Development of atopic disease in relation to family history and cord blood IgE levels

The cumulative incidence of atopic disease from birth to about 11 yr of age and the prevalence during the 11th year was investigated in a cohort of 1654 non-selected children by an evaluated questionnaire. The total cumulative incidence of obvious atopic disease was 32. 5%, of bronchial asthma 5. 3%, and allergic rhinoconjunctivitis 14. 4%. The prevalence of itopic disease was 23. 7%. Obvious atopic disease developed in 67% of children with cord blood IgE ≥ 0.9 kU/l and a further 15% developed probable atopic disease. The positive predictive value of a family history of atopic disease was 45%. Children with a high cord blood IgE had a 5-fold increased risk for developing bronchial asthma. The sensitivity of cord blood IgE determination using 0.9 kU/l as cut-off was only 26%. Therefore, it can not without modifications be recommended as a single screening test. Neonatal IgE determination is., however, suitable, if used in conjunction with the family history, for identifying candidates at high risk for early development of atopic disease, e. g. for evaluation of the effect of preventive measures. Parents tend to forget symptoms (25%) that their children presented some years ago. Questionnaires are thus more suitable for establishing prevalence compared with cumulative rate of atopic disease.     

Age-related changes in intracellular cytokine profiles and Th2 dominance in allergic children

The unbalanced T helper response has been pointed out in allergic diseases. Especially in childhood, it is important to consider the development of acquired immunity. We investigated the relationship between age and Th1, Th2, Tc1 or Tc2 cells. In addition, Th1, Th2, Tc1 or Tc2 cells in allergic diseases were compared with control subjects. Thirty-four healthy controls (0-40 years old), 200 samples of cord blood, nine patients with atopic dermatitis (AD) (1-3 years old) and five patients with bronchial asthma (BA) (2-6 years old) were studied. Surface staining with CD4, CD8 and intracellular staining with anti-interferon-gamma (IFN-gamma) and anti-interleukin (IL)-4 were carried out, and analyzed by using flow cytometry. In the healthy controls, the percentages of Th1, Tc1 or Th2 showed positive correlation with age. The absolute numbers of Th1 or Tc1 also correlated with age. Cord blood with a family history of allergic disease showed no significant difference compared to that without a family history. The percentage of Th2 in AD and BA patients was significantly higher than in the age-matched healthy controls. The increase in Th1, Th2 and Tc1 with age might reflect on the development of acquired immunity. Age matching is important when evaluating the cytokine profiles of T cells. In allergic diseases, although cord blood showed a Th1-dominant pattern, it changed to Th2 dominance in childhood, and this may reflect on some genetic background.     

Prediction of allergy from family history and cord blood IgE levels

Screening of total IgE in 1189 cord blood samples was conducted by Phadebas IgE PRIST in a one-year birth cohort 1983-1984 in Viborg. Denmark. 113 children with cord blood IgE levels ≥ 0.5 kU/l and 138 children chosen at random among those with cord blood IgE levels < 0. 5 kU/l were seen at a follow-up at 5 years of age. Based upon history and physical examination a diagnosis of definite atopy or no atopy was established. Allergy (IgE mediated) was defined as atopic disease combined with increased total IgE levels at 5 years of age. The cumulative prevalence of atopic disease was not influenced by cord blood IgE levels or atopic predisposition. Cord blood IgE levels had a low sensitivity as a predictor of atopic disease. A statistically significant correlation between serum levels of IgE at birth and at 5 years was however found (p < 0.001), and a significantly greater number of children with elevated cord blood IgE levels developed allergic disease before 5 years of age (p < 0.01). A cut-off limit of 0. 3 kU/l was superior to the originally suggested limit of 0. 5 kU/l. A total IgE level > 63 kU/l (geometric mean + 1 SD) at the age of 5 years can be regarded as being an elevated level. A cord blood IgE level ≥ 0.3 kU/l in combination with atopic predisposition was predictive of allergic disease, especially allergic bronchial asthma. With regard to allergic disease, the positive predictive value was 26%, the sensitivity 33% and the rate ratio for development of allergic disease 4. In the case of the most serious atopic disease, allergic bronchial asthma, the positive predictive value was 20%, the sensitivity 87% and the rate ratio 68.     

