RESUMO
Levels of cytokines are used for in-depth characterization of patients with asthma; however, the variability over time might be a critical confounder. To analyze the course of serum cytokines in children, adolescents and adults with asthma and in healthy controls and to propose statistical methods to control for seasonal effects. Of 532 screened subjects, 514 (91·5%) were included in the All Age Asthma Cohort (ALLIANCE). The cohort included 279 children with either recurrent wheezing bronchitis (more than two episodes) or doctor-diagnosed asthma, 75 healthy controls, 150 adult asthmatics and 31 adult healthy controls. Blood samples were collected and 25 µl serum was used for analysis with the Bio-Plex Pr human cytokine 27-Plex assay. Mean age, body mass index and gender in the three groups of wheezers, asthmatic children and adult asthmatics were comparable to healthy controls. Wheezers (34·5%), asthmatic children (78·7%) and adult asthmatics (62·8%) were significantly more often sensitized compared to controls (4·5, 22 and 22·6%, respectively). Considering the entire cohort, interleukin (IL)-1ra, IL-4, IL-9, IL-17, macrophage inflammatory protein (MIP)-1- α and tumor necrosis factor (TNF)- α showed seasonal variability, whereas IL-1ß, IL-7, IL-8, IL-13, eotaxin, granulocyte colony-stimulating factor (G-CSF), interferon gamma-induced protein (IP)-10, MIP-1 ß and platelet-derived growth factor (PDGF)-BB did not. Significant differences between wheezers/asthmatics and healthy controls were observed for IL-17 and PDGF-BB, which remained stable after adjustment for the seasonality of IL-17. Seasonality has a significant impact on serum cytokine levels in patients with asthma. Because endotyping has achieved clinical importance to guide individualized patient-tailored therapy, it is important to account for seasonal effects.
Assuntos
Asma/imunologia , Citocinas/imunologia , Sons Respiratórios/imunologia , Estações do Ano , Adolescente , Adulto , Algoritmos , Asma/sangue , Asma/diagnóstico , Criança , Pré-Escolar , Estudos de Coortes , Citocinas/sangue , Feminino , Humanos , Masculino , Modelos Teóricos , Sons Respiratórios/diagnóstico , Fatores de TempoRESUMO
Cross-sectional studies have shown that exposure to indoor moisture damage and mold may be associated with subclinical inflammation. Our aim was to determine whether early age exposure to moisture damage or mold is prospectively associated with subclinical systemic inflammation or with immune responsiveness in later childhood. Home inspections were performed in children's homes in the first year of life. At age 6 years, subclinical systemic inflammation was measured by serum C-reactive protein (CRP) and blood leukocytes and immune responsiveness by ex vivo production of interleukin 1-beta (IL-1ß), IL-6, and tumor necrosis factor alpha (TNF-α) in whole blood cultures without stimulation or after 24 hours stimulation with phorbol 12-myristate 13-acetate and ionomycin (PI), lipopolysaccharide (LPS), or peptidoglycan (PPG) in 251-270 children. Moisture damage in child's main living areas in infancy was not significantly associated with elevated levels of CRP or leukocytes at 6 years. In contrast, there was some suggestion for an effect on immune responsiveness, as moisture damage with visible mold was positively associated with LPS-stimulated production of TNF-α and minor moisture damage was inversely associated with PI-stimulated IL-1ß. While early life exposure to mold damage may have some influence on later immune responsiveness, it does not seem to increase subclinical systemic inflammation in later life.
