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1.
Neuropediatrics ; 39(1): 51-4, 2008 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-18504684

RESUMEN

Fucosidosis is a rare autosomal recessive lysosomal storage disease, resulting from a deficiency of alpha- L-fucosidase. We report on the clinical and MRI findings of a girl with this disorder. Developmental delay became obvious at an age between 6 and 12 months. Cranial MRI at 16 months revealed severe global hypomyelination of both supra- and infratentorial white matter but no involvement of basal ganglia or thalamus. No clinical signs typical for fucosidosis were present at this time, and psychomotor development still progressed slowly. Since the age of 2 years, progressive neurological deterioration occurred. The diagnosis was established by severely decreased activity of alpha- L-fucosidase in plasma and leukocytes and confirmed by the detection of compound heterozygosity for two missense mutations of the FUCA1 gene. A follow-up imaging at the age of 4 years showed progression of neuroradiological abnormalities, particularly progressive involvement of basal ganglia and thalami. The course of this patient and her MRI findings enlarge the clinical and neuroradiological spectrum of fucosidosis.


Asunto(s)
Enfermedades Desmielinizantes/patología , Fucosidosis/genética , Fucosidosis/patología , alfa-L-Fucosidasa/genética , Secuencia de Aminoácidos , Niño , Preescolar , Enfermedades Desmielinizantes/etiología , Femenino , Estudios de Seguimiento , Fucosidosis/complicaciones , Heterocigoto , Humanos , Lactante , Datos de Secuencia Molecular , Mutación Missense , Fenotipo , Polimorfismo de Longitud del Fragmento de Restricción , Trastornos Psicomotores/etiología , Trastornos Psicomotores/patología , Homología de Secuencia de Aminoácido , alfa-L-Fucosidasa/sangre
2.
Pediatr Pulmonol ; 41(6): 530-7, 2006 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-16617448

RESUMEN

Increased body mass index has been linked to wheezing, a diagnosis of asthma, and morbidity. We investigated the association between body mass index (BMI), breastfeeding, and airway hyperresponsiveness (AHR) in 536 German schoolchildren. We analyzed consecutive surveys in 1994-1995 and 1997, conducted as part of the Child Health and Environment Cohort Study in Hesse, Germany. The questionnaire included questions adapted from the German version of the International Study of Asthma and Allergy in Childhood (ISAAC). A bronchial challenge test using 4.5% hypertonic saline was conducted during the 1997 survey. AHR was defined as a fall in forced expiratory volume in 1 sec (FEV(1)) of > or = 15%. Of 536 children who participated in the 1997 survey (median age, 10.3 years), 82 (15%) tested positive for AHR. In a multivariate analysis, there was no association between AHR determined at age 10 years and the highest quintile of BMI compared to the lowest quintile at age 4 years (odds ratio (OR), 1.4; 95% confidence interval (CI), 0.5-3.6), 7-8 years (OR, 0.6; 95% CI, 0.1-2.5), or 10 years (OR, 1.1; 95% CI, 0.2-4.3). Breastfeeding for 12 weeks or longer protected against AHR (OR, 0.4; 95% CI, 0.2-0.9). However, when children in the highest quintile of BMI at age 4 years had been breastfed for 8 weeks or less, the prevalence of AHR at age 10 years was significantly increased (27.7%, P = 0.01). In conclusion, our results demonstrate a protective effect of breastfeeding against AHR, and reinforce the need to encourage breastfeeding. Although there was no association between BMI and AHR, our finding of an interactive effect of high BMI and short breastfeeding on AHR suggests a complex etiological pathway that needs to be further explored.


Asunto(s)
Índice de Masa Corporal , Hiperreactividad Bronquial/epidemiología , Adolescente , Asma/epidemiología , Asma Inducida por Ejercicio/epidemiología , Lactancia Materna/estadística & datos numéricos , Hiperreactividad Bronquial/diagnóstico , Hiperreactividad Bronquial/etiología , Pruebas de Provocación Bronquial/métodos , Niño , Estudios de Cohortes , Dermatitis Atópica/epidemiología , Femenino , Volumen Espiratorio Forzado/fisiología , Alemania/epidemiología , Humanos , Modelos Logísticos , Masculino , Análisis Multivariante , Oportunidad Relativa , Prevalencia , Ruidos Respiratorios/diagnóstico , Rinitis Alérgica Estacional/epidemiología , Factores Sexuales , Encuestas y Cuestionarios , Contaminación por Humo de Tabaco/estadística & datos numéricos
3.
Clin Exp Allergy ; 34(8): 1220-5, 2004 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-15298561

RESUMEN

BACKGROUND: Sensitization to house dust mite (HDM) is an important risk factor for the development of asthma and allergic disease in childhood. Higher levels of HDM allergen are linked to increased sensitization to HDM. OBJECTIVE: To study the effect of mite-impermeable mattress encasings and an educational package on the development of allergies in a newborn cohort. METHODS: Six hundred and ninety-six newborns at high risk of developing allergies were enrolled in three European countries (Germany, Austria, UK) in a prospective, randomized, controlled birth-cohort study. Children were randomly assigned to an intervention and control group. Intervention measures included the use of mite-impermeable mattress encasings for the child's bed and a simple educational package on allergen avoidance. The control group received basic information about allergies. Children were followed up at age 6, 12, 18 and 24 months. RESULTS: 80.9% of the children were followed up to the age of 24 months. No difference in the prevalence of sensitization to HDM (control vs. intervention group: 8.4% vs. 6.1%, P=0.33) or the development of symptoms (recurrent wheezing 10.3% vs. 10.7%, nocturnal cough 12.5% vs. 12.5%) or allergic diseases (asthma 3.5% vs. 5.1%, eczema 20.0% vs. 19.6%, rhinitis 28.9% vs. 25.8%) could be found between the control and intervention group. CONCLUSION: In this study, HDM avoidance did not show a protective effect on the development of sensitization to HDM or symptomatic allergy in children at age 24 months.


