PDE4D gene variants and haplotypes are associated with asthma and atopy in Brazilian children.

PDE4D (Phosphodiesterase 4D) gene encodes a hydrolase of cyclic AMP. PDE4D genetic variants have been associated with asthma susceptibility. Therefore, this study aimed to investigate the association between PDE4D variants (and haplotypes) with asthma and atopy in a Brazilian population. The study comprised 1,246 unrelated participants from the SCAALA (Social Changes Asthma and Allergy in Latin America) program. Genotyping was performed using the Illumina 2.5 Human Omni bead chip. Multivariate logistic regression was used to investigate the association between PDE4D variants and asthma/atopy phenotypes in PLINK 1.09 software. Twenty-four SNVs in PDE4D were associated with atopy or asthma. The rs6898082 (A) variant increased asthma susceptibility (OR 2.76; CI 99% 1.26-6.03) and was also related to a greater PDE4D expression in the GTEx database. Also, the variant rs6870632 was further associated with asthma in meta-analysis with a replication cohort. In addition, the variants rs75699812 (C), rs8007656 (G), and rs958851 (T) were positively associated with atopy. Moreover, these variants formed an atopy risk haplotype (OR 1.82; CI 99% 1.15-2.88). Also, these variants were related to lower levels of IL-10. Functional in silico assessment showed that some PDE4D SNVs may have an impact on gene regulation and expression. Variants in the PDE4D are positively associated with asthma and allergy markers. It is possible that these variants lead to alteration in PDE4D expression and therefore impact immunity and pulmonary function.

Impact of FOXP3 gene polymorphisms and gene-environment interactions in asthma and atopy in a Brazilian population.

BACKGROUND: Polymorphisms in genes related to the activation and development of regulatory T cells (Tregs), such as FOXP3, may be associated with asthma and atopy development. Additionally, environmental factors such as exposure to infections can modify the effect of these associations. This study evaluated the impact of polymorphisms in the FOXP3 on the risk of asthma and atopy as also gene-environment interactions in these outcomes. METHODS: This study included 1,246 children from the SCAALA program, between 4 and 11 years of age. DNA was extracted from peripheral blood and eight SNPs (rs2280883, rs11465476, rs11465472, rs2232368, rs3761549, rs3761548, rs2232365 and rs2294021) were genotyped using the 2.5 HumanOmni Beadchip from Illumina (San Diego, California, USA) or TaqMan qRT-PCR. RESULTS: The rs2232368 (Allele T) was positively associated with asthma symptoms (OR = 1.95, CI = 1.04 to 3.66, p = 0.040) and skin prick test (SPT) reactivity to aeroallergens (OR = 2.31, CI = 1.16 to 4.59, p = 0.017). The rs3761549 (Allele T) was positively associated with SPT reactivity (OR = 1.44, CI = 1.03 to 2.02, p = 0.034). The rs2280883 (Allele C) was negatively associated with specific IgE to aeroallergens (OR = 0.83, CI = 0.70 to 0.99, p = 0.040). Furthermore, the rs2280883 played a protective role in the development of atopy only in individuals seropositive to Epstein-Barr virus (EBV) infection (OR = 0.74, CI = 0.60 to 0.92, p = 0.003 and OR = 0.74; 95% CI = 0.61-0.91, p = 0.007 for SPT and slgE respectively), but not in individuals without EBV infection. CONCLUSION: Polymorphisms in the FOXP3 gene were associated with the risk of atopy and asthma development in our population. In addition, EBV infection had an effect modifier of the observed association for rs2280883 variant.

ADIPOQ and LEP variants on asthma and atopy: Genetic association modified by overweight.