Assuntos
Poluentes Atmosféricos/toxicidade , Poluição do Ar em Ambientes Fechados/efeitos adversos , Exposição Ambiental/efeitos adversos , Fungos , Inflamação/sangue , Poluentes Atmosféricos/análise , Poluição do Ar em Ambientes Fechados/análise , Proteína C-Reativa/análise , Criança , Citocinas/sangue , Exposição Ambiental/análise , Feminino , Humanos , Lactente , Inflamação/etiologia , Interleucina-1beta/sangue , Interleucina-6/sangue , Ionomicina , Contagem de Leucócitos , Leucócitos , Lipopolissacarídeos , Masculino , Peptidoglicano , Estudos Prospectivos , Acetato de Tetradecanoilforbol/análogos & derivados , Fator de Necrose Tumoral alfa/sangueRESUMO
Farm environment has been shown to protect from childhood asthma. Underlying immunological mechanisms are not clear yet, including the role of dendritic cells (DCs). The aim was to explore whether asthma and farm exposures are associated with the proportions and functional properties of DCs from 4.5-year-old children in a subgroup of the Finnish PASTURE birth cohort study. Myeloid DCs (mDCs), plasmacytoid DCs (pDCs) and CD86 expression on mDCs ex vivo (n = 100) identified from peripheral blood mononuclear cells (PBMCs) were analysed using flow cytometry. MDCs and production of interleukin (IL)-6 and tumour necrosis factor alpha (TNF-α) by mDCs were analysed after 5 h in vitro stimulation with lipopolysaccharide (LPS) (n = 88). Prenatal and current farm exposures (farming, stables, hay barn and farm milk) were assessed from questionnaires. Asthma at age 6 years was defined as a doctor's diagnosis and symptoms; atopic sensitization was defined by antigen-specific IgE measurements. Asthma was positively associated with CD86 expression on mDCs ex vivo [adjusted odds ratio (aOR) 4.83, 95% confidence interval (CI) 1.51-15.4] and inversely with IL-6 production in mDCs after in vitro stimulation with LPS (aOR 0.19, 95% CI 0.04-0.82). In vitro stimulation with LPS resulted in lower percentage of mDCs in the farm PBMC cultures as compared to non-farm PBMC cultures. Our results suggest an association between childhood asthma and functional properties of DCs. Farm exposure may have immunomodulatory effects by decreasing mDC proportions.
Assuntos
Agricultura , Asma/epidemiologia , Asma/imunologia , Células Dendríticas/imunologia , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Finlândia , Citometria de Fluxo , Humanos , Hipersensibilidade/epidemiologia , Hipersensibilidade/imunologia , Imunofenotipagem , MasculinoRESUMO
BACKGROUND: The transcription factor STAT6 is crucial for activation of the interleukin (IL)-4/IL-13 pathway and has been linked to regulatory T cells (Tregs). Associations of STAT6 polymorphisms with IgE levels were described; however, their impact on neonatal immune responses and early disease development is unknown. METHODS: STAT6 polymorphisms were genotyped in cord blood mononuclear cells by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Gene expression was assessed by real-time polymerase chain reaction (PCR) and cytokines by Multiplex. At age 3 years, atopic diseases were assessed by questionnaires. RESULTS: STAT6 rs324011 but not rs1059513 polymorphism was associated with significant or borderline significant decreased mRNA expression of Treg-associated genes (FOXP3, GITR, LAG3). Heterozygotes and minor allele homozygotes of rs324011 had low levels of tumor necrosis factor alpha (TNF-α) and increased interferon gamma (IFN-γ) (P ≤ 0.04), while heterozygotes and minor allele homozygotes of rs1059513 had increased TNF-α and Granulocyte-macrophage colony-stimulating factor (GM-CSF) (P ≤ 0.05). In minor allele homozygotes of rs324011, expression of Treg-associated genes was strongly inverse correlated with IFN-γ (unstimulated, r = -0.7, P = 0.111; LpA stimulation, r = -0.8, P = 0.011), but not in heterozygotes or major allele homozygotes. Heterozygotes and minor allele homozygotes of rs324011 presented a lower risk of atopic dermatitis and obstructive bronchitis until age 3 years. CONCLUSIONS: Two STAT6 polymorphisms were associated with altered immune responses already at birth. STAT6 rs324011 was associated with lower neonatal Treg and increased Th1 response. Those neonates had a lower risk of atopic dermatitis and obstructive bronchitis until 3 years. Our data suggest a role for STAT6 polymorphisms in early immune regulation and implications on early atopic disease development.
Assuntos
Citocinas/sangue , Hipersensibilidade Imediata/genética , Hipersensibilidade Imediata/imunologia , Polimorfismo de Nucleotídeo Único , Fator de Transcrição STAT6/genética , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Alelos , Antígenos CD/genética , Antígenos CD/metabolismo , Biomarcadores/metabolismo , Bronquite/genética , Bronquite/imunologia , Bronquite/metabolismo , Pré-Escolar , Estudos de Coortes , Dermatite Atópica/genética , Dermatite Atópica/imunologia , Dermatite Atópica/metabolismo , Feminino , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Regulação da Expressão Gênica , Estudos de Associação Genética , Genótipo , Humanos , Hipersensibilidade Imediata/diagnóstico , Hipersensibilidade Imediata/metabolismo , Recém-Nascido , Masculino , Avaliação de Resultados da Assistência ao Paciente , Proteína do Gene 3 de Ativação de LinfócitosRESUMO
The leading priority for the Polish Presidency of the Council of the European Union was to reduce health inequalities across European societies, and, within its framework, prevention and control of respiratory diseases in children. This very important paper contain proposal of international cooperation on the prevention, early detection and monitoring of asthma and allergic diseases in childhood which will be undertaken by the EU member countries as a result of EU conclusion developed during the Polish Presidency of the Council of the European Union. This will result in collaboration in the field of chronic diseases, particularly respiratory diseases, together with the activity of the network of national institutions and NGOs in this area. Paper also contains extensive analysis of the socio-economic, political, epidemiological, technological and medical factors affecting the prevention and control of childhood asthma and allergy presented during Experts presidential conference organized in Warsaw-Ossa 21-22 September 2011.
