Factors associated to recurrent wheezing in infants under one year of age in the province of Salamanca, Spain: Is intervention possible? A predictive model

OBJECTIVES: Wheezing is a very common problem in infants in the first months of life. The objective of this study is to identify risk factors that may be acted upon in order to modify the evolution of recurrent wheezing in the first months of life, and to develop a model based on certain factors associated to recurrent wheezing in nursing infants capable of predicting the probability of developing recurrent wheezing in the first year of life. METHODS: The sample was drawn from a cross-sectional, multicentre, descriptive epidemiological study based on the general population. A total of 1164 children were studied, corresponding to a questionnaire response rate of 71%. The questionnaire of the Estudio Internacional de Sibilancias en Lactantes (EISL) was used. Multiple logistic regression analysis was used to estimate the probability of developing recurrent wheezing and to quantify the contribution of each individual variable in the presence of the rest. RESULTS: Infants presenting eczema and attending nursery school, with a mother who has asthma, smoked during the third trimester of pregnancy, and did not consume a Mediterranean diet during pregnancy were found to have a probability of 79.7% of developing recurrent wheezing in the first year of life. In contrast, infants with none of these factors were seen to have a probability of only 4.1% of developing recurrent wheezing in the first year of life. These results in turn varied according to modifications in the risk or protective factors. CONCLUSIONS: The mathematical model estimated the probability of developing recurrent wheezing in infants under one year of age in the province of Salamanca (Spain), according to the risk or protective factors associated to recurrent wheezing to which the infants are or have been exposed

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Factors associated to recurrent wheezing in infants under one year of age in the province of Salamanca, Spain: Is intervention possible? A predictive model.

OBJECTIVES: Wheezing is a very common problem in infants in the first months of life. The objective of this study is to identify risk factors that may be acted upon in order to modify the evolution of recurrent wheezing in the first months of life, and to develop a model based on certain factors associated to recurrent wheezing in nursing infants capable of predicting the probability of developing recurrent wheezing in the first year of life. METHODS: The sample was drawn from a cross-sectional, multicentre, descriptive epidemiological study based on the general population. A total of 1164 children were studied, corresponding to a questionnaire response rate of 71%. The questionnaire of the Estudio Internacional de Sibilancias en Lactantes (EISL) was used. Multiple logistic regression analysis was used to estimate the probability of developing recurrent wheezing and to quantify the contribution of each individual variable in the presence of the rest. RESULTS: Infants presenting eczema and attending nursery school, with a mother who has asthma, smoked during the third trimester of pregnancy, and did not consume a Mediterranean diet during pregnancy were found to have a probability of 79.7% of developing recurrent wheezing in the first year of life. In contrast, infants with none of these factors were seen to have a probability of only 4.1% of developing recurrent wheezing in the first year of life. These results in turn varied according to modifications in the risk or protective factors. CONCLUSIONS: The mathematical model estimated the probability of developing recurrent wheezing in infants under one year of age in the province of Salamanca (Spain), according to the risk or protective factors associated to recurrent wheezing to which the infants are or have been exposed.

Wheezing and risk factors in the first year of life in Cantabria, Spain. The EISL study

