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.

Olfactory Impairment and the Risk of Major Adverse Cardiovascular Outcomes in Older Adults.

BACKGROUND: Olfactory impairment is common in older adults and may be associated with adverse cardiovascular health; however, empirical evidence is sparse. We examined olfaction in relation to the risk of coronary heart disease (CHD), stroke, and congestive heart failure (CHF). METHODS AND RESULTS: This study included 2537 older adults (aged 75.6±2.8 years) from the Health ABC (Health, Aging, and Body Composition) study with olfaction assessed by the 12-item Brief Smell Identification Test in 1999 to 2000, defined as poor (score ≤8), moderate (9-10), or good (11-12). The outcomes were incident CHD, stroke, and CHF. During up to a 12-year follow-up, 353 incident CHD, 258 stroke, and 477 CHF events were identified. Olfaction was statistically significantly associated with incident CHF, but not with CHD or stroke. After adjusting for demographics, risk factors, and biomarkers of CHF, the cause-specific hazard ratio (HR) of CHF was 1.32 (95% CI, 1.05-1.66) for moderate and 1.28 (95% CI, 1.01-1.64) for poor olfaction. These associations were robust in preplanned subgroup analyses by age, sex, race, and prevalent CHD/stroke. While the subgroup results were not statistically significantly different, the association of olfaction with CHF appeared to be evident among participants who reported very good to excellent health (HR, 1.47 [95% CI, 1.01-2.14] for moderate; and 1.76 [95% CI, 1.20-2.58] for poor olfaction), but not among those with fair to poor self-reported health (HR, 1.04 [95% CI, 0.64-1.70] for moderate; and 0.92 [95% CI, 0.58-1.47] for poor olfaction). CONCLUSIONS: In community-dwelling older adults, a single olfaction test was associated with a long-term risk for incident CHF, particularly among those reporting very good to excellent health.

Types of sensory disability are differentially associated with mental health in older US adults over time.

BACKGROUND: Sensory disability in older adults is associated with increased rates of depressive symptoms and loneliness. Here, we examined the impact of hearing, vision, and olfaction disability on mental health outcomes in older US adults. METHODS: We studied respondents from the first three rounds (2005/6, 2010/11, and 2015/16) of the National Social Life, Health and Aging Project, a nationally representative, longitudinal study of older US adults. Sensory function was assessed by structured interviewer ratings (hearing and vision) and objective assessment (olfaction). Cox proportional hazards models and one degree of freedom tests for trend were utilized to analyze the relationships between sensory disability and self-rated mental health, frequent depressive symptoms, frequent perceived stress, frequent anxiety symptoms, and frequent loneliness symptoms over time, adjusting for demographics, health behaviors, comorbidities, and cognitive function. RESULTS: We analyzed data from 3940 respondents over 10 years of follow-up. A greater number of sensory disabilities was associated with greater hazard of low self-rated mental health, frequent depressive symptoms, frequent perceived stress, and frequent loneliness symptoms over time (p ≤ 0.003, all). After adjusting for covariates, older adults with a greater number of sensory disabilities had greater hazard of low self-rated mental health (HR = 1.22, CI = [1.08, 1.38], p = 0.002) and loneliness symptoms (HR = 1.13, CI = [1.05, 1.22], p = 0.003) over time in our tests for trend. In our Cox proportional hazards model, older adults with vision disability had greater hazard of low self-rated mental health (HR = 1.34, 95% CI = [1.05, 1.72], p = 0.02) and loneliness symptoms (HR = 1.21, CI = [1.04, 1.41], p = 0.01). CONCLUSIONS: Older US adults with greater numbers of sensory disabilities face worse subsequent mental health. Future longitudinal studies dissecting the relationship of all five classical senses will be helpful in further understanding how improving sensory function might improve mental health in older adults.

Synthesized novel chromogenic reagent and sensor: Detection and identification of dichlorvos.

We developed a novel chromogenic reagent and sensor by selective approach, for the detection and identification of dichlorvos, which we tested with the thin layer chromatography method. For the first time, we reported in situ-generated glyoxal as a hydrolysis product, which then interacts with isoniazid to produce a yellow-colored cyclic compound. We used well-known spectroscopic techniques to confirm the chemical identity of the final product. We initially investigated the reaction using a variety of approaches, followed by attempts to establish the reaction mechanism using Density Functional Theory by Gaussian software.