Hospital admission with neonatal sepsis and development of atopic disease: Is there a link?

The role of suspected or confirmed neonatal sepsis in modifying the risk of atopic disease during childhood was assessed. Children with early-onset neonatal sepsis were identified from a cohort of neonates, hospitalized between 1990 and 1995. Of 196 individuals, 140 were recruited (71.4%). Pre- and postnatal history was ascertained from neonatal medical records. Based on clinical symptoms and a positive blood culture or at least three of initially defined laboratory or bacteriological criteria, they were stratified in either confirmed neonatal sepsis (CS) or suspected sepsis (SS) group. A control group (C) comprised children who were never hospitalized during infancy (n = 696). Primary end-point was the development of atopic dermatitis, bronchial asthma or allergic rhinitis during childhood (mean age 8.4 yr, range 5.7-12.4). CS and SS children had a higher prevalence of atopic dermatitis (CS 15.7%, SS 21.4%) compared with controls (C 5.2%, p < 0.001). Similarly, children with SS (7.1%), but not with CS (4.3%) had significantly more often a doctor's diagnosis of bronchial asthma compared to controls (1.9%, p = 0.02). No difference in the prevalence of allergic rhinitis was observed (CS 4.3%, SS 10%, C 8.3%). After adjusting for parental history of atopic disease and demographic factors, no significant difference for the risk to develop atopic dermatitis, asthma or allergic rhinitis among the groups was calculated in children with normal birth weight (>2500 g). Our data failed to show a possible link between hospital admission with SS and development of atopic disease.     

The prevalence of allergic diseases in an unselected group of 6-year-old children. The DARC birth cohort study

This study determines the prevalence of atopic dermatitis, asthma, rhinoconjunctivitis, food hypersensitivity and urticaria and the frequency of sensitization in children with and without clinical allergic disease. In an ongoing prospective non-interventional birth cohort study of 562 unselected children, 404 children were subjected to interview, clinical examination, lung function measurements and allergy testing at 6 yr of age. Sensitization measured by skin prick test (SPT) and specific immunoglobulin E (S-IgE) was determined for 24 different allergens. The 1-yr period prevalence of atopic dermatitis, asthma and rhinoconjunctivitis was 14.4%, 6.2% and 13.6%. 25.7% of the children suffered from at least one of the three diseases. The frequency of sensitization in children with no disease (controls), any allergic disease, atopic dermatitis, asthma and rhinoconjunctivitis was 17%, 45%, 47%, 56% and 55% (defined as SPT ≥3 mm and/or S-IgE ≥0.35 kU/l for at least one allergen). Symptoms were linked to sensitization for 44% in the asthma group and 42% in the rhinoconjunctivitis group, whereas sensitization could not be linked to worsening of the eczema in any cases of atopic dermatitis. Overlap between the three diseases was significantly more frequent in sensitized children than in non-sensitized (19/46 = 41% vs. 9/58 = 16%, p = 0.004). The prevalence of food hypersensitivity and urticaria was 1.2% and 5.4% respectively. In unselected 6 yr old children, approximately half of the children with atopic dermatitis, asthma or rhinoconjunctivitis are IgE-sensitized. Sensitization tends to link these diseases to each other.     

Relation between stressful life events,neuropeptides and cytokines: results from the LISA birth cohort study

Stressful life events evidently have an impact on development of allergic diseases, but the mechanism linking stress to pathological changes of immune system function is still not fully understood. The aim of our study was to investigate the relationship between stressful life events, neuropeptide and cytokine concentrations in children. Within the LISAplus (Life style-Immune system-Allergy) study, blood samples from children of 6 yr of age were analysed for concentration of the neuropeptides vasoactive intestinal peptide (VIP), somatostatin (SOM), substance P (SP) and the Th1/Th2 cytokines interferon-γ (IFN-γ) and interleukin (IL)-4. Life events such as severe disease or death of a family member, unemployment or divorce of the parents were assessed with a questionnaire filled in by the parents. For 234 children, blood analysis and questionnaire data regarding life events were available. Children with separated/divorced parents showed high VIP levels and high concentrations of the Th2 cytokine IL-4 in their blood. Severe diseases and death of a family member were neither associated with neuropeptide levels nor with cytokine concentrations. Unemployment of the parents was associated with decreased IFN-γ concentrations in children’s blood but not with neuropeptide levels, whereas children experiencing concomitant severe disease and death of a family member had reduced SP blood levels. The neuropeptide VIP might be a mediator between stressful life events and immune regulation contributing to the Th2 shifted immune response in children with separated/divorced parents. Unemployment of the parents was associated with immune regulation in children on the basis of a still unknown mechanism whereas reduced SP levels seem to have no effect on immune regulation.     