Asunto(s)
Ropa de Cama y Ropa Blanca , Hipersensibilidad/prevención & control , Educación del Paciente como Asunto , Alérgenos/inmunología , Animales , Antígenos Dermatofagoides/inmunología , Europa (Continente) , Estudios de Seguimiento , Humanos , Hipersensibilidad/diagnóstico , Hipersensibilidad/inmunología , Recién Nacido , Estudios Prospectivos , Insuficiencia del Tratamiento
4.
Allergy ; 59(9): 973-9, 2004 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-15291906

RESUMEN

BACKGROUND: Specific immunotherapy (SIT) and treatment with anti-immunoglobulin (Ig)E antibody are complementary approaches to treat allergic rhinoconjunctivitis, which may be used for single or combined treatment. OBJECTIVE: A randomized, double-blind, placebo-controlled trial was conducted to compare the efficacy of single and combined treatment with SIT and anti-IgE (Omalizumab) in reducing symptom severity and rescue medication use. METHODS: A total of 221 subjects with birch and grass pollen allergic rhinoconjunctivitis aged 6-17 years were analysed during the grass pollen season. Group A (SITbirch + placebo) served as a reference group obtaining no effective treatment for grass pollen allergy. Group B received anti-IgE monotherapy during grass pollen season, group C SIT grass pollen monotherapy, and group D the combined treatment of SIT and Omalizumab. RESULTS: Preseasonal treatment with grass pollen SIT alone compared with SIT with the nonrelated allergen did not reduce symptoms or rescue medication use. Anti-IgE monotherapy significantly diminished rescue medication use and number of symptomatic days. The combined treatment with SIT and anti-IgE showed superior efficacy on symptom severity compared with anti-IgE alone. CONCLUSIONS: Co-seasonal Omalizumab therapy showed considerable effects in children with seasonal allergic rhinitis. The combination of SIT plus Omalizumab was clinically superior to each treatment alone during the first year of observation.


Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Desensibilización Inmunológica , Poaceae/inmunología , Polen/inmunología , Rinitis Alérgica Estacional/terapia , Adolescente , Anticuerpos Antiidiotipos , Anticuerpos Monoclonales Humanizados , Niño , Método Doble Ciego , Humanos , Omalizumab , Estudios Prospectivos
5.
Clin Exp Allergy ; 34(7): 1079-85, 2004 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-15248853

RESUMEN

BACKGROUND: Binding of allergens to IgE on mast cells and basophils causes release of inflammatory mediators in nasal secretions. OBJECTIVE: The combined effect of specific immunotherapy (SIT) and omalizumab, a humanized monoclonal anti-IgE antibody, on release of eosinophilic cationic protein (ECP), tryptase, IL-6, and IL-8 in nasal secretion was evaluated. METHODS: Two hundred and twenty five children (aged 6-17 years) with a history of seasonal allergic rhinoconjunctivitis induced by birch and grass pollen were randomized into four groups: either birch- or grass-pollen SIT in combination with either anti-IgE or placebo. Complete sets of nasal secretion samples before treatment Visit 1 (V1), during birch- (V2) and grass (V3)-pollen season and after the pollen season (V4) were collected from 53 patients. RESULTS: A significant reduction in tryptase only was seen in the anti-IgE-treated group at V2 (P<0.05) and V4 (P<0.05) compared with the placebo group. During the pollen season, patients with placebo showed an increase of ECP compared with baseline (V2: +30.3 microg/L; V3: +134.2 microg/L, P< 0.005; V4: +79.0 microg/L, P< 0.05), and stable levels of tryptase, IL-6 and IL-8. Treatment with anti-IgE resulted in stable ECP values and a significant decrease of tryptase compared with V1 (baseline): V2: -80.0 microg/L (P< 0.05); V3: -56.3 microg/L, which persisted after the pollen season with V4: -71.6 microg/L (P< 0.05). After the pollen season, a decrease of IL-6 was observed in both groups (V4 placebo group: -37.5 ng/L; V4 anti-IgE group: -42.9 ng/L, P< 0.01). CONCLUSION: The combination of SIT and anti-IgE is associated with prevention of nasal ECP increase and decreased tryptase levels in nasal secretions.


Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Desensibilización Inmunológica/métodos , Inmunoglobulina E/inmunología , Mucosa Nasal/inmunología , Rinitis Alérgica Estacional/terapia , Adolescente , Anticuerpos Antiidiotipos , Anticuerpos Monoclonales Humanizados , Betula , Proteínas Sanguíneas/análisis , Líquidos Corporales/química , Niño , Método Doble Ciego , Proteínas en los Gránulos del Eosinófilo , Femenino , Humanos , Interleucina-6/análisis , Interleucina-8/análisis , Masculino , Mucosa Nasal/metabolismo , Omalizumab , Poaceae , Polen , Rinitis Alérgica Estacional/inmunología , Ribonucleasas/análisis , Serina Endopeptidasas/análisis , Triptasas
6.
Eur Respir J ; 23(2): 292-9, 2004 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-14979506