Assuntos
Asma/epidemiologia , Asma/prevenção & controle , Hipersensibilidade/epidemiologia , Hipersensibilidade/prevenção & controle , Criança , Diagnóstico Precoce , União Europeia , Humanos , Cooperação Internacional , Programas Nacionais de Saúde , Polônia/epidemiologia , Saúde Pública/métodosRESUMO
BACKGROUND: Toll-like receptor (TLR) polymorphisms have been associated with atopic diseases in children and adults. Development of atopic diseases may be modified by TLR-mediated signals that modulate T-regulatory cells (Tregs) early in life when maternal influences are still present and relevant. The aim of this study was to assess whether genetic TLR variants influence Tregs in neonates. METHODS: Twelve single nucleotide polymorphisms located in TLR1, TLR2, TLR4, TLR6, and TLR10 were genotyped in 200 cord blood samples (72 samples from atopic, 128 from nonatopic mothers). Cord blood mononuclear cells were cultured without or with stimulation [lipid A (LpA), peptidoglycan (Ppg), phytohemagglutinin, house dust mite]. mRNA expression of Treg marker genes [forkhead box protein P3 (FOXP3), glucocorticoid-induced tumor necrosis factor receptor (GITR), lymphocyte activation gene 3 (LAG3)], TLR2, Th1/Th2 cytokines, and tumor necrosis factor alpha (TNF-α) was measured. RESULTS: In children with the AA genotype of the TLR2 promoter variant rs4696480, gene expression of FOXP3 and Treg marker genes GITR and LAG3 as well as Th2 cytokines and TNF-α secretion was significantly increased in the presence of maternal atopy and Tregs decreased without maternal atopy. In carriers of the GG genotype for TLR2 rs1898830, gene expression of Treg marker genes was significantly decreased with and increased without maternal atopy. FOXP3 expression was also modified by TLR1 rs4833095 (P ≤ 0.03) and trendwise by TLR10 rs4129009 after LpA and Ppg stimulation. CONCLUSIONS: Genetic variations of TLR2, TLR1, and TLR10 affect Treg marker gene expression in cord blood. Gene-immunological interactions of the TLR pathway influence Tregs early in life, modulated by maternal atopy. This may be relevant for immune maturation in the development of atopic diseases in childhood.
Assuntos
Hipersensibilidade Imediata , Polimorfismo Genético/imunologia , Linfócitos T Reguladores/imunologia , Receptor 2 Toll-Like/genética , Biomarcadores/análise , Feminino , Sangue Fetal/citologia , Genótipo , Humanos , Recém-Nascido , Troca Materno-Fetal , Mães , Polimorfismo de Nucleotídeo Único , Gravidez , Receptor 1 Toll-Like , Receptor 10 Toll-LikeRESUMO
BACKGROUND: Common polymorphisms have been identified in genes suspected to play a role in asthma. We investigated their associations with wheeze and allergy in a case-control sample from Phase 2 of the International Study of Asthma and Allergies in Childhood. METHODS: We compared 1105 wheezing and 3137 non-wheezing children aged 8-12 years from 17 study centres in 13 countries. Genotyping of 55 candidate single nucleotide polymorphisms (SNPs) in 14 genes was performed using the Sequenom System. Logistic regression models were fitted separately for each centre and each SNP. A combined per allele odds ratio and measures of heterogeneity between centres were derived by random effects meta-analysis. RESULTS: Significant associations with wheeze in the past year were detected in only four genes (IL4R, TLR4, MS4A2, TLR9, P<0.05), with per allele odds ratios generally <1.3. Variants in IL4R and TLR4 were also related to allergen-specific IgE, while polymorphisms in FCER1B (MS4A2) and TLR9 were not. There were also highly significant associations (P<0.001) between SPINK5 variants and visible eczema (but not IgE levels) and between IL13 variants and total IgE. Heterogeneity of effects across centres was rare, despite differences in allele frequencies. CONCLUSIONS: Despite the biological plausibility of IgE-related mechanisms in asthma, very few of the tested candidates showed evidence of association with both wheeze and increased IgE levels. We were unable to confirm associations of the positional candidates DPP10 and PHF11 with wheeze, although our study had ample power to detect the expected associations of IL13 variants with IgE and SPINK5 variants with eczema.
