RESUMEN
The present addendum of the guideline for the diagnosis and treatment of asthma (2017) complements new insights into the diagnosis and management of asthma as well as for the newly approved drugs for the treatment of asthma. Current, evidence-based recommendations on diagnostic and therapeutic approaches are presented for children and adolescents as well as for adults with asthma.
Asunto(s)
Asma , Neumología , Adolescente , Adulto , Asma/diagnóstico , Asma/tratamiento farmacológico , Asma/epidemiología , Austria , Niño , Humanos , Sociedades MédicasRESUMEN
The present guideline aims to improve the evidence-based management of children and adolescents with pediatric community-acquired pneumonia (pCAP). Despite a prevalence of approx. 300 cases per 100â000 children per year in Central Europe, mortality is very low. Prevention includes infection control measures and comprehensive immunization. The diagnosis can and should be established clinically by history, physical examination and pulse oximetry, with fever and tachypnea as cardinal features. Additional signs or symptoms such as severely compromised general condition, poor feeding, dehydration, altered consciousness or seizures discriminate subjects with severe pCAP from those with non-severe pCAP. Within an age-dependent spectrum of infectious agents, bacterial etiology cannot be reliably differentiated from viral or mixed infections by currently available biomarkers. Most children and adolescents with non-severe pCAP and oxygen saturation >â92â% can be managed as outpatients without laboratory/microbiology workup or imaging. Anti-infective agents are not generally indicated and can be safely withheld especially in children of young age, with wheeze or other indices suggesting a viral origin. For calculated antibiotic therapy, aminopenicillins are the preferred drug class with comparable efficacy of oral (amoxicillin) and intravenous administration (ampicillin). Follow-up evaluation after 48â-â72 hours is mandatory for the assessment of clinical course, treatment success and potential complications such as parapneumonic pleural effusion or empyema, which may necessitate alternative or add-on therapy.
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Antibacterianos/uso terapéutico , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Neumonía/tratamiento farmacológico , Guías de Práctica Clínica como Asunto , Neumología/normas , Adolescente , Antibacterianos/administración & dosificación , Niño , Infecciones Comunitarias Adquiridas/diagnóstico , Infecciones Comunitarias Adquiridas/virología , Europa (Continente) , Alemania , Humanos , Lactante , Neumonía/diagnóstico , Neumonía/virología , Sociedades MédicasRESUMEN
BACKGROUND: Farm exposure protects against development of allergies early in life. At 4.5 years, protection against asthma by farm-milk exposure was partially mediated by regulatory T cells (Tregs). The aim of this study was to investigate the critical time window of the 'asthma-protective' farm effect via Tregs during childhood immune maturation. METHODS: Tregs were assessed longitudinally at 4.5 and 6 years in 111 children (56 farm and 55 reference children) from the PASTURE/EFRAIM birth cohort (flow cytometry). Peripheral blood mononuclear cells were cultured unstimulated (U), with phorbol 12-myristate 13-acetate/ionomycin (PI) or lipopolysaccharide (LPS), and stained for Tregs (CD4+ CD25high FOXP3upper20% ). mRNA expression of Treg/Th1/Th2/Th17-associated cell markers was measured ex vivo. Suppressive capacity of Tregs on effector cells and cytokines was assessed. Detailed questionnaires assessing farm exposures and clinical phenotypes from birth until age 6 years were answered by the parents. RESULTS: Treg percentage before and after stimulation and FOXP3mRNA expression ex vivo decreased from age 4.5 to 6 years (P(U,LPS) < 0.001; P(PI) = 0.051; P(FOXP3) < 0.001). High vs low farm-milk and animal-stable exposure was associated with decreased LPS-stimulated Treg percentage at age 6 years (P(LPS) = 0.045). Elevated LPS-stimulated-Treg percentage at age 6 was associated with increased risk of asthma (aOR = 11.29, CI: 0.96-132.28, P = 0.053). Tregs from asthmatics vs nonasthmatics suppressed IFN-γ (P = 0.015) and IL-9 (P = 0.023) less efficiently. mRNA expression of Th1/Th2/Th17-associated cell markers decreased between 4.5 and 6 years (P < 0.001). CONCLUSIONS: Tregs at the age of 6 years were decreased with farm exposure and increased within asthmatics, opposite to age 4.5 years. This immunological switch defines a critical 'time window' for Treg-mediated asthma protection via environmental exposure before age 6 years.