RESUMEN

The effects of semi-annual and 3.5 yr mean ozone (O3) concentrations on children's forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were assessed over a study period of 3.5 yrs in 2,153 schoolchildren from 15 study sites in South Western Germany and Lower Austria. Spirometric parameters were assessed twice a year, and differences between consecutive measurements divided by days were considered as a measure of lung growth. Exposure was analysed in four classes, separately for winter and summer (semi-annual mean O3 concentrations 22-30, 30-38, 38-46, 46-54 parts per billion (ppb) in summer and 4-12, 12-20, 20-28, 28-36 ppb in winter). Regression methods for repeated measurements were used, and these revealed a significantly lower FVC (FEV1) increase estimated at -19.2 (-18.5) mL x 100 days(-1) for semi-annual mean O3 exposure in summer between 46 and 54 ppb compared to exposure between 22 and 30 ppb. However, in winter, the estimated difference in FVC (FEV1) was 16.4 (10.9) mL x 100 days(-1) between the semi-annual O3 class 28-36 ppb and the 4-12 ppb class. By means of linear regression the study found that there was no association between growth rates and mean summer O3 for FVC and FEV1 over a 3.5 yr period. The authors conclude that medium-term effects on schoolchildren's lung growth are possibly present, but are in the long-term not detectable for forced vital capacity and forced expiratory volume in one second over a 3.5 yr period due to partial reversibility.


Asunto(s)
Contaminantes Atmosféricos/toxicidad , Volumen Espiratorio Forzado/efectos de los fármacos , Pulmón/crecimiento & desarrollo , Estudios Multicéntricos como Asunto , Ozono/toxicidad , Capacidad Vital/efectos de los fármacos , Austria , Niño , Femenino , Estudios de Seguimiento , Alemania , Humanos , Modelos Lineales , Pulmón/efectos de los fármacos , Masculino , Medición de Riesgo , Espirometría/estadística & datos numéricos
7.
Clin Exp Allergy ; 33(11): 1537-43, 2003 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-14616866

RESUMEN

OBJECTIVE: The aim of our study was to conduct a prospective investigation into the potential association of cord blood proliferative response and cytokine production in response to various stimuli on the development of atopic dermatitis (AD) at the age of 3 years. METHODS: Cord blood mononuclear cells (CBMC) from 40 healthy term neonates were isolated. The proliferative response of CBMC stimulated with IL-2, betalactoglobulin (BLG) and house dust mite allergen (Der p 1) was assessed by liquid scintillation counting and the stimulation index (SI) was calculated. The cytokines interleukin (IL-)13, interferon (IFN-)gamma, IL-10 and IL-18 in the cell culture supernatants in response to phytohaemagglutinin (PHA), Der p 1 and BLG were measured using the ELISA technique. After 3 years, symptoms of AD were obtained with a questionnaire completed by the parents. RESULTS: We observed significantly higher IL-13 levels in response to PHA in children who subsequently developed symptoms of AD (S: median, 291 pg/mL) compared with asymptomatic children (No-S: 149 pg/mL; P=0.021, Wilcoxon test). Similarly, in response to Der p 1 significantly higher IL-13 levels were observed in symptomatic children (S: 168.6; No-S: 61.6 pg/mL; P=0.0084). In response to BLG, IL-13 levels were 287.2 (S) and 123.6 pg/mL (No-S; P=0.19). No significant differences were found when comparing the IFN-gamma levels in CBMC cultures stimulated with PHA (S: 10.2; No-S: 17.6 IU/L; P=0.78), Der p 1 (S: 307.6; No-S: 616.2 IU/L; P=0.2) or BLG (S: 18; No-S: 28.5 IU/L; P=0.83; Fig. 2). The IL-18 and IL-10 levels and the stimulation index in response to IL-2, BLG and Der p 1 showed no significant difference between children who subsequently developed symptoms of AD and asymptomatic children. CONCLUSION: Our data suggest that enhanced IL-13 levels at birth are associated with the subsequent development of atopic symptoms at the age of 3 years.


Asunto(s)
Alérgenos/inmunología , Dermatitis Atópica/inmunología , Sangre Fetal/inmunología , Interleucina-13/biosíntesis , Leucocitos Mononucleares/inmunología , Antígenos Dermatofagoides/inmunología , Proteínas de Artrópodos , División Celular/inmunología , Células Cultivadas , Preescolar , Cisteína Endopeptidasas , Femenino , Humanos , Recién Nacido , Interferón gamma/biosíntesis , Masculino , Fitohemaglutininas/inmunología , Estudios Prospectivos
8.
Clin Exp Allergy ; 32(6): 843-9, 2002 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-12047429

RESUMEN

BACKGROUND: Sensitization to dust mites predisposes to asthma and allergic rhinitis, and prevention of this sensitization might reduce the rising prevalence of these disorders. OBJECTIVE: To test the effectiveness of dust mite avoidance measures on the development of sensitization to dust mites in children. METHODS: As part of a multicentre study (Study of Prevention of Allergy in Children of Europe), 242 children, aged 5-7 years, in three European countries (United Kingdom, Greece and Lithuania), were randomized to prophylactic group (n = 127) and control group (n = 115). At randomization these children were required to have a family history of atopy and positive skin test to an aeroallergen but not to house dust mite. Children in the prophylactic group were provided with dust mite impermeable mattress covers and advice on environmental measures to reduce exposure to dust-mite allergen. Control group children were given non-specific advice. After 12 months a standardized questionnaire was completed and skin prick tests were performed. RESULTS: Ten children in the prophylactic group and 19 in the control group were lost to follow-up. Three of 117 (2.56%) children in the prophylactic group and nine of 96 (9.38%) in the control group developed sensitization to dust mites. Logistic regression analysis confirmed an independent effect of prophylactic measures (adjusted odds ratio (OR): 0.14, 95% confidence interval (CI): 0.03-0.79, P = 0.03). Fifteen children need to be treated to prevent sensitization in one child. CONCLUSION: Dust mite sensitization can be reduced in school age children with simple mite avoidance measures.