Assuntos
Estudos de Associação Genética , Hipersensibilidade/genética , Sons Respiratórios/genética , Alérgenos/imunologia , Ásia , Asma/genética , Criança , Proteínas de Ligação a DNA/genética , Dipeptidil Peptidases e Tripeptidil Peptidases/genética , Equador , Eczema/genética , Europa (Continente) , Frequência do Gene/genética , Fatores de Troca do Nucleotídeo Guanina/genética , Humanos , Hipersensibilidade/sangue , Hipersensibilidade/imunologia , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Interleucina-13/genética , Subunidade alfa de Receptor de Interleucina-4/genética , Desequilíbrio de Ligação/genética , Receptores de Lipopolissacarídeos/genética , Nova Zelândia , Polimorfismo de Nucleotídeo Único/genética , Proteínas Secretadas Inibidoras de Proteinases/genética , Receptores de IgE/genética , Sons Respiratórios/imunologia , Rinite Alérgica Perene/genética , Rinite Alérgica Sazonal/genética , Inibidor de Serinopeptidase do Tipo Kazal 5 , Testes Cutâneos , Receptor 2 Toll-Like/genética , Receptor 4 Toll-Like/genética , Receptor Toll-Like 9/genética , Fatores de Transcrição/genética , Fator de Crescimento Transformador beta1/genética , Fator de Necrose Tumoral alfa/genéticaRESUMO
Asthma prevalence is increasing in adult and paediatric patients. In the present study, the association between different leisure time activities and new onset of wheezing was analysed in adolescents aged 16-18 yrs taking part in a questionnaire-based follow-up of the International Study on Asthma and Allergies in Childhood in Munich and Dresden, Germany. Of the 3,785 adolescents who took part in the follow-up (76% response), 2,910 adolescents without earlier episodes of wheezing in childhood were included in the analyses. Of these, 330 (11.3%) reported new onset of wheeze during the previous 12 months. In the bivariate analyses, exercising more than once per week or performing computer work >1 h.day(-1) were inversely related to new onset of wheeze. In contrast, visiting discotheques on a regular basis increased the risk of new onset of wheeze (12.9 versus 9.9%). The observed inverse relationship between physical activity and new onset of wheeze was not an independent effect but mediated by differences in active smoking. The association between physical activity and new onset of wheeze disappeared when active smoking was taken into account. However, the present data do not allow for determining whether smoking operated as a confounder or as an intermediate factor, i.e. whether physical activities prevented active smoking.
Assuntos
Asma/epidemiologia , Sons Respiratórios/diagnóstico , Adolescente , Asma/etiologia , Exercício Físico , Alemanha , Passatempos , Humanos , Hipersensibilidade , Atividades de Lazer , Atividade Motora , Prevalência , Sons Respiratórios/etiologia , Fatores de Risco , Fumar , Inquéritos e Questionários , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Eosinophilic inflammation is considered to play an important role in the development as well as in the perpetuation of asthma. As eosinophil production and survival is under genetic control we investigated whether polymorphisms in eosinophil regulation pathway genes (IL-3, IL-5, GM-CSF and their respective enhancers and receptors) may influence the development of atopic diseases. METHODS: In two large study populations of children, the German part of the International Study of Asthma and Allergy in Childhood (ISAAC II) and the German Multicentre Atopy Study (MAS), 3099 and 824 children, seven polymorphisms previously associated with the development of atopic diseases were genotyped: two in and around the GM-CSF gene (Ile117Thr and T3085G), one in IL-3 (Pro27Ser), in IL-5 (C-746T), and in the IL-5 high affinity receptor chain IL-5R (G-80A) and two in the common receptor chain CSFR2b for IL-3, IL-5, and GM-CSF (Asp312Asn and Glu249Gln). Statistical analyses were performed using chi-squared tests and variance analyses. Gene by gene interactions were evaluated in logistic regression models. RESULTS: The T allele at position -746 in the IL-5 gene was significantly protective for atopy in the ISAAC II population (P = 0.006). Furthermore, the risk for atopic asthma was decreased in carriers of the T allele (P = 0.036) and evidence for interaction with the enhancer polymorphism 3085 bp 3' of GM-CSF was detected. CONCLUSIONS: IL-5 C-746T influenced atopic outcomes and showed evidence for gene by gene interaction. No significant associations were found with all other tested polymorphisms in the eosinophil regulation pathway after correction for multiple testing.
