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2.
Environ Pollut ; 256: 113434, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31672350

RESUMO

BACKGROUND: Little information exists on interaction effects between air pollution and influenza vaccination on allergic respiratory diseases. We conducted a large population-based study to evaluate the interaction effects between influenza vaccination and long-term exposure to ambient air pollution on allergic respiratory diseases in children and adolescents. METHODS: A cross-sectional study was investigated during 2012-2013 in 94 schools from Seven Northeastern Cities (SNEC) in China. Questionnaires surveys were obtained from 56 137 children and adolescents aged 2-17 years. Influenza vaccination was defined as receipt of the influenza vaccine. We estimated air pollutants exposure [nitrogen dioxide (NO2) and particulate matter with aerodynamic diameters ≤1 µm (PM1), ≤2.5 µm (PM2.5) and ≤10 µm (PM10)] using machine learning methods. We employed two-level generalized linear mix effects model to examine interactive effects between influenza vaccination and air pollution exposure on allergic respiratory diseases (asthma, asthma-related symptoms and allergic rhinitis), after controlling for important covariates. RESULTS: We found statistically significant interactions between influenza vaccination and air pollutants on allergic respiratory diseases and related symptoms (doctor-diagnosed asthma, current wheeze, wheeze, persistent phlegm and allergic rhinitis). The adjusted ORs for doctor-diagnosed asthma, current wheeze and allergic rhinitis among the unvaccinated group per interquartile range (IQR) increase in PM1 and PM2.5 were significantly higher than the corresponding ORs among the vaccinated group [For PM1, doctor-diagnosed asthma: OR: 1.89 (95%CI: 1.57-2.27) vs 1.65 (95%CI: 1.36-2.00); current wheeze: OR: 1.50 (95%CI: 1.22-1.85) vs 1.10 (95%CI: 0.89-1.37); allergic rhinitis: OR: 1.38 (95%CI: 1.15-1.66) vs 1.21 (95%CI: 1.00-1.46). For PM2.5, doctor-diagnosed asthma: OR: 1.81 (95%CI: 1.52-2.14) vs 1.57 (95%CI: 1.32-1.88); current wheeze: OR: 1.46 (95%CI: 1.21-1.76) vs 1.11 (95%CI: 0.91-1.35); allergic rhinitis: OR: 1.35 (95%CI: 1.14-1.60) vs 1.19 (95%CI: 1.00-1.42)]. The similar patterns were observed for wheeze and persistent phlegm. The corresponding p values for interactions were less than 0.05, respectively. We assessed the risks of PM1-related and PM2.5-related current wheeze were decreased by 26.67% (95%CI: 1.04%-45.66%) and 23.97% (95%CI: 0.21%-42.08%) respectively, which was attributable to influenza vaccination (both p for efficiency <0.05). CONCLUSIONS: Influenza vaccination may play an important role in mitigating the detrimental effects of long-term exposure to ambient air pollution on childhood allergic respiratory diseases. Policy targeted at increasing influenza vaccination may yield co-benefits in terms of reduced allergic respiratory diseases.


Assuntos
Poluição do Ar/estatística & dados numéricos , Exposição Ambiental/estatística & dados numéricos , Doenças Respiratórias/epidemiologia , Adolescente , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Asma/epidemiologia , Criança , Pré-Escolar , China , Cidades , Estudos Transversais , Feminino , Humanos , Hipersensibilidade/epidemiologia , Influenza Humana , Modelos Logísticos , Masculino , Dióxido de Nitrogênio , Material Particulado/análise , Transtornos Respiratórios , Sons Respiratórios , Fatores de Risco , Instituições Acadêmicas , Inquéritos e Questionários , Vacinação
3.
Environ Pollut ; 256: 113422, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31672364

RESUMO

Evidence suggests that residential greenness may be protective of high blood pressure, but there is scarcity of evidence on the associations between greenness around schools and blood pressure among children. We aimed to investigate this association in China. Our study included 9354 children from 62 schools in the Seven Northeastern Cities Study. Greenness around each child's school was measured by NDVI (Normalized Difference Vegetation Index) and SAVI (Soil-Adjusted Vegetation Index). Particulate matter ≤ 1 µm (PM1) concentrations were estimated by spatiotemporal models and nitrogen dioxide (NO2) concentrations were collected from air monitoring stations. Associations between greenness and blood pressure were determined by generalized linear and logistic mixed-effect models. Mediation by air pollution was assessed using mediation analysis. Higher greenness was consistently associated with lower blood pressure. An increase of 0.1 in NDVI corresponded to a reduction in SBP of 1.39 mmHg (95% CI: 1.86, -0.93) and lower odds of hypertension (OR = 0.76, 95% CI: 0.69, 0.82). Stronger associations were observed in children with higher BMI. Ambient PM1 and NO2 mediated 33.0% and 10.9% of the association between greenness and SBP, respectively. In summary, greater greenness near schools had a beneficial effect on blood pressure, particularly in overweight or obese children in China. The associations might be partially mediated by air pollution. These results might have implications for policy makers to incorporate more green space for both aesthetic and health benefits.