Asunto(s)
Alérgenos/efectos adversos , Alérgenos/inmunología , Hipersensibilidad Inmediata/prevención & control , Inmunización , Pyroglyphidae/inmunología , Contaminación del Aire Interior , Antígenos Dermatofagoides/inmunología , Niño , Protección a la Infancia , Preescolar , Europa (Continente)/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Modelos Logísticos , Masculino , Cooperación del Paciente , Estudios Prospectivos , Ruidos Respiratorios/inmunología , Factores de Riesgo , Servicios de Salud Escolar , Método Simple Ciego , Pruebas Cutáneas
9.
Allergy ; 57(6): 488-92, 2002 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-12028113

RESUMEN

BACKGROUND: In order to prevent pollen asthma by immunotherapy it is mandatory to know the best time to initiate it. Children with hay fever complaints are at considerable risk of developing pollen asthma. Population-based data on their natural history is urgently needed. METHODS: A longitudinal cohort study was conducted over four years in six rural towns in Baden-Württemberg, Germany. A questionnaire with questions taken from the International Study of Asthma and Allergies in childhood (ISAAC) was filled in every spring and autumn. Hay fever complaints, asthma defining symptoms and new doctors' diagnosis of hay fever and asthma were recorded. Additionally a skin prick test with pollen allergens was performed every autumn. RESULTS: In 1996, 19.7% of 1101 elementary school children (age: 8.1-9.9 years (5-95%)) were found to be sensitized to pollen and 8.7% had already been diagnosed as having hay fever. In a pooled analysis of 2478 children-summers, children with positive pollen sensitization had a significantly higher risk of developing hay fever symptoms (2.63; 2.17-3.10 odds ratio (OR); 95% confidence interval (CI)) and of being diagnosed as suffering from hay fever (7.88; 4.70-13.20). Furthermore, although their OR for the development of asthma symptoms during the pollen season was 3.88 (2.48-6.07 CI), it was only 0.69 (0.24-2.01 CI) for doctors' diagnosis of pollen asthma. CONCLUSION: Children of elementary school age with pollen sensitization and a history of hay fever are at considerable risk of getting pollen asthma, but they are not quickly diagnosed as such. Specific immunotherapy might be a means of preventing asthma completely in such a situation. Our data helps to estimate the sample size for intervention studies of this kind.


Asunto(s)
Alérgenos/efectos adversos , Alérgenos/inmunología , Asma/diagnóstico , Asma/etiología , Inmunización , Polen/efectos adversos , Polen/inmunología , Rinitis Alérgica Estacional/diagnóstico , Rinitis Alérgica Estacional/etiología , Contaminantes Atmosféricos/efectos adversos , Contaminantes Atmosféricos/inmunología , Asma/epidemiología , Niño , Protección a la Infancia , Intervalos de Confianza , Femenino , Alemania/epidemiología , Humanos , Modelos Logísticos , Masculino , Oportunidad Relativa , Prevalencia , Ruidos Respiratorios , Rinitis Alérgica Estacional/epidemiología , Salud Rural , Servicios de Salud Escolar , Encuestas y Cuestionarios , Resultado del Tratamiento
10.
J Investig Allergol Clin Immunol ; 11(2): 94-102, 2001.
Artículo en Inglés | MEDLINE | ID: mdl-11642579

RESUMEN

BACKGROUND: Atopy is an important risk factor for asthma and allergic diseases. However, the relationship between atopy and allergic symptoms is not fully understood, and may not be the same for different allergy related symptoms and in differing environmental conditions. OBJECTIVE: To study the differences in the association of allergy-related symptoms and atopy, in an adult population from five European countries. METHODS: A prospective, multi-national study was conducted. Centres included Isle of Wight (UK), Vienna (Austria), Freiburg (Germany), Athens (Greece), and Kaunas (Lithuania). We used five questions derived from the ISAAC (International Study of Asthma and Allergy in Children) and other validated questionnaire, to evaluate the presence of allergic symptoms in a selected adult population. Atopy was assessed by SPT or IgE measurement to 3 core allergens (dust mite, cat and grass pollen) in all centres and 1-2 additional allergens relevant to each area (parietaria, olive, birch pollen, tree pollen mix, dog). RESULTS: Of 3985 subjects, 2478 (62%) responded positively to one or more core ISAAC questions. Sensitisation rate was high in Austria and UK and relatively low in Greece. Dust mite and cat were important allergens for asthma, odds ratio (OR): 2.24, 95% confidence interval (CI): 1.63-3.08 and OR: 2.31, CI: 1.69-3.14, respectively. Grass pollen was strongly associated with hay fever in all centres (OR: 3.62 CI: 2.81-4.66) and with birch pollen in Austria (OR: 3.57, CI: 2.09-6.09) and with parietaria in Greece (4.61 (2.99-7.12). In the comparative analysis, using UK as a reference, Lithuanians had a 10-20-fold reduced risk of asthma and hay fever, but were twice more likely to report chronic itching. The risk of dust mite allergy was 3- and 10-fold lower in Lithuania and Greece, respectively, whereas the risk of cat and grass pollen allergy was one and half times higher in Austria. CONCLUSION: The risk of allergic symptoms and sensitisation and their association vary widely in different European countries.