Assuntos
Asma/genética , Hipersensibilidade Imediata/genética , Rinite Alérgica Sazonal/genética , Adolescente , Asma/epidemiologia , Asma/imunologia , Asma/fisiopatologia , Hiper-Reatividade Brônquica , Testes de Provocação Brônquica , Criança , Pré-Escolar , Eosinófilos/imunologia , Genótipo , Alemanha/epidemiologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Histamina/administração & dosagem , Humanos , Hipersensibilidade Imediata/epidemiologia , Hipersensibilidade Imediata/imunologia , Hipersensibilidade Imediata/fisiopatologia , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Lactente , Recém-Nascido , Interleucina-5/genética , Polimorfismo Genético , Testes de Função Respiratória , Rinite Alérgica Sazonal/epidemiologia , Rinite Alérgica Sazonal/imunologia , Rinite Alérgica Sazonal/fisiopatologia , Testes Cutâneos , Cloreto de Sódio/administração & dosagemRESUMO
BACKGROUND: The association between smoking and asthma or wheeze has been extensively studied in cross sectional studies, but evidence from large prospective cohort studies on the incidence of asthma during adolescence is scarce. METHODS: We report data from a cohort study in two German cities, Dresden and Munich. The study population (n = 2936) was first studied in 1995/6 at age 9-11 years as part of phase II of the International Study of Asthma and Allergies in Childhood (ISAAC II) and followed up in 2002/3. At baseline the parents completed a questionnaire and children underwent clinical examination and blood sampling. At follow up the young adults completed questionnaires on respiratory health, living, and exposure conditions. Incidence risk ratios (IRR) were calculated and adjusted for potential confounders using a modified Poisson regression approach. RESULTS: The adjusted IRR for incident wheeze for active smokers compared with non-smokers was 2.30 (95% confidence interval (CI) 1.88 to 2.82). The adjusted IRR was slightly higher for incident wheeze without a cold (2.76, 95% CI 1.99 to 3.84) and the incidence of diagnosed asthma (2.56, 95% CI 1.55 to 4.21). Analysis of duration and intensity of active smoking indicated dose dependent associations. Stratified analyses showed that the risk of incident wheeze without a cold in atopic smokers increased with decreasing plasma alpha(1)-antitrypsin levels at baseline (1.64, 95% CI 1.22 to 2.20 per interquartile range). CONCLUSIONS: Active smoking is an important risk factor for the incidence of asthma during adolescence. Relatively lower plasma levels of alpha(1)-antitrypsin, although well above currently accepted thresholds, may increase susceptibility to respiratory disease among atopic smokers.
Assuntos
Asma/etiologia , Fumar/efeitos adversos , Adolescente , Asma/epidemiologia , Métodos Epidemiológicos , Feminino , Humanos , Masculino , Exame Físico , Prognóstico , Fumar/epidemiologia , Inquéritos e QuestionáriosRESUMO
BACKGROUND: It has been suggested that the genetically determined deficiency of glutathione S transferase (GST) enzymes involved in the detoxification of environmental tobacco smoke (ETS) components may contribute to the development of asthma. METHODS: A large population of German schoolchildren (n = 3054) was genotyped for deficiencies of the GST isoforms M1 and T1. The association between GSTM1 and GSTT1 genotypes and asthma as well as atopy was investigated with respect to current and in utero ETS exposure. RESULTS: In children lacking the GSTM1 allele who were exposed to current ETS the risk for current asthma (OR 5.5, 95% CI 1.6 to 18.6) and asthma symptoms such as wheeze ever (OR 2.8, 95% CI 1.3 to 6.0), current wheezing (OR 4.7, 95% CI 1.8 to 12.6) and shortness of breath (OR 8.9, 95% CI 2.1 to 38.4) was higher than in GSTM1 positive individuals without ETS exposure. Hints of an interaction between ETS exposure and GSTM1 deficiency were identified. In utero smoke exposure in GSTT1 deficient children was associated with significant decrements in lung function compared with GSTT1 positive children not exposed to ETS. CONCLUSIONS: GSTM1 and GSTT1 deficiency may increase the adverse health effects of in utero and current smoke exposure.