Assuntos
Exposição Ambiental/estatística & dados numéricos , Hipertensão/epidemiologia , Desenvolvimento Sustentável , Poluição do Ar/análise , Poluição do Ar/estatística & dados numéricos , Pressão Sanguínea , Criança , China/epidemiologia , Cidades , Feminino , Humanos , Masculino , Dióxido de Nitrogênio/análise , Obesidade , Material Particulado/análise , Risco , Instituições Acadêmicas
4.
Hypertension ; 75(2): 347-355, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31838909

RESUMO

Evidence on the associations between airborne particulates of diameter ≤1 µm (PM1) and airborne particulates of diameter ≤2.5 µm (PM2.5) and childhood blood pressure (BP) is scarce. To help to address this literature gap, we conducted a study to explore the associations in Chinese children. Between 2012 and 2013, we recruited 9354 children, aged 5 to 17 years, from 62 schools in 7 northeastern Chinese cities. We measured their BP with a mercury sphygmomanometer. We used a spatiotemporal model to estimate daily ambient PM1 and PM2.5 exposures, which we assigned to participants' home addresses. Associations between particulate matter exposure and BP were evaluated with generalized linear mixed regression models. The findings indicated that exposure to each 10 mg/m3 greater PM1 was significantly associated with 2.56 mm Hg (95% CI, 1.47-3.65) higher systolic BP and 61% greater odds for hypertension (odds ratio=1.61 [95% CI, 1.18-2.18]). PM1 appears to play an important role in associations reported between PM2.5 exposure and BP, and we found that the ambient PM1/PM2.5 ratio (range, 0.80-0.96) was associated with BP and with hypertension. Age and body weight modified associations between air pollutants and BP (P<0.01), with stronger associations among younger (aged ≤11 years) and overweight/obese children. This study provides the first evidence that long-term exposure to PM1 is associated with hypertension in children, and that PM1 might be a leading contributor to the hypertensive effect of PM2.5. Researchers and policy makers should pay closer attention to the potential health impacts of PM1.

5.
J Allergy Clin Immunol ; 144(6): 1684-1696.e12, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31381928

RESUMO

BACKGROUND: Childhood asthma prevalence is significantly greater in urban areas compared with rural/farm environments. Murine studies have shown that TNF-α-induced protein 3 (TNFAIP3; A20), an anti-inflammatory regulator of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling, mediates environmentally induced asthma protection. OBJECTIVE: We aimed to determine the role of TNFAIP3 for asthma development in childhood and the immunomodulatory effects of environmental factors. METHODS: In a representative selection of 250 of 2168 children from 2 prospective birth cohorts and 2 cross-sectional studies, we analyzed blood cells of healthy and asthmatic children from urban and rural/farm environments from Europe and China. PBMCs were stimulated ex vivo with dust from "asthma-protective" farms or LPS. NF-κB signaling-related gene and protein expression was assessed in PBMCs and multiplex gene expression assays (NanoString Technologies) in isolated dendritic cells of schoolchildren and in cord blood mononuclear cells from newborns. RESULTS: Anti-inflammatory TNFAIP3 gene and protein expression was consistently decreased, whereas proinflammatory Toll-like receptor 4 expression was increased in urban asthmatic patients (P < .05), reflecting their increased inflammatory status. Ex vivo farm dust or LPS stimulation restored TNFAIP3 expression to healthy levels in asthmatic patients and shifted NF-κB signaling-associated gene expression toward an anti-inflammatory state (P < .001). Farm/rural children had lower expression, indicating tolerance induction by continuous environmental exposure. Newborns with asthma at school age had reduced TNFAIP3 expression at birth, suggesting TNFAIP3 as a possible biomarker predicting subsequent asthma. CONCLUSION: Our data indicate TNFAIP3 as a key regulator during childhood asthma development and its environmentally mediated protection. Because environmental dust exposure conferred the anti-inflammatory effects, it might represent a promising future agent for asthma prevention and treatment.

