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Poor nutrition is the leading cause of poor health, health care spending, and lost productivity in the United States and globally, which acts through cardiometabolic diseases as precursors to cardiovascular disease, cancer, and other conditions. There is great interest in how the social determinants of health (the conditions in which people are born, live, work, develop, and age) impact cardiometabolic disease. Food insecurity is an example of a powerful social determinant of health that impacts health outcomes. Nutrition insecurity, a distinct but related concept to food insecurity, is a direct determinant of health. In this article, we provide an overview of how diet in early life relates to cardiometabolic disease and then continue to focus on the concepts of food insecurity and nutrition insecurity. In the discussions herein we make important distinctions between the concepts of food insecurity and nutrition insecurity and provide a review of their concepts, histories, measurement and assessment devices, trends and prevalence, and links to health and health disparities. The discussions here set the stage for future research and practice to directly address the negative consequences of food and nutrition insecurity.
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Enfermedades Cardiovasculares , Desnutrición , Humanos , Estados Unidos/epidemiología , Dieta , Estado Nutricional , Alimentos , Enfermedades Cardiovasculares/epidemiologíaRESUMEN
PURPOSE OF REVIEW: This review seeks to provide important information on each of the major domains of social determinants of health (SDOH) in the context of atherosclerotic cardiovascular disease. RECENT FINDINGS: SDOH can be classified into five domains: social and community context, health care access and quality, neighborhood and built environment, economic stability, and education access and quality. SDOH are major drivers for cardiovascular health outcomes that exceed the impact from traditional risk factors, and explain inequities in health outcomes observed across different groups of individuals. SDOH profoundly impacts healthcare's receipt, delivery, and outcomes. Many patients fall within various disenfranchised groups (e.g., identify with minority race, low socioeconomic status, low educational attainment, LGBTQ+), which impact overall health status and care. Learning to understand, recognize, and address SDOH as the driving force of disparities are critical for achieving health equity in the prevention and adequate treatment of ASCVD.
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Aterosclerosis , Determinantes Sociales de la Salud , Humanos , Aterosclerosis/epidemiología , Accesibilidad a los Servicios de Salud , Disparidades en Atención de Salud , Factores de Riesgo , Disparidades en el Estado de Salud , Factores Socioeconómicos , Enfermedades Cardiovasculares/epidemiologíaRESUMEN
BACKGROUND: A major route of sensitization to food allergen is through an impaired skin barrier. IL-33 and thymic stromal lymphopoietin (TSLP) have both been implicated in epicutaneous sensitization and food allergy, albeit in different murine models. OBJECTIVE: We assessed the respective contributions of TSLP and IL-33 to the development of atopic dermatitis (AD) and subsequent food allergy in TSLP and IL-33 receptor (ST2)-deficient mice using an AD model that does not require tape stripping. METHOD: TSLP receptor (TSLPR)-/-, ST2-/-, and BALB/cJ control mice were exposed to 3 weekly epicutaneous skin patches of one of saline, ovalbumin (OVA), or a combination of OVA and Aspergillus fumigatus (ASP), followed by repeated intragastric OVA challenges and development of food allergy. RESULTS: ASP and/or OVA patched, but not OVA-alone patched, BALB/cJ mice developed an AD-like skin phenotype. However, epicutaneous OVA sensitization occurred in OVA patched mice and was decreased in ST2-/- mice, resulting in lower intestinal mast cell degranulation and accumulation, as well as OVA-induced diarrhea occurrences on intragastric OVA challenges. In TSLPR-/- mice, intestinal mast cell accumulation was abrogated, and no diarrhea was observed. AD was significantly milder in OVA + ASP patched TSLPR-/- mice compared to wild type and ST2-/- mice. Accordingly, intestinal mast cell accumulation and degranulation were impaired in OVA + ASP patched TSLPR-/- mice compared to wild type and ST2-/- mice, protecting TSLPR-/- mice from developing allergic diarrhea. CONCLUSION: Epicutaneous sensitization to food allergen and development of food allergy can occur without skin inflammation and is partly mediated by TSLP, suggesting that prophylactic targeting of TSLP may be useful in mitigating the development of AD and food allergy early in life in at-risk infants.