BACKGROUND: Asthma and atopy are considered condition associated with obesity, being affected by genetic and environmental factors. The LEP and ADIPOQ genes, responsible for the expression and secretion of leptin and adiponectin, respectively, and polymorphisms in such genes have been linked to both diseases, independently, and also with the obesity-associated asthma phenotype in populations with high European ancestry and high-income countries. However, in mixed populations, there are few studies evaluating the impact of these variants in genes associated with the phenotype of asthma and obesity. Thus, the aim of this study was to investigate variants in LEP and ADIPOQ associated with asthma and atopy, and whether overweight modifies that effect. METHODS: The study involved 203 asthmatics children and 813 control subjects (between 5 and 11 years old), with or without overweight, from the SCAALA (Asthma and Allergy Social Changes in Latin America) program. Among them, 831 had data for allergy markers, being 258 atopic and 573 non-atopic. Genotyping was performed using a commercial panel Omnium Illumina 2.5. Logistic regression was performed to identify associations expected by using PLINK 1.09 and three genetic models: additive, dominant and recessive adjusted for sex, age, helminth infection, BMI and Principal Components (PC) 1 and 2, for ancestry, in order to control the confounding factor by population structure. RESULTS: For asthma, G allele of rs822396, in ADIPOQ, was positively associated in additive model (OR 1.4, 95% CI 1.08-1.83) and T allele of rs1063537 in dominant model (OR 1.52, 95% CI 1.01-2.30). In LEP, rs11763517 (C allele) and rs11760956 (A allele) were both negatively associated with asthma in the additive model (OR 0.70, 95% CI 0.54-0.91; OR 0.66, 95% CI 0.50-0.89) respectively, and the A allele of rs2167270 in dominant model (OR 0.71, 95% CI 0.51-0.98). The G allele of rs12706832 showed a positive association with asthma in the recessive model (OR 1.66, 95% CI 1.06-2.61). When the population was stratified by the BMI / Age Z-Score, the protection observed for asthma between the variants rs11760956, rs11763517 and rs2167270 was lost overweight individuals; The protection observed for atopy was lost in all variants (rs16861205, rs2167270 and rs17151919) in the overweight group. CONCLUSION: These results suggest that SNPs on the LEP and ADIPOQ genes may have an impact on atopy and asthma. Furthermore, we also show that the asthma and atopy protection attributed to variants on LEP and ADIPOQ genes is lost in individuals exposed to overweight.

Expression Quantitative Trait Methylation Analysis Reveals Methylomic Associations With Gene Expression in Childhood Asthma.

BACKGROUND: Nasal (airway) epithelial methylation profiles have been associated with asthma, but the effects of such profiles on expression of distant cis-genes are largely unknown. RESEARCH QUESTION: To identify genes whose expression is associated with proximal and distal CpG probes (within 1 Mb), and to assess whether and how such genes are differentially expressed in atopic asthma. STUDY DESIGN AND METHODS: Genome-wide expression quantitative trait methylation (eQTM) analysis in nasal epithelium from Puerto Rican subjects (aged 9-20 years) with (n = 219) and without (n = 236) asthma. After the eQTM analysis, a Gene Ontology Enrichment analysis was conducted for the top 500 eQTM genes, and mediation analyses were performed to identify paths from DNA methylation to atopic asthma through gene expression. Asthma was defined as physician-diagnosed asthma and wheeze in the previous year, and atopy was defined as at least one positive IgE to allergens. Atopic asthma was defined as the presence of both atopy and asthma. RESULTS: We identified 16,867 significant methylation-gene expression pairs (false-discovery rate-adjusted P < .01) in nasal epithelium from study participants. Most eQTM methylation probes were distant (average distance, ∼378 kb) from their target genes, and also more likely to be located in enhancer regions of their target genes in lung tissue than control probes. The top 500 eQTM genes were enriched in pathways for immune processes and epithelial integrity and were more likely to have been previously identified as differentially expressed in atopic asthma. In a mediation analysis, we identified 5,934 paths through which methylation markers could affect atopic asthma through gene expression in nasal epithelium. INTERPRETATION: Previous epigenome-wide association studies of asthma have estimated the effects of DNA methylation markers on expression of nearby genes in airway epithelium. Our findings suggest that distant epigenetic regulation of gene expression in airway epithelium plays a role in atopic asthma.

Variants in the CYSLTR2 are associated with asthma, atopy markers and helminths infections in the Brazilian population.

BACKGROUND: Asthma is a chronic disease of the airways and its most common phenotype is characterized by a T2 type response with IgE production and inflammatory mediators in response to common allergens. Cysteinyl leukotrienes (CysLTs), LTC4, LTD4 and LTE4, are mediators known to possess important proinflammatory action. CysLTs can bind to the Cysteinyl leukotriene receptor type 2 (CysLTR2) and activate an inflammatory. Polymorphisms in CysLTR2 have been associated with asthma and atopy, although the mechanism is not clear. OBJECTIVE: To evaluate the association between genetic polymorphisms in CYSLTR2 with asthma phenotypes, atopy markers and helminth infection. METHODS: Genotyping was performed using a panel Illumina and carried out in 1245 participants of SCAALA program (Social Change, Asthma, Allergy in Latin American). Logistic regressions for asthma, helminth infections (Trichuris trichiura and Ascaris lumbricoides) and allergy markers (skin tests and IgE production) were performed using PLINK 1.9 software adjusted for sex, age, helminth infection and ancestry markers. RESULTS: The G allele of rs1323556 was negatively associated with asthma in the additive model (OR 0.74, 95% CI 0.59-0.93) and in the dominant model (OR 0.71, 95% CI 0.53-0.74). The G allele of rs1575464 was also negatively associated with asthma in two genetic models, additive (OR 0.77, 95% CI 0.62-0.96) and dominant (OR 0.73, 95% CI 0.55-0.97). The G allele of rs61735175 was positively associated with asthma severity in the additive model (OR 1.72, 95% CI 1.07-2.77) and in the dominant model (OR 1.77, 95% CI 1.09-2.85). Five SNVs were associated with atopy markers and four SNVs were associated with helminth infections. CONCLUSION: Polymorphisms in the CYSLTR2 gene are associated with asthma, atopy markers and helminth infection in Brazilian individuals, which may lead to protection or risk for such conditions, however, more studies are needed to evaluate the functional of this variants here in described.