7.
Nat Med ; 25(7): 1089-1095, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31209334

RESUMO

Asthma prevalence has increased in epidemic proportions with urbanization, but growing up on traditional farms offers protection even today1. The asthma-protective effect of farms appears to be associated with rich home dust microbiota2,3, which could be used to model a health-promoting indoor microbiome. Here we show by modeling differences in house dust microbiota composition between farm and non-farm homes of Finnish birth cohorts4 that in children who grow up in non-farm homes, asthma risk decreases as the similarity of their home bacterial microbiota composition to that of farm homes increases. The protective microbiota had a low abundance of Streptococcaceae relative to outdoor-associated bacterial taxa. The protective effect was independent of richness and total bacterial load and was associated with reduced proinflammatory cytokine responses against bacterial cell wall components ex vivo. We were able to reproduce these findings in a study among rural German children2 and showed that children living in German non-farm homes with an indoor microbiota more similar to Finnish farm homes have decreased asthma risk. The indoor dust microbiota composition appears to be a definable, reproducible predictor of asthma risk and a potential modifiable target for asthma prevention.


Assuntos
Asma/prevenção & controle , Poeira , Fazendas , Microbiota , Archaea , Bactérias , Humanos , Estudos Prospectivos
8.
JAMA Netw Open ; 2(5): e194186, 2019 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-31125097

RESUMO

Importance: Breastfeeding and exposure to ambient air pollutants have been found to be independently associated with respiratory health in children; however, previous studies have not examined the association of breastfeeding as a potential moderator of the association. Objective: To assess associations of breastfeeding and air pollution with lung function in children. Design, Setting, and Participants: Using a cross-sectional study design, children were recruited from 62 elementary and middle schools located in 7 Chinese cities from April 1, 2012, to October 31, 2013. Data analyses were conducted from November 1, 2018, to March 31, 2019. Exposures: Long-term concentrations of airborne particulate matter with a diameter of 1 µm or less (PM1), airborne particulate matter with a diameter of 2.5 µm or less (PM2.5), airborne particulate matter with a diameter of 10 µm or less (PM10), and nitrogen dioxide were estimated using a spatial statistical model matched to children's geocoded home addresses, and concentrations of PM10, sulfur dioxide, nitrogen dioxide, and ozone were measured by local air monitoring stations. Main Outcomes and Measures: Breastfeeding was defined as maternal report of having mainly breastfed for longer than 3 months. Lung function was measured using portable electronic spirometers. Using previously published predicted spirometric values for children in Northeast China as the reference, lung impairment was defined as forced vital capacity (FVC) less than 85%, forced expiratory volume in the first second of expiration less than 85%, peak expiratory flow less than 75%, or maximum midexpiratory flow less than 75%. Results: Participants included 6740 children (mean [SD] age, 11.6 [2.1] years; 3382 boys [50.2%]). There were 4751 children (70.5%) who were breastfed. Mean (SD) particulate matter concentrations ranged from 46.8 (6.5) µg/m3 for PM1 to 95.6 (9.8) µg/m3 for PM10. The prevalence of lung function impairment ranged from 6.8% for peak expiratory flow to 11.3% for FVC. After controlling for age, sex, and other covariates, 1-interquartile range greater concentration of pollutants was associated with higher adjusted odds ratios (AORs) for lung function impairment by FVC among children who were not breastfed compared with those who were (PM1: AOR, 2.71 [95% CI, 2.02-3.63] vs 1.20 [95% CI, 0.97-1.48]; PM2.5: AOR, 2.27 [95% CI, 1.79-2.88] vs 1.26 [95% CI, 1.04-1.51]; and PM10: AOR, 1.93 [95% CI, 1.58-2.37] vs 1.46 [95% CI, 1.23-1.73]). Younger age (<12 years) was associated with lower lung function impairment among the children who had been breastfed. In children from elementary schools, 1-interquartile range greater concentration of pollutants was associated with higher AORs for lung function impairment by FVC among children who had not been breastfed compared with those who had (PM1: AOR, 6.43 [95% CI, 3.97-10.44] vs 1.89 [95% CI, 1.28-2.80]; PM2.5: AOR, 3.83 [95% CI, 2.63-5.58] vs 1.50 [95% CI, 1.12-2.01]; and PM10: AOR, 2.61 [95% CI, 1.90-3.57] vs 1.52 [95% CI, 1.19-1.95]). Results from linear regression models also showed associations of air pollution with worse lung function among children who were not breastfed compared with their counterparts who were breastfed, especially for FVC (PM1: ß, -240.46 [95% CI, -288.71 to -192.21] vs -38.21 [95% CI, -69.27 to -7.16] mL) and forced expiratory volume in the first second of expiration (PM1: ß, -201.37 [95% CI, -242.08 to -160.65] vs -30.30 [95% CI, -57.66 to -2.94] mL). Conclusions and Relevance: In this study, breastfeeding was associated with lower risk of lung function impairment among children in China exposed to air pollution, particularly among younger children.


