Air pollution and traffic noise interact to affect cognitive health in older Mexican Americans.

BACKGROUND: Both air pollution and noise exposures have separately been shown to affect cognitive impairment. Here, we examine how air pollution and noise exposures interact to influence the development of incident dementia or cognitive impairment without dementia (CIND). METHODS: We used 1,612 Mexican American participants from the Sacramento Area Latino Study on Aging conducted from 1998 to 2007. Air pollution (nitrogen dioxides, particulate matter, ozone) and noise exposure levels were modeled with a land-use regression and via the SoundPLAN software package implemented with the Traffic Noise Model applied to the greater Sacramento area, respectively. Using Cox proportional hazard models, we estimated the hazard of incident dementia or CIND from air pollution exposure at the residence up to 5-years prior to diagnosis for the members of each risk set at event time. Further, we investigated whether noise exposure modified the association between air pollution exposure and dementia or CIND. RESULTS: In total, 104 incident dementia and 159 incident dementia/CIND cases were identified during the 10 years of follow-up. For each ∼2 µg/m3 increase in time-varying 1- and 5-year average PM2.5 exposure, the hazard of dementia increased 33% (HR = 1.33, 95%CI: 1.00, 1.76). The hazard ratios for NO2-related dementia/CIND and PM2.5-related dementia were stronger in high-noise (≥65 dB) exposed than low-noise (<65 dB) exposed participants. CONCLUSION: Our study indicates that PM2.5 and NO2 air pollution adversely affect cognition in elderly Mexican Americans. Our findings also suggest that air pollutants may interact with traffic-related noise exposure to affect cognitive function in vulnerable populations.

Ozone Exposure, Outdoor Physical Activity, and Incident Type 2 Diabetes in the SALSA Cohort of Older Mexican Americans.

BACKGROUND: Type 2 diabetes is a leading contributor to the global burden of morbidity and mortality. Ozone (O3) exposure has previously been linked to diabetes. OBJECTIVE: We studied the impact of O3 exposure on incident diabetes risk in elderly Mexican Americans and investigated whether outdoor physical activity modifies the association. METHODS: We selected 1,090 Mexican American participants from the Sacramento Area Latino Study on Aging conducted from 1998 to 2007. Ambient O3 exposure levels were modeled with a land-use regression built with saturation monitoring data collected at 49 sites across the Sacramento metropolitan area. Using Cox proportional hazard models, we estimated the risk of developing incident diabetes based on average O3 exposure modeled for 5-y prior to incident diabetes diagnosis or last follow-up. Further, we estimated outdoor leisure-time physical activity at baseline and investigated whether higher vs. lower levels modified the association between O3 exposure and diabetes. RESULTS: In total, 186 incident diabetes cases were identified during 10-y follow-up. Higher levels of physical activity were negatively associated with incident diabetes [hazard ratio (HR)=0.64 (95% CI: 0.43, 0.95)]. The estimated HRs for incident diabetes was 1.13 (95% CI: 1.00, 1.28) per 10-ppb increment of 5-y average O3 exposure; also, this association was stronger among those physically active outdoors [HR=1.52 (95% CI: 1.21, 1.90)], and close to null for those reporting lower levels of outdoor activity [HR=1.04 (95% CI: 0.90, 1.20), pinteraction=0.01]. CONCLUSIONS: Our findings suggest that ambient O3 exposure contributes to the development of type 2 diabetes, particularly among those with higher levels of leisure-time outdoor physical activity. Policies and strategies are needed to reduce O3 exposure to guarantee that the health benefits of physical activity are not diminished by higher levels of O3 pollution in susceptible populations such as older Hispanics. https://doi.org/10.1289/EHP8620.

Native American Ancestry and Air Pollution Interact to Impact Bronchodilator Response in Puerto Rican Children with Asthma.