Time trends of the prevalence of asthma and allergic disease in Austrian children.

After a substantial increase in the prevalence of atopic disease in Europe, recent studies indicate that a plateau has been reached. However, variation across countries and age groups exists. We studied the prevalence and time trends of asthma and allergic disease among schoolchildren in Austria, a country with traditionally low rates of asthma, hay fever, and eczema. As part of the International Study of Asthma and Allergies in Childhood (ISAAC), symptoms and physician diagnoses of asthma and allergic disease of 13,399 Austrian children aged 6-7 yr and 1516 children aged 12-14 yr were surveyed between 1995 and 1997. A similar survey was conducted between 2001 and 2003. Among children aged 6-7 yr, significant increases were seen in the prevalence of physician-diagnosed asthma (+16%; p = 0.013), hay fever (+22%; p < 0.001), and eczema (+37%; p < 0.001) between 1995 and 2003. These changes were paralleled by an increase in the prevalence of symptoms typical for hay fever (itchy eyes and runny nose), but not by an increase in wheeze. Among children aged 12-14 yr, the lifetime prevalence of diagnosed asthma increased by 32%, of hay fever by 19%, and of eczema by 28% (all, p < 0.001). These changes were paralleled by increases in the prevalence of wheezing as documented by both questions before and after a video showing wheezing children but not by symptoms typical for hay fever such as itchy eyes and runny nose. In conclusion, in Austria, contrary to other European countries, the prevalence of asthma and allergic disease increased among schoolchildren. Additional studies are needed to continue monitoring the dynamics of the prevalence of asthma and allergic disease in Austria and to explore trends in their risk factors.     

Early intervention with suplatast tosilate for prophylaxis of pediatric atopic asthma: A pilot study

The onset of asthma may be related to Th2 cytokine dominance at the time when food allergies occur several months after birth. This study investigated the effectiveness of early intervention with a Th2 cytokine inhibitor (suplatast tosilate) for prevention of asthma in infants with food allergies and atopic dermatitis. Suplatast tosilate dry syrup (6 mg/kg daily) or a histamine H₁-blocker (ketotifen fumarate dry syrup: 0.06 mg/kg daily) was administered randomly to 53 infants with atopic dermatitis caused by food allergies. The primary endpoints were the incidence of asthma and the time to the onset of wheezing. The peripheral blood Th1/Th2 ratio, total IgE level, and eosinophil count were measured before and after treatment. After 24 months of treatment, the prevalence of asthma was significantly lower in the suplatast group (20.8%) than in the ketotifen group (65.6%, p < 0.01). Additionally, the time from the start of treatment to the initial episode of wheezing for infants who developed asthma was significantly longer in the suplatast group than the ketotifen group (p < 0.01). Furthermore, the eosinophil count was significantly decreased by suplatast treatment (p < 0.05), and there was a significant difference between the suplatast and ketotifen groups with respect to both the eosinophil count (p < 0.01) and the Th1/Th2 ratio (p < 0.05). The results of the present pilot study suggest that suplatast tosilate is useful for the primary prevention of wheezing and asthma in children.     