Assuntos
Poluição do Ar/análise , Aleitamento Materno/estatística & dados numéricos , Pulmão/fisiopatologia , Adolescente , Poluição do Ar/efeitos adversos , Estudos de Casos e Controles , Criança , China , Estudos Transversais , Exposição Ambiental , Feminino , Humanos , Masculino , Material Particulado/efeitos adversos , Material Particulado/análise , Testes de Função Respiratória/estatística & dados numéricos
9.
Sci Total Environ ; 663: 60-67, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30708217

RESUMO

BACKGROUND: Perfluoroalkyl substances (PFASs) are synthetic chemicals widely used in industry and for commercial products. Their immunomodulatory effects are a growing health concern in children. Hand, Foot and Mouth Disease (HFMD) is a common childhood viral infection, and increased incidence of which has parallel the rise in PFAS exposure in the Asia-Pacific region. OBJECTIVE: We conducted the first study to assess whether prenatal exposure to PFAS was associated with a reduction in HFMD virus antibodies in infants. METHODS: We enrolled 201 mother-infant pairs from the Guangzhou Birth Cohort Study from July to October 2013. High performance liquid chromatography-mass spectrometry was employed to determine concentrations of specific PFAS isomers in cord blood. Neutralizing antibodies titers were measured against two HFMD viruses, enterovirus 71 (EV71) and coxsackievirus A 16 (CA16), in cord blood serum and blood serum at three months of age. RESULTS: Higher umbilical cord blood PFAS concentrations were associated with lower EV71 and CA16 antibody concentrations. A doubling in the composite sum of cord blood PFASs in three month old infants was associated with significant increase in the risk of HFMD antibody concentration below clinical protection level (≥1:8 titers) for CA16 (odds ratio, OR: 2.74 [95% confidence interval (CI): 1.33, 5.61] and for EV71 (OR = 4.55, 95% CI: 1.45, 4.28). This association was higher in boys at three months of age for CA16. CONCLUSIONS: Our findings suggest that cord blood PFAS exposure is associated with lower HFMD antibody in infancy. Given the widespread nature of PFAS exposures and the high global incidence of HFMD globally, these findings have substantial public health implications and therefore, these associations need to be replicated in a larger study to more definitively address the risk.


Assuntos
Anticorpos Antivirais/imunologia , Fluorcarbonetos/efeitos adversos , Vírus da Febre Aftosa/imunologia , Doença de Mão, Pé e Boca/imunologia , Efeitos Tardios da Exposição Pré-Natal/imunologia , Adulto , Anticorpos Neutralizantes/imunologia , China , Estudos de Coortes , Feminino , Sangue Fetal/química , Humanos , Lactente , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/virologia , Fatores Sexuais , Adulto Jovem
10.
Pediatr Allergy Immunol ; 29(8): 815-822, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30152886

RESUMO

BACKGROUND: Studies conducted in farm environments suggest that diverse microbial exposure promotes children's lung health. The underlying mechanisms are unclear, and the development of asthma-preventive strategies has been delayed. More comprehensive investigation of the environment-induced immunoregulation is required for better understanding of asthma pathogenesis and prevention. Exposure to air pollution, including particulate matter (PM), is a risk factor for asthma, thus providing an excellent counterpoint for the farm-effect research. Lack of comparable data, however, complicates interpretation of the existing information. We aimed to explore the immunoregulatory effects of cattle farm dust (protective, Finland) and urban air PM (high-risk, China) for the first time using identical research methods. METHODS: We stimulated PBMCs of 4-year-old children (N = 18) with farm dust and size-segregated PM and assessed the expression of immune receptors CD80 and ILT4 on dendritic cells and monocytes as well as cytokine production of PBMCs. Environmental samples were analysed for their composition. RESULTS: Farm dust increased the percentage of cells expressing CD80 and the cytokine production of children's immune cells, whereas PM inhibited the expression of important receptors and the production of soluble mediators. Although PM samples induced parallel immune reactions, the size-fraction determined the strength of the effects. CONCLUSIONS: Our study demonstrates the significance of using the same research framework when disentangling shared and distinctive immune pathways operating in different environments. Observed stimulatory effects of farm dust and inhibitory effects of PM could shape responses towards respiratory pathogens and allergens, and partly explain differences in asthma prevalence between studied environments.


Assuntos
Poluentes Atmosféricos/imunologia , Poluição do Ar/efeitos adversos , Antígeno B7-1/metabolismo , Exposição Ambiental/efeitos adversos , Glicoproteínas de Membrana/metabolismo , Receptores Imunológicos/metabolismo , Alérgenos/imunologia , Técnicas de Cultura de Células , Pré-Escolar , Citocinas/metabolismo , Fazendas/estatística & dados numéricos , Feminino , Humanos , Imunofenotipagem , Leucócitos Mononucleares/metabolismo , Masculino , Material Particulado/imunologia , Fatores de Risco
11.
Environ Int ; 120: 516-524, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30153645