Assuntos
Asma/enzimologia , Glutationa Transferase/deficiência , Poluição por Fumaça de Tabaco/efeitos adversos , Asma/fisiopatologia , Criança , Estudos Transversais , Feminino , Volume Expiratório Forçado/fisiologia , Frequência do Gene , Genótipo , Glutationa Transferase/genética , Humanos , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Sons Respiratórios , Fatores de Risco , Capacidade Vital/fisiologiaRESUMO
Conflicting results have been reported for the relationship between traffic exposure and inception of atopy. The effect of traffic on the prevalence of asthma and atopy at school age was investigated in a representative population. Random samples of schoolchildren (n=7,509, response rate 83.7%) were studied using the International Study of Asthma and Allergies in Childhood phase-II protocol with skin-prick tests, measurements of specific immunoglobulin E and lung function. Traffic exposure was assessed via traffic counts and by an emission model which predicted soot, benzene and nitrogen dioxide (NO2). Traffic counts were associated with current asthma, wheeze and cough. In children with tobacco-smoke exposure, traffic volume was additionally associated with a positive skin-prick test. Cough was associated with soot, benzene and NO2, current asthma with soot and benzene, and current wheeze with benzene and NO2. No pollutant was associated with allergic sensitisation. High vehicle traffic was associated with asthma, cough and wheeze, and in children additionally exposed to environmental tobacco smoke, with allergic sensitisation. However, effects of socioeconomic factors associated with living close to busy roads cannot be ruled out.
Assuntos
Asma/epidemiologia , Asma/etiologia , Exposição Ambiental/efeitos adversos , Hipersensibilidade Imediata/epidemiologia , Hipersensibilidade Imediata/etiologia , Veículos Automotores/estatística & dados numéricos , Avaliação de Resultados em Cuidados de Saúde , Transtornos Respiratórios/epidemiologia , Transtornos Respiratórios/etiologia , População Urbana/estatística & dados numéricos , Emissões de Veículos/efeitos adversos , Asma/sangue , Criança , Pré-Escolar , Exposição Ambiental/análise , Humanos , Hipersensibilidade Imediata/sangue , Imunoglobulina E/sangue , Prevalência , Distribuição Aleatória , Transtornos Respiratórios/sangue , Testes de Função Respiratória , Testes Cutâneos , Fatores Socioeconômicos , Emissões de Veículos/análiseRESUMO
Exposure to environmental tobacco smoke (ETS) and other air pollutants has been associated with small decrements in lung function. The susceptibility to pollution exposure may, however, vary substantially between individuals. Children with an impaired protease-antiprotease balance may be particularly vulnerable. Therefore this study aimed to investigate the effects of ETS exposure on children with reduced levels of alpha1-antitrypsin (alpha1-AT). Random samples of school children (aged 9-11 yrs) (n=3,526) were studied according to the International Study of Asthma and Allergies in Childhood (ISAAC) phase II protocol, including parental questionnaires, pulmonary function and allergy testing. Blood samples were obtained to measure plasma levels of alpha1-AT and to genotype for pleomorphic protein inhibitor (Pi)Z and PiS alleles. Children with low levels of alpha1-AT (< or = 116 mg x dL(-1)) showed significant, albeit small decrements in baseline lung function. When exposed to ETS, pronounced decrements of pulmonary function, particularly in measures of mid- to end-expiratory flow rates, were seen in these children as compared to exposed children with normal levels of alpha1-AT. The mean levels of % predicted+/-SE in both groups were: maximum expiratory flow at 50% of vital capacity 79.4+/-7.2 versus 99.0+/-1.5, maximum expiratory flow at 25% of vital capacity 67.4+/-10.0 versus 100.3+/-2.1, maximal midexpiratory flow 73.7+/-8.6 versus 99.9+/-1.7. These findings suggest that school children with low levels of alpha1-antitrypsin are at risk of developing pronounced decrements in pulmonary function, particularly if they are exposed to environmental tobacco smoke. Parents of children with heterozygous alpha1-antitrypsin deficiency resulting in significantly reduced blood concentrations should be advised to prevent their children from being exposed to environmental tobacco smoke and dissuade them from taking up smoking.
