (BMI 25 to <30), and did not smoke (women: 339 [63.0%] and 1355 [63.0%]; White patients: 318 [59.1%] and 1343 [62.4%]; had overweight: 179 [33.3%] and 653 [30.3%]; and did not smoke: 328 [61.0%] and 1248 [58.0%]). Mean (SD) exposure to PM2.5 was significantly higher in patients with anosmia compared with healthy control participants at 12-, 24-, 36-, 60-month time points: 10.2 (1.6) µg/m3 vs 9.9 (1.9) µg/m3; 10.5 (1.7) µg/m3 vs 10.2 (1.9) µg/m3; 10.8 (1.8) µg/m3 vs 10.4 (2.0) µg/m3; and 11.0 (1.8) µg/m3 vs 10.7 (2.1) µg/m3, respectively. There was an association between elevated PM2.5 exposure level and odds of anosmia in multivariate analyses that adjusted for age, sex, race/ethnicity, body mass index, alcohol or tobacco use, and medical comorbidities (12 mo: odds ratio [OR], 1.73; 95% CI, 1.28-2.33; 24 mo: OR, 1.72; 95% CI, 1.30-2.29; 36 mo: OR, 1.69; 95% CI, 1.30-2.19; and 60 mo: OR, 1.59; 95% CI, 1.22-2.08). The association between long-term exposure to PM2.5 and the odds of developing anosmia was nonlinear, as indicated by spline analysis. For example, for 12 months of exposure to PM2.5, the odds of developing anosmia at 6.0 µg/m3 was OR 0.79 (95% CI, 0.64-0.97); at 10.0 µg/m3, OR 1.42 (95% CI, 1.10-1.82); at 15.0 µg/m3, OR 2.03 (95% CI, 1.15-3.58). Conclusions and Relevance: In this study, long-term airborne exposure to PM2.5 was associated with anosmia. Ambient PM2.5 represents a potentially ubiquitous and modifiable risk factor for the loss of sense of smell.

Prenatal Environmental Metal Exposure and Preterm Birth: A Scoping Review.

Preterm birth (PTB) and its complications are the leading causes of under-five year old child deaths, accounting worldwide for an estimated one million deaths annually. The etiology of PTB is complex and multifactorial. Exposures to environmental metals or metalloids are pervasive and prenatal exposures to them are considered important in the etiology of PTB. We conducted a scoping review to determine the extent of prenatal exposures to four metals/metalloids (lead, mercury, cadmium and arsenic) and their association with PTB. We reviewed original research studies published in PubMed, Embase, the Cochrane Library, Scopus, POPLINE and the WHO regional indexes from 2000 to 2019; 36 articles were retained for full text review. We documented a higher incidence of PTB with lead and cadmium exposures. The findings for mercury and arsenic exposures were inconclusive. Metal-induced oxidative stress in the placenta, epigenetic modification, inflammation, and endocrine disruptions are the most common pathways through which heavy metals and metalloids affect placental functions leading to PTB. Most of the studies were from the high-income countries, reflecting the need for additional data from low-middle-income countries, where PTB rates are higher and prenatal exposure to metals are likely to be just as high, if not higher.