Non-atopic Children Research Articles

Interplay of Adaptive Th2 Immunity with Eotaxin‐3/C‐C Chemokine Receptor 3 in Eosinophilic Esophagitis

Pediatric eosinophilic esophagitis (EE) is a recently described disorder associated with atopy. Although studies of esophageal tissue suggest that Th2 cytokines and eotaxin-3 may be crucial in disease pathogenesis, little is known about the systemic immunological phenotypes of children with EE. To define the phenotypes of peripheral blood eosinophils and lymphocytes in EE and to examine for correlations between these parameters and tissue eosinophil numbers and disease severity. Blood was collected from children with EE, atopic control children without EE, and nonatopic control children without EE. Flow cytometry was used to measure eosinophil expression of chemokine receptor 3 (CCR3) and interleukin-5 receptor-alpha (IL-5Ralpha), and intracellular lymphocyte expression of IL-4, IL-5, IL-13, interferon-gamma, and tumor necrosis factor-alpha. Eosinophil numbers and eotaxin-3 mRNA levels were quantitated in esophageal biopsy specimens. Compared with nonatopic control children, EE patients with active disease had increased peripheral blood eosinophil percentages, mean channel of fluorescence (MCF) of CCR3 on eosinophils, and percentage of CD4+ T cells expressing IL-5. Notably, these parameters positively correlated with esophageal eosinophil numbers. Eotaxin-3 tissue expression positively correlated with esophageal eosinophil numbers and peripheral blood eosinophil CCR3 MCF. The percentage of peripheral blood eosinophils, eosinophil CCR3 MCF, and CD4+ T cell expression of IL-5 were lower in EE patients in disease remission than in patients with active disease. Collectively, these studies demonstrate cooperation between systemic CD4+ Th2-cell-mediated immunity and an enhanced eosinophil-CCR3/eotaxin-3 pathway in EE pathogenesis. Furthermore, the imbalanced Th2 immunity and increased CCR3 expression are reversible with disease remission.

Health effects of indoor nitrogen dioxide and passive smoking on urban asthmatic children

Nitrogen dioxide (NO(2)) and environmental tobacco smoke (ETS) have been associated with adverse respiratory effects. We sought to assess the effect of NO(2) and ETS on asthma morbidity among children in inner-city environments. Asthmatic children between the ages of 4 and 9 years had exposure to NO(2) and ETS measured by using Palmes tubes in the home and urinary cotinine. A baseline interview and telephone assessments at 3, 6, and 9 months evaluated health service use, asthma symptoms, and peak flow rates. Gas stoves were present in 87.8% of 469 homes. The median level of indoor NO(2) was 29.8 ppb compared with the US national outdoor median of 18 ppb. Of 1444 children, 48% had urinary cotinine/creatinine ratios of greater than 30 ng/mg. The median level of the cotinine/creatinine ratio was 42.4 ng/mg in smoking homes compared with 18.0 ng/mg in nonsmoking homes. The relative risk for asthma symptoms with increased NO(2) exposure was 1.75 (95% CI, 1.10-2.78) in children who did not have positive skin test responses. Higher NO(2) exposure resulted in lower peak flows during colder months (relative risk, 1.46; 95% CI, 1.07-1.97). Higher ETS exposure in colder months was weakly associated with lower peak flows (relative risk, 1.21; 95% CI, 0.99-1.47). There was no effect of ETS exposure on symptoms or use of health care services. Higher levels of indoor NO(2) are associated with increased asthma symptoms in nonatopic children and decreased peak flows. Interventions to reduce NO(2) exposure, such as venting of gas stoves, might help reduce asthma morbidity.

