Non-atopic Children Research Articles

O058 Children with atopic dermatitis have severe sleep disturbance, but similar bedtimes compared to non-atopic children

Sleep disturbance is common in children with atopic dermatitis (AD), but remains inadequately addressed in research studies and clinically. We sought to characterize sleep patterns in AD using objective and subjective measures, and determine the potential relevance of biomarkers.

Serum Vitamin D Levels in Children with Vernal Keratoconjunctivitis

ABSTRACTPurpose: To evaluate serum 25-hydroxyvitamin D [25(OH)D3] levels of vernal keratoconjunctivitis (VKC) children.Methods: A total of 62 non-atopic healthy children (64.5% male, mean age 10.79 ± 3.3 years) and 29 VKC children (75.9%, mean age 12.17 ± 2.7 years) were included in the study. Serum 25(OH)D3 levels measured by HPLC were compared between the two groups and a p value of <0.05 was considered as statistically significant.Results: The mean serum 25(OH)D3 level of VKC group was significantly lower than in the control group (11.02 ± 5.16 ng/mL and 15.99 ± 7.36 ng/mL, respectively) (p = 0.002). Severe vitamin D deficiency (<10 ng/mL) was detected in 48.3% of VKC children and 22.6% of the controls (p = 0.017). Time spent outdoors during daylight was higher in the control group (229.5 ± 101.2 min) compared with the VKC group (160.7 ± 65.9 min) (p = 0.008), and showed a significant correlation with serum 25(OH)D3 levels (Spearman rho = 0.812) (p<0.001).Conclusions: Children with VKC should be evaluated for vitamin D deficiency, which might occur secondary to sun avoidance.

Changes in the Levels of Interleukin-17 Between Atopic and Non-atopic Children with Mycoplasma pneumoniae Pneumonia.

As previous study showed that Mycoplasma pneumoniae (MP) induced a cellular immune response associated with interleukin-17 (IL-17), we designed this study to explore IL-17 in MP pneumonia patients with atopic sensitization and 144 patients were evaluated and divided into three groups: atopic MP pneumonia group (n = 38), non-atopic MP pneumonia group (n = 74), and atopic non-MP pneumonia group (n = 32). Serum IL-17 was measured at admission acute phase and at recovery phase. We found IL-17 levels only in the atopic MP pneumonia group that were significantly higher at recovery phase than at acute phase, and its levels were also higher in the atopic MP pneumonia group than the other two groups at clinical recovery phase. In addition, acute asthma attack was higher in the atopic MP pneumonia group. Therefore, IL-17 should be related with asthma and it can be a good marker warning an acute asthma attack in atopic MP pneumonia. Necessary measures can be taken as prevention.

Ozone-Induced Nasal Type 2 Immunity in Mice Is Dependent on Innate Lymphoid Cells.

Epidemiological studies suggest that elevated ambient concentrations of ozone are associated with activation of eosinophils in the nasal airways of atopic and nonatopic children. Mice repeatedly exposed to ozone develop eosinophilic rhinitis and type 2 immune responses. In this study, we determined the role of innate lymphoid cells (ILCs) in the pathogenesis of ozone-induced eosinophilic rhinitis by using lymphoid-sufficient C57BL/6 mice, Rag2(-/-) mice that are devoid of T cells and B cells, and Rag2(-/-)Il2rg(-/-) mice that are depleted of all lymphoid cells including ILCs. The animals were exposed to 0 or 0.8 ppm ozone for 9 consecutive weekdays (4 h/d). Mice were killed 24 hours after exposure, and nasal tissues were selected for histopathology and gene expression analysis. ILC-sufficient C57BL/6 and Rag2(-/-) mice exposed to ozone developed marked eosinophilic rhinitis and epithelial remodeling (e.g., epithelial hyperplasia and mucous cell metaplasia). Chitinase-like proteins and alarmins (IL-33, IL-25, and thymic stromal lymphopoietin) were also increased morphometrically in the nasal epithelium of ozone-exposed C57BL/6 and Rag2(-/-) mice. Ozone exposure elicited increased expression of Il4, Il5, Il13, St2, eotaxin, MCP-2, Gob5, Arg1, Fizz1, and Ym2 mRNA in C57BL/6 and Rag2(-/-) mice. In contrast, ozone-exposed ILC-deficient Rag2(-/-)Il2rg(-/-) mice had no nasal lesions or overexpression of Th2- or ILC2-related transcripts. These results indicate that ozone-induced eosinophilic rhinitis, nasal epithelial remodeling, and type 2 immune activation are dependent on ILCs. To the best of our knowledge, this is the first study to demonstrate that ILCs play an important role in the nasal pathology induced by repeated ozone exposure.