Assuntos
Pneumopatias/epidemiologia , Poluição por Fumaça de Tabaco , Deficiência de alfa 1-Antitripsina/epidemiologia , alfa 1-Antitripsina/metabolismo , Criança , Estudos Transversais , Exposição Ambiental , Predisposição Genética para Doença/epidemiologia , Heterozigoto , Homozigoto , Humanos , Pneumopatias/genética , Pneumopatias/metabolismo , Fluxo Expiratório Máximo , Fluxo Máximo Médio Expiratório , Fenótipo , Prevalência , Distribuição Aleatória , Fatores de Risco , Capacidade Vital , Deficiência de alfa 1-Antitripsina/genética , Deficiência de alfa 1-Antitripsina/metabolismoRESUMO
SUMMARY: Environmental factors during early childhood seem to influence the onset of asthma, a disease that affects 10% of all German children, respectively. Prevention strategies are needed to reduce the burden of the disease. Breast feeding and the avoidance of environmental tobacco smoke exposure are recommended for primary prevention. Furthermore, secondary prevention measurements are suggested to reduce the onset of symptoms, once the disease is present.
Assuntos
Asma/prevenção & controle , Aleitamento Materno , Poluição por Fumaça de Tabaco/prevenção & controle , Poluição do Ar em Ambientes Fechados/efeitos adversos , Poluição do Ar em Ambientes Fechados/prevenção & controle , Asma/etiologia , Asma/imunologia , Criança , Pré-Escolar , Exposição Ambiental , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Prevenção Primária , Fatores de Risco , Poluição por Fumaça de Tabaco/efeitos adversosRESUMO
OBJECTIVE: To evaluate whether breast feeding is associated with prevalent overweight in pre-adolescent children. METHODS: Cross-sectional studies of 9 to 10-y-old children attending fourth grade in 1995/1996 in Dresden (n=1046) and Munich (n=1062), Germany, according to the International Study of Asthma and Allergies in Childhood (ISAAC) Phase II protocol. A comprehensive questionnaire including detailed breast feeding history was filled out by the child's parent. Height and weight were measured in a random subsample of children undergoing spirometry. Overweight was defined as body mass index > or =90th age- and sex-specific percentile of the German reference. RESULTS: While the prevalence of overweight differed substantially between Dresden (girls 9.1%, boys 12.5%) and Munich (17% both), we observed a markedly lower overweight prevalence among breast fed than non-breast fed children in both cities. Controlling for age, sex and city, breast-fed children were substantially less likely to be overweight at 9-10 y (OR 0.55, 95% CI 0.41-0.74). Results were slightly attenuated after adjustment for nationality, socio-economic status, number of siblings, parental smoking (OR 0.66, 95% CI 0.52-0.87). A longer overall duration and duration of exclusive breast feeding was associated significantly with decreasing prevalence of overweight. CONCLUSION: The results highlight the importance and possible preventive potential of early nutrition in the development of overweight in children. Both feeding behaviors acquired by the nursing infant and metabolic effects may contribute to the observed inverse association of breast feeding and overweight in children.
Assuntos
Aleitamento Materno/estatística & dados numéricos , Obesidade/epidemiologia , Índice de Massa Corporal , Criança , Estudos Transversais , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Obesidade/etiologia , Prevalência , Inquéritos e QuestionáriosRESUMO
BACKGROUND: An increase in the prevalence of obesity and asthma over recent decades has been reported in affluent societies. Both overweight and obesity have been shown to be inversely related to having been breastfed, which is also a potential protective factor against childhood atopic diseases. The aim of this analysis was to explore the relation of body mass index (BMI) to asthma and atopy in a large representative sample of the United States population. METHODS: Children aged 4-17 years were included in the NHANES III survey. Prevalences of atopic diseases and potential confounding factors such as exposure to environmental tobacco smoke, birth weight, breast feeding, and household size were assessed using structured interviews with parents. Height and weight were measured, and BMI was calculated as kg/m(2) and transformed into Z scores. Children underwent skin prick tests for atopy to a battery of food and inhalant allergens. RESULTS: The prevalence of asthma (8.7% v 9.3% v 10.3% v 14.9%, p=0.0001) and atopy (48.6% v 50.5% v 53.0% v 53.2%, p=0.05) rose significantly with increasing quartiles of BMI. After adjustment for confounders, a significant positive association between BMI and asthma remained (adjusted OR 1.77, 95% confidence interval 1.44 to 2.19 between the highest and lowest quartiles of BMI), whereas no independent relation between BMI and atopy was evident. No effect modification by sex or ethnic group was seen. CONCLUSIONS: The effects of increased BMI on asthma may be mediated by mechanical properties of the respiratory system associated with obesity or by upregulation of inflammatory mechanisms rather than by allergic eosinophilic inflammation of the airway epithelium.