Pulmonary function in non‐atopic and atopic childhood asthma

Previous conclusions concerning pulmonary function in non-atopic and atopic asthma in childhood appear to differ depending on whether the cohorts studied are drawn from the community or clinic. In studies on community-based cohorts Kelley et al. found no differences in asthma severity and pulmonary function and Kurukulaaratchy et al. found that baseline spirometric parameters (FEV1 FVC or PEF) were not significantly different when comparing nonatopic and atopic children with asthma. In contrast Ostergaard who identified 84 cases from an allergy clinic found that non-atopic asthmatics had significantly more hyperinflation reduced pulmonary function and more hospital admissions than atopic asthmatics. These observations raise questions as to whether non-atopic asthma presenting to specialist clinics differs from that detected in the community and whether it differs qualitatively from atopic asthma. In this study we compare pulmonary function in children with non-atopic and atopic asthma presenting to a tertiary hospital specialist clinic. (excerpt)

The influence of birch pollination on the adenoid size in children with intermittent allergic rhinitis

Allergic sensitization of the airways occurs not only in the mucosa of the shock organ, but also in the lymphatic stations draining these structures. The lymphatic structure closest to the nasal mucosa in humans is the adenoid. Many researches show that in part of children allergic rhinitis can be a risk factor for adenoid hypertrophy. We used acoustic rhinometry and endoscopy to evaluate the influence of the birch pollination on the adenoid size in 67 children between 5 and 12 years old. Four separate groups of children were examined. The study group consisted of 28 children hypersensitive to tree pollen with seasonal allergic rhinitis (interview, positive skin prick test results, presence of sIgE in the serum and positive nasal provocation test with birch pollen allergens). The first control group consisted of 14 atopic children hypersensitive to motherwort pollen. The second control group consisted of 15 non-atopic children. The third control group consisted of 10 children hypersensitive to tree pollen, they have got anti-allergic treatment (topical nasal steroid and antihistaminic) a week before birch pollination. In all of the groups the adenoid size was examined before, during and after birch pollination. In the study group, we examined the influence of specific nasal provocation test on the adenoid size too. In most children from the study group (71.4%) we observed the significant increase of adenoid size in endoscopic examination and decrease of nasopharyngeal cavity volume in acoustics rhinometry (92.9%) during the birch pollination. The changes returned after pollination period in most children (90%). In the first and the second control group there were almost no changes observed (p>0.05). The medical treatment used in the third control group avoided the increase of adenoid size during birch pollination season. In the study group there was no statistically significant correlation between the changes in nasopharyngeal volume during the pollination period and the results of nasal provocation test (r=0.18). The result of our study suggests that in children with seasonal allergic rhinitis the exposure on the allergenic factor can influence the adenoid size. Properly administered nasal glucocorticoid together with antihistaminic in standard doses can probably avoid this effect.

Early‐onset atopy is associated with enhanced lymphocyte cytokine responses in 11‐year‐old children

Early age at onset of atopy is associated with more severe asthma and increased airway responsiveness (AR); the underlying mechanism is unclear but may involve T cell responses. To test the hypothesis that enhanced T cell responses may be associated with early-onset atopy. In a longitudinal study, atopy was determined in infancy and at 6 and 11 years of age. Individuals were categorized as persistent infant-onset atopy (PIOA), early childhood-onset atopy (ECOA) and later childhood-onset atopy (LCOA). At 11 years of age, peripheral blood T cell cytokine responses, AR, exhaled nitric oxide (FE(NO)) and forced expiratory volume in 1 s were determined. The age at onset of atopy was determined for 60 children, of whom 15 had PIOA, 24 had ECOA and 21 had LCOA. An additional 76 children who were never atopic were also included. T cell responses to house dust mite, including interleukin-5, -9, -10 and tumour necrosis factor alpha, were higher among children with PIA and ECOA, and lower in children with LCOA, P<0.05. In contrast, those children with LCOA or who were not atopic had the highest IL-10 response to PHA (P=0.014). Children with PIOA and ECOA, but not LCOA, had higher AR and FE(NO) compared with non-atopic children (P<0.05). The group with PIOA were more likely among the atopic children to be admitted to hospital for asthma (P<0.05) and also had lower %FEV(1) compared with non-atopic children (P=0.023). Early age at sensitization is associated with enhanced T cell cytokine responses and indices of adverse asthma outcome. T cell cytokine responses might be programmed at the time of initial atopic sensitization.