Oral cancer incidence rate is associated with access to dental care: City and statewide analyses.

INTRODUCTION: Access to dental care may affect diagnosis of oral squamous cell carcinoma (OSCC). We tested whether the incidence rate of OSCC is higher in regions with less dental care access in the city of Chicago and state of Illinois. STUDY DESIGN: Ecological cohort. SETTING: Population, outpatients, and inpatients. METHODS: We extracted 5-year averages of the state-wide county-level and city-level OSCC incidence rates from 2015 to 2019 from the Illinois Department of Public Health. Dental care access information was also collected for each county for the same period, as well as the percentage of people that had ≥1 visit to a dentist in the previous year in Chicago. Multivariate Poisson regression was used to investigate the relationship between county-level access to dental care (and city-level dentist visits) and OSCC incidence rate, controlling for confounders, with additional flexible semiparametric models for confirmatory sensitivity analysis. RESULTS: In Illinois, higher 5-year incidence rate of OSCC was significantly associated with low access to dental care by county (IRR = 0.96, 95% CI 0.91, 0.98). Southern/southwestern counties had higher incidence rates of OSCC (15.5%-28.4%) and the lowest rates of dental care access (47.5%-69.2%) compared to northern counties (10.3%-15% and 55.4%-80.6%, respectively). In Chicago, people with more dentist visits had a reduced chance of being diagnosed with OSCC (IRR = 0.97, 95% CI 0.91, 0.99), consistent with state-wide analyses. CONCLUSION: OSCC incidence rate is closely associated with poor local dental healthcare access in a major state and urban city. Increasing dental access could improve cancer outcomes via improved oral health and earlier detection.

Examining the Longitudinal Relationship Between Olfactory Dysfunction and Frailty in Community-Dwelling, older US Adults.

OBJECTIVE: Olfactory dysfunction is a "canary in the coalmine" for aging conditions. We evaluated olfactory dysfunction as a biomarker of early frailty in older adults living in the United States. STUDY DESIGN: Prospective, longitudinal, nationally representative study. SETTING: National Social Life, Health and Aging Project (NSHAP). METHODS: We examined data from 1061 community-dwelling older US adults. Odor identification (5-item Sniffin' Stick) and frailty scores were measured at baseline and 5-year follow-up. Multivariate logistic regressions evaluated the association between olfactory dysfunction and frailty at baseline in cross-section and over time in the transition from robust to prefrail to frail, adjusting for confounding factors measured at baseline. RESULTS: Older US adults who were anosmic at baseline were more likely to be frail 5 years later compared to normosmic peers (odds ratio [OR]: 3.83, 95% confidence interval [CI]: 1.10-13.31, P = .035). Examining changes in frailty stage over time, we found that anosmics were more likely to transition from prefrail to frail over 5 years (OR: 3.25, 95% CI: 1.31-8.08, P = .011). Interestingly, hyposmics did not show a similar trajectory toward frailty (P > .05). In contrast, olfactory dysfunction was not associated with frailty in cross-section (OR: 0.90, 95% CI: 0.43-1.89, P = .787, hyposmia; OR: 0.72, 95% CI: 0.15-3.35, P = .673, anosmia). CONCLUSION: Older US adults with anosmia face higher odds of becoming frail over 5 years, especially those in the prefrail stage. Olfactory dysfunction may serve as a surrogate marker for early-stage neurodegenerative diseases, which are strong contributors to frailty.

A Social Media Quality Review of Popular Sinusitis Videos on TikTok.