African biogeographical ancestry, atopic and non-atopic asthma and atopy: A study in Latin American children.

BACKGROUND: Genetic variants underlying African ancestry have been suggested be implicated in the ethnic-racial inequalities reported for asthma and allergies. OBJECTIVES: To investigate the association between individual African ancestry and asthma symptoms, atopic and non-atopic asthma, and atopy in children. METHODS: A cross-sectional study encompassing 1190 individuals was conducted. African biogeographic ancestry was estimated using 370 539 genome-wide SNPs. Serum levels of specific IgE were measured, and skin prick test (SPT) performed for the most common local aeroallergens. Information on asthma symptoms was obtained by applying the International Study of Allergy and Asthma in Childhood questionnaire. The associations between the proportion of individual African ancestry and the outcomes investigated were analyzed through multivariate models adjusted for socio-environmental variables, infections markers, and psychosocial factors. RESULTS: Each 20% increase in the proportion of African ancestry was negatively associated with SPT reactivity (OR: 0.79, 95%CI: 0.66-0.96) and positively associated with asthma symptoms in non-atopic individuals (OR: 1.40, 95%CI: 1.03-1.89). We estimated that socioeconomic status and number of infections mediated 28.4% of the effect of African ancestry on SPT reactivity, while 20.2% of the effect on non-atopic asthma was explained by socioeconomic status and behavioral problems in children. CONCLUSIONS: The negative association observed between African ancestry and atopy is most probably explained by unobserved environmental or social factors that covariate with ancestry. For non-atopic asthma, in turn, putative genetic variants of risk underlying African ancestry may play some role.

Polymorphisms in the DAD1 and OXA1L genes are associated with asthma and atopy in a South American population.

Atopic asthma, which is characterized by the chronic inflammation and morbidity of airways, is a disease of great complexity, and multiple genetic and environmental factors are involved in its etiology. In the first genome-wide association study (GWAS) conducted in Brazil for asthma, a positive association was found between atopic asthma and a variant (rs1999071), which is located between the DAD1 and OXA1L genes, although neither gene has previously been reported to be associated with asthma or allergies. The DAD1 gene is involved in the regulation of programmed cell death, and OXA1L is involved in biogenesis and mitochondrial oxidative phosphorylation. This study aimed to evaluate how polymorphisms in DAD1 and OXA1L are associated with asthma and markers of atopy in individuals from the Salvador cohort of the SCAALA (Social Change Asthma and Allergy in Latin America) program. The DNA of 1220 individuals was genotyped using the Illumina 2.5 Human Omni Bead chip. Logistic regression analyses were performed with PLINK 1.9 software to verify the association between DAD1 and OXA1L polymorphisms and asthma and atopic markers, adjusted for sex, age, helminth infections and ancestry markers, using an additive model. The DAD1 and OXA1L genes were associated with some of the evaluated phenotypes, such as asthma, skin prick test (SPT), specific IgE for aeroallergens, and Th1/Th2-type cytokine production. Using qPCR, as well as in silico gene expression analysis, we have demonstrated that some of the polymorphisms in both genes are able to affect their respective gene expression levels. In addition, DAD1 was over-expressed in asthmatic patients when compared with controls. Thus, our findings demonstrate that variants in both the DAD1 and OXA1L genes may affect atopy and asthma in a Latin American population with a high prevalence of asthma.

Polymorphisms in DENND1B gene are associated with asthma and atopy phenotypes in Brazilian children.