Asunto(s)
Alérgenos/efectos adversos , Alérgenos/inmunología , Hipersensibilidad/inmunología , Inmunización , Poaceae/efectos adversos , Poaceae/inmunología , Polen/efectos adversos , Polen/inmunología , Adolescente , Adulto , Animales , Especificidad de Anticuerpos/inmunología , Gatos , Europa (Continente)/epidemiología , Femenino , Humanos , Inmunoglobulina E/inmunología , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Prospectivos , Sensibilidad y Especificidad , Pruebas Cutáneas
11.
Clin Exp Allergy ; 31(10): 1536-43, 2001 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-11678853

RESUMEN

BACKGROUND: Successful pregnancy is dependent upon T helper (Th)2-type-dominated immunological responsiveness in gestation-associated compartments. OBJECTIVE: In our study we observed the influence of the maternal Th2-associated cytokine pattern on the naive fetal T cell phenotype and asked if circulating Th2 cytokines of atopic mothers affects the Th1/Th2 differentiation of the fetus. METHODS: Cord blood mononuclear cells (CBMC) and peripheral blood mononuclear cells (PBMC) of the corresponding mothers were isolated. The proliferative response of CBMC and PBMC to Betalactoglobulin (BLG) was assessed by liquid scintillation counting. The cytokines interferon (IFN)-gamma, and interleukin (IL)-5, IL-10 and IL-13 in the cell culture supernatants were measured using the ELISA technique. We then defined two subgroups based on maternal levels of specific IgE against aeroallergens: sensitized mothers (MA(+)) and their neonates (NMA(+)) (n = 18) and non-sensitized mothers (MA(-)) and their neonates (NMA(-)) (n = 29). RESULTS: Nearly all mothers (98%) and neonates (92%) had a positive proliferation response after stimulation with BLG (mean stimulation index (10-90 percentile): neonates: 7 (2-15); mothers 14 (5-29)). In supernatants of BLG-stimulated cell cultures, sensitized mothers showed a significantly lower IFN-gamma concentration in comparison to non-sensitized mothers (MA(+) = 25; MA(-) = 123 IU/L; P < 0,05), whereas the neonates did not differ significantly (NMA(+) = 306; NMA(-) = 224 IU/L; n. s.). Nor was any difference found in the IL-13 concentration between the two groups of sensitized and non-sensitized mothers (MA(+) = 48; MA(-) = 125 pg/mL; n. s.). CBMC of neonates with a sensitized mother showed significantly higher IL-13 concentrations in response to BLG than neonates of non-sensitized mothers (NMA(+) = 1442, NMA(-) 738 pg/mL; P < 0.05). The IL-5 and IL-10 concentrations did not differ significantly within the neonatal and the maternal subgroups. CONCLUSIONS: Our data suggests that maternal sensitization to allergens is associated with the reduced maternal production of the Th2 antagonist IFN-gamma and elevated production of the Th2 cytokine IL-13 in the offspring.


Asunto(s)
Alérgenos/inmunología , Sangre Fetal/citología , Sangre Fetal/inmunología , Linfocitos T/metabolismo , Estudios de Cohortes , Citocinas/biosíntesis , Citocinas/sangre , Citocinas/inmunología , Ensayo de Inmunoadsorción Enzimática , Epítopos , Femenino , Humanos , Inmunización , Inmunoglobulina E/sangre , Bienestar del Lactante , Recién Nacido , Lactoglobulinas/farmacología , Activación de Linfocitos/efectos de los fármacos , Masculino , Bienestar Materno , Distribución Aleatoria , Pruebas Cutáneas , Linfocitos T/inmunología
12.
Allergy ; 56(9): 883-8, 2001 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-11551254

RESUMEN

BACKGROUND: Eosinophilic airways inflammation forms the pathophysiologic basis for a proportion of children at risk of developing recurrent wheezing. Early preventive measures and/or anti-inflammatory treatment may be guided by the identification of such children. We aimed to study the relationship between respiratory symptoms and indirect markers of airway inflammation. METHODS: We measured eosinophil protein X (EPX) and leukotriene E(4) (LTE(4)) in urine, as well as eosinophil cationic protein (ECP) in nasal lavages, in a random sample of 1-year-old children with a family history of atopy who participated in an international multicenter study on the prevention of allergy in Europe. For urine analyses, 10 children with upper respiratory illness and 19 healthy children without a family history of atopy were also enrolled. Endogenous urinary LTE(4) was separated by HPLC and determined by enzyme immunoassay with a specific antibody. The concentrations of nasal ECP and urinary EPX were determined by RIA analysis. RESULTS: One hundred and ten children (mean age: 1.05+/-0.1 years) were enrolled. Prolonged coughing during the first year of life was reported in 29 children, wheezy breathing in 17 children, and dry skin in 33 children. A doctor's diagnosis of wheezy bronchitis was given to 17 children. Sensitization to dust mites (specific IgE > or =1.43 ML/units) was detected in two children. Children with a doctor's diagnosis of atopic dermatitis within the first 12 months of life (n=6) had significantly higher urinary EPX than children without this (66.7 vs 30.1 microg/mmol creatinine, P=0.01). Urinary excretion of EPX and LTE4 showed a weak correlation (r=0.22, P=0.02). There were no significant differences in urinary excretion of EPX and LTE(4) or nasal ECP between children with and without respiratory symptoms (P>0.1). CONCLUSIONS: At the age of 1 year, urinary EPX is increased in children with atopic dermatitis. With regard to respiratory symptoms, urinary and nasal inflammatory parameters are not helpful in characterizing the phenotype of a single patient.