OBJECTIVE: Social media may inform health care decisions among younger patient populations. TikTok is a social media platform that allows users to post short-form videos. This study aimed to assess the quality of sinusitis-related videos on TikTok. STUDY DESIGN: We searched TikTok on January 29, 2023, for sinusitis-related hashtags: #sinusitis, #sinus, #sinusinfection. SETTING: Internet. METHODS: The number of views/shares per day, uploader type (nonmedical influencer, lay individual, and medical professional) content categories (medical advice, marketing, comedy, and lifestyle/acceptability), and content type (educational vs factual) were collected. The Patient Education Materials Assessment Tool for Audiovisual Material and Journal of the American Medical Association criteria score was used to measure understandability, actionability, and reliability. The Global Quality Scale (GQS) was used to evaluate the quality of videos; the harm/benefit score was used to evaluate causative effects. Analyses were performed using analysis of variance (α = .05). RESULTS: There were 221 videos identified, which garnered over 300 million views and 1 million shares. Almost half of the videos were published by nonmedical influencers. When controlling for covariates, nonmedical influencers and lay uploaders were more likely to have harmful harm/benefit scores, less understandable videos, and lower GQS scores compared to medical professionals. Less than half of videos posted by nonmedical influencers categorized as educational were factual (46.7%); lay individuals and medical professionals had higher rates of factual educational content (79.9% and 83.7%, respectively). CONCLUSION: Most nonmedical influencer-posted TikTok videos about sinusitis are inaccurate, despite being portrayed as medical advice/educational. Rhinologists must find modern ways to disseminate true disease-related content via social media to combat medical misinformation.

Impact of social determinants of health on access to rhinology care and patient outcomes: A pilot study.

Objective: This novel pilot study constructs a social deprivation index (SDI) and utilizes an area deprivation index (ADI) to evaluate the link between social determinants of health and rhinology patient experiences. Methods: Adult patients undergoing outpatient care of chronic rhinitis and chronic rhinosinusitis at a tertiary academic medical center were recruited to participate in a telephone survey assessing symptoms, social/emotional consequences of disease, and barriers to care on a 5-point Likert scale. Sociodemographic characteristics were utilized to rate SDI on an 8-point scale. ADI was obtained by area code of residence. Ordered logistic regression was used to examine associations between the SDI/ADI and perceptions of rhinology care. Results: Fifty patients were included. Individuals with higher SDI scores (i.e., more socially deprived) experienced more severe nasal congestion (p = .007). Furthermore, higher national ADI correlated with increased severity of smell changes (p = .050) and facial pressure (p = .067). No association was seen between either deprivation index and global/psychiatric symptoms. While no correlations were found between higher SDI and difficulties with the costs of prescriptions, rhinologist's visits, or saline, higher SDI was correlated with decreased difficulty with surgery costs (p = .029), and individuals with higher national ADI percentile had increased difficulties obtaining nasal saline (p = .029). Conclusion: Worse social deprivation is associated with difficulties obtaining saline rinses and increased severity of nasal/sinus symptoms in an urban, underserved, majority-Black population. These findings suggest social factors affect access to and quality of rhinology care in a complex and nuanced way and highlight the need for a specific SDI to further study social determinants of health in rhinology. Level of Evidence: 2c.

Air pollution is associated with increased incidence-rate of head and neck cancers: A nationally representative ecological study.

INTRODUCTION: Early studies show conflicting findings regarding particulate matter ≤ 2.5 µm in diameter (PM2.5) exposure and development of head and neck cancers (HNC). We analyzed the relationship between PM2.5 exposure and various types of HNC in a nationally representative ecological sample. METHODS: We determined HNC incidence in 608 US counties from 2011 to 2019 using the Surveillance, Epidemiology and End Results (SEER) Program from the National Cancer Institute. We also collected information on sociodemographic factors from SEER and data on smoking and alcohol intake from CDC data frames (county level). PM2.5 exposure levels were estimated using satellite and meteorological data via previously validated general additive models. Flexible semi-nonparametric regression models were used to test the relationship between PM2.5 exposure levels and HNC incidence, adjusting for demographics, socioeconomic factors, and comorbidity. RESULTS: Increased PM2.5 exposure levels were associated with higher incidence-rates of oral cavity and pharyngeal cancers controlling for confounders in our primary analyses (IRR = 1.04, 95 % CI 1.01, 1.07, p = 0.02 per 1 µg/m3 increase in PM2.5). This relationship was maintained after adjusting for multiple testing (Holm s method, p = 0.04) and in ordinary least squares (OLS) regression (ß = 0.17, 95 % CI 0.01, 0.57, p = 0.01). Increased exposure was also associated with other HNC: esophagus (IRR = 1.06, 95 % CI 1.01, 1.11, p = 0.02), lip (IRR = 1.16, 95 % CI 1.03, 1.31, p = 0.01), tonsil (IRR = 1.10, 95 % CI 1.03, 1.16, p < 0.01). However, these relationships were not maintained in secondary analyses. CONCLUSIONS: This nationally representative ecological study shows that increased levels of air pollution are associated with increased incidence of overall oral cavity and pharyngeal cancers in the US.