Effect of Antireflux Treatment on Asthma Exacerbations in Nonatopic Children

To evaluate the asthma outcome of treatment with ranitidine or esomeprazole plus metoclopramide in older children with moderate-persistent asthma and gastroesophageal reflux disease (GERD). The study patients included 44 patients with asthma and GERD who had received 1 year of treatment with a proton pump inhibitor/prokinetic combination and had shown significant clinical improvement in asthma symptoms and no exacerbations for more than 3 months. For further treatment, 30 of the 44 patients continued treatment with esomeprazole/metoclopramide (group A), and 14 switched to ranitidine (group B). Nine patients with GERD and asthma who had previously undergone fundoplication were used as control individuals (group C). All patients were followed up closely for exacerbation of asthma symptoms and treated according to a standardized protocol. During the 6-month follow-up, group B patients experienced significantly more exacerbations per patient (2.2) than did those in group A (0.33) or group C (0.77) (P < 0.05). Fundoplication or continued treatment with esomeprazole and metoclopramide is associated with significantly fewer exacerbations of asthma symptoms in children with moderate-persistent asthma and concomitant GERD in comparison with treatment with ranitidine.

Clinical, functional, and epidemiological differences between atopic and nonatopic asthmatic children from a tertiary care hospital in a developing country

Differences between children with atopic asthma (AA) and nonatopic asthma (non-AA) have been shown in epidemiologic studies. In developing countries, even when non-AA is more prevalent than AA among schoolchildren, no data are available regarding clinical, functional, and epidemiological differences between these 2 groups. To evaluate differences between Chilean children with AA and non-AA. In this cross-sectional study, skin prick tests were performed on all patients (age range, 4-14 years) admitted to our tertiary care hospital with the diagnosis of asthma who were consequently classified as having AA or non-AA. Demographic characteristics, spirometry results, exercise bronchial challenge test results, and eosinophil counts measured in the last 12 months were recorded. Among the 237 asthmatic children, 62.5% had AA. Non-AA children had a significantly earlier onset of asthma and a more frequent history of pneumonia and tobacco consumption at home. Children with AA had higher nasal eosinophilia levels and a higher prevalence of dermatitis and severe exacerbation episodes of asthma in the past year (emergency department consultation and oral corticosteroids courses). Lung function was similar in both groups. After the multivariate analysis, only the number of oral steroid courses was significantly different between the groups and was associated with AA. In this selected population of asthmatic schoolchildren, the prevalence of non-AA (37.6%) is not negligible, and some differences between AA and non-AA children exist.

Risk factors for asthma symptoms at school age: An 8-year prospective study

Childhood recurrent wheezing is a very prevalent heterogeneous clinical entity. An 8-year prospective study was performed to correlate the clinical outcome of recurrent wheezing in the first years of life with prognostic risk factors. A cohort of 308 children with recurrent wheezing, aged <7 years, were enrolled in 1993, studied using a questionnaire, skin-prick tests, and serum total IgE. According to the study protocol, in 1996 and 2001, the cohort was assessed. In 2001, 81% of the initial sample was reevaluated (n=249); 61% remained symptomatic. Prevalence of atopy was 48% in 1993, 65% in 1996, and 75% in 2001. By logistic regression analysis, we identified the following as independent risk factors for asthma symptoms in the last year of the follow-up: personal history of rhinitis (odds ratio [OR] = 15.8, 95% confidence interval [CI], 6.1-40.8; p < 0.001), paternal asthma (OR =, 7.2; 95% CI = 1.7-29.7; p = 0.007), personal history of atopic dermatitis (OR = 5.9, 95% CI = 2.2-15.7; p < 0.001), maternal asthma (OR = 5.4, 95% CI = 1.7-17.1; p = 0.004), allergen sensitization (OR = 3.4, 95% CI = 1.2-10.4; p = 0.03), and onset of symptoms in the 2nd year or later in preschool-aged children (OR = 2.1, 95% CI = 1.1-4.8; p = 0.04). Kindergarten attendance before 12 months was identified as a protective factor (OR = 0.4, 95% CI = 0.2-0.9; p = 0.04). Among the 128 nonatopic children in 1993, 52% developed allergen sensitization. We identified as prognostic risk factors for asthma symptoms personal history of allergic disease, parental asthma, atopy, and late onset of symptoms. In a significant number of children clinical symptoms can occur years before allergen sensitization.