Asthma is a heterogeneous disease associated with a complex basis involving environmental factors and individual variabilities. The DENN Domain Containing 1B (DENND1B) gene has an important role on T cell receptor (TCR) down-regulation on Th2 cells and studies have shown that mutations or loss of this factor can be associated with increased Th2 responses and asthma. The aim of this work is to evaluate the association of polymorphisms in the DENND1B with asthma and allergy markers phenotypes in Brazilian children. Genotyping was performed using a commercial panel from Illumina (2.5 Human Omni bead chip) in 1309 participants of SCAALA (Social Change, Asthma, Allergy in Latin American) program. Logistic regressions for asthma and atopy markers were performed using PLINK software 1.9. The analyzes were adjusted for sex, age, helminth infections and ancestry markers. The DENND1B gene was associated with different phenotypes such as severe asthma and atopic markers (specific IgE production, skin prick test and IL-13 production). Among the 166 SNPs analyzed, 72 were associated with asthma and/or allergy markers. In conclusion, polymorphisms in the DENND1B are significantly associated with development of asthma and atopy and these polymorphisms can influence DENND1B expression and consequently, asthma.

IL33 and IL1RL1 variants are associated with asthma and atopy in a Brazilian population.

Atopic asthma is a chronic inflammatory disease in airways resulting from genetic and environmental factors, characterized by production of the Th2 cytokines interleukin-4 (IL-4), interleukin-5 (IL-5) and interleukin-13 (IL-13). Interleukin-33 (IL-33) appears to be a potent inducer of Th2 immune response. This occurs when IL-33 binds and activates its receptor, the membrane ST2 (ST2L) in mast cells, dendritic cells, basophils, eosinophils, innate lymphoids and Th2 cells, leading to the release of these cytokines and intensifying allergic inflammation. Polymorphisms in the IL33 and IL1RL1 can act as protective or risk factors for asthma and/or allergy in humans. No study was conducted to replicate such findings in a European and African descendent mixed population. DNA was extracted from peripheral blood from 1223 subjects, and the samples were genotyped using Illumina 2.5 Human Omni Beadchip. We tested for possible associations between SNPs in the IL33 and ST2 with asthma and allergy markers such as specific IgE (sIgE), IL-5 and IL-13 production and skin prick test (SPT). Logistics regressions were performed using PLINK software 1.07. The analyses were adjusted for sex, age, helminth infection and ancestry markers. The G allele of IL33 SNP rs12551256 was negatively associated with asthma (OR 0.71, 95% CI: 0.53-0.94, P = 0.017). In contrast, the A allele of IL1RL1 rs1041973 was positively associated with IL-5 production (OR 1.36, 95% CI: 1.09-1.84, P = 0.044), sIgE levels (OR 1.40, 95% CI: 1.07-1.84, P = 0.013) and positive SPT (OR 1.48, 95% CI: 1.08-2.03, P = 0.014), for Blomia tropicalis mite. The same allele, in atopic subjects, was associated with decreased production of soluble ST2 (sST2) (P < 0.05). Moreover, expression quantitative trait loci (eQTL) analysis suggests that rs1041973 and rs873022 regulate the expression of IL1RL1 gene. This latest SNP, rs873022, the T allele, was also associated with a lower production of sST2 in plasma of Brazilians. The genetic risk score for rs1041973 and rs16924161 demonstrated a higher risk for SPT positivity against B. tropicalis, the greater the number of risk alleles for both SNPs. Our findings demonstrate a robust association of genetic variants in IL1RL1 and IL33 SNPs with allergy markers and asthma.

Papular urticaria: A review of causal agents in Colombia.

Papular urticaria is a chronic allergic reaction induced by insect bites, which is common in the tropics. The objective of this review was to deepen on epidemiological and immunological aspects of this disease, focused on data published in Latin American countries.We conducted a non-systematic review of the literature through electronic search on the epidemiology of papular urticaria, the entomological characteristics of the causative agents and associated immunological mechanisms.Several reports from medical centers suggest that papular urticaria is common in Latin America. Only one epidemiological survey designed to estimate prevalence of papular urticaria has been published, reporting that about a quarter of children under six years of age is affected by this condition in Bogotá. There is evidence on the causal relationship among exposure to indoor fleas, poverty and papular urticaria in Bogotá, a representative city of the Andean altitudes. Information about causal insects in tropical warmer areas is scarce, although from clinical reports Aedes aegypti and Culex quienquefasciatus appear to be the most common. Th2 cellular-mediated mechanisms are involved in its pathogenesis, which explains its delayed hypersensitivity. The role of immunoglobulin E is not clear in this disease. Insect-derived antigens directly involved in papular urticaria etiology are unknown. However, it is possible that common molecules among causal insects mediate cross-reactive reactions, such as Cte f 2 allergen, found in cat fleas, and its counterparts in mosquitoes.Papular urticaria is a frequent disease in Latin America that should be further investigated. Immunological characterization of the molecular components that cause this condition may solve questions about its pathogenesis.

