Predictive features for persistence of atopic dermatitis in children

Allergen exposure plays an important role in atopic dermatitis (AD). Because immunological mechanisms underlying asthma and AD have great similarities, we evaluated whether features such as allergen sensitization, immune response, disease severity and duration or allergen exposure could be considered predictive for AD persistence. Seventy-one AD children (age range 14–158 months) were enrolled and followed for 3 consecutive years for AD severity using the SCORAD index (SI). At enrollment, reactivity to inhalant and food allergens using the skin prick test (SPT) and house dust mite (HDM) atopy patch test (APT), and HDM allergens in house dust were evaluated. After 3 years, 38 children outgrew their AD (AD^– group), while in 33 AD persisted (AD⁺ group). At enrollment, AD⁺ children had a higher SI, higher rate of positivity to SPT and APT for mites (p = 0.001), and higher environmental exposure to HDM allergens (p = 0.035). The AD⁺ children developed more respiratory symptoms in comparison to AD^– children (p < 0.001). None of the AD^– children presented APT positivity. In our study population, positivity of SPT and APT for HDM, environmental allergen exposure levels and severity of the disease at enrollment presented a significant predictive power towards AD persistence. Subjects with positive skin reactivity to HDM should be considered at risk of AD persistence and of possible development of allergic respiratory disorders.     

Application and efficacy of the multi‐dose powder inhaler, Easyhaler®, in children with asthma

With powder inhalers, optimal performance is dependent on the inspiratory flow produced by the patient through the devices. The objective of this open, non‐randomized study was to evaluate the suitability of a new, multi‐dose, dry powder inhaler, the Easyhaler^®, for children with asthma. The peak inspiratory flow (PIF) through the Easyhaler (PIF_EH) was measured with a pneumotachograph in 120 asthmatic children aged 4–16 yr. The bronchodilatory effect of 0.2 mg salbutamol through the Easyhaler was compared with that of 0.2 mg salbutamol through a metered dose inhaler (MDI) with a spacer, in 15 children with obstruction. The mean PIF_EH was 56 l/min (range 22–83 l/min). The PIF_EH correlated significantly with age, height, and absolute peak expiratory flow (PEF), but not with the level of obstruction (PEF percentage of predicted, range 45–146%). Only four children (aged 5, 6, 10, and 16 yr) had PIF_EH values below 28 l/min, which has been shown in in vitro studies to be the threshold for effective use of the Easyhaler. In 15 children with PEF, < 85% of predicted bronchodilatory effects of 0.2 mg salbutamol through the Easyhaler and from an MDI‐cum‐spacer were equal. Most children aged 6–16 yr produce PIF values sufficient for the use of the Easyhaler. The gain of 0.2 mg salbutamol from the Easyhaler was equal to that from a new, unprimed, MDI with a spacer in children with asthma.     

Low‐dose budesonide improves exercise‐induced bronchospasm in schoolchildren

The aim of this study was to compare the clinical efficacy of low‐dose inhaled budesonide (once or twice daily) and placebo, administered via Turbuhaler^®, on exercise‐induced bronchoconstriction (EIB) in children with mild asthma. Fifty‐seven steroid‐naive children (7–16 years old; 41 boys, 16 girls) with EIB participated in this sub‐population study according to the following inclusion criterion: a maximum fall in forced expiratory volume in 1 s ( FEV ₁) ≥ 10% after a standardized treadmill test. Mean baseline FEV ₁ was 100.3% of predicted, and mean maximum fall in FEV ₁ after the standardized exercise test was 22%. The study was a double‐blind, randomized, parallel‐group design. After 2 weeks of run‐in, the children received inhaled budesonide 100 µg or 200 µg once daily in the morning, 100 µg twice daily, or placebo, for 12 weeks. After 12 weeks of treatment, the fall in FEV ₁ after the exercise test was significantly less in all three budesonide groups (7.2–7.8%) vs. placebo (16.7%). Daytime symptom scores were significantly lower in all three budesonide groups compared with placebo (p < 0.02). The three budesonide groups did not differ significantly, and no significant change in lung function was found in any group. Therefore children with mild asthma, but with significant EIB, improved their exercise tolerance and symptom control after 3 months of treatment with a low dose of inhaled budesonide given once or twice daily.     