OBJECTIVES: To determine the prevalence of wheezing during the first year of life in Cantabria, Spain and its associated risk factors. METHODOLOGY: A cross-sectional, multicentre, descriptive epidemiological study was carried out in a representative sample of 958 infants in the first year of life, born in Cantabria. A previously validated and standardised written questionnaire was completed by the parents of infants seen between 12 and 15 months of age in the Primary Care Centres. RESULTS: The prevalence of wheezing was 32.7%. A relationship was found with male gender (OR 1.38, 95%CI [1.05-1.81]), the presence of a sibling (OR 2.43 [1.38-3.98]), attending nursery school (OR 2.40 [1.71-3.35]), exclusive breastfeeding for <3 months (OR 1.47 [1.12-1.93]), a first cold at ≤3 months (OR 2.07 [1.56-2.74]), asthma in siblings (OR 2.17 [1.25-3.77]), parental allergic rhinitis (OR 1.62 [1.10-2.37]) and paracetamol use >1 a week (OR 2.49 [1.31-4.73]), and maternal smoking during pregnancy (OR 2.18 [1.51-3.15]). The prevalence of recurrent wheezing (≥3 episodes) was 14.3%. Significant associations were observed with the male gender (OR 1.79 [1.23-2.60]), attending nursery school (OR 2.92 [1.96-4.35]), first cold at ≤3 months (OR 2.11 [1.46-3.04]), eczema (OR 1.92 [1.21-3.04]), maternal asthma (OR 1.77 [1.00-3.14]), exclusive breastfeeding for <3 months (OR 1.53 [1.06-2.22]), and maternal smoking during pregnancy (OR 1.53 [1.05-2.22]). CONCLUSIONS: One third of the infants experienced wheezing during the first year of life; those who were less exclusively breastfed, attended nursery school, presented eczema, family asthma or allergic rhinitis, and maternal smoking during pregnancy

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Genome-wide association studies (GWAS) and their importance in asthma

Asthma is a complex disease determined by the interaction of different genes and environmental factors. The first genetic investigations in asthma were candidate gene association studies and linkage studies. In recent years research has focused on association studies that scan the entire genome without any prior conditioning hypothesis: the so-called genome-wide association studies (GWAS). The first GWAS was published in 2007, and described a new locus associated to asthma in chromosome 17q12-q21, involving the ORMDL3, GSDMB and ZPBP2 genes (a description of the genes named in the manuscript are listed in Table 1). None of these genes would have been selected in a classical genetic association study since it was not known they could be implicated in asthma. To date, a number of GWAS studies in asthma have been made, with the identification of about 1000 candidate genes. Coordination of the different research groups in international consortiums and the application of new technologies such as new generation sequencing will help discover new implicated genes and improve our understanding of the molecular mechanisms underlying the disease

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Wheezing and risk factors in the first year of life in Cantabria, Spain. The EISL study.

OBJECTIVES: To determine the prevalence of wheezing during the first year of life in Cantabria, Spain and its associated risk factors. METHODOLOGY: A cross-sectional, multicentre, descriptive epidemiological study was carried out in a representative sample of 958 infants in the first year of life, born in Cantabria. A previously validated and standardised written questionnaire was completed by the parents of infants seen between 12 and 15 months of age in the Primary Care Centres. RESULTS: The prevalence of wheezing was 32.7%. A relationship was found with male gender (OR 1.38, 95%CI [1.05-1.81]), the presence of a sibling (OR 2.43 [1.38-3.98]), attending nursery school (OR 2.40 [1.71-3.35]), exclusive breastfeeding for <3 months (OR 1.47 [1.12-1.93]), a first cold at ≤3 months (OR 2.07 [1.56-2.74]), asthma in siblings (OR 2.17 [1.25-3.77]), parental allergic rhinitis (OR 1.62 [1.10-2.37]) and paracetamol use >1 a week (OR 2.49 [1.31-4.73]), and maternal smoking during pregnancy (OR 2.18 [1.51-3.15]). The prevalence of recurrent wheezing (≥3 episodes) was 14.3%. Significant associations were observed with the male gender (OR 1.79 [1.23-2.60]), attending nursery school (OR 2.92 [1.96-4.35]), first cold at ≤3 months (OR 2.11 [1.46-3.04]), eczema (OR 1.92 [1.21-3.04]), maternal asthma (OR 1.77 [1.00-3.14]), exclusive breastfeeding for <3 months (OR 1.53 [1.06-2.22]), and maternal smoking during pregnancy (OR 1.53 [1.05-2.22]). CONCLUSIONS: One third of the infants experienced wheezing during the first year of life; those who were less exclusively breastfed, attended nursery school, presented eczema, family asthma or allergic rhinitis, and maternal smoking during pregnancy.

