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Prediction of mortality has focused on disease and frailty, although antecedent biomarkers may herald broad physiological decline. Olfaction, an ancestral chemical system, is a strong candidate biomarker because it is linked to diverse physiological processes. We sought to determine if olfactory dysfunction is a harbinger of 5-year mortality in the National Social Life, Health and Aging Project [NSHAP], a nationally representative sample of older U.S. adults. 3,005 community-dwelling adults aged 57-85 were studied in 2005-6 (Wave 1) and their mortality determined in 2010-11 (Wave 2). Olfactory dysfunction, determined objectively at Wave 1, was used to estimate the odds of 5-year, all cause mortality via logistic regression, controlling for demographics and health factors. Mortality for anosmic older adults was four times that of normosmic individuals while hyposmic individuals had intermediate mortality (p<0.001), a \"dose-dependent\" effect present across the age range. In a comprehensive model that included potential confounding factors, anosmic older adults had over three times the odds of death compared to normosmic individuals (OR, 3.37 [95%CI 2.04, 5.57]), higher than and independent of known leading causes of death, and did not result from the following mechanisms: nutrition, cognitive function, mental health, smoking and alcohol abuse or frailty. Olfactory function is thus one of the strongest predictors of 5-year mortality and may serve as a bellwether for slowed cellular regeneration or as a marker of cumulative toxic environmental exposures. This finding provides clues for pinpointing an underlying mechanism related to a fundamental component of the aging process.

Olfactory dysfunction affects millions of people worldwide. This sensory impairment is associated with neurodegenerative disease and significantly decreased quality of life. Exposure to airborne pollutants has been implicated in olfactory decline, likely due to the anatomic susceptibility of the olfactory nerve to the environment. Historically, studies have focused on occupational exposures, but more recent studies have considered effects from exposure to ambient air pollutants. To examine all relevant human data evaluating a link between ambient pollution exposure and olfaction and to review supporting animal data in order to examine potential mechanisms for pollution-associated olfactory loss. We identified and reviewed relevant articles from 1950 to 2015 using PubMed and Web of Science and focusing on human epidemiologic and pathophysiologic studies. Animal studies were included only to support pertinent data on humans. We reviewed findings from these studies evaluating a relationship between environmental pollutant exposure and olfactory function. We identified and reviewed 17 articles, with 1 additional article added from a bibliography search, for a total of 18 human studies. There is evidence in human epidemiologic and pathologic studies that increased exposure to ambient air pollutants is associated with olfactory dysfunction. However, most studies have used proxies for pollution exposure in small samples of convenience. Human pathologic studies, with supporting animal work, have also shown that air pollution can contact the olfactory epithelium, translocate to the olfactory bulb, and migrate to the olfactory cortex. Pollutants can deposit at each location, causing direct damage and disruption of tissue morphology or inducing local inflammation and cellular stress responses. Ambient air pollution may impact human olfactory function. Additional studies are needed to examine air pollution-related olfactory impacts on the general population using measured pollution exposures and to link pollution exposure with olfactory dysfunction and related pathology. Citation: Ajmani GS, Suh HH, Pinto JM. 2016. Effects of ambient air pollution exposure on olfaction: a review. Environ Health Perspect 124:1683-1693; http://dx.doi.org/10.1289/EHP136.