Asunto(s)
Exposición a Riesgos Ambientales , Granjas , Inmunidad , Subgrupos de Linfocitos T/inmunología , Linfocitos T Reguladores/inmunología , Factores de Edad , Alérgenos/inmunología , Animales , Asma/epidemiología , Asma/etiología , Biomarcadores , Niño , Preescolar , Citocinas/metabolismo , Femenino , Estudios de Seguimiento , Expresión Génica , Humanos , Inmunoglobulina E/inmunología , Lactante , Recién Nacido , Recuento de Linfocitos , Masculino , Fenotipo , Vigilancia de la Población , Embarazo , ARN Mensajero/genética , Encuestas y Cuestionarios , Subgrupos de Linfocitos T/metabolismo , Linfocitos T Reguladores/metabolismoRESUMEN
BACKGROUND: Accurate assessment of atopic sensitization is pivotal to clinical practice and research. Skin prick test (SPT) and specific IgE (sIgE) are often used interchangeably. Some studies have suggested a disagreement between these two methods, and little is known about their association with allergic diseases. The aims of our study were to evaluate agreement between SPT and sIgE, and to compare their association with allergic diseases in 10-year-old children. METHODS: Skin prick test, sIgE measurements, and assessment of allergic diseases were performed in children aged 10 years in the Protection against Allergy: STUdy in Rural Environments (PASTURE) cohort. The agreement between SPT and sIgE was assessed by Cohen's kappa coefficient with different cutoff values. RESULTS: Skin prick tests and sIgE were performed in 529 children. The highest agreement (κ=.44) was found with a cutoff value of 3 and 5 mm for SPT, and 3.5 IU/mL for sIgE. The area under the curve (AUC) obtained with SPT was not significantly different from that obtained with sIgE. For asthma and hay fever, SPT (cutoff value at 3 mm) had a significantly higher specificity (P<.0001) than sIgE (cutoff value at 0.35 IU/mL) and the specificity was not different between both tests (P=.1088). CONCLUSION: Skin prick test and sIgE display moderate agreement, but have a similar AUC for allergic diseases. At the cutoff value of 3 mm for SPT and 0.35 IU/mL for sIgE, SPT has a higher specificity for asthma and hay fever than sIgE without difference for sensitivity.
Asunto(s)
Hipersensibilidad/diagnóstico , Inmunoglobulina E/análisis , Pruebas Cutáneas/normas , Área Bajo la Curva , Asma/diagnóstico , Niño , Humanos , Rinitis Alérgica Estacional/diagnóstico , Sensibilidad y EspecificidadRESUMEN
The present guideline is a new version and an update of the guideline for the diagnosis and treatment of asthma, which replaces the previous version for german speaking countries from the year 2006. The wealth of new data on the pathophysiology and the phenotypes of asthma, and the expanded spectrum of diagnostic and therapeutic options necessitated a new version and an update. This guideline presents the current, evidence-based recommendations for the diagnosis and treatment of asthma, for children and adolescents as well as for adults with asthma.
Asunto(s)
Asma/diagnóstico , Asma/terapia , Asma/clasificación , Asma/etiología , Austria , Alemania , Humanos , Pronóstico , Factores de Riesgo , Sociedades MédicasRESUMEN
BACKGROUND: Gut microbiota and intestinal inflammation regulate the development of immune-mediated diseases, such as allergies. Fecal calprotectin is a biomarker of intestinal inflammation. OBJECTIVE: We evaluated the association of early-age fecal calprotectin levels to the later development of allergic diseases in children from farming and non-farming environments and further studied the effect of gut microbiota on the fecal calprotectin levels. METHODS: Fecal calprotectin was measured from 758 infants participating in the PASTURE study at the age of 2 months using the ELISA method. Serum-specific IgE levels were measured at 6 years of age. Data of environmental factors, doctor-diagnosed atopic dermatitis (AD) and asthma were collected by questionnaire. Multivariate logistic regression models were used for analysis. The composition of fecal microbiota was analysed in a subgroup of 120 infants with 16S rRNA pyrosequencing. The effect of Escherichia coli lipopolysaccharide (LPS) on in vitro monocyte IL-10 secretion was studied by flow cytometry. RESULTS: The infants with high fecal calprotectin levels at 2 months, that is above the 90th percentile, had an increased risk of developing AD and asthma/asthmatic bronchitis by the age of 6 years (aOR 2.02 (1.06-3.85) and 2.41 (1.25-4.64), respectively). High fecal calprotectin levels correlated negatively with fecal Escherichia. LPS from E. coli stimulated production of IL-10 in monocytes. CONCLUSION AND CLINICAL RELEVANCE: High degree intestinal inflammation at 2 months of age, detected as high fecal calprotectin, predicted asthma and AD by the age of 6 years and was linked to low abundance of fecal Escherichia. Impaired IL-10 activation due to the lack of colonization with E. coli could explain the intestinal inflammation associated high fecal calprotectin and later risk of asthma and AD. Our results have implications for the design of probiotic treatments and suggest that early intestinal colonization has long-term health effects.