RESUMO

BACKGROUND AND OBJECTIVES: Little is known about PM1 effects on respiratory health, relative to larger size fractions (PM2.5). To address this literature gap, we assessed associations between PM1 exposure and asthmatic symptoms in Chinese children and adolescents, compared with PM2.5. METHODS: A total of 59,754 children, aged 2-17 years, were recruited from 94 kindergartens, elementary and middle schools in the Seven Northeast Cities (SNEC) study, during 2012-2013. We obtained information on asthma and asthma-related symptoms including wheeze, persistent phlegm, and persistent cough using a standardized questionnaire developed by the American Thoracic Society. PM1 and PM2.5 concentrations were estimated using a spatial statistical model matched to the children's geocoded home addresses. To examine the associations, mixed models with school/kindergarten as random intercept were used, controlling for covariates. RESULTS: Odds ratios (ORs) of doctor-diagnosed asthma associated with a 10-µg/m3 increase for PM1 and PM2.5 were 1.56 (95% CI: 1.46-1.66) and 1.50 (1.41-1.59), respectively, and similar pattern were observed for other outcomes. Interaction analyses indicated that boys and the individuals with an allergic predisposition may be vulnerable subgroups. For example, among children with allergic predisposition, the ORs for doctor diagnosed asthma per 10 µg/m3 increase in PM1 was 1.71 (95% CI: 1.60-1.83), which was stronger than in their counterparts (1.46; 1.37-1.56) (pfor interaction < 0.05). CONCLUSIONS: This study indicated that long-term exposure to PM1 may increase the risk of asthma and asthma-related symptoms, especially among boys and those with allergic predisposition. Furthermore, these positive associations for PM1 were very similar to those for PM2.5.


Assuntos
Poluentes Atmosféricos/análise , Asma/epidemiologia , Tosse/epidemiologia , Hipersensibilidade/epidemiologia , Material Particulado/análise , Adolescente , Criança , Pré-Escolar , China/epidemiologia , Cidades/epidemiologia , Monitoramento Ambiental , Feminino , Humanos , Masculino , Razão de Chances , Tamanho da Partícula , Sons Respiratórios
13.
JAMA Pediatr ; 171(7): 655-662, 2017 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-28531273

RESUMO

Importance: Atopic dermatitis is an inflammatory, pruritic skin disease that often occurs in early infancy with a chronic course. However, a specific description of subtypes of atopic dermatitis depending on the timing of onset and progression of the disease in childhood is lacking. Objective: To identify different phenotypes of atopic dermatitis using a definition based on symptoms before age 6 years and to determine whether some subtypes are more at risk for developing other allergic diseases. Design, Setting, and Participants: The Protection Against Allergy Study in Rural Environments (PASTURE) is a European birth cohort where pregnant women were recruited between August 2002 and March 2005 and divided in 2 groups dependent on whether they lived on a farm. Children from this cohort with data on atopic dermatitis from birth to 6 years of age were included. Exposures: Atopic dermatitis, defined as an itchy rash on typical locations from birth to 6 years. Main Outcomes and Measures: The latent class analysis was used to identify subtypes of atopic dermatitis in childhood based on the course of symptoms. Multivariable logistic regressions were used to analyze the association between atopic dermatitis phenotypes and other allergic diseases. Results: We included 1038 children; of these, 506 were girls. The latent class analysis model with the best fit to PASTURE data separated 4 phenotypes of atopic dermatitis in childhood: 2 early phenotypes with onset before age 2 years (early transient [n = 96; 9.2%] and early persistent [n = 67; 6.5%]), the late phenotype with onset at age 2 years or older (n = 50; 4.8%), and the never/infrequent phenotype (n = 825; 79.5%), defined as children with no atopic dermatitis. Children with both parents with history of allergies were 5 times more at risk to develop atopic dermatitis with an early-persistent phenotype compared with children with parents with no history of allergies. Both early phenotypes were strongly associated with food allergy. The risk of developing asthma was significantly increased among the early-persistent phenotype (adjusted odds ratio, 2.87; 95% CI, 1.31-6.31). The late phenotype was only positively associated with allergic rhinitis. Conclusions and Relevance: Using latent class analysis, 4 phenotypes of atopic dermatitis were identified depending on the onset and course of the disease. The prevalence of asthma and food allergy by 6 years of age was strongly increased among children with early phenotypes (within age 2 years), especially with persistent symptoms. These findings are important for the development of strategies in allergy prevention.