Sensory Health Among Older Adults in the United States: A Neighborhood Context Approach.

OBJECTIVES: Sensory health declines with age but remains critical to the navigation and enjoyment of everyday life. Neighborhoods are key sites of environmental exposure, social engagement, and access to resources that can shape sensory health, yet the residential neighborhood is understudied as a determinant of sensory function. METHODS: We use data from Rounds 1 and 2 of the National Social Life, Health, and Aging Project to examine how subjective and objective measures of older adults' residential areas are associated with sensory health in a series of cross-sectional and multilevel regression models. RESULTS: In cross-sectional models, higher levels of perceived neighborhood social ties are associated with significantly better self-rated vision. Older adults who reside in more densely populated tracts are more likely to have significantly worse olfactory identification, whereas residing in tracts with higher levels of concentrated disadvantage is associated with significantly lower levels of self-rated vision. In multilevel models, residing in more densely populated tracts is associated with significantly worse olfactory identification, whereas tract-level concentrated disadvantage is associated with significantly worse hearing and vision. DISCUSSION: We propose that neighborhood characteristics could influence certain environmental exposures, the amount of time that older adults spend out of the home, patterns of social engagement, and access to preventative care that collectively affect sensory health. Residential neighborhoods may be important sites of potential intervention to slow age-related sensory declines and other related conditions.

Use of nonsteroidal anti-inflammatory drugs and poor olfaction in women.

BACKGROUND: It is unclear whether regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with poor olfaction in older adults. METHODS: We selected 4020 participants, aged 50 to 79 years in 2018, from 36,492 eligible participants in the National Institute of Environmental Health Sciences Sister Study, according to their self-reported olfaction status. Of these, 3406 women completed the 12-item Brief Smell Identification Test. We defined poor olfaction as a test score ≤9 in the primary analysis. We then estimated odds ratios (ORs) and 95% confidence intervals (CIs) from weighted logistic models, accounting for the study design, missing exposures/outcomes, and covariates. RESULTS: Overall, NSAID use was not associated with poor olfaction. However, we found evidence for potential multiplicative interactions. Specifically, the OR comparing regular versus never use of aspirin was 1.8 (95% CI, 1.1-3.2) among women who had not regularly used nonaspirin NSAIDs, while the corresponding OR was 0.8 (95% CI, 0.5-1.2) among nonaspirin NSAID users (P for interaction = 0.016). Similar results were seen for ibuprofen alone versus ibuprofen with other NSAID use (P for interaction = 0.010). Among women using either drug alone, associations with poor olfaction increased with increasing duration and cumulative dose. Post hoc analyses showed that the interactions could not be readily explained by potential biases. Other NSAIDs were not associated with olfaction. CONCLUSION: Long-term regular use of aspirin or ibuprofen was associated with poor olfaction among women who never regularly used other types of NSAIDs. These preliminary findings warrant independent confirmation.

Air pollution exposure is associated with rhinitis in older US adults via specific immune mechanisms.

BACKGROUND: Pathophysiology of rhinitis in older adults is largely unknown. We tested whether air pollution is associated with this condition and how immune mechanisms may play a role in this relationship. METHODS: We analyzed cross-sectional data from the National Social Life, Health, and Aging Project, a nationally representative study of older adults born between 1920 and 1947. Particulate matter ≤2.5 µm (PM2.5 ) air pollution exposure estimates were generated using validated spatiotemporal models. Presence of rhinitis was defined based on medication use (≥1: intranasal medications: steroids, antihistamines, lubricants, and/or decongestants, and/or oral medications: antihistamines and/or decongestants). K-means cluster analysis (Jaccard method) was used to group 13 peripheral blood cytokines into 3 clusters to facilitate functional determination. We fitted multivariate logistic regressions to correlate PM2.5 exposure with presence of rhinitis, controlling for confounders, and then determined the role of cytokines in this relationship. RESULTS: Long- (but not short-) term exposure to PM2.5 was associated with presence of rhinitis: 3-year exposure window, odds ratio (OR) = 1.32, 95% confidence interval (CI): 0.98, 1.80, per 1 standard deviation (SD) PM2.5 increase. Inclusion of cytokine cluster in the model led to a modestly stronger effect of PM2.5 exposure on rhinitis (OR = 1.37; 95% CI: 1.00, 1.87; 3-year exposure window). The particular immune profile responsible for this result was composed of elevated IL-3, IL-12, and IFN-γ (OR = 4.86, 95% CI: 1.10, 21.58, immune profile-PM2.5 exposure interaction term). CONCLUSION: We show for the first time that IL-3, IL-12, and IFN-γ explain in part the relationship between PM2.5 exposure and rhinitis in older US adults. If confirmed, these immune pathways may be used as therapeutic targets.