Viral infection is a common cause of olfactory dysfunction. The complexities of studying post-viral olfactory loss in humans have impaired further progress in understanding the underlying mechanism. Recently, evidence from clinical studies has implicated Parainfluenza virus 3 as a causal agent. An animal model of post viral olfactory disorders (PVOD) would allow better understanding of disease pathogenesis and represent a major advance in the field. To develop a mouse model of PVOD by evaluating the effects of Sendai virus (SeV), the murine counterpart of Parainfluenza virus, on olfactory function and regenerative ability of the olfactory epithelium. C57BL/6 mice (6-8 months old) were inoculated intranasally with SeV or ultraviolet (UV)-inactivated virus (UV-SeV). On days 3, 10, 15, 30 and 60 post-infection, olfactory epithelium was harvested and analyzed by histopathology and immunohistochemical detection of S-phase nuclei. We also measured apoptosis by TUNEL assay and viral load by real-time PCR. The buried food test (BFT) was used to measure olfactory function of mice at day 60. In parallel, cultured murine olfactory sensory neurons (OSNs) infected with SeV or UV-SeV were tested for odorant-mixture response by measuring changes in intracellular calcium concentrations indicated by fura-4 AM assay. Mice infected with SeV suffered from olfactory dysfunction, peaking on day 15, with no loss observed with UV-SeV. At 60 days, four out of 12 mice infected with SeV still had not recovered, with continued normal function in controls. Viral copies of SeV persisted in both the olfactory epithelium (OE) and the olfactory bulb (OB) for at least 60 days. At day 10 and after, both unit length labeling index (ULLI) of apoptosis and ULLI of proliferation in the SeV group was markedly less than the UV-SeV group. In primary cultured OSNs infected by SeV, the percentage of cells responding to mixed odors was markedly lower in the SeV group compared to UV-SeV (P = 0.007). We demonstrate that SeV impairs olfaction, persists in OE and OB tissue, reduces their regenerative ability, and impairs the normal physiological function of OSNs without gross cytopathology. This mouse model shares key features of human post-viral olfactory loss, supporting its future use in studies of PVOD. Further testing and development of this model should allow us to clarify the pathophysiology of PVOD.

In older adults, kidney function declines with age. People with advanced kidney diseases may have poor olfaction. However, it is unclear whether poor olfaction is a marker for declining renal function or future risk of chronic kidney disease (CKD). We therefore investigated olfaction in relation to kidney function and risk of CKD. These secondary data analyses were limited to participants of the year 3 clinical visit of the Health Aging and Body Composition Study. The analytic sample size varied between 1427 to 2531, depending on participant eligibility and data availability for each analysis. Olfaction was tested using the Brief Smell Identification Test (B-SIT), defined as anosmia (score≤6), hyposmia (7-8), moderate (9-10), and good function (10-11) at baseline. We estimated glomerular filter rate (eGFR) at baseline and seven years later using the CKD-EPI creatinine-cystatin C equation, and defined incident CKD as eGFR<60 ml/min/1.73m2 and eGFR decline ≥1 ml/min/1.73m2/year. Further, we identified CKD hospitalization events from hospitalization and death records. We used inverse probability weighting and weighted multivariable regressions to account for censoring in the prospective analyses and used absolute risk regression to account for competing risk of death. At baseline, compared to participants with good olfaction, the multivariable-adjusted mean eGFR was 3.00 ml/min/1.73m2 lower (95% confidence interval (CI): -5.25, -0.75) for those with anosmia and 1.87 lower (95% CI: -3.94, 0.21) for those with hyposmia with a P for linear trend < 0.001. Those with anosmia at baseline was had a significantly lower eGFR seven years later (-5.31, 95% CI: -8.58, -2.04, P for trend = 0.002), but the association was attenuated after further accounting for baseline eGFR (-2.37, 95%CI: -4.91, 0.16, P for linear trend = 0.147). Olfactory function was not associated with incident CKD or CKD hospitalization. In older adults > age 70 years, poor olfaction is associated with lower kidney function, but not future CKD risk. These associations should be further investigated in relatively younger population.

Background Radon, a naturally occurring radioactive gas, is ubiquitous in the environment. Little is known about radon’s impact on cardiovascular disease (CVD). This study aims to evaluate the association between residential radon exposure and incident myocardial infarction (MI) and stroke. Methods This cohort study included participants with electronic health records (EHR) and residential address information from the All of Us Research Program between May 31, 2017, and October 1, 2023. Residential radon exposures were estimated from a 2024 high-resolution model incorporating over six million measurements across the USA. The main outcome was MI and stroke diagnosis or condition, obtained from EHR. Stratified Cox proportional hazards regression models were used to estimate the hazard ratios (HRs) and 95% CIs for the risk of incident MI and stroke for log-2 transformed radon exposure and quartiles of radon exposure, adjusting for sociodemographic, behavioral, and clinical covariates. Sex- and smoker-stratified analyses were conducted. Penalized spline models were used to estimate the nonlinear association. Results A total of 304,050 participants were included. The mean (SD) age was 58.5 (12.9) years old. Among them, 59.2% were female, 18.2% non-Hispanic Black, and 59.0% non-Hispanic White. The median radon exposure was 1.14 pCi/L (interquartile range: 0.90–1.71 pCi/L). Over 950,895 person-years, 1334 MI and 1869 stroke cases were identified. Per doubling of radon exposure was associated with increased risks for incident MI ( HR  = 1.46, 95% CI 1.04–2.08) and stroke ( HR  = 1.60, 1.02–2.49). Participants in the third and fourth quartiles had a significantly higher risk for MI and stroke compared to the lowest quartile. Specifically, the fourth quartile was associated with HR  = 2.20 (95% CI 1.18–4.10) for MI and HR  = 2.38 (95% CI 1.16–4.89) for stroke. Associations persisted across sexes and current smoking status. Nonlinear analyses revealed steep risk increased starting at 1 pCi/L, plateauing at 1.5 pCi/L. Conclusions In this cohort study of 304,050 participants, residential radon exposure was significantly associated with elevated risks for incident MI and stroke. Our results suggest that risks may emerge at levels well below this action level. These findings call for further research incorporating household-level exposure measures and lifetime residential histories to confirm the association.