Assuntos
Asma/etiologia , Índice de Massa Corporal , Hipersensibilidade/etiologia , Adolescente , Asma/epidemiologia , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Hipersensibilidade/epidemiologia , Masculino , Prevalência , Fatores de Risco , Testes Cutâneos , Estatística como Assunto , Estados Unidos/epidemiologiaRESUMO
The increasing prevalence of atopic diseases, particularly atopy-associated asthma, has become a major challenge for allergists and public health authorities in many countries. The understanding of the natural history of the atopic march, including the determinants that are modifiable and might become candidates for preventive intervention, is still very limited. Information provided by cross-sectional studies can only generate hypotheses, which need to be supported by prospective, longitudinal, cohort studies. Ultimately, it will depend on the results of well-controlled intervention studies to identify which nutritional, environmental, or lifestyle-related factors should be considered for early intervention and might be useful to reverse the epidemiologic trend.
Assuntos
Hipersensibilidade/etiologia , Biomarcadores , Criança , Poluentes Ambientais/toxicidade , Humanos , Hipersensibilidade/genética , Hipersensibilidade/prevenção & controle , Infecções/imunologia , Estilo de Vida , Fatores de Risco , Fumar/efeitos adversosAssuntos
Asma/etiologia , Adolescente , Adulto , Fatores Etários , Asma/epidemiologia , Asma/fisiopatologia , Criança , Pré-Escolar , Feminino , Humanos , Hipersensibilidade Imediata/epidemiologia , Lactente , Pulmão/fisiopatologia , Masculino , Pneumonia/complicações , Prevalência , Fatores de Risco , Fatores Sexuais , Fumar/efeitos adversos , Poluição por Fumaça de Tabaco/efeitos adversosRESUMO
Paediatric asthma is a major clinical concern worldwide and represents a huge burden on family and society. It accounts for a large number of lost school days and may deprive the child of both academic achievement and social interaction. Childhood asthma also places strain on healthcare resources as a result of doctor and hospital visits and the cost of treatment. The prevalence of asthma varies worldwide, possibly because of different exposure to respiratory infection, indoor and outdoor pollution, and diet. Certain risk factors appear to predispose children to developing asthma and atopic disease, including incidence and severity of wheezing, atopy, maternal smoking, and number of fever episodes. This paper discusses the burden, prevalence, and risk factors associated with paediatric asthma.
Assuntos
Asma/epidemiologia , Efeitos Psicossociais da Doença , Adolescente , Asma/etiologia , Asma/prevenção & controle , Criança , Febre/complicações , Humanos , Hipersensibilidade Imediata/complicações , Prognóstico , Sons Respiratórios , Infecções Respiratórias/complicações , Fatores de RiscoRESUMO
BACKGROUND: Some studies suggest that the prevalence of sensitization to cockroach allergens may be higher in the United States than in Europe, but there are no comparable data from population-based studies. OBJECTIVES: To determine the prevalence of allergic sensitization to German cockroach (GCR) in German schoolchildren and to assess its clinical relevance; and to determine the exposure to the major GCR allergen Bla g 2 in non-selected homes and nurseries. METHODS: The prevalence of allergic sensitization to GCR and other allergens was determined by measurement of specific IgE and skin-prick tests in a cross-sectional study of 2993 children aged 5-11 years in Dresden, Germany. The prevalence of atopic disease was determined by questionnaire, and pulmonary function and bronchial hyperresponsiveness to hypertonic saline were measured. Bla g 2 exposure was determined on floors of 187 kitchens and 47 nurseries by a commercial sandwich ELISA. RESULTS: One hundred and twenty-seven (4.2%) of the children had specific IgE (> 0.7 kU/L) against GCR. Among children with current wheeze, 8.4% were GCR-sensitized. Compared to data from the United States, the prevalence of sensitization to cockroach was similar in children without asthma (3.9%), but less frequent in asthmatic children from Dresden (6.1%). After adjustment for positive reactions to other allergens (SX1 test) no significant impact of GCR sensitization on wheeze or other symptoms and diagnoses was found. Bla g 2 was detected in 29% of the kitchens and 43% of the nurseries. None of these sites had exposure levels above the proposed threshold for causing disease of 80 ng/g dust. CONCLUSION: The data suggest that allergic sensitization to GCR is less frequent in asthmatics from Dresden, Germany than in US cities. The data indicate that GCR sensitization is not an independent risk factor for asthma and other atopic diseases in 5-11-year-olds from this city.