Copper-mediated [3 + 2] oxidative cyclization of oxime acetate and its utility in the formal synthesis of fentiazac.

A new protocol for the direct synthesis of 2-aminothiazole has been developed from oxime acetate and readily available sodium thiocyanate using a copper catalyst. The present transformation has good functional group tolerance. Various thiazoles were smoothly synthesized in good to excellent yields. The applicability of the present method has been extended to the formal synthesis of the non-steroidal and anti-inflammatory drug, fentiazac via the Sandmeyer reaction and Suzuki coupling.

Olfactory decline develops in parallel with frailty in older US adults with obstructive lung diseases.

BACKGROUND: Frailty is prevalent among older adults with asthma or chronic obstructive pulmonary disease (obstructive lung diseases [OLDs]). Frailty and OLD's co-occurrence is associated with increased hospitalization/mortality. Chemosensory dysfunction is closely connected to both OLD and frailty. We evaluated the utility of olfactory decline as a biomarker of frailty in the setting of OLD. METHODS: We performed a prospective, longitudinal, nationally representative study of community-dwelling older US adults in the National Social Life, Health and Aging Project, an omnibus in-home survey. Respondents reported a physician's diagnosis of OLD. Decline in odor identification and sensitivity over 5 years and frailty (adapted fried frailty phenotype criteria) were measured using standard tools. Multivariate logistic regressions evaluated the association between OLD status, olfactory decline, and frailty. RESULTS: We compared individuals with OLD (n = 98; mean age 71.2 years, 59.2% women) and those without OLD (n = 1036; mean age 69.5 years, 58.9% women). Olfactory identification decline was associated with developing frailty over the 5-year follow-up period in individuals with OLD (odds ratio [OR] = 9.1, 95% confidence interval [CI] = 2.1-38.6, p = 0.003). Olfactory decline predicted incidence of frailty in individuals with OLD (identification: OR = 4.8, 95% CI = 1.3-17.5, P = 0.018; sensitivity: OR = 6.1, 95%CI = 1.2-31.0, p = 0.030) but not in those without OLD adjusting for demographics, heavy alcohol use, current smoking, and comorbidity. Results were robust to different thresholds for olfactory decline and frailty development. CONCLUSIONS: Older adults with OLD who experience olfactory decline face higher odds of developing frailty. Use of olfactory decline as a biomarker to identify frailty could allow earlier intervention and decrease adverse outcomes for high-risk older adults with OLD.

Olfactory impairment and the risk of major adverse cardiovascular outcomes in older adults.

Background: Olfactory impairment is common in older adults and may be associated with adverse cardiovascular health; however, empirical evidence is sparse. Objective: To examine olfaction and the risk of coronary heart disease (CHD), stroke, and congestive heart failure (CHF). Methods: This study included 2,537 older adults (aged 75.6±2.8 years) from the Health ABC Study with olfaction assessed by the 12-item Brief Smell Identification Test in 1999-2000, defined as poor (score ≤8), moderate (9-10), or good (11-12). The outcomes were incident CHD, stroke, and CHF. Results: During up to 12-year follow-up, 353 incident CHD, 258 stroke, and 477 CHF events were identified. Olfaction was associated with incident CHF, but not with CHD or stroke. After adjusting for demographics, the cause-specific hazard ratio (HR) of CHF was 1.35 (95% confidence interval (CI): 1.08, 1.70) for moderate and 1.39 (95%CI: 1.09, 1.76) for poor olfaction. With additional adjustment for lifestyle, chronic diseases, and biomarkers of CHF, the HR was modestly attenuated to 1.32 (95%CI: 1.05, 1.66) for moderate and 1.28 (95%CI: 1.01, 1.64) for poor olfaction. These associations were robust in pre-planned subgroup analyses by age, sex, race, and prevalent CHD/stroke. However, the associations appeared to be evident among participants who reported very-good-to-excellent health (HR=1.47 (95%CI: 1.02, 2.13) for moderate and 1.76, (95%CI: 1.20, 2.57) for poor olfaction). In contrast, null association with CHF was found among those with fair-to-poor self-reported health. Conclusions: In community-dwelling older adults, a single olfaction test was associated with a long-term risk for incident CHF, particularly among those reporting very-good-to-excellent health.