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Dermatitis Atópica , Hipersensibilidad a los Alimentos , Ratones , Animales , Linfopoyetina del Estroma Tímico , Interleucina-33/genética , Proteína 1 Similar al Receptor de Interleucina-1 , Citocinas/metabolismo , Hipersensibilidad a los Alimentos/metabolismo , Alérgenos , Ratones Endogámicos BALB C , Ovalbúmina , Modelos Animales de EnfermedadRESUMEN
Lipoprotein(a)(Lp[a]) is a low-density lipoprotein-cholesterol (LDL-C)-like particle with potent pro-atherothrombotic properties. The association of Lp(a) with several circulating factors, including vitamins, remains unresolved. We performed an observational analysis using the National Health and Nutrition Examination Survey III cohort, a cohort used to monitor the nutrition status of US-citizens. We used multivariable linear regression to test associations of Lp(a) and LDL-C with levels of serum vitamins and minerals and whole-blood lead. Analyses controlled for factors known to associate with Lp(a) (age, sex, race/ethnicity, statin use, hemoglobin A1c, body mass index, hypertension, diabetes, glomerular filtration rate, alcohol intake, and saturated fat intake). LDL-C was corrected for Lp(a) mass. Multiple sensitivity tests were performed, including considering factors as categorical variables (deficient, normal, elevated). Among 7,662 subjects, Lp(a) correlated (ß-coefficient) positively (change per 1 conventional unit increase) with carotenoids (lycopene (0.17(0.06,0.28), p=0.005), lutein (0.19(0.07,0.30), p=0.002), ß-cryptoxanthin (0.21(0.05,0.37), p=0.01), ß-carotene (0.05(0.02,0.09), p=0.003), and α-carotene (0.15(0.01,0.30), p=0.04)) and lead (0.54(0.03,1.05), p=0.04) levels when tested as continuous variables. LDL-C had similar associations. Lp(a) did not associate with vitamins A, B12, C, or E retinyl esters, folate, RBC-folate, selenium, ferritin, transferrin saturation, or calcium. With factors as categorical variables, Lp(a) but not LDL-C negatively associated with elevated vitamin B12 (-5.41(-9.50, -1.53), p=0.01) and folate (-2.86(-5.09, -0.63), p=0.01). In conclusion, Lp(a) associated similarly to LDL-C when vitamins, minerals, and lead were tested as continuous variables, while only Lp(a) correlated with vitamin B12 and folate when tested as categorical variables. These observations are hypotheses generating and require further studies to determine causality.
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Selenio , Vitaminas , Humanos , Adulto , Lipoproteína(a) , Encuestas Nutricionales , Estudios Transversales , Vitamina A , Ácido Fólico , Vitamina K , Vitamina B 12RESUMEN
INTRODUCTION: Low-density lipoprotein cholesterol (LDL) is a known contributing factor to atherosclerotic cardiovascular disease (ASCVD) and a primary therapeutic target for medical management of ASCVD. Non-high-density lipoprotein cholesterol (non-HDL) has recently been identified as a secondary therapeutic target but is not yet widely used in vascular surgery patients. We sought to assess if vascular surgery patients were undertreated per non-HDL therapeutic guidelines. METHODS: This was an observational study that used a single-center database to identify a cohort of adult patients who received care from a vascular surgery provider from 01/2001 to 07/2021. ICD-9/10-CM codes were used to identify patients with a medical history of hyperlipidemia (HLD), coronary artery disease (CAD), cerebrovascular occlusive disease (CVOD), peripheral artery disease (PAD), hypertension (HTN), or diabetes mellitus (DM). Patient smoking status and medications were also identified. Lab values were obtained from the first and last patient encounter within our system. Primary outcomes were serum concentrations of LDL and non-HDL, with therapeutic thresholds defined as 70 mg/dL and 100 mg/dL, respectively. RESULTS: The cohort included 2465 patients. At first encounter, average age was 59.3 years old, 21.4% were on statins, 8.4% were on a high-intensity statin, 25.7% were diagnosed with HLD, 5.2% with CAD, 15.3% with PAD, 26.3% with DM, 18.6% with HTN, and 2.1% with CVOD. At final encounter, mean age was 64.8 years, 23.5% were on statins with 10.1% on high-intensity statin. Diagnoses frequency did not change at final encounter. At first encounter, nearly two-thirds of patients were not at an LDL <70 mg/dL (62.3%) or non-HDL <100 mg/dL (66.0%) with improvement at final encounter to 45.2 and 40.5% of patients not at these LDL or non-HDL treatment thresholds, respectively. Patients on statins exhibited similar trends with 51.1 and 50.1% of patients not at LDL or non-HDL treatment thresholds at first encounter and 39.9 and 35.4% not at LDL or non-HDL treatment thresholds at last encounter. Importantly, 6.9% of patients were at LDL but not non-HDL treatment thresholds. DISCUSSION: Among vascular surgery patients, over half did not meet non-HDL targets. These results suggest that we may be vastly under-performing adequate medical optimization with only about one-fourth of patients on a statin at their final encounter and approximately one-tenth of patients being treated with a high-intensity statin. With recent evidence supporting non-HDL as a valuable measurement for atherosclerotic risk, there is potential to optimize medical management beyond current high-intensity statin therapy. Further investigation is needed regarding the risk of adverse events between patients treated with these varied therapeutic targets.
