Effects of environment on human cytokine responses during childhood in the tropics: role of urban versus rural residence.

BACKGROUND: Environment may have a key role in the development of the immune system in childhood and environmental exposures associated with rural residence may explain the low prevalence of allergic and autoimmune diseases in the rural tropics. We investigated the effects of urban versus rural residence on the adaptive immune response in children living in urban and rural areas in a tropical region of Latin America. METHODS: We recruited school children in either rural communities in the Province of Esmeraldas or in urban neighborhoods in the city of Esmeraldas, Ecuador. We collected data on environmental exposures by questionnaire and on intestinal parasites by examination of stool samples. Peripheral blood leukocytes (PBLs) in whole blood were stimulated with superantigen, parasite antigens and aeroallergens and IFN-γ, IL-5, IL-10, IL-13, and IL-17 were measured in supernatants. RESULTS: We evaluated 440 school children; 210 living in rural communities and 230 in the city of Esmeraldas. Overall, urban children had greater access to piped water (urban 98.7 % vs. rural 1.9 %), were more likely to have a household bathroom (urban 97.4 % vs. rural 54.8 %), and were less likely to be infected with soil-transmitted helminth infections (urban 20.9 % vs. rural 73.5 %). Generally, detectable levels of cytokines were more frequent in blood from children living in urban than rural areas. Urban residence was associated with a significantly greater frequency of IL-10 production spontaneously (adjusted OR 2.56, 95 % CI 1.05-6.24) and on stimulation with Ascaris (adj. OR 2.5, 95 % CI 1.09-5.79) and house dust mite (adj. 2.24, 95 % CI 1.07-4.70) antigens. Analysis of effects of environmental exposures on SEB-induced IL-10 production within urban and rural populations showed that some environmental exposures indicative of poor hygiene (urban - higher birth order, A. lumbricoides infection; rural - no bathroom, more peri-domiciliary animals, and living in a wood/bamboo house) were associated with elevated IL-10. CONCLUSIONS: In our study population, the immune response of children living in an urban environment was associated more frequently with the production of the immune regulatory cytokine, IL-10. Some factors related to poor hygiene and living conditions were associated with elevated IL-10 production within urban and rural populations.

Risk factors for death in patients with severe asthma.

OBJECTIVE: To identify risk factors for death among patients with severe asthma. METHODS: This was a nested case-control study. Among the patients with severe asthma treated between December of 2002 and December of 2010 at the Central Referral Outpatient Clinic of the Bahia State Asthma Control Program, in the city of Salvador, Brazil, we selected all those who died, as well as selecting other patients with severe asthma to be used as controls (at a ratio of 1:4). Data were collected from the medical charts of the patients, home visit reports, and death certificates. RESULTS: We selected 58 cases of deaths and 232 control cases. Most of the deaths were attributed to respiratory causes and occurred within a health care facility. Advanced age, unemployment, rhinitis, symptoms of gastroesophageal reflux disease, long-standing asthma, and persistent airflow obstruction were common features in both groups. Multivariate analysis showed that male gender, FEV1 pre-bronchodilator < 60% of predicted, and the lack of control of asthma symptoms were significantly and independently associated with mortality in this sample of patients with severe asthma. CONCLUSIONS: In this cohort of outpatients with severe asthma, the deaths occurred predominantly due to respiratory causes and within a health care facility. Lack of asthma control and male gender were risk factors for mortality.

Risk factors for death in patients with severe asthma / Fatores de risco de morte em pacientes portadores de asma grave

OBJECTIVE: To identify risk factors for death among patients with severe asthma. METHODS: This was a nested case-control study. Among the patients with severe asthma treated between December of 2002 and December of 2010 at the Central Referral Outpatient Clinic of the Bahia State Asthma Control Program, in the city of Salvador, Brazil, we selected all those who died, as well as selecting other patients with severe asthma to be used as controls (at a ratio of 1:4). Data were collected from the medical charts of the patients, home visit reports, and death certificates. RESULTS: We selected 58 cases of deaths and 232 control cases. Most of the deaths were attributed to respiratory causes and occurred within a health care facility. Advanced age, unemployment, rhinitis, symptoms of gastroesophageal reflux disease, long-standing asthma, and persistent airflow obstruction were common features in both groups. Multivariate analysis showed that male gender, FEV1 pre-bronchodilator < 60% of predicted, and the lack of control of asthma symptoms were significantly and independently associated with mortality in this sample of patients with severe asthma. CONCLUSIONS: In this cohort of outpatients with severe asthma, the deaths occurred predominantly due to respiratory causes and within a health care facility. Lack of asthma control and male gender were risk factors for mortality. .