Polygenic risk score for Parkinson's disease and olfaction among middle-aged to older women.

INTRODUCTION: Olfactory impairment and Parkinson's disease (PD) may share common genetic and environmental risk factors. This study investigates the association of a PD polygenic risk score (PRS) with olfaction, and whether the associations are modified by environmental exposures of PM2.5, NO2, or smoking. METHODS: This analysis included 3358 women (aged 50-80) from the Sister Study with genetic data and results from the Brief Smell Identification Test (B-SIT) administered in 2018-2019. PD PRS was calculated using 90 single nucleotide polymorphisms. Olfactory impairment was defined with different B-SIT cutoffs, and PD diagnosis was adjudicated via expert review. We report odds ratios (ORs) and 95% confidence intervals (CIs) from multivariable logistic regression. RESULTS: As expected, PD PRS was strongly associated with the odds of having PD (OR highest vs. lowest quartile = 3.79 (1.64, 8.73)). The highest PRS quartile was also associated with olfactory impairment, with OR ranging from 1.24 (0.98, 1.56) for a B-SIT cutoff of 9 to 1.42 (1.04, 1.92) for a cutoff of 6. For individual B-SIT items, the highest PRS quartile was generally associated with lower odds of correctly identifying the odorant, albeit only statistically significant for pineapple (0.72 (0.56, 0.94), soap (0.76 (0.58, 0.99)) and rose (0.70 (0.54, 0.92)). The association of PD PRS with olfactory impairment was not modified by airborne environmental exposures or smoking. CONCLUSION: These preliminary data suggest that high PD genetic susceptibility is associated with olfactory impairment in middle-aged and older women.

Ambient Air Pollutants and Olfaction among Women 50-79 Years of Age from the Sister Study.

BACKGROUND: Poor olfaction is common in older adults and may have profound adverse implications on their health. However, little is known about the potential environmental contributors to poor olfaction. OBJECTIVE: We investigated ambient fine particulate matter [PM ≤2.5µm in aerodynamic diameter (PM2.5)] and nitrogen dioxide (NO2) in relation to poor olfaction in middle-aged to older women. METHODS: The Sister Study is a nationwide cohort of 50,884 women in the United States with annual average air pollutant exposures estimated based on participants' residences from enrollment (2003-2009) through 2017. This analysis was limited to 3,345 women, 50-79 years of age as of January 2018, who completed the Brief Smell Identification Test (B-SIT) in 2018-2019. Poor olfaction was defined as a B-SIT score of ≤9 in the primary analysis. We conducted multivariable logistic regressions, accounting for covariates and study sampling design. RESULTS: Overall, we found little evidence for associations of air pollutants with poor olfaction. The odds ratio (OR) and 95% confidence interval (CI) of poor olfaction for each interquartile range (IQR) increment of air pollutants in 2006 were 1.03 (95% CI: 0.91, 1.17) for PM2.5 (per 3.3 µg/m3) and 1.08 (95% CI: 0.96, 1.22) for NO2 (per 5.7 ppb). Results were similar in the analyses using the most recent (2017) or the cumulative average (2006-2017) air pollutant exposure data. Secondary analyses suggested potential association in certain subgroups. The OR per IQR was 1.35 (95% CI: 1.11, 1.65) for PM2.5 among younger participants (<54.2 years of age) and 1.87 (95% CI: 1.29, 2.71) for NO2 among current smokers. DISCUSSION: This study did not find convincing evidence that air pollutants have lasting detrimental effects on the sense of smell of women 50-79 years of age. The subgroup analyses are exploratory, and the findings need independent confirmation. https://doi.org/10.1289/EHP12066.

Epigenetic responses to rhinovirus exposure in airway epithelial cells are correlated with key transcriptional pathways in chronic rhinosinusitis.