Childhood atopic dermatitis-Brain-derived neurotrophic factor correlates with serum eosinophil cationic protein and disease severity.

Several studies have shown that neurotrophins including brain-derived neurotrophic factor (BDNF) play a role in chronic inflammatory skin diseases such as atopic dermatitis (AD). BDNF is increased in the serum samples of adults with AD. Interestingly, eosinophils of these patients can release and produce BDNF. We analyzed BDNF serum levels with ELISA and their correlation with SCORAD score, eosinophil cationic protein (ECP), total IgE, IL-4, IL-13 and IL-31 in children with AD (n = 56) compared to nonatopic healthy children (n = 25). In addition, we analyzed FLG loss-of-function mutations in 17 children with AD and their connection to BDNF. BDNF serum levels were significantly higher in children with AD. Further, BDNF correlated with disease activity, serum ECP, and total IgE serum levels in AD. There was no difference in BDNF levels of filaggrin-positive or filaggrin-negative children with AD, and there was no correlation of BDNF with IL-31 and Th2 cytokines including IL-4 and IL-13. Together, our data add new insights into the pathophysiology of AD, suggesting that serum BDNF which correlates with disease severity contributes to the regulation of inflammation in an eosinophil-, but not Th2-dependent manner.

Evaluation of the Interleukin-1 Receptor Antagonist and Immunoregulatory Interleukin-10 in the Middle Ear in Chronic Otitis Media With Effusion in Children With and Without Atopy.

ObjectivesThe role of pro-inflammatory cytokines in the course of chronic otitis media with effusion (COME) has been documented. However, there are fewer studies on the action of anti-inflammatory cytokines in the middle ear. We sought determine whether there is an association between COME and anti-inflammatory cytokines and whether there are any differences in the cytokine profile in COME children with and without atopy.MethodsEighty-four children were divided into 3 groups: 32 nonatopic children with COME (group NA), 31 atopic children with COME (group A), and 21 children without COME and without atopy (control group C). Specimens from the middle ear were collected and evaluated by enzyme-linked immunosorbent assay for the cytokines interleukin-1 receptor antagonist (IL-1Ra) and immunoregulatory IL-10.ResultsSignificantly higher IL-10 concentrations were found in both nonatopic and atopic children with COME compared to controls. No significant differences in IL-1Ra levels were found between atopic and nonatopic children with COME and the control group.ConclusionWe found no differences in the levels of IL-1Ra in atopic and nonatopic children with COME compared to controls. However, we found elevated IL-10 levels in the middle ear effusions from children with COME, with or without atopy. These elevated immunoregulatory cytokine levels suggest a role for new immunomodulatory treatments to prevent disease progression in COME, regardless of atopy.

Common environmental chemicals do not explain atopy contrast in the Finnish and Russian Karelia.

BackgroundAtopic allergy is much more common in Finnish compared with Russian Karelia, although these areas are geographically and genetically close. To explore the role of environmental chemicals on the atopy difference a random sample of 200 individuals, 25 atopic and 25 non-atopic school-aged children and their mothers, were studied. Atopy was defined as having at least one positive skin prick test response to 14 common inhalant and food allergens tested. Concentrations of 11 common environmental pollutants were measured in blood samples.ResultsOverall, the chemical levels were much higher in Russia than in Finland, except for 2,2′,4,4′-tetra-bromodiphenyl ether (BDE47). In Finland but not in Russia, the atopic children had higher concentrations of polychlorinated biphenyls and 1,1-Dichloro-2,2-bis-(p-chlorophenyl)-ethylene (DDE) than the non-atopic children. In Russia but not in Finland, the atopic mothers had higher DDE concentrations than the non-atopic mothers.ConclusionsHigher concentrations of common environmental chemicals were measured in Russian compared with Finnish Karelian children and mothers. The chemicals did not explain the higher prevalence of atopy on the Finnish side.