Allergen-induced cytokine secretion in atopic and non-atopic asthmatic children

Atopic asthma is characterized by excessive T helper 2 (Th2)-like immunity to allergens in the bronchial mucosa. The Th2-cytokine interleukin (IL)-4 induces IgE production, while the Th2-cytokine IL-5 promotes eosinophilic inflammation in the airways of asthmatics. Most asthmatics are atopic, but a subgroup is non-atopic. We hypothesize that allergen-induced Th2, particularly IL-5, responses can be observed in peripheral blood in both atopic and non-atopic asthmatic children but not in healthy control children. The aim of the present study was to determine IL-4, IL-5, IL-9, IL-10, IL-13 and IFN-γ secretion induced from peripheral blood mononuclear cells (PBMC) by a broad panel of inhalant allergens (timothy, cat, birch, dog and house dust mite) in asthmatic children with and without sensitization. The study included 13 atopic asthmatic, 5 non-atopic asthmatic, and 12 non-atopic non-asthmatic children. PBMC were stimulated with allergens and cytokine production was measured with enzyme-linked immunosorbent assay (ELISA). Higher levels of cat and dog antigen-induced IL-5 release were more commonly observed in both atopic and non-atopic asthmatics than in controls. Children with atopic, but not non-atopic, asthma produced higher levels of allergen-induced IL-4 and IL-9 than controls. Non-atopic asthmatics produced more IL-10 than atopic asthmatics after cat stimulation. High levels of eosinophilia-associated IL-5 responses are induced by cat and dog allergen in both atopic and non-atopic asthmatic children. The Th2 cytokines IL-4 and IL-9 were associated only with atopic asthma, probably due to their IgE-inducing properties.     

Atopic disease in preadolescence - an evaluation of questionnaires, association with cord blood IgE and month of birth

During a prospective study of 1654 children, followed from birth for 11 years, we evaluated the validity of a detailed questionnaire for establishing the prevalence of atopic disease in preadolescence. In 133 randomly selected children the questionnaire-based diagnoses were accurate in 128 (96.2%). If the cord blood IgE concentration was high (≥ 0.9 kU/l) then it was 1.7 times more common to have any prevalent atopic disease. The corresponding relative risk for multiple atopic disease was 11.5. Boys had high IgE levels significantly more often than girls, regardless of the degree of pubertal maturation. Sensitization to timothy pollen developed more often in children born during May compared to November. At least one allergy test (IgE, Phadiatop or SPT) was positive in 20 of 70 (28.6%) 11-year-old children with no history of atopic disease, indicating latent allergy. Among the healthy children with positive tests, those with cord blood IgE ≥ 1.3 kU/l were over-represented. IgE concentrations at 11 years of age corresponded poorly with neonatal IgE concentrations, indicating that after birth environmental influences are more important for the present IgE level than genetic factors.     

Time trends of the prevalence of asthma and allergic disease in Austrian children

After a substantial increase in the prevalence of atopic disease in Europe, recent studies indicate that a plateau has been reached. However, variation across countries and age groups exists. We studied the prevalence and time trends of asthma and allergic disease among schoolchildren in Austria, a country with traditionally low rates of asthma, hay fever, and eczema. As part of the International Study of Asthma and Allergies in Childhood (ISAAC), symptoms and physician diagnoses of asthma and allergic disease of 13,399 Austrian children aged 6–7 yr and 1516 children aged 12–14 yr were surveyed between 1995 and 1997. A similar survey was conducted between 2001 and 2003. Among children aged 6–7 yr, significant increases were seen in the prevalence of physician-diagnosed asthma (+16%; p = 0.013), hay fever (+22%; p < 0.001), and eczema (+37%; p < 0.001) between 1995 and 2003. These changes were paralleled by an increase in the prevalence of symptoms typical for hay fever (itchy eyes and runny nose), but not by an increase in wheeze. Among children aged 12–14 yr, the lifetime prevalence of diagnosed asthma increased by 32%, of hay fever by 19%, and of eczema by 28% (all, p < 0.001). These changes were paralleled by increases in the prevalence of wheezing as documented by both questions before and after a video showing wheezing children but not by symptoms typical for hay fever such as itchy eyes and runny nose. In conclusion, in Austria, contrary to other European countries, the prevalence of asthma and allergic disease increased among schoolchildren. Additional studies are needed to continue monitoring the dynamics of the prevalence of asthma and allergic disease in Austria and to explore trends in their risk factors.     