An analysis of the incidence of adenoid hypertrophy in allergic children

The adenoidectomy is the most often made operation in small children but the reasons of adenoid hypertrophy are not completely explained. Some researches show that in part of children, allergy can be a risk factor for adenoid hypertrophy. The main aim of this study was the analysis of adenoid hypertrophy in children with different allergic diseases. Two separate groups of children were examined. The study group consisted of 436 children between 4 and 9 years old with allergic rhinitis and/or bronchial asthma and/or atopic dermatitis hypersensitive to house dust mites (interview, positive skin-prick test results). The control group consisted of 229 non-atopic children (negative interview and skin-prick tests) in the similar age. In the both groups we examined the incidence of adenoid hypertrophy and its dependence of the kind of allergic disease, age, sex, infections, results of skin-prick test and other sensitization. The probability of adenoid hypertrophy was statistically more significant (logistic regression analysis) only in children from the study group with allergic rhinitis. There were no differences in adenoid hypertrophy incidence between children with other allergic diseases and the control group. The children from the study group with adenoid hypertrophy were more often hypersensitive to pollen and moulds allergens than the children without adenoid hypertrophy (chi square test). But there were no differences in the incidence of infection, age, sex and results of skin-prick tests. The result of our study suggests that the chance of adenoid hypertrophy in allergic children hypersensitive to dust mites is greater only in them with allergic rhinitis.

Role of Human Leucocyte Antigen DQ in the Presentation of T Cell Epitopes in the Major Cow’s Milk Allergen αs1-Casein

Background: Little is known about the association between human leucocyte antigen (HLA) and cow’s milk allergy (CMA). The aim of the present study was to determine the HLA restriction of T cell clones (TCCs) specific to αs1-casein, the most abundant milk protein, and to study possible HLA class II allele associations with CMA. Methods: αs1-Casein-specific TCCs were derived from 6 children with CMA, 9 atopic children without CMA and 5 non-atopic children. T cell epitope specificity was defined by stimulation with overlapping peptides, spanning the αs1-casein molecule. HLA restriction was determined in proliferation assays using antibodies blocking either HLA-DP, HLA-DQ or HLA-DR. HLA genotyping was performed in 32 subjects with CMA, 23 atopic and 22 non-atopic individuals. Results: Ten TCCs were restricted to HLA-DQ, 6 TCCs to HLA-DR and 4 TCCs to HLA-DP. The sequence in αs1-casein that was most immunogenic to T cells from children with CMA contained T cell epitopes restricted to DQB1*0201, DPB1*0401 and DRB1*1501. The DQB1*0501 allele frequency was lower in children with CMA than in non-atopic children, but this difference could not be confirmed in an additional group of subjects with and without CMA. Conclusions: HLA-DQ plays a substantial role in the presentation of T cell epitopes in αs1-casein. However, HLA class II allele frequencies do not show major differences between cow’s milk allergic, atopic and non-atopic subjects. T cell epitopes in the most immunogenic region are presented by various abundantly present HLA genotypes. Therefore, this sequence may be a suitable target for peptide immunotherapy.