BACKGROUND: Viruses may drive immune mechanisms responsible for chronic rhinosinusitis with nasal polyposis (CRSwNP), but little is known about the underlying molecular mechanisms. OBJECTIVES: To identify epigenetic and transcriptional responses to a common upper respiratory pathogen, rhinovirus (RV), that are specific to patients with CRSwNP using a primary sinonasal epithelial cell culture model. METHODS: Airway epithelial cells were collected at surgery from patients with CRSwNP (cases) and from controls without sinus disease, cultured, and then exposed to RV or vehicle for 48 h. Differential gene expression and DNA methylation (DNAm) between cases and controls in response to RV were determined using linear mixed models. Weighted gene co-expression analysis (WGCNA) was used to identify (a) co-regulated gene expression and DNAm signatures, and (b) genes, pathways, and regulatory mechanisms specific to CRSwNP. RESULTS: We identified 5585 differential transcriptional and 261 DNAm responses (FDR <0.10) to RV between CRSwNP cases and controls. These differential responses formed three co-expression/co-methylation modules that were related to CRSwNP and three that were related to RV (Bonferroni corrected p < .01). Most (95%) of the differentially methylated CpGs (DMCs) were in modules related to CRSwNP, whereas the differentially expressed genes (DEGs) were more equally distributed between the CRSwNP- and RV-related modules. Genes in the CRSwNP-related modules were enriched in known CRS and/or viral response immune pathways. CONCLUSION: RV activates specific epigenetic programs and correlated transcriptional networks in the sinonasal epithelium of individuals with CRSwNP. These novel observations suggest epigenetic signatures specific to patients with CRSwNP modulate response to viral pathogens at the mucosal environmental interface. Determining how viral response pathways are involved in epithelial inflammation in CRSwNP could lead to therapeutic targets for this burdensome airway disorder.

Association of APOE ε4 Status With Long-term Declines in Odor Sensitivity, Odor Identification, and Cognition in Older US Adults.

BACKGROUND AND OBJECTIVES: The APOE ε4 allele confers susceptibility to faster decline in odor identification and subsequently to Alzheimer disease (AD). Odor identification requires recognizing and naming odors and detecting them (odor sensitivity). Whether APOE ε4 is associated with decline of odor sensitivity and whether such decline serves as a harbinger of cognitive decline and AD remains unclear. We determined whether and when APOE ε4 affects decline in odor sensitivity, odor identification, and cognition in the National Social Life Health and Aging Project (NSHAP). METHODS: We used data from NSHAP, a nationally representative survey study of home-dwelling US older adults. Olfaction was measured over time (odor identification in 2005, 2010, and 2015; odor sensitivity in 2010 and 2015; both using validated tests). Cognition was measured with a modified version of the Montreal Cognitive Assessment in 2010 and 2015. Genotyping was performed using DNA samples collected in 2010. Odor sensitivity and identification were compared among APOE ε4 carriers and noncarriers stratified by age. Relationships between APOE ε4, odor sensitivity, odor identification, and cognition were analyzed in cross-section using ordinal logistic regression and longitudinally using mixed-effects models adjusted for confounders. RESULTS: Odor sensitivity was measured in 865 respondents, odor identification in 1,156 respondents, and cognition in 864 respondents; all these respondents had genetic data available. Odor sensitivity deficits in APOE ε4 carriers were apparent at ages 65-69 years, whereas odor identification deficits did not appear until ages 75-79 years. Subsequently, odor sensitivity did not decline more rapidly with aging in APOE ε4 carriers compared with that in noncarriers (carrier status and aging interaction: odds ratio [OR] 1.44, 95% CI 0.94-2.19, p = 0.092), whereas odor identification declined more rapidly in carriers (aging 10 years interaction: OR 0.26, 95% CI 0.13-0.52, p < 0.001). As expected, and in parallel to odor identification, cognition declined more rapidly in APOE ε4 carriers (interaction: OR 0.55, 95% CI 0.34-0.89, p = 0.015). DISCUSSION: APOE ε4 affects decline of odor sensitivity earlier than odor identification or cognition. Thus, testing odor sensitivity may be useful to predict future impaired cognitive function. Identifying the mechanism underlying these relationships will elucidate the key role of olfaction in neurodegeneration during aging.