Sensitization to turnip rape and oilseed rape in children with atopic dermatitis: a case-control study

Turnip rape and oilseed rape 2S albumins are new allergens in children with atopic dermatitis suspected for food allergy. We recently found that 11% (206/1887) of these children had a positive skin prick test to seeds of oilseed rape ( Brassica napus ) and/or turnip rape ( Brassica rapa ). In the present case-control study we examined how the children with atopic dermatitis sensitized to turnip rape and oilseed rape had been breast-fed and whether they had some common sensitization pattern to certain foods or pollens. A total of 64 children with atopic dermatitis and a positive skin prick test to turnip rape and/or oilseed rape (≥5 mm) were examined. Sixty-four age- and sex-matched children with atopic dermatitis but negative skin prick tests to turnip rape and oilseed rape served as case controls. The turnip rape and/or oilseed rape sensitized children with atopic dermatitis had significantly more often positive skin prick tests reactions and IgE antibodies to various foods (cow's milk, egg, wheat, mustard; p < 0.01) and pollens (birch, timothy, mugwort; p < 0.01) than the control children. They had been exclusively breast-fed for a longer period (median 4 months; p < 0.05) and had more often associated asthma (36%) and allergic rhinitis (44%). Children with atopic dermatitis sensitized to oilseed rape and turnip rape had high frequency of associated sensitizations to all foods and pollens tested showing that oilseed plant sensitization affects especially atopic children who have been sensitized to multiple allergens.     

Leukocyte‐reduction to prevent transfusion‐transmitted cytomegalovirus infections

Abstract: Certain infectious organisms, including cytomegalovirus, are associated 'exclusively' with blood leukocytes (WBC), and their transmission by transfusion is strikingly diminished by marked WBC‐reduction of cellular blood components. Based on several reports of WBC‐reduction, it is clear that the risk of CMV is nearly eliminated by consistently removing WBC to a level < 1–5 × 10⁶ WBCs/unit (≤ 1 × 10⁶ preferred in Europe; ≤ 5 × 10⁶ in the United States). Alternatively, the rate of CMV infections is reduced by transfusing blood components collected from donors negative for CMV antibody. However, neither technique is perfect, with a failure rate of 1–4%. Although WBC‐reduction is favored by many experts, practitioners must choose the method that they believe to be most efficacious – being mindful that data do not exist to establish additive protection by combining WBC‐reduction and transfusion of blood components collected from antibody negative donors.     

Nutrition, anthropometry, gastrointestinal dysfunction, and circulating levels of tumour necrosis factor alpha receptor I and interleukin-1 receptor antagonist in children during stem cell transplantation

Abstract:  To evaluate anthropometry, nutrition and gastrointestinal dysfunction, and to characterize the relation between these parameters and the inflammatory activity evaluated by plasma levels of soluble tumour necrosis factor alpha receptor I (sTNFRI) and interleukin-1 receptor antagonist (IL-1Ra) levels during stem cell transplantation (SCT) in children. Clinical assessments and blood sampling were performed on days −3, 0, +7, +15 and +31 in eight children undergoing SCT. Energy intake, anthropometry, gastrointestinal dysfunction (WHO toxicity score) and sTNFRI and IL-1Ra were evaluated. The energy intake was below recommended levels. There was a loss of lean body mass (arm muscle area)(median, 2031 mm² (day -3) vs 1477 mm² (day 31); p = 0.04), and of fat mass (arm fat area) (791 mm² (day -3) vs 648 mm² (day +31); p = 0.04). sTNFRI was elevated throughout the course of transplantation, and peaked after the day of graft infusion (day 0). sTNFRI levels at day 0 predicted changes in weight SDS (r = 0.65; p = 0.05), triceps skinfold SDS (r = 0.85; p = 0.007) and gastrointestinal dysfunction (r = 0.88; p = 0.004). Likewise, IL-1Ra levels at day 0 correlated with the gastrointestinal dysfunction (r = 0.83; p = 0.01) and with the change in weight SDS (r = 0.77; p = 0.03). This study suggests that pretransplant levels of inflammatory markers are associated with posttransplant symptoms of gastrointestinal dysfunction and loss of both fat and lean body mass. Future studies should adress if the use of conditioning regimens with limited proinflammatory cytokine inducing activity, anti-inflammatory agents, or more optimised nutritional support can reduce the burden of such posttransplant complications.     