Genome-wide association studies (GWAS) and their importance in asthma.

Asthma is a complex disease determined by the interaction of different genes and environmental factors. The first genetic investigations in asthma were candidate gene association studies and linkage studies. In recent years research has focused on association studies that scan the entire genome without any prior conditioning hypothesis: the so-called genome-wide association studies (GWAS). The first GWAS was published in 2007, and described a new locus associated to asthma in chromosome 17q12-q21, involving the ORMDL3, GSDMB and ZPBP2 genes (a description of the genes named in the manuscript are listed in Table 1). None of these genes would have been selected in a classical genetic association study since it was not known they could be implicated in asthma. To date, a number of GWAS studies in asthma have been made, with the identification of about 1000 candidate genes. Coordination of the different research groups in international consortiums and the application of new technologies such as new generation sequencing will help discover new implicated genes and improve our understanding of the molecular mechanisms underlying the disease.

Implications of cytokine genes in allergic asthma

Asthma is a complex disease involving numerous mediator molecules and effector cells, in combination with a range of environmental determining factors. Cytokines play a key role in the physiopathological mechanisms of asthma; the study of the structure, regulation and variations of the genes that encode for these molecules is therefore crucial. Cytokines have extremely diverse roles, and exert effects both as activators and inhibitors of the innate and adaptive immune response. Certain modifications in the expression or structure of these molecules, resulting from the presence of polymorphisms, may give rise to deregulation of the mentioned effects, and therefore to a predisposition to develop concrete asthma phenotypes

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Implications of cytokine genes in allergic asthma.

Asthma is a complex disease involving numerous mediator molecules and effector cells, in combination with a range of environmental determining factors. Cytokines play a key role in the physiopathological mechanisms of asthma; the study of the structure, regulation and variations of the genes that encode for these molecules is therefore crucial. Cytokines have extremely diverse roles, and exert effects both as activators and inhibitors of the innate and adaptive immune response. Certain modifications in the expression or structure of these molecules, resulting from the presence of polymorphisms, may give rise to deregulation of the mentioned effects, and therefore to a predisposition to develop concrete asthma phenotypes.

The prostaglandin D2 receptor (PTGDR) gene in asthma and allergic diseases

The prostaglandin D2 receptor (PTGDR) gene has been associated to asthma and related phenotypes by linking and association studies. Functional studies involving animal models and other expression studies based on in vitro cell models also point to a possible role of polymorphisms in the promoter region, in the differential binding of transcription factors, and thus in PTGDR expression, which appear to be associated to the development of asthma or of susceptibility to the disease

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The prostaglandin D2 receptor (PTGDR) gene in asthma and allergic diseases.

The prostaglandin D2 receptor (PTGDR) gene has been associated to asthma and related phenotypes by linking and association studies. Functional studies involving animal models and other expression studies based on in vitro cell models also point to a possible role of polymorphisms in the promoter region, in the differential binding of transcription factors, and thus in PTGDR expression, which appear to be associated to the development of asthma or of susceptibility to the disease.

Presentación del Profesor Dr D Julio Ardura Fernández / Presentation of Professor Dr Mr Julio Ardura Fernández

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Study of wheezing and its risk factors in the first year of life in the Province of Salamanca, Spain. The EISL Study