Association of GST Genes Polymorphisms with Asthma in Tunisian Children

Background. A positive association between genetic polymorphism and asthma may not be extrapolated from one ethnic group to another based on intra- and interethnic allelic and genotype frequencies differences. Objective. We assessed whether polymorphisms of GST genes (GSTM1, GSTT1, and GSTP1) are associated with asthma and atopy among Tunisian children. Methods. 112 unrelated healthy individuals and 105 asthmatic (73 atopic and 32 nonatopic) children were studied. Genotyping the polymorphisms in the GSTT1 and GSTM1 genes was performed using the multiplex PCR. The GSTP1 ILe105Val polymorphism was determined using PCR-RFLP. Results. GSTM1 null genotype was significantly associated with the increased risk of asthma (P = .002). Asthmatic children had a higher prevalence of the GSTP1Ile105 allele than the control group (43.8% and 33.5%, respectively; P = .002). Also, the presence of the GSTP1 homozygote Val/Val was less common in subjects with asthma than in control group. We have found that GSTT1 null genotype (GSTT1 *0/*0) was significantly associated with atopy (P = .008). Conclusion. Polymorphisms within genes of the GST superfamily were associated with risk of asthma and atopy in Tunisia.

Gene–gene interaction between IL-13 and IL-13Rα1 is associated with total IgE in Korean children with atopic asthma

Interleukin (IL)-13, which is essential for IgE synthesis, mediates its effects by binding with a receptor composed of IL-4Ralpha and IL-13Ralpha1. We investigated the effects of IL-13 and IL-13Ralpha1 polymorphisms in Korean children with asthma, and whether these have been associated with IgE production. We enrolled 358 atopic asthmatic, 111 non-atopic asthmatic, and 146 non-atopic healthy children. IL-13 and IL-13Ralpha1 genotypes were identified using the PCR-RFLP method. There was an association between the asthma susceptibility and homozygosity for risk allele of IL-13 G+2044A. In children with atopic asthma, risk alleles in IL-13 (A-1512C and C-1112T) and IL-13Ralpha1 (A+1398G) showed increased total IgE (P=0.012, 0.015 and 0.017, respectively). Three-loci haplotype analysis for IL-13 showed that the haplotype composed of -1512C, -1112T and +2044A was associated with higher total IgE than other tested haplotypes in children with atopic asthma (P=0.003). The gene-gene interaction between risk alleles of each IL-13 promoter polymorphism and IL-13Ralpha1 polymorphism was associated with higher total IgE in children with atopic asthma (P=0.002, 0.010). These findings indicate that the IL-13 G+2044A is associated with asthma development and the IL-13 and IL-13Ralpha1 polymorphisms may interact to enhance IgE production.

Serum eosinophil cationic protein in children with atopic dermatitis

Eosinophil cationic protein (ECP) is a cytotoxic agent secreted by activated eosinophils during allergic and inflammatory processes. The aim of the study was to determine the ECP level, absolute and relative eosinophil count and IgE antibodies in children with atopic dermatitis (AD) compared with those of nonatopic children, and to assess the correlation of these laboratory parameters with the clinical severity of AD. This prospective study comprised 70 children. There were 49 children with AD aged 3-36 months, and the control group comprised 21 children with a negative personal and family history for atopic diseases. Detailed history, serum ECP levels (UniCAP FEIA), relative and absolute eosinophil counts and total serum IgE antibodies were determined in both groups. In the children with AD, skin involvement was measured by the SCORAD index. The calculated SCORAD index was between 16 and 83. IgE antibodies, relative and absolute eosinophil counts showed a significantly wider range of values and a statistically higher median (P < 0.001) in the patients with AD compared with the control group. These laboratory parameters did not correlate with the severity of AD. The serum ECP median level, in the children with AD, was 16.2 microg/L (range 3.01-65.30) compared with 5.92 microg/L (range 2.76-21.90) in the control group. Correlation of the total SCORAD index and the serum ECP levels was negative, weak (r = -0.065) and statistically not significant (P > 0.05). The same was found for the correlation of serum ECP and intensity of skin changes (r = -0.095) and serum ECP and subjective symptoms (r = -0.045). The correlation was positive, but weak and statistically not significant for the serum ECP and extent of the skin lesions (r = 0.079, P > 0.05). Elevated levels of ECP, relative and absolute eosinophil counts, as well as IgE antibodies were determined in the patients with AD. As these laboratory findings did not correlate with the severity of AD, they can be considered only as additional methods in the evaluation of patients with AD.