Objective: Asthma is the most common chronic disease in children. Short-acting bronchodilator medications are the most commonly prescribed asthma treatment worldwide, regardless of disease severity. Puerto Rican children display the highest asthma morbidity and mortality of any US population. Alarmingly, Puerto Rican children with asthma display poor bronchodilator drug response (BDR). Reduced BDR may explain, in part, the increased asthma morbidity and mortality observed in Puerto Rican children with asthma. Gene-environment interactions may explain a portion of the heritability of BDR. We aimed to identify gene-environment interactions associated with BDR in Puerto Rican children with asthma. Setting: Genetic, environmental, and psycho-social data from the Genes-environments and Admixture in Latino Americans (GALA II) case-control study. Participants: Our discovery dataset consisted of 658 Puerto Rican children with asthma; our replication dataset consisted of 514 Mexican American children with asthma. Main Outcome Measures: We assessed the association of pairwise interaction models with BDR using ViSEN (Visualization of Statistical Epistasis Networks). Results: We identified a non-linear interaction between Native American genetic ancestry and air pollution significantly associated with BDR in Puerto Rican children with asthma. This interaction was robust to adjustment for age and sex but was not significantly associated with BDR in our replication population. Conclusions: Decreased Native American ancestry coupled with increased air pollution exposure was associated with increased BDR in Puerto Rican children with asthma. Our study acknowledges BDR's phenotypic complexity, and emphasizes the importance of integrating social, environmental, and biological data to further our understanding of complex disease.

Whole-Genome Sequencing Identifies Novel Functional Loci Associated with Lung Function in Puerto Rican Youth.

Rationale: Puerto Ricans have the highest childhood asthma prevalence in the United States (23.6%); however, the etiology is uncertain.Objectives: In this study, we sought to uncover the genetic architecture of lung function in Puerto Rican youth with and without asthma who were recruited from the island (n = 836).Methods: We used admixture-mapping and whole-genome sequencing data to discover genomic regions associated with lung function. Functional roles of the prioritized candidate SNPs were examined with chromatin immunoprecipitation sequencing, RNA sequencing, and expression quantitative trait loci data.Measurements and Main Results: We discovered a genomic region at 1q32 that was significantly associated with a 0.12-L decrease in the lung volume of exhaled air (95% confidence interval, -0.17 to -0.07; P = 6.62 × 10-8) with each allele of African ancestry. Within this region, two SNPs were expression quantitative trait loci of TMEM9 in nasal airway epithelial cells and MROH3P in esophagus mucosa. The minor alleles of these SNPs were associated with significantly decreased lung function and decreased TMEM9 gene expression. Another admixture-mapping peak was observed on chromosome 5q35.1, indicating that each Native American ancestry allele was associated with a 0.15-L increase in lung function (95% confidence interval, 0.08-0.21; P = 5.03 × 10-6). The region-based association tests identified four suggestive windows that harbored candidate rare variants associated with lung function.Conclusions: We identified common and rare genetic variants that may play a critical role in lung function among Puerto Rican youth. We independently validated an inflammatory pathway that could potentially be used to develop more targeted treatments and interventions for patients with asthma.

Air pollution, noise exposure, and metabolic syndrome - A cohort study in elderly Mexican-Americans in Sacramento area.

BACKGROUND: Previous studies suggested that air pollutants may increase the incidence of metabolic syndrome, but the potential impact from traffic sources is not well-understood. This study aimed to investigate associations between traffic-related nitrogen oxides (NOx) or noise pollution and risk of incident metabolic syndrome and its components in an elderly Mexican-American population. METHODS: A total of 1,554 Mexican-American participants of the Sacramento Area Latino Study on Aging (SALSA) cohort were followed from 1998 to 2007. We used anthropometric measures and biomarkers to define metabolic syndrome according to the recommendations of the Third Adult Treatment Panel of the National Cholesterol Education Program (NCEP ATP III). Based on participants' residential addresses at baseline, estimates of local traffic-related NOx were generated using the California Line Source Dispersion Model version 4 (CALINE4), and of noise employing the SoundPLAN software package. We used Cox regression models with calendar time as the underlying time scale to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations of air pollution or noise with metabolic syndrome or its components. RESULTS: Each per unit increase of traffic-related NOx (2.29 parts per billion (ppb)) was associated with a 15% (HR = 1.15, 95% CI: 1.04-1.28) lower level of high-density lipoprotein cholesterol (HDL-cholesterol), and each 11.6 decibels (dB) increase in noise increased the risk of developing metabolic syndrome by 17% (HR = 1.17, 95% CI: 1.01-1.35). CONCLUSION: Policies aiming to reduce traffic-related air pollution and noise might mitigate the risk of metabolic syndrome and its components in vulnerable populations.

Traffic-related Noise Exposure and Late-life Dementia and Cognitive Impairment in Mexican-Americans.