Asunto(s)
Proteínas Sanguíneas/análisis , Leucotrieno E4/orina , Líquido del Lavado Nasal/química , Hipersensibilidad Respiratoria/metabolismo , Ribonucleasas/análisis , Animales , Biomarcadores , Bronquitis/epidemiología , Bronquitis/etiología , Estudios de Cohortes , Tos/epidemiología , Tos/etiología , Polvo/efectos adversos , Proteínas en los Gránulos del Eosinófilo , Neurotoxina Derivada del Eosinófilo , Europa (Continente)/epidemiología , Salud de la Familia , Femenino , Humanos , Inmunoglobulina E/sangre , Lactante , Bienestar del Lactante , Masculino , Ácaros , Prevalencia , Ruidos Respiratorios/etiología , Encuestas y Cuestionarios
13.
Pediatr Pulmonol ; 31(1): 44-50, 2001 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-11180674

RESUMEN

SUMMARY. To evaluate the importance of a past history of asthma-like symptoms over a period of 2 years and current bronchial hyperreactivity (BHR), 538 randomly selected schoolchildren, initially aged 7-8 years, were examined. At yearly intervals, three standardized questionnaires, including items from the ISAAC panel, were answered by parents. Following the last questionnaire, BHR to 4.5% hypertonic saline (HS) was recorded. In survey 1, lifetime prevalence of asthma was 4.9%. During the 12-month period, prevalence of wheeze and dyspnea ranged between 9.3 and 5.2% (Survey 1) and 5.9% and 4.4% (Survey 2). Among children with wheeze or dyspnea in Survey 3, BHR (defined as a fall of baseline FEV(1) > or = 15%) was significantly more frequent (50.0% and 60.7%, respectively) than among children without these symptoms (12.8%, P < 0.001, and 12.8%, P < 0.001, respectively). The negative predictive value of BHR to have neither wheeze nor dyspnea was about 88% and did not vary throughout the study (Survey 1, 87%; Survey 2, 88%; Survey 3, 88%). The relative risk of showing BHR was significantly increased in children with wheeze (survey 2, odds ratio (OR) 3.0 (95% confidence interval (CI) 1.0-8.7)) or dyspnea (Survey 1: OR 5.9 (95% CI 1.9-18.5), Survey 3: 5.2 (1.7-16.2), but not in children with dry cough or nocturnal cough (data not shown). Wheeze and dyspnea occurred repeatedly in the same individuals with BHR in a high percentage of children (83.3% and 76.5%, respectively). In conclusion, there is a strong association between recent and previous dyspnea and current BHR, and it indicates intraindividual persistence of symptom history.


Asunto(s)
Asma/diagnóstico , Hiperreactividad Bronquial/diagnóstico , Solución Salina Hipertónica , Asma/fisiopatología , Hiperreactividad Bronquial/fisiopatología , Pruebas de Provocación Bronquial , Niño , Intervalos de Confianza , Tos/diagnóstico , Disnea/diagnóstico , Femenino , Estudios de Seguimiento , Volumen Espiratorio Forzado/fisiología , Humanos , Modelos Logísticos , Estudios Longitudinales , Masculino , Oportunidad Relativa , Valor Predictivo de las Pruebas , Prevalencia , Ruidos Respiratorios/diagnóstico , Factores de Riesgo , Estadísticas no Paramétricas , Encuestas y Cuestionarios , Capacidad Vital/fisiología
14.
Arch Environ Health ; 56(6): 485-92, 2001.
Artículo en Inglés | MEDLINE | ID: mdl-11958547

RESUMEN

The authors investigated whether organochlorine exposure is associated with prevalence of otitis media, pneumonia, pertussis, asthma, and increased immunoglobulin E levels in children. Organochlorine concentrations and histories of infection and atopic manifestation were available for 343 children, and immunoglobulin E levels were available for 340 children. The authors applied logistic and linear regressions and controlled for confounders. In general, the prevalence of infections in children was not related to organochlorine exposure. However, for the combined effect of dichlorodiphenyldichloroethene with polychlorinated biphenyls or hexachlorobenzene, a significantly increased relative risk (odds ratios = 3.70 and 2.38, respectively) was found for otitis media. Exposure to dichlorodiphenyldichloroethene resulted in a significantly higher odds ratio for asthma (odds ratio = 3.71; 95% confidence interval = 1.10, 12.56) and in immunoglobulin E concentrations above 200 kU/l (odds ratio = 2.28; 95% confidence interval = 1.20, 4.31). This is the first study in which dichlorodiphenyldichloroethene has been identified as a substantial risk factor for asthma and for increased immunoglobulin E blood levels.


Asunto(s)
Asma/epidemiología , Diclorodifenil Dicloroetileno/efectos adversos , Exposición a Riesgos Ambientales , Fungicidas Industriales/efectos adversos , Hexaclorobenceno/efectos adversos , Insecticidas/efectos adversos , Otitis Media/epidemiología , Neumonía/epidemiología , Tos Ferina/epidemiología , Factores de Edad , Lactancia Materna , Niño , Interpretación Estadística de Datos , Diclorodifenil Dicloroetileno/sangre , Femenino , Fungicidas Industriales/sangre , Alemania/epidemiología , Hexaclorobenceno/sangre , Humanos , Insecticidas/sangre , Modelos Lineales , Modelos Logísticos , Masculino , Prevalencia , Factores de Riesgo , Encuestas y Cuestionarios , Contaminación por Humo de Tabaco/efectos adversos
15.
Am J Respir Cell Mol Biol ; 23(6): 755-61, 2000 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-11104728