ObjectiveExposure to particulate matter of 10 μm or less in diameter (PM10) has been implicated in pulmonary and cardiovascular diseases. However, the effect of PM10 on olfaction has not been well established. We estimated individual acute and chronic PM10 exposure levels in a large Brazilian cohort and related them to the ability to identify odors.MethodsAdults from São Paulo (n = 1358) were recruited from areas with different levels of air pollution. To verify individual exposure to air pollution, the averages of 30, 60, 90, 180 and 364 days of PM10 were interpolated to subjects’ zip codes using the kriging method. Olfactory identification performance was tested using the University of Pennsylvania Smell Identification Test (UPSIT®). Multiple linear regressions were used to calculate the effect of air pollution on olfactory identification performance, controlling for demographic and other variables that affect the sense of smell.ResultsAcute exposures to PM10 were related to worse UPSIT® scores, including 30- (β =  – 0.94, 95% Confidence Interval [CI]  – 0.98,  – 0.89), 60- (β =  – 1.09, 95% CI = – 1.13,  – 1.04) and 90-day intervals (β =  – 1.06, 95% CI  – 1.10,  – 1.02) (reference for β: 1 µm/m3 increase in PM10 exposure per point decrease in UPSIT® score). Chronic exposures were also associated with worse olfaction for both 180- (β =  – 1.06, 95% CI  – 1.10,  – 1.03) and 364-day (β =  – 0.87, 95% CI  – 0.90,  – 0.84) intervals. As in prior work, men, older, low-income, and low-schooling people demonstrated worse olfactory performance.ConclusionAcute and chronic exposure to PM10 is strongly associated with olfactory identification performance in Brazilian adults. Understanding the mechanisms which underlie these relationships could help to improve chemosensory function with a large public health impact.

Δ 4,16-androstadien-3-one (androstadienone) is a putative human pheromone often linked to sexual attraction in young adults, although specific associations with sexual behavior are not yet established. Androstadienone also serves a broader social-emotional function beyond the sexual domain, specifically tuning the brain to efficiently process emotional information. Whether these effects persist throughout the lifespan into post-reproductive life is unknown. In a laboratory study of older adults, those with greater androstadienone odor sensitivity paid greater attention to subliminal emotional information, specifically, angry faces (p = 0.05), with a similar relationship to happy faces. In contrast, the physical odor n -butanol (a control) did not affect emotional attention (p = 0.49). We then extended this laboratory research and determined whether sensitivity to androstadienone affects the everyday lives of older adults by measuring their social and sexual behavior. In this second study, we surveyed in a nationally representative sample of US older adults living in their homes (National Social Life and Aging Project, 62–90 years; n = 2,086), along with their sensitivity to androstadienone, general olfactory function, health and demographics. Greater sensitivity to androstadienone was associated with richer social lives: having more friends, increased communication with close friends and family, and more participation in organized social events and volunteer activities (all p’s ≤ 0.05, generalized linear models, adjusted for age and gender). It was also associated with more recent sexual activity, more frequent sexual thoughts, and viewing sex as an important part of life (all p’s ≤ 0.05). General olfactory function did not explain these associations, supporting a specialized function for this pheromone during everyday life, and expanding its role to social life as well as sexual behavior, likely mediated by enhanced attention to emotional information.