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PURPOSE FOR REVIEW: Since the coronavirus SARS-CoV-2 outbreak in China in late 2019 turned into a global pandemic, numerous studies have reported associations between environmental factors, such as weather conditions and a range of air pollutants (particulate matter, nitrogen dioxide, ozone, etc.) and the first wave of COVID-19 cases. This review aims to offer a critical assessment of the role of environmental exposure risk factors on SARS-CoV-2 infections and COVID-19 disease severity. RECENT FINDINGS: In this review, we provide a critical assessment of COVID-19 risk factors, identify gaps in our knowledge (e.g., indoor air pollution), and discuss methodological challenges of association and causation and the impact lockdowns had on air quality. In addition, we will draw attention to ethnic and socioeconomic factors driving viral transmission related to COVID-19. The complex role angiotensin-converting enzyme 2 (ACE2) plays in COVID-19 and future promising avenues of research are discussed. To demonstrate causality, we stress the need for future epidemiologic studies integrating personal air pollution exposures, detailed clinical COVID-19 data, and a range of socioeconomic factors, as well as in vitro and in vivo mechanistic studies.
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Contaminación del Aire Interior/estadística & datos numéricos , Contaminación del Aire/estadística & datos numéricos , COVID-19/epidemiología , Animales , COVID-19/diagnóstico , COVID-19/virología , Control de Enfermedades Transmisibles , Humanos , Pandemias , Factores de Riesgo , SARS-CoV-2/aislamiento & purificación , Tiempo (Meteorología)RESUMEN
BACKGROUND: Exposure to traffic pollution, notably diesel exhaust particles (DEP), increases risk for asthma and asthma exacerbations. The contribution of cytokines generated by stressed lung epithelial cells (IL25, IL33, TSLP) to DEP-induced asthma severity remains poorly understood. METHODS: BALB/c mice were exposed intratracheally once to DEP or 9 times over 3-weeks to either saline, DEP, and/or house dust mite extract (HDM). Airway hyper-responsiveness (AHR), pulmonary inflammation, and T-cell subsets were assessed 24 hours after the last exposure in mice sufficient and deficient for the IL33 receptor ST2. RESULTS: DEP exposure induces oxidative stress, IL6, neutrophils and pulmonary accumulation of IL33, but not IL25 or TSLP or other features of allergic disease. When mice are co-exposed to DEP and low doses of HDM, DEP increases IL33 lung levels and Th2 responses. ST2 deficiency partially protected mice from HDM + DEP induced AHR in association with decreased type 2 inflammation and lung levels of IL5+ IL17A+ co-producing T-cells. Upon in vitro HDM challenge of lung cells from HDM ± DEP exposed ST2-/- mice, secretion of IL5, IL13, IL6 and IL17A was abrogated by a mechanism involving IL33 signaling in both dendritic cells and T-cells. HDM + DEP exposed bone marrow derived dendritic cells and IL33 pulsed BMDC promote a mixed Th2/Th17 response that was dependent on ST2 expression by CD4+ T-cells. CONCLUSION: IL33 contributes to DEP mediated increase in allergen-induced Th2 inflammation and AHR in a mouse model of severe steroid resistant asthma, potentially through the accumulation of pathogenic IL5+ IL17A+ CD4+ effector T-cells.