Assuntos
Dermatite Atópica/diagnóstico , Criança , Pré-Escolar , Dermatite Atópica/epidemiologia , Progressão da Doença , Europa (Continente)/epidemiologia , Feminino , Humanos , Lactente , Recém-Nascido , Modelos Logísticos , Masculino , Fenótipo , Prevalência , Fatores de Tempo
14.
Sci Rep ; 7(1): 899, 2017 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-28420867

RESUMO

To evaluate the interactions between polyfluoroalkyl substances (PFASs) and reproductive hormones and associated asthma, a total of 231 asthmatic and 225 non-asthmatic adolescents were selected from northern Taiwan in the Genetic and Biomarkers study for Childhood Asthma from 2009-2010. The interaction between PFASs and reproductive hormones on asthma was analyzed with a two-level binary logistic regression model. The results showed that, among asthmatics, PFASs were positively associated with estradiol levels and negatively associated with testosterone levels. However, only significant association was identified for PFNA and estradiol in control group. After controlling for hormone levels, associations between PFAS exposure and asthma were consistently stronger among children with higher than lower estradiol, with odds ratios (OR) for asthma ranging from 1.25 for PFOS (95% Confidence Interval [CI]: 0.90, 1.72) to 4.01 for PFDA (95% CI: 1.46, 11.06) among boys and 1.25 for PFOS (95% CI: 0.84, 1.86) to 4.16 for PFNA (95% CI: 1.36, 12.73) among girls. Notably, the interactions between estradiol and PFASs were significant for PFOS (p = 0.026) and PFNA (p = 0.043) among girls. However, testosterone significantly attenuated the association between PFOS and asthma across sex. In conclusions, our findings suggested that reproductive hormones amplify the association between PFASs and asthma among adolescents.


Assuntos
Asma/epidemiologia , Poluentes Ambientais/sangue , Estradiol/sangue , Fluorcarbonetos/sangue , Testosterona/sangue , Adolescente , Asma/sangue , Criança , Feminino , Humanos , Masculino
15.
Am J Reprod Immunol ; 77(3)2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28044379

RESUMO

PROBLEM: Birth-related factors and neonatal treatments could affect the maturation of immune system and thus have lasting effects on immune responses. We investigated the effect of obstetric factors other than being born by cesarean section on immune responses later in life. METHOD OF STUDY: Regulatory, inflammatory, TH1 and TH2 cytokines, and a chemokine were analyzed in unstimulated and Toll-like receptors (TLRs) 2-, 3-, and 4-stimulated PBMCs of teenagers born by cesarean delivery (CD; N=79). Data on obstetric factors were collected from patient data archives. RESULTS: Advanced cervical dilatation at the time of CD associated with higher unstimulated production of cytokines compared to adolescents who were delivered before the onset of labor. Neonatal intensive care treatment associated with lower unstimulated production of cytokines. Similar associations were found following TLR stimulations. CONCLUSION: The lack of natural processes of delivery and neonatal intensive care treatment might lead to long-lasting impairment of immune responses.


Assuntos
Cesárea , Sistema Imunitário , Terapia Intensiva Neonatal , Leucócitos Mononucleares/imunologia , Células Th1/imunologia , Células Th2/imunologia , Útero/metabolismo , Adolescente , Células Cultivadas , Citocinas/metabolismo , Feminino , Humanos , Masculino , Gravidez , Receptores Toll-Like/metabolismo
16.
Pediatr Allergy Immunol ; 28(1): 53-59, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27633913

RESUMO

BACKGROUND: Respiratory tract infections and their symptoms are frequent during early childhood, but their risk factors, including the effect of early immune regulation, are less known. The aim of the study was to analyze whether stimulated cord blood cytokine production is associated with the frequency of respiratory tract infection symptoms or infections during the first year of life. METHODS: The study population consisted of children of mothers from farm or non-farm rural environment from Austria, Finland, Germany, and Switzerland who participated in a prospective birth cohort study (PASTURE: Protection against Allergy-Study in Rural Environments) (N = 550). Cord blood samples were stimulated with the combination of phorbol ester and ionomycin (P/I) for 24 h, and the production of IL-5, IL-10, TNF-α, and IFN-γ was determined using ELISA. Information about infectious morbidity was collected using weekly diaries. RESULTS: P/I-stimulated production of IL-5 (adjusted risk ratio (aRR) for ≤median production, 0.37; 95% confidence interval (CI), 0.25-0.55, aRR for >median production, 0.41; 95% CI, 0.27-0.61 vs. production median production, 0.39; 95% CI, 0.25-0.62 vs. production

Assuntos
Citocinas/sangue , Orelha Média/imunologia , Sangue Fetal/imunologia , Infecções Respiratórias/imunologia , População Rural , Células Th1/imunologia , Células Th2/imunologia , Células Cultivadas , Estudos de Coortes , Europa (Continente)/epidemiologia , Humanos , Imunidade , Lactente , Recém-Nascido , Ionomicina/imunologia , Estudos Prospectivos , Infecções Respiratórias/epidemiologia , Inquéritos e Questionários , Acetato de Tetradecanoilforbol/imunologia
17.
Pediatr Allergy Immunol ; 27(7): 687-695, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27171815