Objectives: To determine the prevalence of wheezing and its associated risk factors in infants in the first year of life in the province of Salamanca, Spain. Methods: A multicentre, cross-sectional, descriptive epidemiological study was designed to evaluate a representative sample of 750 infants in the first year of life, born in the province of Salamanca between 1 June 2008 and 30 September 2009.The study was based on a previously validated and standardised written questionnaire administered among the parents of those children seen for control at 12 months of age in any of the Primary Care centres in the province of Salamanca. Results: The recorded wheezing rate was 32.3%. Feeding and sleep were seen to be affected in 46.3% and 80.9% of the wheezing children, respectively, and parent activity was also altered in 39.3% of the cases. A relationship was found between wheezing and nursery attendance (OR: 1.66, 95% confidence interval [1.19-2.31]); weight at birth >3500g (OR: 1.45 [1.02-2.06]); the presence of eczema at this age (OR: 2.72 [1.75-4.24]); exclusive breastfeeding for <3 months (OR: 1.33 [0.98-1.81]); and maternal smoking during the last three months of pregnancy (OR: 1.60 [0.96-2.68]).The prevalence of recurrent wheezing (defined as three or more episodes) was 11.9%. Significant differences were observed with respect to nursery attendance (OR: 1.71 [1.08-2.72]), the presence of eczema at this age (OR: 2.55 [1.48-4.42]), a history of maternal asthma (OR: 2.19 [1.08-4.44]) and exclusive breastfeeding for <3 months (OR: 1.53 [0.98-2.38]). Conclusions: In the province of Salamanca, one third of the infants studied suffered wheezing in the first year of life. Infants exclusively breastfed for less than three months; attending a nursery; having suffered eczema; or with an asthmatic mother showed significantly more wheezing than the rest. Wheezing proved recurrent in 11.9% of the cases(AU)

Study of wheezing and its risk factors in the first year of life in the Province of Salamanca, Spain. The EISL Study.

OBJECTIVES: To determine the prevalence of wheezing and its associated risk factors in infants in the first year of life in the province of Salamanca, Spain. METHODS: A multicentre, cross-sectional, descriptive epidemiological study was designed to evaluate a representative sample of 750 infants in the first year of life, born in the province of Salamanca between 1 June 2008 and 30 September 2009. The study was based on a previously validated and standardised written questionnaire administered among the parents of those children seen for control at 12 months of age in any of the Primary Care centres in the province of Salamanca. RESULTS: The recorded wheezing rate was 32.3%. Feeding and sleep were seen to be affected in 46.3% and 80.9% of the wheezing children, respectively, and parent activity was also altered in 39.3% of the cases. A relationship was found between wheezing and nursery attendance (OR: 1.66, 95% confidence interval [1.19-2.31]); weight at birth >3500 g (OR: 1.45 [1.02-2.06]); the presence of eczema at this age (OR: 2.72 [1.75-4.24]); exclusive breastfeeding for <3 months (OR: 1.33 [0.98-1.81]); and maternal smoking during the last three months of pregnancy (OR: 1.60 [0.96-2.68]). The prevalence of recurrent wheezing (defined as three or more episodes) was 11.9%. Significant differences were observed with respect to nursery attendance (OR: 1.71 [1.08-2.72]), the presence of eczema at this age (OR: 2.55 [1.48-4.42]), a history of maternal asthma (OR: 2.19 [1.08-4.44]) and exclusive breastfeeding for <3 months (OR: 1.53 [0.98-2.38]). CONCLUSIONS: In the province of Salamanca, one third of the infants studied suffered wheezing in the first year of life. Infants exclusively breastfed for less than three months; attending a nursery; having suffered eczema; or with an asthmatic mother showed significantly more wheezing than the rest. Wheezing proved recurrent in 11.9% of the cases.