RESUMEN

Cystic fibrosis (CF) airway epithelia are characterized by enhanced Na(+) absorption probably due to a lack of downregulation of epithelial Na(+) channels by mutant CF transmembrane conductance regulator. Extracellular nucleotides adenosine 5'-triphosphate (ATP) and uridine 5'-triphosphate (UTP) have been shown to activate alternative Ca(2+)-dependent Cl(-) channels in normal and CF respiratory epithelia. Recent studies suggest additional modulation of Na(+) absorption by extracellular nucleotides. In this study we examined the role of mucosal ATP and UTP in regulating Na(+) transport in native human upper airway tissues from patients with 16 patients with CF and 32 non-CF control subjects. To that end, transepithelial voltage and equivalent short-circuit current (I(SC)) were assessed by means of a perfused micro-Ussing chamber. Mucosal ATP and UTP caused an initial increase in lumen-negative I(SC) that was followed by a sustained decrease of I(sc) in both non-CF and CF tissues. The amiloride-sensitive portion of I(SC) was inhibited significantly in normal and CF tissues in the presence of either ATP or UTP. Both basal Na(+) transport and nucleotide-dependent inhibition of amiloride-sensitive I(SC) were significantly enhanced in CF airways compared with non-CF. Nucleotide-mediated inhibition of Na(+) absorption was attenuated by pretreatment with the Ca(2+)-adenosine triphosphatase inhibitor cyclopiazonic acid but not by inhibition of protein kinase C with bisindolylmaleimide. These data demonstrate sustained inhibition of Na(+) transport in non-CF and CF airways by mucosal ATP and UTP and suggest that this effect is mediated by an increase of intracellular Ca(2+). Because ATP and UTP inhibit Na(+) absorption and stimulate Cl(-) secretion simultaneously, extracellular nucleotides could have a dual therapeutic effect, counteracting the ion transport defect in CF lung disease.


Asunto(s)
Amilorida/farmacología , Fibrosis Quística/metabolismo , Epitelio/efectos de los fármacos , Cavidad Nasal/efectos de los fármacos , Nucleótidos/farmacología , Sodio/farmacocinética , Absorción/efectos de los fármacos , Adenosina Trifosfato/farmacología , Adolescente , Adulto , Anciano , Calcio/metabolismo , Niño , Preescolar , Inhibidores Enzimáticos/farmacología , Epitelio/metabolismo , Femenino , Humanos , Indoles/farmacología , Masculino , Maleimidas/farmacología , Persona de Mediana Edad , Cavidad Nasal/metabolismo , Proteína Quinasa C/antagonistas & inhibidores , Transducción de Señal , Uridina Trifosfato/farmacología
16.
Clin Exp Allergy ; 30(11): 1555-61, 2000 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-11069563

RESUMEN

BACKGROUND: Several studies have shown linkage of bronchial asthma, allergic rhinitis and total serum IgE concentration to the chromosomal region 12q13-24 in ethnical diverse populations. This region harbours a number of candidate genes for asthma and atopy, including stem cell factor (SCF), leukotriene A4 hydrolase (LTA4H), thyroid receptor 2 (TR2), and signal transducer and activator of transcription 6 (STAT6). However, the same region was shown as well to be linked to other diseases with inflammatory character. So far no variants in any of these genes have been published which would allow association studies and confirm the pathogenicity of any of these genes. OBJECTIVE: We wanted to test for linkage of the chromosomal region 12q13-24 with the atopic phenotype without regard to clinical manifestations. Furthermore we screened for common nucleotide polymorphisms in candidate genes to enable association studies. METHODS: We employed sib-pair linkage analysis and transmission disequilibrium testing with regard to four highly polymorphic microsatellite markers in 12q13-24 in atopic nuclear families. In addition, we looked for polymorphisms in the genes coding for SCF, LTA4H, TR2 and STAT6 performing SSCP-analysis and direct genomic sequencing. RESULTS: We found no evidence for linkage of the genomic region 12q13-24 to elevated total serum IgE levels, specific sensitization to common inhalant allergens or atopy. Furthermore we identified three nucleotide polymorphisms including one common variant in the gene coding for SCF. No association of this polymorphism and any of the atopic phenotypes was seen. CONCLUSION: We conclude from our data that genes in the chromosomal region 12q13-24 and in particular SCF are unlikely to exert a major effect on the induction of the atopic phenotype in our Caucasian population. However, we did not focus on the asthmatic and thereby inflammatory aspect of atopy which might explain these results in contradiction to previous studies.


Asunto(s)
Cromosomas Humanos Par 12 , Ligamiento Genético , Hipersensibilidad Inmediata/genética , ADN Satélite/análisis , Epóxido Hidrolasas/genética , Frecuencia de los Genes , Humanos , Hipersensibilidad Inmediata/inmunología , Inmunoglobulina E/análisis , Núcleo Familiar , Polimorfismo Genético , Receptores de Hormona Tiroidea/genética , Factor de Transcripción STAT6 , Factor de Células Madre/genética , Transactivadores/genética
17.
Am J Respir Cell Mol Biol ; 23(5): 696-702, 2000 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-11062149

RESUMEN

Reduced mucociliary clearance in primary ciliary dyskinesia (PCD) causes recurrent infections of the upper and lower respiratory tract. The disease is usually inherited as an autosomal recessive trait. To identify a gene locus for PCD, we studied a large consanguineous family of Arabic origin. Direct examination of the respiratory cilia revealed ciliary akinesia. Electron microscopic examination of cilia showed absence of the outer dynein arms. Two of four affected individuals exhibited a situs inversus, typical for Kartagener syndrome, due to randomization of the left/right body axis. A total genome scan with 340 highly polymorphic microsatellites was performed. We localized a new gene locus for PCD to a region of homozygosity by descent on chromosome 5p15-p14 with a parametric multipoint logarithm of odds ratio (LOD) score of Zmax = 3.51 flanked by markers D5S2095 and D5S502 within an interval of 20 centimorgans sex-averaged genetic distance. Applying a polymerase chain reaction-based approach, we identified a 1.5-kb partial complementary DNA of DNAH5 encoding a Chlamydomonas-related axonemal heavy dynein chain within the critical disease interval of this new PCD locus. On the basis of the Chlamydomonas model for PCD, this gene represents an excellent candidate for PCD.