Use of a pocket‐sized turbine spirometer in monitoring exercise‐induced bronchospasm and bronchodilator responses in children

For field studies of asthma, portable hand‐held pulmonary function testing devices are required. Other than for peak flow measurements, little has been done to validate their use in children. Fifty children aged 5–15 years having asthma symptoms were examined using an exercise challenge (8 min free running outdoors) and a bronchodilation test (salbutamol inhalation at a dose of 0.15 mg/kg). Pulmonary function was measured with a turbine spirometer, with a Wright peak flow meter (WPEF) and with a flow–volume spirometer (FVS). A fall of 15% or more in WPEF associated with wheezing or cough was considered diagnostic for bronchial hyper‐responsiveness to exercise (BHRE). A rise of 15% or more from baseline in WPEF after salbutamol inhalation was considered as a positive bronchodilator response (BDR). BHRE was present in 16 children (32%). Using the limit of a 15% or greater fall in FEV₁, turbine spirometry identified 12 as BHRE‐positive and no additional cases, giving a sensitivity of 75% and a specificity of 100%. The turbine spirometer showed lower FEV₁ values than the FVS, the difference increasing with airway obstruction. BDR was positive in eight children (16%). Using the limit of a 10% or greater rise in FEV₁, turbine spirometry was positive in six cases. FEV₁ measured by turbine spirometry could not be used interchangeably with conventional FVS. However, the turbine spirometer offers the possibility to measure FEV₁ repeatedly in field conditions, such as during exercise challenges outdoors.     

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.     

Low-dose cyclosporin A microemulsion in children with severe atopic dermatitis: Clinical and immunological effects

Cyclosporin A (CsA) is an effective and well-tolerated treatment for severe childhood atopic dermatitis (AD). By starting at a low dose, the therapeutic safety should be further increased. The aim of this study was to evaluate low-dose CsA in childhood AD with respect to clinical outcome and modulation of T-cell dysregulation. In an open prospective study, 10 children (age: 22–106 months) with severe AD (mean objective SCORAD score > 40 on two baseline measurements at a minimum interval of 2 weeks) were treated with CsA solution for 8 weeks. All patients received a starting dose of 2.5 mg/kg/day, which was increased stepwise in non-responders to a maximum of dose of 5 mg/kg/day. Disease activity was monitored using the SCORAD index. The frequency of cytokine-producing peripheral blood T lymphocytes was analyzed by intracellular cytokine staining, and T-cell numbers were measured by fluorescence-activated cell sorter (FACS) analysis. Twenty healthy age-matched children were included as controls for the immunological data. Nine of the 10 patients had a SCORAD reduction of at least 35%. In seven patients this was achieved with low-dose CsA at 2.5 mg/kg/day (n = 4) and 3.5 mg kg/day (n = 3). Seven of the nine responders experienced no relapse within the 4-week follow-up period. At baseline the percentage of interleukin-4 (IL-4), IL-13, and human leucocyte antigen (HLA)-DR-positive CD3⁺ cells was higher in the patient group than in the controls. After CsA treatment there was a significant reduction in interferon-γ (IFN-γ), IL-2, IL-4, IL-13, and HLA-DR-positive CD3⁺ cells. Hence, in severe pediatric AD, CsA microemulsion, when started at a low dose (2.5 mg/kg/day), improves clinical measures of disease, reduces T-lymphocyte cytokine production, and regulates T-cell activation.     