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Asma , Hipersensibilidad Respiratoria , Animales , Citocinas , Modelos Animales de Enfermedad , Interleucina-33 , Pulmón , Ratones , Ratones Endogámicos BALB C , Pyroglyphidae , Células Th2RESUMEN
Epidemiologic studies have found air pollution to be causally linked to respiratory health including the exacerbation and development of childhood asthma. Accurately characterizing exposure is paramount in these studies to ensure valid estimates of health effects. Here, we provide a brief overview of the evolution of air pollution exposure assessment ranging from the use of ground-based, single-site air monitoring stations for population-level estimates to recent advances in spatiotemporal models, which use advanced machine learning algorithms and satellite-based data to accurately estimate individual-level daily exposures at high spatial resolutions. In addition, we review recent advances in sensor technology that enable the use of personal monitoring in epidemiologic studies, long-considered the "holy grail" of air pollution exposure assessment. Finally, we highlight key advantages and uses of each approach including the generalizability and public health relevance of air pollution models and the accuracy of personal monitors that are useful to guide personalized prevention strategies. Investigators and clinicians interested in the effects of air pollution on allergic disease and asthma should carefully consider the pros and cons of each approach to guide their application in research and practice.
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Contaminantes Atmosféricos/análisis , Contaminación del Aire/análisis , Monitoreo del Ambiente/métodos , Exposición por Inhalación/análisis , Estudios Epidemiológicos , Humanos , Hipersensibilidad/epidemiología , Modelos Teóricos , Medición de RiesgoRESUMEN
BACKGROUND: Recent literature suggests that children who are vitamin D deficient are uniquely susceptible to the effects of traffic-related air pollution (TRAP) exposure. This is highly significant because large segments of the population reside in zones of high TRAP exposure. OBJECTIVE: We sought to determine whether vitamin D supplementation mitigates the effect of TRAP exposure on asthma development, asthma exacerbation, and/or airway inflammation and to determine the timing of vitamin D supplementation that confers maximal health benefit. METHODS: Using established mouse models of asthma, we examined the effect of prenatal and postnatal vitamin D supplementation on asthma development, as well as the utility of vitamin D as a treatment for established asthma in the context of diesel exhaust particle (DEP) exposure. RESULTS: DEP and allergen coexposure resulted in increased airway hyperresponsiveness (AHR) and accumulation of pathogenic TH2/TH17 cells in the lungs of vitamin D-deficient mice compared with control mice. Prenatal and postnatal vitamin D supplementation significantly attenuated the development of AHR and decreased pulmonary accumulation of TH2/TH17 cells after coexposure to TRAP and allergen but not to allergen alone. Restoration of normal vitamin D status had no effect on AHR once asthma was already established. CONCLUSIONS: Our data establish that vitamin D confers protection against asthma development specifically in the context of TRAP exposure. Although vitamin D replacement did not reverse established asthma, restoration of normal vitamin D status in early life significantly attenuated the development of AHR in the setting of DEP-exacerbated allergic asthma and reduced numbers of lung TH2/TH17 cells, which portend the development of severe asthma.
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Asma , Pulmón , Células Th17 , Células Th2 , Contaminación por Tráfico Vehicular/efectos adversos , Emisiones de Vehículos/toxicidad , Vitamina D/farmacología , Animales , Asma/inducido químicamente , Asma/inmunología , Asma/patología , Asma/prevención & control , Modelos Animales de Enfermedad , Pulmón/inmunología , Pulmón/patología , Ratones , Ratones Endogámicos BALB C , Células Th17/inmunología , Células Th17/patología , Células Th2/inmunología , Células Th2/patologíaAsunto(s)
Dermatitis Atópica , Trombina , Ratones , Animales , Humanos , Lactante , Fibrinógeno , Modelos Animales de EnfermedadRESUMEN
Campylobacter causes an estimated 1.3 million diarrheal illnesses in the United States annually (1). In August 2017, the Florida Department of Health notified CDC of six Campylobacter jejuni infections linked to company A, a national pet store chain based in Ohio. CDC examined whole-genome sequencing (WGS) data and identified six isolates from company A puppies in Florida that were highly related to an isolate from a company A customer in Ohio. This information prompted a multistate investigation by local and state health and agriculture departments and CDC to identify the outbreak source and prevent additional illness. Health officials from six states visited pet stores to collect puppy fecal samples, antibiotic records, and traceback information. Nationally, 118 persons, including 29 pet store employees, in 18 states were identified with illness onset during January 5, 2016-February 4, 2018. In total, six pet store companies were linked to the outbreak. Outbreak isolates were resistant by antibiotic susceptibility testing to all antibiotics commonly used to treat Campylobacter infections, including macrolides and quinolones. Store record reviews revealed that among 149 investigated puppies, 142 (95%) received one or more courses of antibiotics, raising concern that antibiotic use might have led to development of resistance. Public health authorities issued infection prevention recommendations to affected pet stores and recommendations for testing puppies to veterinarians. This outbreak demonstrates that puppies can be a source of multidrug-resistant Campylobacter infections in humans, warranting a closer look at antimicrobial use in the commercial dog industry.