Asunto(s)
Mapeo Cromosómico , Cromosomas Humanos Par 5 , Trastornos de la Motilidad Ciliar/genética , Dineínas/genética , Secuencia de Aminoácidos , Ligamiento Genético , Marcadores Genéticos , Homocigoto , Humanos , Datos de Secuencia Molecular , Alineación de Secuencia
18.
J Allergy Clin Immunol ; 106(5): 925-32, 2000 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-11080716

RESUMEN

BACKGROUND: Sensitization to mite allergens represents a prominent feature of atopy and an important predictor of bronchial asthma. OBJECTIVE: It was the intention of this study to define genetic loci linked to mite sensitization because these could represent the genetic basis of the important atopic component of asthma. METHODS: We studied a multiethnic white population of 99 families, including 224 sib pairs sensitized to Dermatophagoides pteronyssinus. A genome-wide candidate-region search was performed that covered potential asthma and atopy regions. RESULTS: As for nonparametric linkage (NPL) analysis, 14 of the candidate regions showed evidence for linkage (NPL > 2.0), and 4 of them showed prominent linkage (NPL > 3.0). However, there were substantial ethnic differences. Maximizing the LOD score analysis identified candidate regions with suspected dominant and recessive mode of inheritance. Furthermore, genetic imprinting models provided significant evidence for linkage in the 8p23 region and revealed potential maternal imprinting. The regions found are distinct to those in asthma searches that have been found to be linked to asthma, as well to other inflammatory diseases. In addition, we could not find linkage to the HLA region. By different cutoff points of the phenotype definition, the IL cluster showed evidence of being linked to the degree of sensitization rather than to sensitization per se. CONCLUSION: The results indicate that the genetic basis of the atopic component of asthma is different from that of the inflammatory component. Furthermore, it seems reasonable to assume that specific sensitizations are influenced by distinct genetic variants leading to their initiation versus those leading to their enhancement.


Asunto(s)
Alérgenos/inmunología , Glicoproteínas/inmunología , Hipersensibilidad/genética , Ácaros/inmunología , Animales , Antígenos Dermatofagoides , Niño , Europa (Continente) , Ligamiento Genético , Impresión Genómica , Humanos , Hipersensibilidad/etiología , Hipersensibilidad/inmunología , Inmunoglobulina E/sangre , Modelos Genéticos
20.
Am J Respir Cell Mol Biol ; 23(3): 283-9, 2000 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-10970817

RESUMEN

Ion transport defects underlying cystic fibrosis (CF) lung disease are characterized by impaired cyclic adenosine monophosphate (cAMP)-dependent Cl(-) conductance. Activation of Cl(-) secretion in airways depends on simultaneous activation of luminal Cl(-) channels and basolateral K(+) channels. We determined the role of basolateral K(+) conductance in cAMP- dependent Cl(-) secretion in native human airway epithelium obtained from non-CF and CF patients. CF tissues showed typical alterations of short-circuit currents with enhanced amiloride-sensitive Na(+) conductance and defective cAMP-mediated Cl(-) conductance. In non-CF tissues, Cl(-) secretion was significantly inhibited by the chromanol 293B (10 micromol/liter), a specific inhibitor of K(V)LQT1 K(+) channels. Inhibition was increased after cAMP-dependent stimulation. Similar effects were obtained with Ba(2+) (5 mmol/liter). In patch-clamp experiments with a human bronchial epithelial cell line, stimulation with forskolin (10 micromol/liter) simultaneously activated Cl(-) and K(+) conductance. The K(+) conductance was reversibly inhibited by Ba(2+) and 293B. Analysis of reverse-transcribed messenger RNA from non-CF and CF airways showed expression of human K(V)LQT1. We conclude that the K(+) channel K(V)LQT1 is important in maintaining cAMP-dependent Cl(-) secretion in human airways. Activation of K(V)LQT1 in CF airways in parallel with stimulation of residual CF transmembrane conductance regulator Cl(-) channel activity or alternative Cl(-) channels could help to circumvent the secretory defect.


Asunto(s)
Bronquios/metabolismo , Cloruros/metabolismo , AMP Cíclico/metabolismo , Canales de Potasio con Entrada de Voltaje , Canales de Potasio/metabolismo , Mucosa Respiratoria/metabolismo , 1-Metil-3-Isobutilxantina/farmacología , Amilorida/farmacología , Transporte Biológico/efectos de los fármacos , Transporte Biológico/fisiología , Bronquios/citología , Línea Celular Transformada , Cromanos/farmacología , Colforsina/farmacología , Fibrosis Quística/metabolismo , Regulador de Conductancia de Transmembrana de Fibrosis Quística/metabolismo , Diuréticos/farmacología , Expresión Génica/fisiología , Humanos , Canales de Potasio KCNQ , Canal de Potasio KCNQ1 , Potenciales de la Membrana/efectos de los fármacos , Potenciales de la Membrana/fisiología , Técnicas de Placa-Clamp , Inhibidores de Fosfodiesterasa/farmacología , Potasio/metabolismo , Bloqueadores de los Canales de Potasio , Canales de Potasio/genética , Mucosa Respiratoria/citología , Sulfonamidas/farmacología
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