Airborne pollen calendar of Salamanca, Spain, 2000–2007

Background: The determination of pollen types and their proportions in the atmosphere of relevant urban areas have increasingly been evaluated in different regions. The final goal has been to elaborate a pollen calendar, providing data about the occurrence of pollen grains in the air, thus permitting medical treatment and prophylaxis. Methods: An aerobiological study was carried out in the atmosphere of the city of Salamanca, Spain, during eight years (2000–2007) by means of a Hirst type volumetric spore trap. A pollen calendar was elaborated following exponential classes obtained from 10-day average concentrations of the main pollen types. Results: Mean annual pollen index was 16,916, coming from 72 different types of pollen. During the studied period, an increase of annual pollen levels was registered by means of regression analysis index. The most important types of pollen were Quercus, Poaceae, Cupressaceae, Olea, and Plantago. Arboreal pollen grains (62.7%) were more represented in airborne pollen spectrum than non-arboreal pollen (37.3%). Airborne pollen levels were particularly high between April and July, showing the highest values in May and June. Conclusions: In aerobiological terms Poaceae pollen seems to be a major risk for potential sensitised individuals due to its known allergenicity and its high atmospheric concentrations between late spring and early summer, followed by Cupressaceae, Olea and Platanus pollen grains, and taking into account the possible role of Fraxinus and Quercus in earl spring allergenic courses and in processes of cross-sensitivity, respectively

Airborne pollen calendar of Salamanca, Spain, 2000-2007.

BACKGROUND: The determination of pollen types and their proportions in the atmosphere of relevant urban areas have increasingly been evaluated in different regions. The final goal has been to elaborate a pollen calendar, providing data about the occurrence of pollen grains in the air, thus permitting medical treatment and prophylaxis. METHODS: An aerobiological study was carried out in the atmosphere of the city of Salamanca, Spain, during eight years (2000-2007) by means of a Hirst type volumetric spore trap. A pollen calendar was elaborated following exponential classes obtained from 10-day average concentrations of the main pollen types. RESULTS: Mean annual pollen index was 16,916, coming from 72 different types of pollen. During the studied period, an increase of annual pollen levels was registered by means of regression analysis index. The most important types of pollen were Quercus, Poaceae, Cupressaceae, Olea, and Plantago. Arboreal pollen grains (62.7%) were more represented in airborne pollen spectrum than non-arboreal pollen (37.3%). Airborne pollen levels were particularly high between April and July, showing the highest values in May and June. CONCLUSIONS: In aerobiological terms Poaceae pollen seems to be a major risk for potential sensitised individuals due to its known allergenicity and its high atmospheric concentrations between late spring and early summer, followed by Cupressaceae, Olea and Platanus pollen grains, and taking into account the possible role of Fraxinus and Quercus in early spring allergenic courses and in processes of cross-sensitivity, respectively.

Enseñanza de la pediatría en el Espacio Europeo de Educación Superior / Teaching of pediatrics in the European Space of Upper Education

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Interactions between genes and the environment. Epigenetics in allergy.

Epigenetics is defined as those inheritable changes occurring in gene expression, without actual modification in the genic DNA sequence. Epigenetic factors are chemically stable, potentially reversible, and can be modulated or induced by environmental factors. In the case of allergic disease, epigenetics could explain not only the discordances observed between monozygous twins but also phenomena such as incomplete penetrance, variable expression, gender and progenitor effects, and sporadic cases. In this sense, the hypothesis of hygiene is of great relevance in that it integrates genetic and epidemiological data in the context of environmental exposures. Among the different epigenetic factors, mention must be made of DNA methylation, covalent histone modifications, and other mechanisms that include different protein complexes and RNA-mediated modifications. The regulatory effect of these phenomena upon immune response has important implications for allergic diseases. At present, different lines of pharmacological research are being conducted, based on the modulation of epigenetic factors, modifying expression of the genes that encode for proteins implicated in allergic processes. Among such modulators, mention can be made of antisense oligonucleotides, ribozymes and interference RNA. The applications of epigenetics to the diagnosis and treatment of allergic disorders offer a very promising future of this specialty.