Prevalence of latex sensitization and allergy in Portuguese children

The prevalence of latex allergy has been increasing not only in risk groups but also in the general population, where it is accepted to average 1%. In children, latex sensitization prevalence studies are scarce and involve different population sampling and allergy testing methods, which makes it difficult to compare across studies. Nevertheless, existing studies point towards a low prevalence of latex allergy in children, which still needs to be confirmed in the Portuguese population. Aiming at studying the prevalence of latex sensitization and allergy in a sample of Portuguese children, we studied 182 children from two different hospital outpatient clinics. A standardized questionnaire focusing on atopic background, previous history and allergic signs or symptoms on exposure to latex or fruits was given to all children and parents. Skin prick testing was performed with a battery of common aeroallergens as well as latex. Serum total IgE, Phadiatop, F x 5E and latex-specific IgE were determined in all children. Specific IgE to latex-crossreacting fruits was determined in latex-sensitized children. Based upon the questionnaire, the prevalence of latex allergy would be 0.5%. The prevalence of latex sensitization would be 3.8%, when based solely upon skin prick testing, and 12.1% (>/=0.35 IU/ml) or 6.6% (>/=0.70 IU/ml) when based singly upon determination of latex-specific IgE. When positive results for either test were considered, the prevalence of latex sensitization was 14.3%. All latex-sensitized children were atopic. Sensitivity to latex-crossreacting foodstuffs was demonstrated in 61.5% of latex-sensitized children (16/26). This study shows that the prevalence of latex allergy and sensitization in Portuguese atopic and non-atopic children, as analysed using various diagnostic methods, is similar to that observed in other countries. In addition, the assessment of latex allergy and sensitization should always include skin prick testing and determination of serum IgE.

An Immunoepidemiological Approach to Asthma: Identification of in-Vitro T-Cell Response Patterns Associated With Different Wheezing Phenotypes in Children

Purpose of the Study. To determine if variations in clinical asthma phenotypes are the result of differences in underlying T-cell immune responses to inhalant allergens. Study Population. One hundred forty-seven children (aged 8.6–13.5 years) and 25 of their siblings (aged 7.4–17.4 years) were recruited from 194 members of a birth cohort studied prospectively for asthma development. Methods. Wheeze and asthma were defined by parental questionnaire. Atopy was defined as at least 1 positive skin-prick test for environmental or food allergens. Increased bronchial hyperreactivity (BHR) was defined as a ≥20% drop in forced expiratory volume in 1 second after inhaled histamine up to 7.8 μmol/L. T-cell responses to allergens and mitogens, blood eosinophils, and immunoglobulin E (IgE) were measured and compared with clinical phenotypes. Results. Ninety-five (55.2%) of the children were atopic, sensitized predominantly to house dust mite (42.4%). Asthma was present in 26 (15.1%) children, of whom 22 (85%) were atopic; BHR was present in 62 (35.9%) children, of whom 45 (73%) were atopic. Atopy was associated with T-helper 2 (Th2) cytokine responses (interleukin-4 [IL-4], IL-5, IL-9, IL-13), whereas Th1 responses (IL-10, interferon-γ [IFN-γ], tumor necrosis factor-α [TNF]) occurred in all children. Skin-prick test wheal size was positively associated with house dust mite allergen-induced IL-5 (P &amp;lt; .0001) and IFN-γ (P = .003) and negatively associated with IL-10. Asthma was associated with eosinophilia and elevated house dust mite–specific IL-5, IL-9, IL-13, and IgE. BHR was associated with eosinophilia, elevated allergen-specific IL-5 and IgE, increased total IgE, and a polyclonal cytokine response (IL-5, IL-13, IFN-γ, and TNF-α). In atopics, current asthma or wheeze was associated with house dust mite allergen-specific IL-5 and IL-13; BHR was associated with IL-5 and IgE. In nonatopics, BHR was associated with increased house dust mite allergen-specific and polyclonal IL-10 and polyclonal IFN-γ and TNF-α. Conclusions. In atopic and nonatopic children, distinctive immune-response patterns were identified for asthma and BHR. Immunologic Th1 and Th2 hyperresponsiveness was identified as a hallmark of BHR. Reviewer Comments. Modification of T-cell responses has become an increasingly important focus in the investigation of treatments for atopic disease. Although this study further highlights the prominence of Th2-driven responses in atopic individuals, the results also demonstrate allergen-specific and polyclonal Th1 responses associated with BHR in atopic and nonatopic children. These findings suggest a nonantagonistic interaction between Th1 and Th2 pathways in the production of asthma symptoms. Further understanding of the associations between T-cell response patterns and clinical wheezing phenotypes in children may lead to future asthma therapies in this population.