RESUMO

BACKGROUND: IL-33 polymorphisms influence the susceptibility to asthma. IL-33 indirectly induces Th2-immune responses via dendritic cell activation, being important for development of atopic diseases. Furthermore, IL-33 upregulates regulatory T cells (Tregs), which are critical for healthy immune homeostasis. This study investigates associations between IL-33 polymorphisms during the development of childhood atopic diseases and underlying mechanisms including immune regulation of Tregs. METHODS: Genotyping of IL-33-polymorphisms (rs928413, rs1342326) was performed by MALDI-TOF-MS in 880 of 1133 PASTURE/EFRAIM children. In 4.5-year-old German PASTURE/EFRAIM children (n = 99), CD4+ CD25high FOXP3+ Tregs were assessed by flow cytometry following 24-h incubation of PBMCs with PMA/ionomycin, LPS or without stimuli (U). SOCS3, IL1RL1, TLR4 mRNA expression and sST2 protein levels ex vivo were measured in PASTURE/EFRAIM children by real-time PCR or ELISA, respectively. Health outcomes (hay fever, asthma) were assessed by questionnaires at the age of 6 years. RESULTS: rs928413 and rs1342326 were positively associated with hay fever (OR = 1.77, 95%CI = 1.02-3.08; OR = 1.79, 95%CI = 1.04-3.11) and CD4+ CD25high FOXP3+ Tregs (%) decreased in minor allele homozygotes/heterozygotes compared to major allele homozygotes (p(U) = 0.004; p(LPS) = 0.005; p(U) = 0.001; p(LPS) = 0.012). SOCS3 mRNA expression increased in minor allele homozygotes and heterozygotes compared with major allele homozygotes for both IL-33-polymorphisms (p(rs928413) = 0.032, p(rs1342326) = 0.019) and negatively correlated to Tregs. CONCLUSIONS: IL-33-polymorphisms rs928413 and rs1342326 may account for an increased risk of hay fever with the age of 6 years. Lower Tregs and increased SOCS3 in combined heterozygotes and minor allele homozygotes may be relevant for hay fever development, pointing towards dysbalanced immune regulation and insufficient control of allergic inflammation.


Assuntos
Interleucina-33/genética , Rinite Alérgica Sazonal/genética , Proteína 3 Supressora da Sinalização de Citocinas/metabolismo , Linfócitos T Reguladores/imunologia , Células Cultivadas , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Fatores de Transcrição Forkhead/metabolismo , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Alemanha , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Risco , Proteína 3 Supressora da Sinalização de Citocinas/genética
18.
Chest ; 149(4): 1030-41, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26836923

RESUMO

BACKGROUND: Environmental factors may play important roles in asthma, but findings have been inconsistent. OBJECTIVE: The goal of this study was to determine the associations between early life exposures, environmental factors, and asthma in urban and rural children in southeast China. METHODS: A screening questionnaire survey was conducted in 7,164 children from urban Guangzhou and 6,087 from rural Conghua. In the second stage, subsamples of 854 children (419 from Guangzhou, 435 from Conghua) were recruited for a case-control study that included a detailed questionnaire enquiring on family history, early life environmental exposures, dietary habits, and laboratory tests (including histamine airway provocation testing, skin prick tests, and serum antibody analyses). House dust samples from 76 Guangzhou families and 80 Conghua families were obtained to analyze levels of endotoxins, house dust mites, and cockroach allergens. RESULTS: According to the screening survey, the prevalence of physician-diagnosed asthma was lower in children from Conghua (3.4%) than in those from Guangzhou (6.9%) (P < .001). A lower percentage of asthma was reported in rural subjects compared with urban subjects (2.8% vs. 29.4%; P < .001) in the case-control study. Atopy (OR, 1.91 [95% CI, 1.58-2.29]), parental atopy (OR, 2.49 [95% CI, 1.55-4.01]), hospitalization before 3 years of age (OR, 2.54 [95% CI, 1.37-4.70]), high consumption of milk products (OR, 1.68 [95% CI, 1.03-2.73]), and dust Dermatophagoides farinae group 1 allergen (OR, 1.71 [95% CI, 1.34-2.19]) were positively associated with asthma. Living in a crop-farming family at < 1 year of age (OR, 0.15 [95% CI, 0.08-0.32]) and dust endotoxin levels (OR, 0.69 [95% CI, 0.50-0.95]) were negatively associated with asthma. CONCLUSIONS: Rural children from an agricultural background exhibited a reduced risk of asthma. Early life exposure to crop farming and high environmental endotoxin levels might protect the children from asthma in southern China.