Cross-sectional study of allergic disorders associated with breastfeeding in Japan: The Ryukyus Child Health Study

Uncertainties remain as to whether breastfeeding is protective against childhood allergic disorders. Positive relationships of breastfeeding with asthma and atopic eczema were observed in two previous Japanese studies. This cross-sectional study investigated the association between the feeding pattern after birth and the prevalence of allergic disorders during the past 12 months in Japanese schoolchildren. Study subjects were 24,077 children aged 6-15 yr in Okinawa. The outcomes were based on diagnostic criteria from the International Study of Asthma and Allergies in Childhood. Allowance was made for age, sex, number of siblings, smoking in the household, paternal and maternal history of asthma, atopic eczema, and allergic rhinitis, and paternal and maternal educational level. Breastfeeding, regardless of exclusivity, for 13 months or longer and exclusive breastfeeding for 4-11 months were independently associated with a higher prevalence of atopic eczema, particularly among children without a parental allergic history. A clear positive dose-response relationship was observed between prolonged duration of breastfeeding, regardless of exclusivity, but not exclusive breastfeeding, and the prevalence of atopic eczema. We found a significant positive trend for atopic eczema across the three categories (formula milk, partial and exclusive breastfeeding) in the first 4 months of life although the odds ratio for exclusive breastfeeding was not statistically significant. No material association was found between the feeding pattern after birth and the prevalence of wheeze or allergic rhinoconjunctivitis. Prolonged breastfeeding may be associated with a higher prevalence of atopic eczema in Japanese children.     

Soluble CD30 and CD23 in cord blood are not related to atopy in early childhood

Atopic disease, including atopic dermatitis (AD), is associated with a T-helper 2 (Th2)-dependent immune response. The cytokine receptor CD30 appears to be preferentially expressed on, and its soluble form (sCD30) released by, Th2 cells. Therefore, sCD30 may be a potential marker for atopic disorders. The aim of this study was to test the hypothesis that the sCD30 level in cord blood could be used to predict the development of atopy or AD in early childhood. In a case-control study, levels of sCD30, as well as soluble low-affinity immunoglobulin E (IgE) receptor (sCD23), interleukin-4 (IL-4) and IgE, were measured in cord blood in 35 children who subsequently developed allergic sensitization and AD before the age of three, and the results were compared to those of 35 matched children without a history of atopy. There was no difference in cord blood levels of sCD30 between controls (32.5 U/ml; 19.7–80.1) and children with subsequent atopy and AD (32.2 U/ml; 22–75.9) (median; quartiles). The concentration of sCD30 showed no relation to the levels of total IgE, sCD23 or IL-4. Levels of sCD23 were similar in children with subsequent atopy (60.2 U/ml; 44.5–76.8) and controls (55.2 U/ml; 38.3–72.5), whereas IL-4 was detectable in 10 of the atopic children and in only two of the controls (p < 0.05). In conclusion, cord blood levels of sCD30 or sCD23 do not seem to be related to the subsequent development of atopy or AD at the age of three.     

Serum measurement of thymus and activation-regulated chemokine/CCL17 in children with atopic dermatitis: elevated normal levels in infancy and age-specific analysis in atopic dermatitis