Both allergen-specific CD4 and CD8 Type 2 T cells decreased in asthmatic children with immunotherapy

Allergen-specific immunotherapy (IT) has been used for the treatment of atopic diseases since the turn of this century. The precise working mechanisms, however, remain to be clarified. The aim of this study was to investigate the role of particular subsets of allergen-specific T cells in the non-atopic individuals, untreated asthmatic children and the asthmatic children receiving immunotherapy. We collected peripheral blood from 16 untreated asthmatic children and 17 asthmatic children receiving immunotherapy over one and half years. All the patients were sensitive to mite allergen. Peripheral blood mononuclear cells (PBMC) were isolated and, in vitro , stimulated with crude mite extract to enrich the mite-specific T-cell population. After 14 days, the enriched mite-specific T cells were stimulated with phorbol-12-myristate-13-acetate (PMA) and ionomycin for intracellular detection of cytokines such as IFN-γ, IL-4 in CD4⁺ and CD8⁺ T lymphocytes. The data here demonstrated that the levels of mite-specific IgG4 and IgA increased significantly in asthmatic children after immunotherapy. In addition, both IL-4 expressing CD4⁺ and CD8⁺ T cells were significantly lower in asthmatic children after immunotherapy compared with those of before treatment and the normal control (p < 0.05). In contrast, the frequency of IFN-γ expressing CD4⁺ and CD8⁺ T cells did not significantly differ between untreated and SIT-treated groups. All these data suggested that decreased Type 2 CD4⁺ and CD8⁺ T cells might be closely correlated with the regulatory mechanisms of immunotherapy.     

Soluble E-selectin and soluble ICAM-1 levels as markers of the activity of atopic dermatitis in children

The expression of adhesion molecules is up-regulated in the skin of atopic dermatitis (AD) patients, and the levels of the soluble adhesion molecules sE-selectin and sICAM-1 have been reported to reflect the endothelial activation in the skin of AD patients. The objective of the study was to investigate the relationship between symptom score and levels of sE-selectin, sICAM-1 and sVCAM-1 before and after 2 weeks of treatment. Eighteen children with an exacerbation of AD were admitted and treated with corticosteroid dilutions under occlusive wet dressings (wet-wrap treatment). Symptom score (objective SCORAD) and levels of sE-selectin, sICAM-1, and sVCAM-1 were assessed before and after 2 weeks of treatment. A significant correlation between the objective SCORAD before treatment and the level of sE-selectin (p < 0.05), but not the level of sICAM-1 (p = 0.7) or sVCAM-1 (p = 0.5) was observed. The treatment resulted in a high degree of remission, which was reflected by a significant decrease in the level of sICAM-1 (p < 0.01), whereas there was only a trend in the level of sE-selectin to decrease (p = 0.08). The level of sE-selectin after 2 weeks of treatment still correlated significantly with the objective SCORAD before treatment (p < 0.005). Soluble E-selectin is a relative objective marker for the severity of AD. SCORAD is a treatment-sensitive symptom of AD, whereas E-selectin may be a more stable underlying systemic representation of AD.     

Clinical pharmacology of the H1‐receptor antagonists cetirizine and loratadine in children

H₁‐receptor antagonists are widely used in children but are not as well‐studied in children as they are in adults. Our objective was to determine the onset and duration of action and the relative potency of the H₁‐receptor antagonists cetirizine and loratadine in children. We performed a prospective, randomized, placebo‐controlled, double‐blind, crossover, single‐dose study of cetirizine and loratadine using suppression of the histamine‐induced wheal and flare as the primary outcome. In 15 allergic children, mean age 9 years, compared with baseline, cetirizine (10 mg) suppressed the wheals and flares significantly from 0.25 to 24 h, achieving nearly 100% of flare suppression from 2 to 24 h, inclusive, and loratadine (10 mg) suppressed the wheals and flares significantly from 0.75 to 24 h, inclusive. Cetirizine suppressed the wheals and flares significantly more than loratadine from 0.25 to 1 h, inclusive, and at 0.5, 1, 2, 3, 5, 6, 7, and 24 h, respectively. Placebo also suppressed the wheal and flare significantly at some assessment times. Cetirizine and loratadine both have excellent antihistaminic activity in children, with a rapid onset of action and a 24‐h duration of action in this population.     