Interactions between genes and the environment. Epigenetics in allergy / Interacciones genes-ambiente. Epigenética en alergia

Epigenetics is defined as those inheritable changes occurring in gene expression, without actual modification in the genic DNA sequence. Epigenetic factors are chemically stable, potentially reversible, and can be modulated or induced by environmental factors. In the case of allergic disease, epigenetics could explain not only the discordances observed between monozygous twins but also phenomena such as incomplete penetrance, variable expression, gender and progenitor effects, and sporadic cases. In this sense, the hypothesis of hygiene is of great relevance in that it integrates genetic and epidemiological data in the context of environmental exposures. Among the different epigenetic factors, mention must be made of DNA methylation, covalent histone modifications, and other mechanisms that include different protein complexes and RNA-mediated modifications. The regulatory effect of these phenomena upon immune response has important implications for allergic diseases. At present, different lines of pharmacological research are being conducted, based on the modulation of epigenetic factors, modifying expression of the genes that encode for proteins implicated in allergic processes. Among such modulators, mention can be made of antisense oligonucleotides, ribozymes and interference RNA. The applications of epigenetics to the diagnosis and treatment of allergic disorders offer a very promising future of this specialty

La Epigenética se define como aquellos cambios heredables que se producen en la expresión génica sin modificar la secuencia de DNA. Los factores epigenéticos se caracterizan por ser químicamente estables, potencialmente reversibles y modulables o inducibles por factores ambientales. En el caso de las enfermedades alérgicas la epigenética podría contribuir a explicar no sólo las discordancias observadas en los gemelos monocigóticos, sino también fenómenos como la penetrancia incompleta, la expresión variable, los efectos del sexo y del progenitor de origen y los casos esporádicos. En este sentido, la hipótesis de la higiene cobra gran relevancia al integrar datos genéticos y epidemiológicos en el marco de las exposiciones ambientales. Entre los factores epigenéticos destacan la metilación del DNA, las modificaciones covalentes de las histonas y otros mecanismos que incluyen distintos complejos proteicos y las modificaciones mediadas por RNA. El efecto regulador de estos fenómenos sobre la respuesta inmune tiene grandes implicaciones en las enfermedades alérgicas. En la actualidad se están desarrollando distintas líneas de investigación farmacológica basadas en la modulación de los factores epigenéticos, modificando la expresión de los genes que codifican proteínas implicadas en los procesos alérgicos. Entre estos moduladores destacan los oligonucleótidos antisentido, las ribozimas y los RNA de interferencia. Las aplicaciones de la epigenética al diagnóstico y tratamiento de las enfermedades alérgicas abre un campo muy esperanzador en el futuro de esta especialidad

Interacciones genes-ambiente. Epigenética en alergia / No disponible

La epigenética se define como aquellos cambios heredables que se producen en la expresión génica sin modificar la secuencia de DNA. Los factores epigenéticos se caracterizan por ser químicamente estables, potencialmente reversibles y modulables o inducibles por factores ambientales. En el caso de las enfermedades alérgicas la epigenética podría contribuir a explicar, no sólo las discordancias observadas en los gemelos monocigóticos sino también fenómenos como la penetrancia incompleta, la expresión variable, los efectos del sexo y del progenitor de origen y los casos esporádicos. En este sentido, la hipótesis de la higiene cobra gran relevancia al integrar datos genéticos y epidemiológicos en el marco de las exposiciones ambientales. Entre los factores epigenéticos destacan la metilación del DNA, las modificaciones covalentes de las histonas y otros mecanismos que incluyen distintos complejos proteicos y las modificaciones mediadas por RNA. El efecto regulador de estos fenómenos sobre la respuesta inmune tiene grandes implicaciones en las enfermedades alérgicas. En la actualidad se están desarrollando distintas líneas de investigación farmacológica basadas en la modulación de los factores epigenéticos, modificando la expresión de los genes que codifican proteínas implicadas en los procesos alérgicos. Entre estos moduladores destacan los oligonucleótidos antisentido, las ribozimas y los RNA de interferencia. Las aplicaciones de la epigenética al diagnóstico y tratamiento de las enfermedades alérgicas abre un campo muy esperanzador en el futuro de esta especialidad (AU)

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