Elevated blood levels of thymus and activation‐regulated chemokine (TARC)/CCL17 have been observed in atopic dermatitis (AD) and may serve as a new biomarker for AD. However, the normal levels, especially in children, have not been well determined. We sought to establish an efficient enzyme‐linked immunosorbent assay (ELISA) with a wide range of detection that would be suitable for measurement of serum TARC/CCL17 and to determine the normal ranges of this chemokine in different age groups and its diagnostic usefulness for AD. A sensitive specific ELISA for TARC/CCL17, which we previously reported, was modified to accommodate the wide range of TARC/CCL17 values often found in sera. Twenty‐seven children with AD under 6 yr of age and 25 age‐matched normal non‐atopic controls, and 18 patients with AD and 27 controls who were 6 yr and older were enrolled. The severity of AD was evaluated using the SCORAD index. The serum levels of TARC/CCL17 were measured with the ELISA, and the serum levels of IP‐10/CXCL10 were also measured. With the novel ELISA system, the assayable range of TARC/CCL17 was 14–8000 pg/ml, and the coefficient of variation at various concentrations ranged from 2.3% to 5.0%. The serum levels of TARC/CCL17 in normal individuals were significantly higher in young children, especially in the age group of 0–1 yr. The cut‐off values of TARC/CCL17 for the diagnosis of AD were 1431 pg/ml for 0–1 yr group, 803 pg/ml for 2–5 yr group and 510 pg/ml for the 6 yr and older group, with high sensitivity and specificity of 0.83 and 0.93, 0.83 and 0.92, 0.85 and 0.96, respectively. The magnitude of the decrease in the SCORAD index after treatment with topical steroids correlated significantly with the decrease in serum TARC/CCL17. There was no difference in the serum levels of IP‐10/CXCL10 between AD and the controls. The TARC/CCL17:IP‐10/CXCL10 ratio tended to be higher in the control children aged 0–1 yr than in those aged 2–5 yr. The serum level of TARC/CCL17 reflects the severity and therapeutic response in AD. The high normal levels in infants should be taken into account when assaying TARC/CCL17.     

Neonatal characteristics and risk of atopic asthma in schoolchildren: results from a large prospective birth-cohort study

AIM: Asthma is among the most common chronic diseases in childhood and steadily increasing in prevalence. Identification of risk predictors for a hospitalization for atopic asthma in childhood may help design prevention programmes and improve our understanding of disease pathobiology. METHODS: An ongoing birth-cohort study prospectively enrolled all liveborn infants in Tyrol. Between 1994 and 1999 baseline data were collected for 33,808 infants. From 2000 to 2005, all children hospitalized for atopic asthma at an age of 6 years or over (n = 305) were identified in a careful search of hospital databases. Disease status was ascertained from the typical medical history, a thorough examination and proof of atopy. RESULTS: Male sex (relative risk 2.11, 95% CI 1.65-2.70), urban living environment (vs. rural) (1.93, 1.47-2.54), neonatal admission to hospital (1.70, 1.20-2.40), lack of breastfeeding (1.32, 1.02-1.70), postnatal smoking (1.31, 1.00-1.72) and low birth weight (1.45, 0.94-2.23) all emerged as adverse risk predictors for hospitalization for atopic asthma whereas a low risk was found among children living on a farm (0.22, 0.05-0.87) and children with two to three siblings (vs. no or one sibling) (0.71, 0.51-0.97). CONCLUSION: In this study a number of neonatal characteristics and environmental exposures were associated with hospitalization for atopic asthma in childhood, suggesting that early life is crucial for disease determination and lending further indirect support to the hygiene hypothesis.     

Antenatal risk factors, cytokines and the development of atopic disease in early childhood

Atopic diseases are complex entities influenced by an array of risk factors, including genetic predisposition, environmental allergens, antenatal exposures, infections and psychosocial factors. One proposed mechanism by which these risk factors contribute to the development of atopic disease is through changes in the production of T helper cell type 1 (Th1) and T helper cell type 2 (Th2) cytokines. The objectives of this review are to discuss antenatal exposures that are associated with paediatric atopic diseases, to discuss the influence of the intrauterine environment on neonatal immune responses, to provide an overview of the Th1 and Th2 pathways and how they relate to atopic disease, and to summarise our current understanding of the association between cytokine responses in cord blood and the development of atopic disease in early childhood.     

Filaggrin gene variants and atopic diseases in early childhood assessed longitudinally from birth