OBJETIVO: Identificar os fatores de risco para morte em pacientes com asma grave. MÉTODOS: Estudo caso-controle aninhado a uma coorte de pacientes acompanhados no Ambulatório Central de Referência do Programa para o Controle da Asma na Bahia, em Salvador (BA). No período entre dezembro de 2002 e dezembro de 2010, foram selecionados todos os pacientes com asma grave que foram a óbito e pacientes asmáticos graves vivos como controles na relação 1:4. As informações foram coletadas nos prontuários do serviço e complementadas por meio de visitas domiciliares e atestados de óbitos. RESULTADOS: Foram selecionados 58 óbitos e 232 controles. Os óbitos, na sua maioria, foram atribuídos a causas respiratórias e ocorreram dentro de uma unidade de saúde. Idade avançada, inatividade laboral, presença de rinite, sintomas de doença do refluxo gastroesofágico, tempo prolongado de doença e obstrução ao fluxo aéreo persistente foram aspectos comuns em ambos os grupos. A análise multivariada mostrou que o gênero masculino, VEF1 pré-broncodilatador < 60% do previsto e a ausência de controle dos sintomas da asma foram fatores de risco significativamente e independentemente associados à mortalidade nessa amostra de asmáticos graves. CONCLUSÕES: Nesta coorte ambulatorial de pacientes com asma grave, os óbitos ocorreram predominantemente por causas respiratórias em unidades de saúde. A falta de controle da asma e o gênero masculino foram os fatores de risco para óbito. .

Seroprevalence and risk factors for Toxocara infection in children from an urban large setting in Northeast Brazil.

OBJECTIVES: This study aimed to standardize an "in house" immunoassay to detect anti-Toxocara IgG antibodies in human serum to estimate the seroprevalence of Toxocara infection, and to identify its potential risk factors in children living in poor areas of Salvador, a large northeastern Brazilian city. METHODS: Parents of 1309 children answered a questionnaire containing possible risk factor for acquisition of this infection. Blood was collected and the presence of anti-Toxocara IgG antibodies was detected by indirect ELISA using T. canis larval excretory-secretory antigens in sera previously absorbed with Ascaris lumbricoides antigens. RESULTS: Seroprevalence of Toxocara infection was 48.4%. Children's age, low maternal schooling, contact with dogs and cats, and household located in paved streets were shown to be risk factors for Toxocara infection. CONCLUSIONS: The seroprevalence of Toxocara infection is high among children living in a poor urban setting of Brazil. The association of low maternal education with higher Toxocara infection supports studies showing that low socioeconomic status is a risk factor for the acquisition of this infection as a reflection of hygiene habits of the family. And both infected-dogs and cats may be involved in this parasite transmission in this children population.

The effect of single and multiple infections on atopy and wheezing in children.

BACKGROUND: The current epidemic of asthma and atopy has been explained by alterations in immune responses related to reduction in childhood infections. However, the findings of epidemiologic studies investigating the association between infection with atopy and asthma have been inconsistent. OBJECTIVE: We sought to investigate the effect of single or multiple infections (pathogen burden) on atopy and wheeze in urban children from Latin America. METHODS: Specific IgE against aeroallergens (sIgE) and skin prick test (SPT) reactivity for the most common local allergens were measured in 1128 children aged 4 to 11 years. Data on wheezing and potential confounders were collected by questionnaire. Infections by 8 pathogens were assessed by using serology and stool examination. Associations of wheeze and atopic outcomes with single and multiple infections were analyzed by means of logistic regression. RESULTS: Negative results for Toxoplasma gondii were associated with a higher prevalence of sIgE (≥0.70 kU/L), whereas negative results for Ascaris lumbricoides, T gondii, herpes simplex virus, and EBV were associated with a higher prevalence of SPT reactivity. Children with 3 or fewer infection markers had a higher prevalence of sIgE and SPT reactivity compared with those with 4 or more infection markers. However, isolated infections or pathogen burden were not associated with the prevalence of atopic or nonatopic wheeze. CONCLUSION: The findings provide support for the idea that the hygiene hypothesis is operating in an urban Latin American context, but its expression is thus far restricted to the atopic status of patients and not the perceived asthma symptoms.

Poverty, dirt, infections and non-atopic wheezing in children from a Brazilian urban center.

BACKGROUND: The causation of asthma is poorly understood. Risk factors for atopic and non-atopic asthma may be different. This study aimed to analyze the associations between markers of poverty, dirt and infections and wheezing in atopic and non-atopic children. METHODS: 1445 children were recruited from a population-based cohort in Salvador, Brazil. Wheezing was assessed using the ISAAC questionnaire and atopy defined as allergen-specific IgE ≥ 0.70 kU/L. Relevant social factors, environmental exposures and serological markers for childhood infections were investigated as risk factors using multivariate multinomial logistic regression. RESULTS: Common risk factors for wheezing in atopic and non-atopic children, respectively, were parental asthma and respiratory infection in early childhood. No other factor was associated with wheezing in atopic children. Factors associated with wheezing in non-atopics were low maternal educational level (OR 1.49, 95% CI 0.98-2.38), low frequency of room cleaning (OR 2.49, 95% CI 1.27-4.90), presence of rodents in the house (OR 1.48, 95% CI 1.06-2.09), and day care attendance (OR 1.52, 95% CI 1.01-2.29). CONCLUSIONS: Non-atopic wheezing was associated with risk factors indicative of poverty, dirt and infections. Further research is required to more precisely define the mediating exposures and the mechanisms by which they may cause non-atopic wheeze.