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Infecciones por Campylobacter/epidemiología , Campylobacter jejuni/efectos de los fármacos , Brotes de Enfermedades , Perros/microbiología , Farmacorresistencia Bacteriana Múltiple , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Infecciones por Campylobacter/tratamiento farmacológico , Infecciones por Campylobacter/prevención & control , Campylobacter jejuni/aislamiento & purificación , Niño , Preescolar , Trazado de Contacto , Brotes de Enfermedades/prevención & control , Heces/microbiología , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Estados Unidos/epidemiología , Adulto Joven , ZoonosisRESUMEN
KIF3A, the gene encoding kinesin family member 3A, is a susceptibility gene locus associated with asthma; however, mechanisms by which KIF3A might influence the pathogenesis of the disorder are unknown. In this study, we deleted the mouse Kif3a gene in airway epithelial cells. Both homozygous and heterozygous Kif3a gene-deleted mice were highly susceptible to aeroallergens from Aspergillus fumigatus and the house dust mite, resulting in an asthma-like pathology characterized by increased goblet cell metaplasia, airway hyperresponsiveness, and Th2-mediated inflammation. Deletion of the Kif3a gene increased the severity of pulmonary eosinophilic inflammation and expression of cytokines (Il-4, Il-13, and Il-17a) and chemokine (Ccl11) RNAs following pulmonary exposure to Aspergillus extract. Inhibition of Kif3a disrupted the structure of motile cilia and impaired mucociliary clearance, barrier function, and epithelial repair, demonstrating additional mechanisms by which deficiency of KIF3A in respiratory epithelial cells contributes to pulmonary pathology. Airway epithelial KIF3A suppresses Th2 pulmonary inflammation and airway hyperresponsiveness following aeroallergen exposure, implicating epithelial microtubular functions in the pathogenesis of Th2-mediated lung pathology.
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Alérgenos/inmunología , Aspergillus fumigatus/inmunología , Asma/inmunología , Células Epiteliales/inmunología , Cinesinas/inmunología , Mucosa Respiratoria/inmunología , Células Th2/inmunología , Animales , Asma/inducido químicamente , Asma/genética , Asma/patología , Citocinas/genética , Citocinas/inmunología , Células Epiteliales/patología , Cinesinas/genética , Pulmón/inmunología , Pulmón/patología , Ratones , Ratones Transgénicos , Mucosa Respiratoria/patología , Células Th2/patologíaRESUMEN
PURPOSE OF THE REVIEW: To summarize advances in genomic medicine and anticipated future directions to improve cardiovascular risk reduction. RECENT FINDINGS: Mendelian randomization and genome-wide association studies have given significant insights into the role of genetics in dyslipidemia and cardiovascular disease (CVD), with over 160 gene loci found to be associated with coronary artery disease to date. This has enabled the creation of genetic risk scores that have demonstrated improved risk prediction when added to clinical markers of CVD risk. Incorporation of genomic data into clinical patient care is on the horizon. Genomic medicine is expected to offer improved risk assessment, determination of targeted treatment strategies, and improved detection of lipid disorders causal to CVD development.