Assuntos
Agricultura/estatística & dados numéricos , Asma/epidemiologia , Laticínios/estatística & dados numéricos , Dieta/estatística & dados numéricos , Exposição Ambiental/estatística & dados numéricos , População Rural/estatística & dados numéricos , População Urbana/estatística & dados numéricos , Adolescente , Alérgenos , Animais , Antígenos de Dermatophagoides , Estudos de Casos e Controles , Criança , China/epidemiologia , Baratas/imunologia , Poeira/análise , Endotoxinas , Feminino , Humanos , Hipersensibilidade Imediata/epidemiologia , Modelos Logísticos , Masculino , Análise Multivariada , Prevalência , Testes Cutâneos , Inquéritos e Questionários
19.
J Pharm Biomed Anal ; 96: 151-5, 2014 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-24742773

RESUMO

Cytokine concentrations in biological fluids are widely used markers for activation of immunological processes. Confirming the reproducibility of measurements is important, especially in longitudinal or multicenter studies where time between analyses or different analyzing laboratories increases the intra-assay variability. In this study, the reproducibility of the cytokine analysis conducted with different assay platforms was studied by comparing the results of two cytokines [interleukin (IL)-6 in serum and nasal lavage fluid (NAL) and IL-8 in NAL] analyzed with Meso Scale Discovery (MSD) ultra-sensitive single and multiplex assay kits (n=76). In addition, the difference in cytokine levels between two biological sample matrices was studied by comparing the results of altogether 9 cytokines [IL-6, IL-2, IL-8, IL12p70, IL-1ß, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon (IFN)γ, IL-10 and tumor necrosis factor (TNF)α] measured from serum and NAL of the same study subjects (n=460). The results show that the cytokine concentrations analyzed with single and multiplex assays are concordant but not equal. Comparison of the different matrices revealed that cytokine concentrations in serum do not correspond with concentrations detected in nasal lavage fluid. It can be concluded that comparability of the results from single and multiplex analysis of cytokines is high, but the concentrations should not be compared directly with each other. The differences between concentrations analyzed from serum and nasal lavage fluid indicate that the levels are specific for each matrix and represent distinct immunological conditions.


Assuntos
Citocinas/análise , Líquido da Lavagem Nasal/química , Estudos Transversais , Citocinas/sangue , Citocinas/metabolismo , Humanos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
20.
J Allergy Clin Immunol ; 133(2): 551-9, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23993223

RESUMO

BACKGROUND: European cross-sectional studies have suggested that prenatal and postnatal farm exposure decreases the risk of allergic diseases in childhood. Underlying immunologic mechanisms are still not understood but might be modulated by immune-regulatory cells early in life, such as regulatory T (Treg) cells. OBJECTIVE: We sought to assess whether Treg cells from 4.5-year-old children from the Protection against Allergy: Study in Rural Environments birth cohort study are critical in the atopy and asthma-protective effect of farm exposure and which specific exposures might be relevant. METHODS: From 1133 children, 298 children were included in this study (149 farm and 149 reference children). Detailed questionnaires until 4 years of age assessed farming exposures over time. Treg cells were characterized as upper 20% CD4(+)CD25(+) forkhead box protein 3 (FOXP3)(+) (intracellular) in PBMCs before and after stimulation (with phorbol 12-myristate 13-acetate/ionomycin or LPS), and FOXP3 demethylation was assessed. Atopic sensitization was defined by specific IgE measurements; asthma was defined by a doctor's diagnosis. RESULTS: Treg cells were significantly increased in farm-exposed children after phorbol 12-myristate 13-acetate/ionomycin and LPS stimulation. Exposure to farm milk was defined as a relevant independent farm-related exposure supported by higher FOXP3 demethylation. Treg cell (upper 20% CD4(+)CD25(+), FOXP3(+) T cells) numbers were significantly negatively associated with doctor-diagnosed asthma (LPS stimulated: adjusted odds ratio, 0.26; 95% CI, 0.08-0.88) and perennial IgE (unstimulated: adjusted odds ratio, 0.21; 95% CI, 0.08-0.59). Protection against asthma by farm milk exposure was partially mediated by Treg cells. CONCLUSIONS: Farm milk exposure was associated with increased Treg cell numbers on stimulation in 4.5-year-old children and might induce a regulatory phenotype early in life, potentially contributing to a protective effect for the development of childhood allergic diseases.


Assuntos
Agricultura , Asma/imunologia , Hipersensibilidade Imediata/imunologia , Leite , Linfócitos T Reguladores/imunologia , Animais , Asma/diagnóstico , Contagem de Linfócito CD4 , Pré-Escolar , Metilação de DNA , Europa (Continente) , Feminino , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/imunologia , Humanos , Hipersensibilidade Imediata/diagnóstico , Imunoglobulina E/sangue , Lactente , Masculino , Gravidez , Estudos Prospectivos , Linfócitos T Reguladores/citologia
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