The effect of montelukast on soluble interleukin-2 receptor and tumor necrosis factor α in pediatric asthma

Proinflammatory cytokines such as tumor necrosis factor (TNF) alpha and soluble interleukin 2 receptor (sIL-2R) are very important mediators in induction of inflammatory response in lung. The aim of this study was to investigate anti-inflammatory response of cysteinyl leukotriene receptor antagonist montelukast on macrophage and T-cell activation by sIL-2R and TNF-alpha in mild atopic asthmatic children. Fifteen children with mild-to-moderate atopic asthma and 15 nonatopic children as control, enrolled in the study. Asthmatic children were treated with montelukast, 5-mg tablets, for 1 month. Lung function test forced expiratory volume in 1 second (FEV1) was performed before and after treatment. Serum TNF-alpha, sIL-2R, and eosinophil cationic protein levels were determined in the control group and in asthmatic children before and after treatment. The mean eosinophil cationic protein value was significantly decreased (33.1 +/- 14.8 and 22.2 +/- 12.1; p < 0.05) and FEV1 was significantly increased (86.9 +/- 20.9 and 102.1 +/- 12.7; p < 0.05) after 1 month treatment with montelukast. The mean serum IL-2R levels were significantly higher in the before treatment group than in the after treatment group (1061.9 +/- 491 and 794 +/- 230.9; p < 0.05) or in control subjects (581.1 +/- 123; p < 0.01). The mean serum TNF-alpha level was higher in the before treatment group than in the after treatment group and control group (7.30 +/- 3.93, 5.20 +/- 1.46, and 4.95 +/- 1.27; p < 0.05). There was a significant correlation between TNF-alpha and sIL-2R in patients before montelukast treatment (r = 0.674; p < 0.01). This study indicates that montelukast improves clinical parameters and shows anti-inflammatory response by decreasing serum sIL-2R and TNF-alpha levels.

Tacrolimus ointment does not affect the immediate response to vaccination, the generation of immune memory, or humoral and cell-mediated immunity in children

Background: Concern exists that the prolonged application of immunomodulators to treat atopic dermatitis may cause systemic immunosuppression. Aims: In a 7-month, multicentre, randomised, controlled trial, we investigated the equivalence of...