Background Genome-wide association studies (GWASs) have identified thousands of variants associated with asthma and other complex diseases. However, the functional effects of most of these variants are unknown. Moreover, GWASs do not provide context-specific information on cell types or environmental factors that affect specific disease risks and outcomes. To address these limitations, we used an upper airway epithelial cell (AEC) culture model to assess transcriptional and epigenetic responses to rhinovirus (RV), an asthma-promoting pathogen, and provide context-specific functional annotations to variants discovered in GWASs of asthma. Methods Genome-wide genetic, gene expression, and DNA methylation data in vehicle- and RV-treated upper AECs were collected from 104 individuals who had a diagnosis of airway disease ( n =66) or were healthy participants ( n =38). We mapped cis expression and methylation quantitative trait loci ( cis -eQTLs and cis -meQTLs, respectively) in each treatment condition (RV and vehicle) in AECs from these individuals. A Bayesian test for colocalization between AEC molecular QTLs and adult onset asthma and childhood onset asthma GWAS SNPs, and a multi-ethnic GWAS of asthma, was used to assign the function to variants associated with asthma. We used Mendelian randomization to demonstrate DNA methylation effects on gene expression at asthma colocalized loci. Results Asthma and allergic disease-associated GWAS SNPs were specifically enriched among molecular QTLs in AECs, but not in GWASs from non-immune diseases, and in AEC eQTLs, but not among eQTLs from other tissues. Colocalization analyses of AEC QTLs with asthma GWAS variants revealed potential molecular mechanisms of asthma, including QTLs at the TSLP locus that were common to both the RV and vehicle treatments and to both childhood onset and adult onset asthma, as well as QTLs at the 17q12-21 asthma locus that were specific to RV exposure and childhood onset asthma, consistent with clinical and epidemiological studies of these loci. Conclusions This study provides evidence of functional effects for asthma risk variants in AECs and insight into RV-mediated transcriptional and epigenetic response mechanisms that modulate genetic effects in the airway and risk for asthma.

Current methods of olfactory sensitivity testing are logistically challenging and therefore infeasible for use in in-home surveys and other field settings. We developed a fast, easy and reliable method of assessing olfactory thresholds, and used it in the first study of olfactory sensitivity in a nationally representative sample of U.S. home-dwelling older adults. We validated our method via computer simulation together with a model estimated from 590 normosmics. Simulated subjects were assigned n-butanol thresholds drawn from the estimated normosmic distribution and based on these and the model, we simulated administration of both the staircase and constant stimuli methods. Our results replicate both the correlation between the two methods and their reliability as previously reported by studies using human subjects. Further simulations evaluated the reliability of different constant stimuli protocols, varying both the range of dilutions and number of stimuli (6-16). Six appropriately chosen dilutions were sufficient for good reliability (0.67) in normosmic subjects. Finally, we applied our method to design a 5-minute, in-home assessment of older adults (National Social Life, Health and Aging Project, or NSHAP), which had comparable reliability (0.56), despite many subjects having estimated thresholds above the strongest dilution. Thus, testing with a fast, 6-item constant stimuli protocol is informative, and permits olfactory testing in previously inaccessible research settings.

Purpose : To assess household air pollution levels in urban Chicago households and examine how socioeconomic factors influence these levels. Methods : We deployed wireless air monitoring devices to 244 households in a diverse population in Chicago to continuously record household fine particulate matter (PM 2.5 ) concentration. We calculated hourly average PM 2.5 concentration in a 24-hour cycle. Four factors—race, household income, area deprivation, and exposure to smoking—were considered in this study. Results : A total of 93085 h of exposure data were recorded. The average household PM 2.5 concentration was 43.8 μg m −3 . We observed a significant difference in the average household PM 2.5 concentrations between Black/African American and non-Black/African American households (46.3 versus 31.6 μg m −3 ), between high-income and low-income households (18.2 versus 52.5 μg m −3 ), and between smoking and non-smoking households (69.7 versus 29.0 μg m −3 ). However, no significant difference was observed between households in less and more deprived areas (43.7 versus 43.0 μg m −3 ). Implications : Household air pollution levels in Chicago households are much higher than the recommended level, challenging the hypothesis that household air quality is adequate for populations in high income nations. Our results indicate that it is the personal characteristics of participants, rather than the macro environments, that lead to observed differences in household air pollution.