Bønnelykke K, Pipper CB, Tavendale R, Palmer CNA, Bisgaard H. Filaggrin gene variants and atopic diseases in early childhood assessed longitudinally from birth.
Pediatr Allergy Immunol 2010: 21: 954–961.
© 2010 John Wiley & Sons A/S Copenhagen Prospective Study on Asthma in Childhood (COPSAC) was one of the discovery cohorts of the association between eczema and variants in the filaggrin coding gene (FLG). Here, we study the FLG‐associated risk of asthma symptoms in early life and describe the temporal relationship in the development of the different FLG‐associated atopic outcomes: asthma, sensitization and eczema, assessed longitudinally from birth. A high‐risk cohort of 411 children was assessed in a prospective clinical study from birth to school‐age. Asthma, acute severe asthma exacerbations, sensitization and eczema were diagnosed prospectively by the investigators. FLG variants R501X and Del4 were determined in 382 Caucasians. Filaggrin variants increased risk of developing recurrent wheeze, asthma and asthma exacerbations (hazard ratio 1.82 [1.06–3.12], p = 0.03), which was expressed within the first 1.5 yr of life. Children with filaggrin variants had a marked and persistent increase in acute severe asthma exacerbations from 1 yr of age (incidence ratio 2.40 [1.19–4.81], p = 0.01) and increased risk of asthma by age 5 (odds ratio 2.62 [1.12–6.11], p = 0.03). FLG variants increased the risk of eczema, manifesting fully in the first year of life (point prevalence ratio for age 0–5 was 1.75 [1.29–2.37]; p‐value = 0.0003) contrasting the increased risk of specific sensitization by age 4 (odds ratio 3.52 [1.72–7.25], p = 0.0007) but not age 1.5. This study describes a FLG‐associated pattern of atopic diseases characterized by the early onset of asthma symptoms and eczema and later development of sensitization. The association of filaggrin variants with asthma suggests skin barrier dysfunction as a novel, and potentially modifiable, mechanism driving early childhood asthma.     

Intrathecal production of neopterin in meningitis in childhood

A major activator of antigen presenting cells (APC) is gamma interferon a product of activated T-lymphocytes. CNS is not well studied and represents a unique system with respect to the immune reactions. Neopterin is an indirect marker of gamma interferon deliberation and may give some new information on the role of APC in CNS. Neopterin in serum and cerebrospinal fluid (CSF) was determined by specific RIA in children who were lumbar punctured to exclude meningitis. Neopterin was found in various concentrations in serum and CSF of all patients (n = 47). Bacterial meningitis (group 3) was diagnosed in 12 and aseptic meningitis in 18 children (group 2). CSF was drawn in 17 children with febrile convulsions (group 1). Elevated serum neopterin in childhood was only reported in children with an atypical PKU, while data on CSF neopterin were published only in a few cases of adults with CNS involvement. The results show that the APC is stimulated rapidly in childhood similar as in adults following severe viral or bacterial infections. Furthermore neopterin in CSF is not only explained by alteration of the blood-brain barrier but also it may reflect local intrathecal response with activation of accessory cells (APC) in the CNS itself. Between the stimulation of the cellular immune system indicated by increased levels of neopterin and the severity of the disease seems to be a positive correlation.     

Association of parental eczema, hayfever, and asthma with atopic dermatitis in infancy: birth cohort study.

OBJECTIVE: To evaluate the association of parental history of atopic disease with childhood atopic dermatitis, and to examine the relative strength of associations with maternal and paternal disease. DESIGN: Mothers were recruited to the Avon longitudinal study of parents and children (ALSPAC) from the eighth week of pregnancy. Before parturition, both parents were asked, separately, to report their lifetime history of eczema, asthma, and hayfever. Parents reported symptoms of atopic dermatitis in their children at ages 6, 18, 30, and 42 months. RESULTS: Of 8530 children with complete information on rash at ages 6, 18, 30, and 42 months, 7969 had complete information on maternal atopic disease and 5658 on maternal and paternal atopic disease. There was a strong association between parental eczema and childhood atopic dermatitis: odds ratio 1.69 (95% confidence interval, 1.47 to 1.95) for maternal eczema only, 1.74 (1.44 to 2.09) for paternal eczema only, and 2.72 (2.09 to 3.53) for eczema in both parents. Associations with parental asthma or hayfever were attenuated after controlling for parental eczema. There was no evidence that associations with maternal atopy were stronger than with paternal. CONCLUSIONS: Associations between parents' atopic disease and the risk of atopic dermatitis in offspring vary according to the type of atopic disease in the parents, but not according to parental sex. These results are at variance with previous studies reporting stronger associations with maternal than paternal atopy, and suggest that there is no "parent-of-origin" effect in atopic dermatitis. Parental eczema may be a better marker than parental asthma/hayfever in predisposing to childhood eczema.