Urticaria papular y sus agentes causales en Colombia / Papular urticaria: A review of causal agents in Colombia

Resumen La urticaria papular es una enfermedad alérgica causada por la picadura de insectos, la cual predomina en el trópico. El objetivo de esta revisión fue profundizar en sus aspectos epidemiológicos e inmunológicos, particularmente con base en datos publicados en Latinoamérica. Se hizo una revisión no sistemática mediante la búsqueda electrónica de artículos sobre la epidemiología de la urticaria papular, las características entomológicas de los agentes causales y los mecanismos inmunológicos asociados. Según los diversos reportes de centros médicos de Latinoamérica la urticaria papular es frecuente; el único estudio de prevalencia publicado indica que afecta a una cuarta parte de los niños escolares de Bogotá. Hay información sobre la relación causal entre la exposición domiciliaria a la pulga, la pobreza y la urticaria papular en Bogotá, una ciudad representativa de las altitudes andinas. No hay estudios que indaguen directamente sobre los insectos causales en zonas cálidas, aunque se sospecha clínicamente de los mosquitos Aedes aegypti y Culex quinquefasciatus. En cuanto a su patogenia, se destaca la participación de mecanismos celulares que involucran las células colaboradoras Th2, lo cual explica que sea una condición de hipersensibilidad retardada. El papel de la inmunoglobulina E (IgE) en la urticaria papular no está tan claro. Se desconocen los antígenos derivados de los insectos que causan la enfermedad, aunque se plantea que existen moléculas comunes de reacción cruzada entre los insectos, tales como el alérgeno Cte f 2 en la pulga, y sus homólogos en los mosquitos. La urticaria papular es una condición frecuente en Latinoamérica que debe investigarse en profundidad. La caracterización inmunológica de los componentes moleculares que causan esta condición puede resolver interrogantes sobre su etiología y su patogenia.

Abstract Papular urticaria is a chronic allergic reaction induced by insect bites, which is common in the tropics. The objective of this review was to deepen on epidemiological and immunological aspects of this disease, focused on data published in Latin American countries. We conducted a non-systematic review of the literature through electronic search on the epidemiology of papular urticaria, the entomological characteristics of the causative agents and associated immunological mechanisms. Several reports from medical centers suggest that papular urticaria is common in Latin America. Only one epidemiological survey designed to estimate prevalence of papular urticaria has been published, reporting that about a quarter of children under six years of age is affected by this condition in Bogotá. There is evidence on the causal relationship among exposure to indoor fleas, poverty and papular urticaria in Bogotá, a representative city of the Andean altitudes. Information about causal insects in tropical warmer areas is scarce, although from clinical reports Aedes aegypti and Culex quienquefasciatus appear to be the most common. Th2 cellular-mediated mechanisms are involved in its pathogenesis, which explains its delayed hypersensitivity. The role of immunoglobulin E is not clear in this disease. Insect-derived antigens directly involved in papular urticaria etiology are unknown. However, it is possible that common molecules among causal insects mediate cross-reactive reactions, such as Cte f 2 allergen, found in cat fleas, and its counterparts in mosquitoes. Papular urticaria is a frequent disease in Latin America that should be further investigated. Immunological characterization of the molecular components that cause this condition may solve questions about its pathogenesis.

Factors associated with degree of atopy in Latino children in a nationwide pediatric sample: the Genes-environments and Admixture in Latino Asthmatics (GALA II) study.

BACKGROUND: Atopy varies by ethnicity, even within Latino groups. This variation might be due to environmental, sociocultural, or genetic factors. OBJECTIVE: We sought to examine risk factors for atopy within a nationwide study of US Latino children with and without asthma. METHODS: Aeroallergen skin test responses were analyzed in 1830 US Latino subjects. Key determinants of atopy included country/region of origin, generation in the United States, acculturation, genetic ancestry, and site to which subjects migrated. Serial multivariate zero-inflated negative binomial regressions stratified by asthma status examined the association of each key determinant variable with the number of positive skin test responses. In addition, the independent effect of each key variable was determined by including all key variables in the final models. RESULTS: In baseline analyses African ancestry was associated with 3 times (95% CI, 1.62-5.57) as many positive skin test responses in asthmatic participants and 3.26 times (95% CI, 1.02-10.39) as many positive skin test responses in control participants. Generation and recruitment site were also associated with atopy in crude models. In final models adjusted for key variables, asthmatic patients of Puerto Rican (exp[ß] [95% CI], 1.31 [1.02-1.69]) and mixed (exp[ß] [95% CI], 1.27 [1.03-1.56]) ethnicity had a greater probability of positive skin test responses compared with Mexican asthmatic patients. Ancestry associations were abrogated by recruitment site but not region of origin. CONCLUSIONS: Puerto Rican ethnicity and mixed origin were associated with degree of atopy within US Latino children with asthma. African ancestry was not associated with degree of atopy after adjusting for recruitment site. Local environment variation, represented by site, was associated with degree of sensitization.