Daily home measurements of exhaled nitric oxide in asthmatic children during natural birch pollen exposure

Fractional exhaled nitric oxide (FENO) is a sensitive marker of eosinophilic airway inflammation in asthma. Available methods have restricted measurements to the clinic, giving only a snapshot of the disease, which by nature is highly variable. We sought to investigate the feasibility, repeatability, accuracy, sensitivity, and biologic plausibility of new handheld equipment for FENO measurements. We studied day-to-day home measurements of FENO during the birch pollen season in children with allergy to birch pollen and a history of mild asthma and rhinoconjunctivitis during this season, as well as in nonatopic children. Eleven children with mild asthma and allergy to birch pollen, performed daily home measurements of FENO for 6 weeks before and during the birch pollen season by using a handheld FENO monitor (NIOX MINO). Additionally, FENO (chemiluminescence equipment [NIOX]) and spirometry were measured at the inclusion and completion visit in the clinic. Peak expiratory flow rate (PEFR) and symptoms were recorded daily. Daily FENO (NIOX MINO) increased significantly (P < .001) with increasing pollen count. FENO (NIOX MINO) and FENO (NIOX) exhibited a correlation coefficient of 0.98, but FENO (NIOX MINO) was significantly higher than FE(NO) (NIOX) (P < .01). PEFR and FEV1 remained unchanged, and few symptoms were recorded. Exhaled nitric oxide levels increased significantly during the pollen season, even though the patients reported only few asthmatic symptoms and no change in PEFR or spirometry. Daily measurements of FENO (NIOX MINO) might allow early detection of disease deterioration, and future studies could address such a measure for dynamic treatment strategies. This simple handheld device expands the potential use of FENO to a wider group of asthma clinics and even home measurements.

Exhaled nitric oxide in healthy nonatopic school‐age children: Determinants and height‐adjusted reference values

Exhaled nitric oxide (FENO) was proposed as a marker of airway inflammation, but data about FENO in healthy children measured with standardized methods are so far limited. In order to assess the determinants of FENO in healthy children, we investigated a population-based sample of school-age children (n = 276) with a questionnaire, skin-prick tests, spirometry, and the measurement of FENO. The FENO of 114 nonatopic and nonsmoking children considered healthy were analyzed with stepwise multiple regression analysis, which showed significant associations with age, standing height, weight, and body surface area, but not with gender. Height was found to be the best independent variable for the regression equation for FENO, which on average showed an increase in the height range of 120-180 cm from 7 to 14 ppb. In the random sample of children, increased FENO was associated with atopy (odds ratio, 9.0; 95% confidence interval, 3.9-21.1; P < 0.0001), and significantly with allergic rhinitis and atopic dermatitis, but not with asthma. Respiratory symptom-free children with skin-prick test positivity had significantly higher FENO than healthy nonatopic subjects. We conclude that height is the best determinant of FENO in healthy children. Due to the strong effect of atopy, FENO data should not be interpreted without knowing the atopic status of the child. The present reference values of FENO may serve in clinical assessments for measuring airway inflammation in children.

Epidemiology of Tick Bites and Borreliosis in Children Attending Kindergarten or So-Called “Forest Kindergarten” in Southwest Germany

The so-called "forest kindergartens" have been increasingly popular in Germany since the beginning of the 1990s. These are nurseries located in forested areas where children spend all-season full-time outdoors. Fifty-three kindergartens in the state of Baden-Württemberg, Germany participated in this study. In a prospective clinical cohort study, the child's personal data, history, protective parental habits concerning tick bites, number of tick bites, and cases of borreliosis were recorded monthly (March-October 2004) using a questionnaire. Altogether, 1,707 children of 25 "forest kindergartens" (506 children) and 28 conventional kindergartens (1,201 children) were included. The response rate was 75% in "forest kindergartens" and 65% in conventional kindergartens. In the "forest kindergartens", 1,503 tick bites especially on the trunk and on the head were found, whereas 502 tick bites were registered in conventional kindergartens. Sixteen cases of borreliosis were diagnosed (10 in "forest kindergartens", six in conventional kindergarten), most frequently manifesting as erythema migrans. Children attending a "forest kindergarten" have a 2.8 times increased risk of experiencing tick bites and a 4.6 times increased risk of suffering from borreliosis compared to conventional kindergarten in Germany, although protective parental behavior in "forest kindergarten" children was significantly better than that in conventional kindergarten.