Asunto(s)
Asma/epidemiología , Asma/metabolismo , Dermatitis Atópica/epidemiología , Dermatitis Atópica/metabolismo , Enfermedades Intestinales/epidemiología , Enfermedades Intestinales/metabolismo , Complejo de Antígeno L1 de Leucocito/metabolismo , Factores de Edad , Asma/etiología , Bacterias , Biomarcadores , Niño , Preescolar , Estudios de Cohortes , Dermatitis Atópica/etiología , Heces/química , Femenino , Microbioma Gastrointestinal , Humanos , Hipersensibilidad/epidemiología , Hipersensibilidad/etiología , Hipersensibilidad/metabolismo , Lactante , Interleucina-10/metabolismo , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/metabolismo , Masculino , Oportunidad Relativa , Embarazo , Factores de Riesgo , Encuestas y CuestionariosRESUMEN
BACKGROUND: The role of breastfeeding for the development of atopic diseases in childhood is contradictory. This might be due to differences in the composition of breast milk and levels of antimicrobial and anti-inflammatory components. OBJECTIVE: The objective of this study was to examine whether levels of total immunoglobulin A (IgA) or transforming growth factor-ß1 (TGF-ß1) in breast milk were associated with the risk of developing atopic dermatitis (AD), atopic sensitization or asthma at early age taking breastfeeding duration into account. METHODS: The birth cohort study PASTURE conducted in Finland, France, Germany and Switzerland provided 610 breast milk samples collected 2 months after delivery in which soluble IgA (sIgA) and TGF-ß1 levels were measured by ELISA. Duration of breastfeeding was assessed using weekly food frequency diaries from month 3 to month 12. Data on environmental factors, AD and asthma were collected by questionnaires from pregnancy up to age 6. Atopic status was defined by specific IgE levels in blood collected at the ages of 4 and 6 years. Multivariate logistic regression models were used for statistical analysis. RESULTS: Soluble IgA and TGF-ß1 levels in breast milk differed between countries, and sIgA levels were associated with environmental factors related to microbial load, for example, contact to farm animals or cats during pregnancy, but not with raw milk consumption. sIgA levels were inversely associated with AD up to the of age 2 years (P-value for adjusted linear trend: 0.005), independent of breastfeeding duration. The dose of sIgA ingested in the first year of life was associated with reduced risk of AD up to the age of 2 (aOR, 95% CI: 0.74; 0.55-0.99) and 4 years (0.73; 0.55-0.96). No clear associations between sIgA and atopy or asthma up to age 6 were observed. TGF-ß1 showed no consistent association with any investigated health outcome. CONCLUSION AND CLINICAL RELEVANCE: IgA in breast milk might protect against the development of AD.