[Association between unplanned pregnancy and adolescence onset asthma]. / Asociación entre embarazo no planeado y asma de inicio en la adolescencia.

BACKGROUND: The association between asthma and pregnancy has been documented previously. The relationship between unplanned pregnancy and onset asthma in adolescence has not been studied. OBJECTIVE: To determine the association between unplanned pregnancy and adolescence onset asthma. MATERIAL AND METHODS: A cross-sectional study was done gathering information about asthma, unplanned pregnancy, family atopy and active or passive smoking in 3,130 adolescents aged 13-19 years. Asthma diagnosis was established through a selfquestionnaire based on the International Study of Asthma and Allergy in Childhood. Odds ratios for asthma were determined using logistic regression model and chi-squared test. RESULTS: Mean age of the participants was 16.37 ± 1.93 years. The prevalence of active smoking was 16.1%, of passive smoking 40% and of family atopy 9.8%. From the pregnant adolescents (785), 59.5% reported had planned not to have a child before pregnancy. Prevalence of wheezing during the year prior to the study was 9.3% and of wheezing during the pregnancy 2%. The prevalence of adolescence onset asthma was 5.4%. The age of initiation of asthma in the adolescence was 14.75 ± 1.60 years. The analysis showed that unplanned pregnancy has a slight risk for the development of asthma during adolescence. (Crude OR=1.03; CI 95% 1.02-1.05; p=0.000). CONCLUSION: Unplanned pregnancy, family atopy, active smoking and smoking friends are associated with the onset-asthma in the adolescence.

ANTECEDENTES: la asociación entre embarazo y asma se ha documentado previamente. La relación entre embarazo no planeado y asma de inicio en la adolescencia no se ha estudiado. OBJETIVO: determinar la asociación entre embarazo no planeado y asma de inicio en la adolescencia. MATERIAL Y MÉTODOS: estudio transversal en el que se recogió información de asma, embarazo no planeado, atopia familiar y tabaquismo activo o pasivo en 3,130 adolescentes de 13-19 años de edad. El asma se diagnosticó mediante un cuestionario autoadministrado basado en el utilizado en el Estudio Internacional de Asma y Alergia en Niños (ISAAC por sus siglas en inglés). Se determinó la razón de momios para asma mediante regresión logística y chi cuadrada. RESULTADOS: la edad media de las participantes fue 16.37 ± 1.93 años. La prevalencia del tabaquismo activo fue 16.1%, del pasivo 40% y la atopia familiar 9.8%. De las adolescentes embarazadas (785), 59.5% anotó que no había planeado tener un hijo antes del embarazo. La prevalencia de sibilancias durante el último año fue 9.3% y de sibilancias durante el embarazo 2%. La prevalencia de asma de inicio en la adolescencia fue 5.4%. La edad de inicio de asma en la adolescencia fue 14.75 ± 1.60 años. El análisis muestra que el embarazo no planeado tiene un ligero riesgo de padecer asma de inicio en la adolescencia (RM cruda=1.03; IC 95% 1.02-1.05). CONCLUSIONES: el embarazo no planeado, la atopia familiar, el tabaquismo activo y el tabaquismo de las amigas se asocian con el asma de inicio en la adolescencia.

Asthma in late adolescents of Western Mexico: prevalence and associated factors.

INTRODUCTION: Given the number of changes that occur during late adolescence, it is possible that the behavior of asthma may also be different. The aim of our paper is to determine the prevalence of asthma in a population of late adolescents and its possible association with obesity, tobacco smoke exposure and family history of allergic disease. METHODS AND SUBJECTS: In a cross-sectional, population-based analytical study design, we selected a stratified random sample of subjects aged 15 to 18. By modeling risk through logistic regression, we assessed the relationship between asthma and the following covariables: gender, obesity, excess weight, family history of allergic disease and tobacco smoke exposure. RESULTS: 1,600 subjects were included, and the following prevalences were identified: asthma 7.8%, obesity 9.6%, active smoking in the father 2 9.8%, active smoking in the mother 18.6% and active smoking habit in the study subjects 15.1%. In the final model, a significant association was found between asthma and the following variables: 1) asthma in the mother (adjusted OR [aOR]=2.95, 95% CI, 1.55 to 5.6); 2) history of allergic rhinitis (aOR=4.66, 95% CI, 2.63 to 8.25); and 3) male sex (aOR=1.48, 95% CI, 1.02 to 2.15). No association was seen with obesity or tobacco smoking of the parents. CONCLUSION: Our results suggest that maternal history of asthma, personal history of allergic rhinitis and male sex are related with asthma late adolescence, while smoking and being overweight are not.