Infants colonized with enterotoxin‐producing staphylococci at 3 months display a decreased frequency of interferon‐γ‐producing CD45RO lymphocytes upon stimulation with staphylococcal enterotoxin A at birth but not at 6 months of age

The aim of the study was to elucidate the relationship between the cytokine response to staphylococcal enterotoxin A (SEA) at birth and subsequent staphylococcal colonization in the first months of life. In a cohort of 45 newborns, cord blood lymphocytes were stimulated with SEA (10 ng/ml) in vitro , re‐stimulated with PMA (phorbol myristate acetate) and ionomycin at day 3 and assessed for CD45RO expression and cytokine generation by flow cytometry. The infants were classified into three groups according to nasal staphylococcal colonization and enterotoxin generation at 3 months: There were 16 infants with either no colonization or non‐enterotoxin‐producing staphylococci, 16 infants with enterotoxins B, C, D and E, and 13 infants colonized with SEA‐producing staphylococci. At birth, the group without subsequent colonization displayed a significantly higher frequency of CD45RO‐positive interferon‐γ‐producing cells (1.7%; range 0.0–9.3%) in comparison to the SEA‐positive group (0.1%; range 0.0–0.4%) and also to the group positive for other enterotoxins (0.50%; range 0.0–2.5%). Comparable but less pronounced results were found for interleukin‐5 but not for interleukins 2 and 4. At 6 months, no differences in cytokine generation were detected between the three groups. The results provide evidence that a non‐specific immunologic immaturity at birth is a risk factor for early bacterial colonization. Furthermore, it is remarkable that this immaturity is similar to that seen in infants destined to be atopic with respect to disequilibrium of interferon‐γ to interleukin‐4 generation. Thus the link between early staphylococcal colonization and subsequent atopy requires further investigation.     

Reduced IL-2-induced IL-12 responsiveness in atopic children

Atopy may be associated with a reduced T-cell function particularly regarding maturation of T helper 1 (Th1) responses. We hypothesized that atopic children may have a reduced capacity to up-regulate the β₂ subunit of the interleukin-12 (IL-12) receptor (IL-12Rβ₂, the signal-transducing component). The study included 38 children followed from birth to the age of 7 years. Twenty one had a cumulative history of atopic disease, whereas 17 had none. Sixteen out of 21 children also had atopic symptoms within the past year (current), out of whom 10 children had atopic airway symptoms. The expression of IL-12Rβ₂ mRNA was analyzed by quantitative real-time PCR and the secretion of interferon-γ (IFN-γ), IL-5 and IL-10 was assessed by enzyme-linked immunosorbent assay (ELISA). Children with current atopic airway symptoms and high levels of total IgE up-regulated IL-12Rβ₂ mRNA expression less than non-atopic children with low IgE levels after IL-2 stimulation. This was accompanied by a low IL-2- and IL-12-induced IFN-γ production, possibly reflecting the reduced capacity of atopic children to up-regulate the IL-12 receptor. As IL-2 is needed to initiate and sustain immune responses and IL-12 promotes Th1 responses, this may contribute to the Th2-skewed pattern in atopic children.     

Altered T lymphocyte phenotype at birth in babies born to atopic parents

Flow cytometry was used to analyse the cord blood T cells of 33 babies at high risk 'HR' for developing allergy (born to at least one atopic, asthmatic parent), and 10 low risk 'LR' babies (born to non-atopic parents), following normal term deliveries. Significantly lower numbers of CD25⁺, (activated) T cells (p<0.005) were seen in the cord blood of the HR babies who had developed both allergic symptoms and positive skin prick tests by one year of age when compared with the LR group. CD45RO⁺ (memory) T cells were detected in both HR and LR babies with a trend for lower numbers of memory cells to be detected in HR infants who later developed allergic symptoms and/or positive skin prick tests. Significantly lower numbers of CD4⁺/CD45RO⁺ were seen in the cord blood of HR babies who developed allergic symptoms compared to HR babies who showed no sign of allergy by one year and to the LR babies (p<0.05 and p<0.005). The presence of activated and memory T cells at birth implies intra-uterine priming. The significantly lower numbers of memory T cells in the HR babies suggests a suppression of T cell activation or lack of antigenic priming in this group. This prenatal influence on babies born to atopic parents may have important implications with regard to the mechanisms underlying atopic sensitisation.     