Asunto(s)
Dermatitis Atópica/inmunología , Inmunoglobulina A/inmunología , Leche Humana/inmunología , Adulto , Factores de Edad , Animales , Lactancia Materna , Niño , Preescolar , Estudios de Cohortes , Dermatitis Atópica/epidemiología , Dermatitis Atópica/metabolismo , Dieta , Ambiente , Europa (Continente) , Femenino , Humanos , Inmunoglobulina A/metabolismo , Lactante , Recién Nacido , Leche , Leche Humana/química , Leche Humana/metabolismo , Embarazo , Encuestas y Cuestionarios , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
BACKGROUND: Genomewide association and epigenetic studies found a region within the RAD50 gene on chromosome 5q31 to be associated with total serum IgE levels and asthma. In mice, this region harbors a locus control region for nearby TH 2 cytokines, which is characterized by four Rad50 DNase I hypersensitive sites (RHS4-7). Among these, RHS7 seems to have the strongest impact on TH 2 differentiation. We investigated whether within the human homolog of RHS7, functional polymorphisms exist, which could affect DNA methylation or gene expression in the 5q31 locus and might have an influence on asthma status or IgE regulation. METHODS: The human RHS7 region was fine mapped using 1000 genomes database information. In silico analysis and electrophoretic mobility shift assays were used to assess SNP function. Allele-specific effects on DNA methylation were evaluated in cord blood (n = 73) and at age of 4.5 years (n = 61) by pyrosequencing. Allele-specific effects on RAD50, IL4, and IL13 expression were analyzed in 100 subjects. Associations with asthma and IgE levels were investigated in the MAGICS/ISAAC II population (n = 1145). RESULTS: Polymorphism rs2240032 in the RHS7 region is suggestive of allele-specific transcription factor binding, affects methylation of the IL13 promoter region and influences RAD50 and IL4 expression (lowest P = 0.0027). It is also associated with total serum IgE levels (P = 0.0227). CONCLUSION: A functional relevant polymorphism in the TH 2 locus control region, equivalent to RHS7 in mice, affects DNA methylation and gene expression within 5q31 and influences total serum IgE on the population level.
Asunto(s)
Asma/genética , Metilación de ADN , Regulación de la Expresión Génica/inmunología , Región de Control de Posición/genética , Polimorfismo de Nucleótido Simple , Células Th2/inmunología , Ácido Anhídrido Hidrolasas , Adulto , Asma/inmunología , Niño , Metilación de ADN/inmunología , Enzimas Reparadoras del ADN/genética , Enzimas Reparadoras del ADN/inmunología , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/inmunología , Ensayo de Cambio de Movilidad Electroforética , Femenino , Estudio de Asociación del Genoma Completo , Humanos , Inmunoglobulina E/sangre , Interleucina-13/genética , Interleucina-13/inmunología , Región de Control de Posición/inmunología , Masculino , Reacción en Cadena de la PolimerasaRESUMEN
BACKGROUND: Prospective studies investigating the role of serum vitamin E concentrations during early life in the development of childhood allergies and asthma are limited. OBJECTIVE: To study the associations between serum vitamin E concentrations at first year of life and longitudinal development of atopy, atopic dermatitis, wheeze, and asthma up to 6 years of age. METHODS: The setting was the PASTURE study, a multicenter prospective birth cohort study in five European rural settings. Children of 1133 mothers recruited during pregnancy were followed from birth with measurement of serum vitamin E levels at year 1 and repeated assessments of serum immunoglobulin E antibodies (year 1, 4.5, 6), atopic dermatitis, wheezing symptoms, and asthma (year 1, 1.5, 2, 3, 4, 5, 6). RESULTS: At 6 years of age, 66% and 82% of the original 1133 subjects underwent blood test for IgE and answered the questionnaire, respectively. We did not observe any statistically significant associations between serum vitamin E concentrations at year 1 and the endpoints, but borderline inverse associations between alpha tocopherol and wheezing without cold (OR 0.45, 95% CI 0.19-1.09) and any wheezing symptom (OR 0.52, 95% CI 0.27-1.02). CONCLUSIONS: Serum vitamin E concentrations at year 1 were not associated with allergies or asthma by 6 years of age. While further prospective studies with repeated assessments of vitamin E during early life may clarify its putative role in the development of the diseases, it is also possible that the antioxidant hypothesis in the development of allergies and asthma does not hold.