Clinical characteristics and possible phenotypes of an adult severe asthma population.

BACKGROUND: Currently, there are no studies of well-characterized severe asthmatics in Brazil. We aimed to study a population of severe treated asthmatics still uncontrolled to characterize them and define possible phenotypes. METHODS: Descriptive cross-sectional outpatient study of severe asthmatics, evaluating functional and inflammatory markers, health-related quality of life, anxiety and depression symptoms, clinical control status, and characteristics related to atopy, age of asthma onset, induced sputum eosinophil levels, and airflow limitation. We also grouped the subgroups characteristics to identify phenotypes. The study is registered on ClinicalTrial.gov NCT 01089322. RESULTS: From 128 eligible patients with severe/uncontrolled asthma, 74 fulfilled the inclusion criteria. The cohort was comprised of 85% women, frequently with a body mass index higher than 31 kg m(-2), atopy (60%), early-onset disease (50%), sputum eosinophilia (80%), comorbidities, and reduced quality of life. Nonatopics had significant higher asthma onset (19 y.a.) and twice level of induced sputum eosinophil. Late-onset patients had significantly less atopy (57%) and higher levels of induced sputum eosinophils. Non-eosinophilics had lower levels of inflammatory markers. Patients with airflow limitation had more intensive care unit admissions (56%) and 1.5 times more airway resistance. Subgroups characteristics identified a priori four well-characterized phenotypes, with 55% presenting sputum eosinophilia. CONCLUSION: Our data emphasize the high burden of disease, the persistence of inflammation and the existence of clinical possible phenotypes population sharing common features with published cohorts. Despite the necessity of further investigation into pathogenic mechanisms, this study with clinically difficult patient group may help to improve future asthma care.

Algunos aspectos de la prevención primaria y secundaria en alergia y asma / Strategies for primary and secondary prevention of asthma and allergy

Existe un aumento en la prevalencia de las enfermedades alérgicas y el asma. Dicho incremento es más notable en la población urbana de los países occidentales más industrializados. Enfermedades como el eczema atópico, la alergia a alimentos, la rinoconjuntivitis alérgica y el asma bronquial, entre otras, además de generar costos millonarios a los distintos estados, afectan notablemente la calidad de vida de la población que las padece, reflejándose en un gran ausentismo escolar y laboral entre otros aspectos. Las enfermedades alérgicas y el asma surgen de la interacción de factores genéticos y factores ambientales. Dicha interacción que provocará la sensibilización atópica y posteriormente el desarrollo de las distintas enfermedades, comienza en la vida fetal intrauterina, siendo clave el primer, y tal vez el segundo año de vida. Se describen diversas estrategias de prevención primaria para evitar la sensibilización, entre las que se destacan, el control ambiental para evitar o disminuir el contacto a diversos aeroalérgenos interiores, la manipulación en la dieta fomentando lactancia materna exclusiva hasta los 4 a 6 meses, utilizando en niños de riesgo fórmulas hidrolizadas como suplemento, evitar el tabaquismo en la embarazada y el pasivo en los niños pequeños. Entre las estrategias en la prevención secundaria, es decir, el evitar el desarrollo de una enfermedad alérgica después de la sensibilización, se destaca nuevamente el control ambiental (se mencionan distintos consejos de la OMS), la inmunoterapia con alérgenos y la farmacoterapia (antihistamínicos). Por último, se mencionan la influencia de la polución ambiental y el potencial papel de la terapia génica.

There has been an increase in the prevalence of asthma and allergic diseases, more notably in urban population of western developed countries diseases such as atopic eczema, food allergy, allergic rhinoconjunctivitis and bronchial asthma, among other, not only generate millionaire costs to the different states, but also considerably affect the quality of life of the population suffering them, which is reflected in a great work and school absence, among other aspects. Allergic diseases and asthma develop from the interaction between genes and environment. Such an interaction will cause allergic sensitization and lately the development of different diseases. It starts in fetal life and becomes more important in the first, and perhaps second, year of life. Different strategies for primary prevention are described to avoid atopic sensitization, such as allergen avoidance of indoor allergens, diet manipulation to avoid cow's milk protein with exclusive breast feeding until four to six months of life; use of hydrolyzed milk formulae as a replacement for or supplement to breast-feeding, late introduction of solid food, avoidance of active smoking among pregnant women and passive smoking in children. Among other strategies for secondary prevention, this is to avoid the development of an allergic disease after sensitization has occurred, again allergen avoidance is mentioned (with advice measures by WHO), allergen immunotherapy and medication (antihistamines). At last, the influence of air pollution and the potential use of gene therapy are also considered.