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Enfermedades Cardiovasculares/prevención & control , Dislipidemias/prevención & control , Terapia Molecular Dirigida/tendencias , Medicina de Precisión , Prevención Primaria , Enfermedades Cardiovasculares/genética , Enfermedades Cardiovasculares/terapia , Dislipidemias/genética , Dislipidemias/terapia , Diagnóstico Precoz , Estudio de Asociación del Genoma Completo , Genómica , Humanos , Análisis de la Aleatorización Mendeliana , Medicina de Precisión/tendencias , Medición de RiesgoRESUMEN
BACKGROUND: Allergic sensitization to fungi has been associated with asthma severity. As a result, it has been largely assumed that the contribution of fungi to allergic disease is mediated through their potent antigenicity. OBJECTIVE: We sought to determine the mechanism by which fungi affect asthma development and severity. METHODS: We integrated epidemiologic and experimental asthma models to explore the effect of fungal exposure on asthma development and severity. RESULTS: We report that fungal exposure enhances allergen-driven TH2 responses, promoting severe allergic asthma. This effect is independent of fungal sensitization and can be reconstituted with ß-glucan and abrogated by neutralization of IL-17A. Furthermore, this severe asthma is resistant to steroids and characterized by mixed TH2 and TH17 responses, including IL-13+IL-17+CD4+ double-producing effector T cells. Steroid resistance is dependent on fungus-induced TH17 responses because steroid sensitivity was restored in IL-17rc-/- mice. Similarly, in children with asthma, fungal exposure was associated with increased serum IL-17A levels and asthma severity. CONCLUSION: Our data demonstrate that fungi are potent immunomodulators and have powerful effects on asthma independent of their potential to act as antigens. Furthermore, our results provide a strong rationale for combination treatment strategies targeting IL-17A for this subgroup of fungus-exposed patients with difficult-to-treat asthma.
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Alérgenos/inmunología , Asma/inmunología , Hongos/inmunología , Células Th17/inmunología , Células Th2/inmunología , beta-Glucanos/inmunología , Contaminantes Atmosféricos/inmunología , Animales , Antiinflamatorios/uso terapéutico , Antígenos Dermatofagoides/inmunología , Asma/tratamiento farmacológico , Asma/epidemiología , Asma/patología , Niño , Preescolar , Dexametasona/uso terapéutico , Resistencia a Medicamentos/inmunología , Exposición a Riesgos Ambientales , Femenino , Glucocorticoides/uso terapéutico , Humanos , Lactante , Interleucina-17/sangre , Interleucina-17/inmunología , Lectinas Tipo C/genética , Pulmón/efectos de los fármacos , Pulmón/inmunología , Pulmón/patología , Masculino , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Noqueados , Prevalencia , Receptores de Interleucina/genéticaRESUMEN
BACKGROUND: Exposure to traffic pollution particulate matter, predominantly diesel exhaust particles (DEPs), increases the risk of asthma and asthma exacerbation; however, the underlying mechanisms remain poorly understood. OBJECTIVE: We sought to examine the effect of DEP exposure on the generation and persistence of allergen-specific memory T cells in asthmatic patients and translate these findings by determining the effect of early DEP exposure on the prevalence of allergic asthma in children. METHODS: The effect of DEPs on house dust mite (HDM)-specific memory responses was determined by using an asthma model. Data from children enrolled in the Cincinnati Childhood Allergy and Air Pollution Study birth cohort were analyzed to determine the effect of DEP exposure on asthma outcomes. RESULTS: DEP coexposure with HDM resulted in persistent TH2/TH17 CD127(+) effector/memory cells in the lungs, spleen, and lymph nodes of adult and neonatal mice. After 7 weeks of rest, a single exposure to HDM resulted in airway hyperresponsiveness and increased TH2 cytokine levels in mice that had been previously exposed to both HDM and DEPs versus those exposed to HDM alone. On the basis of these data, we examined whether DEP exposure was similarly associated with increased asthma prevalence in children in the presence or absence of allergen exposure/sensitization in the Cincinnati Childhood Allergy and Air Pollution Study birth cohort. Early-life exposure to high DEP levels was associated with significantly increased asthma prevalence among allergic children but not among nonallergic children. CONCLUSION: These findings suggest that DEP exposure results in accumulation of allergen-specific TH2/TH17 cells in the lungs, potentiating secondary allergen recall responses and promoting the development of allergic asthma.