Asunto(s)
Asma/sangre , Asma/epidemiología , Dermatitis Atópica/sangre , Dermatitis Atópica/epidemiología , Hipersensibilidad Inmediata/sangre , Hipersensibilidad Inmediata/epidemiología , Ruidos Respiratorios , Vitamina E/sangre , Niño , Preescolar , Europa (Continente)/epidemiología , Humanos , Incidencia , Lactante , Oportunidad Relativa , Prevalencia , Estudios Prospectivos , Riesgo , Factores de Riesgo , Población RuralRESUMEN
BACKGROUND: Genetic susceptibility and environmental influences are important contributors to the development of asthma and atopic diseases. Epigenetic mechanisms may facilitate gene by environment interactions in these diseases. METHODS: We studied the rural birth cohort PASTURE (Protection against allergy: study in rural environments) to investigate (a) whether epigenetic patterns in asthma candidate genes are influenced by farm exposure in general, (b) change over the first years of life, and (c) whether these changes may contribute to the development of asthma. DNA was extracted from cord blood and whole blood collected at the age of 4.5 years in 46 samples per time point. DNA methylation in 23 regions in ten candidate genes (ORMDL1, ORMDL2, ORMDL3, CHI3L1, RAD50, IL13, IL4, STAT6, FOXP3, and RUNX3) was assessed by pyrosequencing, and differences between strata were analyzed by nonparametric Wilcoxon-Mann-Whitney tests. RESULTS: In cord blood, regions in ORMDL1 and STAT6 were hypomethylated in DNA from farmers' as compared to nonfarmers' children, while regions in RAD50 and IL13 were hypermethylated (lowest P-value (STAT6) = 0.001). Changes in methylation over time occurred in 15 gene regions (lowest P-value (IL13) = 1.57*10(-8)). Interestingly, these differences clustered in the genes highly associated with asthma (ORMDL family) and IgE regulation (RAD50, IL13, and IL4), but not in the T-regulatory genes (FOXP3, RUNX3). CONCLUSIONS: In this first pilot study, DNA methylation patterns change significantly in early childhood in specific asthma- and allergy-related genes in peripheral blood cells, and early exposure to farm environment seems to influence methylation patterns in distinct genes.
Asunto(s)
Agricultura , Asma/genética , Asma/inmunología , Metilación de ADN , Exposición a Riesgos Ambientales , Hipersensibilidad/genética , Hipersensibilidad/inmunología , Niño , Preescolar , Epigénesis Genética , Interacción Gen-Ambiente , Predisposición Genética a la Enfermedad , Humanos , Lactante , Recién Nacido , Proyectos PilotoRESUMEN
BACKGROUND: Early-life exposure to environmental microbial agents may be associated with development of wheezing and allergic diseases. OBJECTIVE: To assess the association of microbial exposure in rural homes with the risk of asthma, wheezing, atopic dermatitis and sensitization. METHODS: Birth cohorts of rural children (n = 1133), half from farmer families, were followed up from birth to 2 years of age by questionnaires in five European centres. Endotoxin and extracellular polysaccharides (EPS) of Penicillium and Aspergillus spp. were determined from living room floor and mother's mattress dust samples collected at 2 months of age. Specific IgE against 19 allergens was measured at 1 year of age. Discrete-time hazard models, generalized estimations equations (GEE) and logistic regression were used for statistical analyses. RESULTS: The incidence of asthma was inversely associated with the amount of dust (adjusted odds ratio (aOR) 0.73, 95% CI 0.58-0.93) and the loads (units/m(2)) of EPS (aOR 0.75, 95% CI 0.55-1.04) and endotoxin (aOR 0.79, 95% CI 0.60-1.05) in the mother's mattress. Similar associations were seen with wheezing and with living room floor dust. The microbial markers were highly correlated and their effects could not be clearly separated. The inverse associations were seen especially among non-farmers. The risk of sensitization to inhalant allergens increased with increasing endotoxin exposure from mattress dust. No associations were observed with concentrations (units/g) or with atopic dermatitis. CONCLUSION AND CLINICAL RELEVANCE: The amount and microbial content of house dust were inversely associated with asthma and wheezing, but due to high correlations between microbial agents and amount of dust, it was not possible to disentangle their individual effects. New ways to better measure and represent exposure to environmental microbes, including indexes of biodiversity, are needed especially among farmers.