BACKGROUND: Recently, it has been suggested that environmental exposures from traffic sources including noise may play a role in cognitive impairment in the elderly. The objective of the study was to investigate the association between local traffic-related noise pollution and incident dementia or cognitive impairment without dementia (CIND) during a 10-year follow-up period. METHODS: 1612 Mexican-American participants from the Sacramento Area Latino Study on Aging (SALSA) were followed every 12-15 months via home visits from 1998 to 2007. We used the SoundPLAN software package to estimate noise originating from local traffic with the input of Annual Average Daily Traffic (AADT) data from Metropolitan Planning Organizations (MPO) based on geocoded residential addresses at baseline (1998-1999). We estimated the risks of incident dementia or CIND from 24-hour and nighttime noise exposure using Cox proportional hazard models. RESULTS: During the follow-up, we identified 159 incident dementia or CIND cases in total. Per 11.6 dB (interquartile range width) increase in 24-hour noise, the hazard of developing dementia or CIND increased (hazard ratio = 1.3 [1.0, 1.6]) during follow-up; estimates were slightly lower (hazard ratio = 1.2 [0.97, 1.6]) when adjusting for modeled local air pollution exposure from traffic sources. Overall, the risk of dementia/CIND was elevated when 24-hour and nighttime noise were higher than 75 and 65 dB respectively. See video Abstract: http://links.lww.com/EDE/B728. CONCLUSIONS: In our study, traffic-related noise exposure was associated with increased risk of dementia or CIND in elderly Mexican-Americans. Future studies taking into account other noise sources and occupational noise exposure before retirement are needed.

Metabolic dysfunction modifies the influence of traffic-related air pollution and noise exposure on late-life dementia and cognitive impairment: A cohort study of older Mexican-Americans.

Cognitive impairment has been linked to traffic-related air pollution and noise exposure as well as to metabolic syndrome or some of its individual components. Here, we investigate whether the presence of metabolic dysfunction modifies associations between air pollution or noise exposures and incident dementia or cognitive impairment without dementia (CIND). METHODS: For 1,612 elderly Mexican-American participants of the Sacramento Area Latino Study on Aging (SALSA) followed for up to 10 years, we estimated residential-based local traffic-related exposures relying on the California Line Source Dispersion Model version 4 (CALINE4) for nitrogen oxides (NOx) and the SoundPLAN software package (Version 8.0; NAVCON, Fullerton, CA) that implements the Federal Highway Administration Traffic Noise Model (TNM) for noise, respectively. We used Cox proportional hazard models to estimate the joint effects of NOx or noise exposures and obesity, hyperglycemia, or low high-density lipoprotein (HDL) cholesterol. RESULTS: The risk of developing dementia/CIND among participants with hyperglycemia who also were exposed to high levels of NOx (≥3.44 parts per billion [ppb] [75th percentile]) or noise (≥65 dB) was 2.4 (1.4, 4.0) and 2.2 (1.7, 3.9), respectively. For participants with low HDL-cholesterol, the estimated hazard ratios for dementia/CIND were 2.5 (1.4, 4.3) and 1.8 (1.0, 3.0) for those also exposed to high levels of NOx (≥3.44 ppb) or noise (≥65 dB), respectively, compared with those without metabolic dysfunction exposed to low traffic-related air pollution or noise levels. CONCLUSIONS: Exposure to traffic-related air pollution or noise most strongly increases the risk of dementia/CIND among older Mexican-Americans living in California who also exhibit hyperglycemia or low HDL-cholesterol.

Pathomechanisms of immune-mediated alopecia.

The hair follicle (HF) is a complex mini-organ that constantly undergoes dynamic cycles of growth and regression throughout life. While proper progression of the hair cycle requires homeostatic interplay between the HF and its immune microenvironment, specific parts of the HF, such as the bulge throughout the hair cycle and the bulb in the anagen phase, maintain relative immune privilege (IP). When this IP collapses, inflammatory infiltrates that aggregate around the bulge and bulb launch an immune attack on the HF, resulting in hair loss or alopecia. Alopecia areata (AA) and primary cicatricial alopecia (PCA) are two common forms of immune-mediated alopecias, and recent advancements in understanding their disease mechanisms have accelerated the discovery of novel treatments for immune-mediated alopecias, specifically AA. In this review, we highlight the pathomechanisms involved in both AA and CA in hopes that a deeper understanding of their underlying disease pathogenesis will encourage the development of more effective treatments that can target distinct disease pathways with greater specificity while minimizing adverse effects.