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Alérgenos/efectos adversos , Asma/inducido químicamente , Susceptibilidad a Enfermedades , Memoria Inmunológica , Material Particulado/efectos adversos , Animales , Animales Recién Nacidos , Asma/sangre , Asma/inmunología , Asma/patología , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Inmunoglobulina E/sangre , Lactante , Pulmón/efectos de los fármacos , Pulmón/inmunología , Pulmón/patología , Ganglios Linfáticos/inmunología , Ganglios Linfáticos/patología , Masculino , Ratones , Modelos Inmunológicos , Pyroglyphidae/química , Pyroglyphidae/inmunología , Bazo/inmunología , Bazo/patología , Células Th17/inmunología , Células Th17/patología , Células Th2/inmunología , Células Th2/patología , Emisiones de VehículosAsunto(s)
Resistencia de las Vías Respiratorias/inmunología , Asma/inmunología , Citocinas/inmunología , Células Epiteliales/inmunología , Pulmón/inmunología , Material Particulado/inmunología , Emisiones de Vehículos , Animales , Antígenos Dermatofagoides/inmunología , Bronquios , Líquido del Lavado Bronquioalveolar/citología , Líquido del Lavado Bronquioalveolar/inmunología , Línea Celular , Citocinas/genética , Modelos Animales de Enfermedad , Células Epiteliales/metabolismo , Inmunidad Innata/inmunología , Inmunoglobulinas/genética , Pulmón/patología , Macrófagos Alveolares/inmunología , Ratones , Ratones Noqueados , Pyroglyphidae , ARN Mensajero/metabolismo , Receptores de Citocinas/genética , Mucosa Respiratoria/inmunología , Mucosa Respiratoria/metabolismo , Células Th2 , Linfopoyetina del Estroma TímicoAsunto(s)
Asma , Hiperreactividad Bronquial , Trastornos Respiratorios , Hipersensibilidad Respiratoria , Asma/tratamiento farmacológico , Asma/etiología , Asma/prevención & control , Hiperreactividad Bronquial/etiología , Hiperreactividad Bronquial/prevención & control , Cisteamina/uso terapéutico , HumanosRESUMEN
PURPOSE OF REVIEW: Exposure to traffic-related air pollutants (TRAPs) has been implicated in asthma development, persistence, and exacerbation. This exposure is highly significant because increasingly large segments of the population worldwide reside in zones that have high levels of TRAP, including children, as schools are often located in high traffic pollution exposure areas. RECENT FINDINGS: Recent findings include epidemiologic and mechanistic studies that shed new light on the impact of traffic pollution on allergic diseases and the biology underlying this impact. In addition, new innovative methods to assess and quantify traffic pollution have been developed to assess exposure and identify vulnerable populations and individuals. SUMMARY: This review will summarize the most recent findings in each of these areas. These findings will have a substantial impact on clinical practice and research by the development of novel methods to quantify exposure and identify at-risk individuals, as well as mechanistic studies that identify new targets for intervention for individuals most adversely affected by TRAP exposure.
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Contaminantes Atmosféricos/efectos adversos , Contaminación del Aire/efectos adversos , Asma/etiología , Eccema/etiología , Exposición a Riesgos Ambientales/efectos adversos , Rinitis Alérgica Estacional/etiología , Emisiones de Vehículos/análisis , Asma/inmunología , Asma/fisiopatología , Niño , Preescolar , Eccema/inmunología , Eccema/fisiopatología , Humanos , Rinitis Alérgica Estacional/inmunología , Rinitis Alérgica Estacional/fisiopatología , Instituciones AcadémicasRESUMEN
Despite its presence on resident skin cells, the role of TLR4 in skin diseases remains poorly understood. This is highly significant because the skin biome is rich with potential TLR4 agonists. We aimed to establish the contribution of TLR4 to atopic dermatitis and determine the mechanism by which TLR4 acts in an experimental model of atopic dermatitis. MyD88, TLR4, or Toll-IL-1R domain-containing adapter-inducing IFN-ß (TRIF)-deficient and wild-type mice were epicutaneously exposed to Aspergillus fumigatus allergen over 3 wk. Impaired skin barrier function was assessed by measuring transepidermal water loss (TEWL). Skin levels of innate and adaptive genes were quantified. In an experimental model of atopic dermatitis, TEWL, allergic sensitization, and epidermal thickness were increased following cutaneous allergen exposure, and these were further enhanced in the absence of TLR4. Increased allergen-induced skin levels of innate (S100A8/A9, IL-1ß, TNF-α, and CXCL2) and Th17 genes (IL-17A and IL-17F) were observed in TLR4-deficient mice compared with wild-type mice. The absence of MyD88 alleviated disease (decreased TEWL, skin thickness, proinflammatory cytokines), whereas TRIF deficiency exacerbated disease. In conclusion, signaling through the TLR4 and TRIF pathways limits skin barrier dysfunction, cutaneous allergic sensitization, and proinflammatory cytokine production.