Asunto(s)
Dermatitis Atópica/inmunología , Polvo/inmunología , Exposición a Riesgos Ambientales , Hipersensibilidad Inmediata/inmunología , Ruidos Respiratorios/inmunología , Población Rural , Adulto , Agricultura , Alérgenos/análisis , Alérgenos/inmunología , Asma/epidemiología , Asma/inmunología , Austria/epidemiología , Biomarcadores/análisis , Estudios de Cohortes , Dermatitis Atópica/epidemiología , Polvo/análisis , Endotoxinas/análisis , Endotoxinas/inmunología , Femenino , Finlandia/epidemiología , Francia/epidemiología , Alemania/epidemiología , Humanos , Hipersensibilidad Inmediata/epidemiología , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , Lactante , Recién Nacido , Polisacáridos/análisis , Polisacáridos/inmunología , Embarazo , Encuestas y Cuestionarios , Suiza/epidemiologíaRESUMEN
BACKGROUND: Recent studies indicate that prenatal vitamin D intake may protect against the development of atopic diseases in young children. Vitamin D has been shown to induce tolerogenic antigen-presenting cells such as dendritic cells. Whether the allergy-protective potential of prenatal vitamin D is mediated through such mechanisms is, however, unknown. OBJECTIVE: To evaluate the association between prenatal vitamin D supplementation and tolerogenic antigen-presenting cells in cord blood (CB) as determined by mRNA measurement of immunoglobulin-like transcripts (ILT)3 and ILT4. METHODS: A prospective multi-centre birth cohort was established in rural areas of five European countries. Information on maternal exposures including vitamin D intake was collected by questionnaires during pregnancy. The gene expression of ILT3 and ILT4 was analysed by real-time PCR in the CB of 927 children. Maternal vitamin D supplementation was assessed in Finland and France (n=349). RESULTS: Maternal vitamin D supplementation during pregnancy was associated with an increase in the gene expression of ILT3 (P=0.012) and ILT4 (P<0.001). This association remained significant for ILT4 (P=0.020) and showed a positive trend for the gene expression of ILT3 (P=0.059) after multivariate analysis controlling for various confounders. CONCLUSIONS: Vitamin D supplementation during pregnancy may increase the mRNA levels of ILT3 and ILT4 in CB. This finding may point towards an early induction of tolerogenic immune responses by maternal vitamin D intake.
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Células Presentadoras de Antígenos/inmunología , Suplementos Dietéticos , Sangre Fetal/inmunología , Expresión Génica , Hipersensibilidad Inmediata/prevención & control , Glicoproteínas de Membrana/genética , Receptores de Superficie Celular/genética , Receptores Inmunológicos/genética , Vitamina D/administración & dosificación , Adulto , Niño , Europa (Continente)/epidemiología , Femenino , Humanos , Hipersensibilidad Inmediata/epidemiología , Hipersensibilidad Inmediata/inmunología , Masculino , Embarazo , Estudios Prospectivos , ARN Mensajero/genética , Factores de Riesgo , Población RuralRESUMEN
BACKGROUND: Little is known about the asthma candidate gene neuropeptide S receptor 1 (NPSR1) in relation to environmental exposures, but recent evidences suggest its role as an effect modifier. OBJECTIVES: To explore the interaction between NPSR1 polymorphisms and environmental exposures related to farming lifestyle and to study the in vitro effects of lipopolysaccharide (LPS) stimulation on NPSR1 expression levels. METHODS: We studied 3113 children from PARSIFAL, a European cross-sectional study on environmental/lifestyle factors and childhood allergy, partly focused on children brought up on a farm. Information on exposures and outcomes was primarily obtained from parental questionnaires. Seven tagging polymorphisms were analysed in a conserved haplotype block of NPSR1. Multivariate logistic regression was used to evaluate a multiplicative model of interaction. NPSR1 protein and messenger RNA (mRNA) levels in monocytes were measured after LPS stimulation by fluorescence activated cell sorting (FACS) and quantitative real-time polymerase chain reaction (PCR). RESULTS: A strong interaction was seen between current regular contact to farm animals and several NPSR1 polymorphisms, particularly rs323922 and rs324377 (p<0.005), with respect to allergic symptoms. Considering the timing of initiation of such current regular farm animal contact, significant interactions with these and two additional polymorphisms (SNP546333, rs740347) were revealed. In response to LPS, NPSR1-A protein levels in monocytes were upregulated (p = 0.002), as were NPSR1-A mRNA levels (p = 0.02). CONCLUSIONS: The effect of farm animal contact on the development of allergic symptoms in children is modified by NPSR1 genetic background.