Lack of association between genetic variation in G-protein-coupled receptor for asthma susceptibility and childhood asthma and atopy.

G-protein-coupled receptor for asthma susceptibility (GPRA or GPR154) was identified as an asthma and atopy candidate gene by positional cloning. Some subsequent studies suggest associations of GPRA single nucleotide polymorphisms (SNPs) and haplotypes with asthma or atopy susceptibility. However, the associated SNPs or haplotypes vary among studies. The role of GPRA genetic variation in asthma and atopy remains unsolved. Published data on GRPA variants and asthma come exclusively from Caucasian and Asian populations. We examined whether GPRA SNPs and haplotypes are associated with asthma and atopy in a Mexican population. We genotyped and analyzed 27 GPRA SNPs in 589 nuclear families consisting of asthmatic children aged 4-17 years of age and their parents in Mexico City. Atopy was determined by skin prick tests to 25 aeroallergens. The 27 SNPs examined provided excellent coverage of the GPRA gene. GPRA SNPs and haplotypes were not associated with childhood asthma and the degree of atopy to aeroallergens in a Mexican population. Our review of studies of GPRA variants in relation to asthma phenotypes shows considerable heterogeneity. Accordingly, our results suggest that GPRA variants are not an important contributor to childhood asthma and atopy susceptibility in a Mexican population.

[Association among familial atopy, smoking (passive and active), allergic rhinitis, labor environment and adult asthma]. / Asociación entre atopia familiar, tabaquismo (pasivo o activo), rinitis alérgica, ambiente laboral y asma del adulto.

BACKGROUND: Studies of association among parental atopy, tobacco exposure (passive or active) and adult asthma have provided conflicting results. OBJECTIVE: To determine the relationship among parental atopy, smoking, exposure to tobacco smoke, allergic rhinitis, work environment and asthma in adults. MATERIAL AND METHODS: In a population of 329,219 inhabitants of a geographically defined area in Northeastern of Mexico, we identified 791 cases of asthma. The patients were 20 to 54 years old, and were divided in three groups: with asthma in remission (263 patients), with symptoms since childhood (270 patients), and with asthma onset in adult age (258 patients). We included 793 randomly selected control subjects. Information on family atopy, passive and active smoking, allergic rhinitis and workplace conditions were collected by using a questionnaire. RESULTS: Parental atopy history, active smoking, allergic rhinitis and pollution in the workplace induce asthma symptoms. Exposure to smoking is a risk factor of persistence of asthma symptoms in adults (OR = 1.33; IC 95%, 1.07-1.66), but no of their development (OR = 1.10; IC 95%, 0.87-1.39). Working in a polluted environment had not significance in remission of asthma (OR =1.32; IC 95%, 0.95-1.85). CONCLUSIONS: Results support hypothesis that family atopy, active smoke, allergic rhinitis and pollution favor the persistence of asthma symptoms and increase the risk of asthma in adults.

Alergia en la infancia: ¿existen realmente? / Allergy in childhood: exist?

Las enfermedades alérgicas constituyen un grupo heterogéneo de enfermedades asociadas clásicamente a una reacción de hipersensibilidad tipo I, en cuya respuesta inmune, mediada principalmente por IgE, participan diversas clases de celulas como linfocitos, especialmente los CD4 polarizados a Th2, linfocitos B antígeno específicos, mastocitos, basófilos y finalmente citoquinas. Durante la última década se ha observado un incremento de la incidencia de las enfermedades alérgicas en los países occidentales, especialmente en niños. Este artículo resume y expone aspectos básicos para comprender la existencia de la alergia en la infancia. Así mismo, se expone la opinión de Comités de expertos internacionales en el área de alergia, quienes han propuesto una nueva nomenclatura para estas enfermedades, según la reacción de hipersensibilidad involucre o no un mecanismo inmune, y esté o no mediada por IgE.

[The Th2 theory in allergy: present and future directions]. / Teoría Th2 en alergia: actualidades y futuras direcciones.

Allergic diseases have been a model study for Th2 cells polarization and it is well known that the synthesis of the human IgE results from collaboration between Th2 and B cells through the cytokines such as IL-4 and IL-13 and surface molecules (CD40-CD40L). In the last decade, some surface molecules have been associated with human Th2 cells. Although recent studies suggest that the receptors of chemokines are the most related markers of Th2 cells, so far it has not found a specific marker to discriminate Th2 cells. The most recent studies suggest that Th1 and Th2 cells are not derived from different cellular lineages, but rather they can be derived from the same precursory Th cell and, under the influence of genetic environmental factors, they can be polarized. Also, some genes conferring susceptibility to production of Th2 cytokines have been located.