Lower levels of plasmacytoid dendritic cells in peripheral blood are associated with a diagnosis of asthma 6 yr after severe respiratory syncytial virus bronchiolitis

Plasmacytoid dendritic cells (pDC) play a crucial role in antiviral immunity and promoting Th1 polarization, possibly protecting against development of allergic disease. Examination of the relationship between peripheral blood plasmacytoid DC levels and manifestations of asthma and atopy early in life. We have isolated peripheral blood mononuclear cells (PBMC) from 73 children (mean age ± SD: 6.6 ± 0.5 yr old) participating in the RSV Bronchiolitis in Early Life (RBEL) study. Flow cytometry was performed on PBMC detecting DC surface-markers: Blood Dendritic Cell Antigens (BDCA) 1, 3, and 2 which identify myeloid type 1, type 2, and plasmacytoid cells, respectively. Total serum IgE, peripheral eosinophil count, and allergy skin tests were documented. About 45% (n = 33) of study participants had physician-diagnosed asthma by 6 yr of age. These children had significantly lower quantities (mean ± SD) of plasmacytoid DC than their non-asthmatic counterparts (1020 ± 921 vs. 1952 ± 1170 cells per 10⁶ PBMC, p = 0.003). We found significantly lower numbers of myeloid dendritic cells in children with asthma (3836 ± 2472 cells per 10⁶ PBMC) compared with those without asthma (4768 ± 2224 cells per 10⁶ PBMC, p = 0.02); however, this divergence was not significant after adjusting for covariates of age, gender, race, skin test reactivity, smoke exposure, and daycare attendance. We did not identify any direct association between DC levels and markers of atopy: skin test reactivity, peripheral eosinophilia, and IgE level. Children who are diagnosed with asthma after severe RSV bronchiolitis appear to have a relative deficiency of plasmacytoid DC in peripheral blood.     

Correlation of nitrites in breath condensates and lung function in asthmatic children

We aimed to evaluate the value of exhaled breath condensates in monitoring airway inflammation in childhood asthma before and after high altitude climate therapy.
Forty-eight asthmatic children on regular anti-asthma treatment with a normal FEV₁ and positive skin prick test for house dust mites were recruited. All children had been referred to an alpine clinic for high altitude climate therapy, because of persistent asthmatic symptoms despite use of daily anti-inflammatory treatment. Subjects were assessed on their arrival and before departure from the alpine clinic. Spirometry, bronchial provocation tests and measurements of nitrites in breath condensates were performed.
Median levels of nitrites were significantly higher before than after high altitude climate therapy (1.27 vs. 0.93 μ m ; p = 0.008). In addition, MEF₅₀ improved significantly (p < 0.0005). There was a significant correlation between nitrites in breath condensates and MEF₅₀ (r = −0.63, p < 0.0001), symptoms (r = 0.47, p = 0.0007) and airway hyper-reactivity (AHR) (r = −0.41, p = 0.004).
In summary, we found a reduction in nitrites in breath condensates after a high altitude climate therapy. Significant correlations were found between nitrites and MEF₅₀, AHR and symptoms. We conclude that the measurement of nitrites may be feasible to objectively assess airway inflammation in asthmatic children in order to detect ongoing inflammation in children with normal FEV₁ but persistent symptoms.     