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Animales Domésticos , Exposición a Riesgos Ambientales , Polimorfismo de Nucleótido Simple , Receptores Acoplados a Proteínas G/genética , Hipersensibilidad Respiratoria/genética , Adolescente , Animales , Niño , Preescolar , Citometría de Flujo , Expresión Génica , Predisposición Genética a la Enfermedad , Humanos , Modelos Logísticos , Monocitos/metabolismo , Análisis Multivariante , Reacción en Cadena de la Polimerasa , ARN Mensajero/genética , Receptores Acoplados a Proteínas G/metabolismo , Hipersensibilidad Respiratoria/epidemiologíaRESUMEN
BACKGROUND: Various studies have found reduced prevalences of atopic sensitization and atopic diseases in children previously exposed to infections or living conditions with a high microbial burden, such as the farming environment. OBJECTIVE: We sought to determine the relationships of cord blood immunoglobulin E (IgE) with maternal health conditions before and during pregnancy. METHODS: Pregnant women living in rural areas in five European countries were recruited in the third trimester of pregnancy. Information on maternal health during pregnancy was collected from maternity records and by questionnaires (n = 497). Specific IgE for inhalant and food allergens was assessed in cord blood and peripheral blood samples of the mothers. RESULTS: Inverse associations of cord blood IgE to seasonal allergens with positive maternal records for Toxoplasma gondii (adjusted odds ratio = 0.37 [0.17-0.81]) and rubella virus (adjusted odds ratio = 0.35 [0.13-0.96]) were found. The previously described effect of prenatal farm exposure on IgE to seasonal allergens was partly confounded by a positive maternal record for T. gondii. The number of maternal siblings, maternal contact to cats during pregnancy or during her first year of life, predicted a positive maternal record for T. gondii. CONCLUSIONS: Maternal immunity to T. gondii and rubella may impact on atopic sensitization in the fetus. A positive T. gondii record explained the previously identified effect of prenatal farm exposure on IgE to seasonal allergens only to a minor extent.
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Alérgenos/inmunología , Sangre Fetal/inmunología , Hipersensibilidad Inmediata/inmunología , Inmunoglobulina E/sangre , Virus de la Rubéola/inmunología , Rubéola (Sarampión Alemán)/inmunología , Toxoplasma/inmunología , Toxoplasmosis/inmunología , Animales , Femenino , Humanos , Hipersensibilidad Inmediata/sangre , Hipersensibilidad Inmediata/microbiología , Hipersensibilidad Inmediata/virología , Embarazo , Encuestas y CuestionariosRESUMEN
Non-isotonic aerosols are being used more commonly to perform bronchial provocation tests. In contrast to histamine and methacholine challenge tests they appear to have higher specificity and a higher predictive value. The aim of the present study was to assess the reproducibility of the response to challenge with 4.5% hypertonic saline administered via an ultrasonic nebulizer in children with mild to severe asthma. Seventeen children with asthma aged 10 to 14 years completed two or three challenge tests at the same time of day within a 10 day period. Of these 17 children 9 had mild, 4 moderate, and 4 severe asthma. Children inhaled 4.5% hypertonic NaCl from an ultrasonic nebulizer with an output of 1.9 to 2.5 mL/min (Timeter) using the protocol developed by Anderson with modifications. A fall in forced expiratory volume in 1 second (FEV1) from baseline of 15% or more was considered a positive response and PD15 was calculated. In 16/17 subjects a greater than 15% fall in FEV1 occurred consistently on all study days. One subject with moderate asthma had a less than 15% fall in FEV1 on both study days. The coefficient of repeatability for PD15 was 1.8. This equals 0.85 of a doubling dose difference between the two or three measurements of PD15. The cumulative time of aerosol inhalation causing a fall in FEV1 > or = 15%) (PT15) showed a coefficient of repeatability of 1.59, similar to 0.67 doubling dose difference. The PD15 and PT15 were highly significantly correlated. The 4.5% NaCl challenge test yields good reproducibility in children with mild to severe asthma under laboratory conditions.