Expression of the T-cell markers CD2 and CD28 in healthy and atopic children during the first 18 months of life

Atopy may be associated with a reduced T-cell function early in life, particularly regarding maturation of Th1 responses. The T-cell surface molecules CD2 and CD28 are involved in important T-cell activation pathways. Stimulation via the CD2 receptor increases the responsiveness to interleukin (IL)-12, which is a potent inducer of Th1 responses, whereas CD28 stimulation is critical for Th2 differentiation. Our aim was to prospectively study the expression of the cell-surface markers CD2 and CD28 on T-cells in relation to development of atopic disease. Children (n = 172) were followed from birth to 18 months and the cumulative history of atopic disease was recorded. Blood samples were obtained at birth and at 18 months, and in a subgroup of 78 infants also at 3, 6 and 12 months. Flow cytometry was used to analyze the T-cell markers CD2 and CD28, the latter also within the subsets of T-helper (CD4+) and T-cytotoxic (CD8+) cells. At 18 months, 31 children had and 118 did not have atopic symptoms. At this age, skin prick test (SPT) positive children with atopic symptoms with or without an atopic family history (AFH) showed a lower expression of CD2 mode fluorescence intensity (FI) as well as a lower proportion of CD2+ cells, as compared with non-sensitized children with neither atopic symptoms nor AFH. This was accompanied by a higher expression of CD28 FI on CD2+CD8+CD28+ cells. No significant differences were seen at time points before 18 months, although the proportion of CD2+ tended to be low also earlier in life. In conclusion, the observed reduced expression of CD2 in atopic infants may support previous findings that atopy is associated with a reduced CD2 function. The high CD28 FI in SPT positive children with atopic symptoms may possibly be a consequence of a TH2-skewed immune system.     

Does the severity of atopic dermatitis correlate with serum IgE levels?

Recent studies suggest an association between atopic phenotypes and serum IgE levels. In contrast to asthma, this association has not been proven for atopic dermatitis. For 345 children (mean age 2.9 years), we investigated a correlation of the severity of eczema (defined by SCORAD score) and serum IgE levels. Additionally, the data was analyzed for differences between children with high and low SCORAD quartile. Parameters such as genetic background, the prevalence of other atopic phenotypes such as bronchial asthma, allergic rhinoconjunctivitis, and allergic sensitization were recorded. Our results indicate a significant correlation between SCORAD and serum IgE levels (R = 0.31, p < 0.001), but the standard deviation was large. Children with atopic dermatitis showed a high prevalence of sensitization to foods independent of the IgE levels; children with high SCORAD levels showed a sensitization to aeroallergens significantly more often (p < 0.02). No differences were found in prevalences of atopic family background, or a number of additional atopic symptoms such as asthma and allergic rhinoconjunctivitis. These results suggest that serum IgE levels seem to correlate with the degree of eczema. Children with severe atopic dermatitis and high IgE levels are at risk for sensitization to food allergens and aeroallergens.     

Exhaled nitric oxide and exercise-induced bronchoconstriction in young wheezy children – interactions with atopy

The association between exercise-induced bronchoconstriction (EIB) and exhaled nitric oxide (FE_NO) has not been investigated in young children with atopic or non-atopic wheeze, two different phenotypes of asthma in the early childhood. Steroid naïve 3- to 7-yr-old children with recent wheeze (n = 84) and age-matched control subjects without respiratory symptoms (n = 71) underwent exercise challenge test, measurement of FE_NO and skin prick testing (SPT). EIB was assessed by using impulse oscillometry, and FE_NO by standard online technique. Although FE_NO levels were highest in atopic patients with EIB, both atopic and non-atopic wheezy children with EIB showed higher FE_NO than atopic and non-atopic control subjects, respectively. In atopic wheezy children, a significant relationship between FE_NO and the severity of EIB was found ( r  = 0.44, p = 0.0004), and FE_NO was significantly predictive of EIB. No clear association between FE_NO and EIB or predictive value was found in non-atopic wheezy children. Both atopic and non-atopic young wheezy children with EIB show increased FE_NO levels. However, the association between the severity of EIB and FE_NO is present and FE_NO significantly predictive of EIB only in atopic subjects, suggesting different interaction between bronchial responsiveness and airway inflammation in non-atopic wheeze.