Asunto(s)
Asma/diagnóstico , Pruebas de Provocación Bronquial , Solución Salina Hipertónica , Adolescente , Aerosoles , Asma/fisiopatología , Niño , Intervalos de Confianza , Relación Dosis-Respuesta a Droga , Femenino , Volumen Espiratorio Forzado/fisiología , Humanos , Masculino , Nebulizadores y Vaporizadores , Recurrencia , Análisis de Regresión , Reproducibilidad de los Resultados , Solución Salina Hipertónica/administración & dosificación , Índice de Severidad de la Enfermedad , Factores de TiempoRESUMEN
Viral colds are an important cause of respiratory symptoms in normal children. Studies in adults suggest that inflammation in the lower respiratory tract is associated with viral colds, but there are no data regarding inflammation and viral infection in the lower airway of normal children with colds. We, therefore, studied the lower airway of two groups of children: Group I, those with active coryzal symptoms and a respiratory virus isolated from bronchoalveolar lavage fluid (BALF); and Group II: asymptomatic children who had had a clinical cold within the previous 2 weeks and no respiratory virus in BALF. Both groups were compared to age- and weight-matched normal noninfected controls, who had had no coryzal symptoms for at least 8 weeks. Viruses isolated from BALF of Group I (n = 7) were: respiratory syncytial virus (n = 2), rhinovirus (n = 3), parainfluenza I (n = 1), and echovirus 11 (n = 1). Compared to normal controls, Group I had an increased BALF lymphocyte and neutrophil differential count (P < 0.05), a concomitant depressed alveolar macrophage differential count (P < 0.05), and increased BALF concentrations of soluble intercellular adhesion molecule-1 (sICAM-1) (P < 0.05, n = 6), total protein (P < 0.05, n = 6) and albumin (P < 0.05, n = 7). Similar changes were seen in Group II (n = 22), with an increased BALF neutrophil (P < 0.05) and lymphocyte (P < 0.01) differential count, and increased concentrations of sICAM-1 (P < 0.01, n = 15), total protein (P < 0.0001, n = 9) and albumin (P = 0.05, n = 17). Our results suggest that inflammation and viral infection in the lower airway are present during active colds, and that inflammation is also present during the convalescent period.
Asunto(s)
Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/citología , Resfriado Común/metabolismo , Resfriado Común/patología , Molécula 1 de Adhesión Intercelular/análisis , Adolescente , Albúminas/análisis , Líquido del Lavado Bronquioalveolar/virología , Recuento de Células , Niño , Preescolar , Resfriado Común/virología , Femenino , Humanos , Lactante , Recuento de Leucocitos , Macrófagos Alveolares , Masculino , Proteínas/análisisRESUMEN
Progressive lung disease in patients with cystic fibrosis (CF) is caused by thick secretions, which cause airway obstruction and subsequent colonization and infection by inhaled pathogenic microorganisms. Recently, recombinant human DNase has been shown to reduce the viscoelasticity of sputum in patients with cystic fibrosis and to improve lung function. Ultrasonically nebulized hypertonic saline (HS) has been demonstrated to enhance mucociliary clearance and sputum expectoration by rehydrating airway secretions, and may therefore provide a low cost alternative. We studied the changes in pulmonary function and symptoms in a group of patients with CF who have moderate to severe lung disease. The patients were evaluated following 2 weeks of treatment with HS in an open-label study. Subjects were randomly allocated to receive 10 ml of either 0.9% NaCl (IS) or 6% NaCl (HS). Twice daily, prior to physiotherapy, treatments were delivered by a portable ultrasonic nebulizer. To prevent bronchoconstriction, 600 mg of salbutamol was administered prior to the nebulized solutions. A symptom score was recorded and spirometry was performed on day 0 before therapy was started, on day 14 (the last day of therapy), and on day 28 (14 days after the last treatment with either IS or HS). Fifty-two patients (32 males), with a mean age of 16.2 (range 7-36) years completed the study. There was no difference in baseline characteristics between the two groups. Following 2 weeks of treatment, there was a significant improvement from baseline in FEV1 of 15.0 +/- 16.0% (mean +/- SD) in patients treated with HS, compared with a change of 2.8 +/- 13% in those on IS therapy (P = 0.004). Furthermore, there was a subjective improvement in the effectiveness of chest physiotherapy as reported by those using HS (P = 0.02). The treatment was well tolerated. We conclude that in patients with CF, ultrasonically nebulized hypertonic saline improves lung function in a way similar to that reported for human recombinant DNase when inhaled over a 2 week period. Nebulized saline also enhances the perception of effectiveness of chest physiotherapy.