T-cell receptor phenotype pattern in atopic children using commercial fluorescently labeled antibodies against 21 human class-specific v segments for the tcrβ chain (vβ) of peripheral blood: a cross sectional study.

BackgroundT-cell receptor (TCR) repertoire development is an integral part of the adaptive immune response. T-cell activation requires recognition of appropriately processed antigens by the TCR. Development of a diverse repertoire of TCRs is therefore essential to ensure adequate protection from potential threats. The majority of T-cells in peripheral blood have TCRs composed of an alpha and a beta chain. At the DNA level, the TCR genes are formed through directed recombination from germline sequences—the so-called VDJ recombination [variable (V) joining (J) diversity (D) gene segments] which results in variations in the repertoire. The most variable part of TCRs is the Vβ region (VβTCR), which has multiple V segment families that can be quantitatively measured. However, only sparse data exists on the normal levels of the VβTCR repertoire in healthy children. We aimed to establish normal values for the VβTCR repertoire in atopic children without immunodeficiency.MethodsFifty-three children were recruited from food allergy, drug allergy, chronic urticaria and anaphylaxis registries and were divided into groups based on age: >0–2 years, 3–6 years, and 6–18 years. We used commercially available and fluorescently labeled antibodies against 21 human class-specific V segments of the TCRβ chain (Vβ) to study in peripheral blood the quantitative pattern of Vβ variation by flow cytometry.ResultsChildren of all ages exhibited a similar pattern of TCR Vβ expression. Vβ 2 was the most commonly expressed family in all three age groups [9.5 % (95 % CI, 8.9, 10 %), 8.8 % (95 % CI, 7.4, 10.2 %) and 7.6 % (7.0, 8.3 %) respectively]. However, the percentage of Vβ 2 decreased in older children and the percentage of Vβ 1 was higher in males. TCR Vβ expression in our sample of atopic children did not differ substantially from previously published levels in non-atopic cohorts.ConclusionTCR Vβ diversity follows a predictable and comparable pattern in atopic and healthy non-atopic children. Establishing normal levels for healthy children with and without atopy will contribute to a better definition of Vβ receptor deviation in children with primary immunodeficiency and/or immunodysregulation conditions.

Indoor microbial communities: Influence on asthma severity in atopic and nonatopic children

Allergic and nonallergic asthma severity in children can be affected by microbial exposures. We sought to examine associations between exposures to household microbes and childhood asthma severity stratified by atopic status. Participants (n=196) were selected from a cohort of asthmatic children in Connecticut and Massachusetts. Children were grouped according to asthma severity (mild with no or minimal symptoms and medication or moderate to severe persistent) and atopic status (determined by serum IgE levels). Microbial community structure and concentrations in house dust were determined by using next-generation DNA sequencing and quantitative PCR. Logistic regression was used to explore associations between asthma severity and exposure metrics, including richness, taxa identification and quantification, community composition, and concentration of total fungi and bacteria. Among all children, increased asthma severity was significantly associated with an increased concentration of summed allergenic fungal species, high total fungal concentrations, and high bacterial richness by using logistic regression in addition to microbial community composition by using the distance comparison t test. Asthma severity in atopic children was associated with fungal community composition (P=.001). By using logistic regression, asthma severity in nonatopic children was associated with total fungal concentration (odds ratio, 2.40; 95% CI, 1.06-5.44). The fungal genus Volutella was associated with increased asthma severity in atopic children (P=.0001, q=0.04). The yeast genera Kondoa might be protective; Cryptococcus species might also affect asthma severity. Asthma severity among this cohort of children was associated with microbial exposure, and associations differed based on atopic status.

Study of Total and Allergen Specific IgE and Salivary IgA, As Well As Leukocyte Populations in Atopic and Non-Atopic Children with Asthma and / or Rhinitis

Study of Total and Allergen Specific IgE and Salivary IgA, As Well As Leukocyte Populations in Atopic and Non-Atopic Children with Asthma and / or Rhinitis

Respiratory syncytial virus infection and bronchial hyperreactivity in children up to two years of age in correlation with atopy.

Bronchiolitis in early childhood caused by respiratory syncytial virus (RSV) is considered to be important risk factor of the recurrent wheezing and asthma development. The aim of this study was to examine the frequency of RSV infection and atopy in children up to two years of age and to determine their correlation with bronchial hyperreactivity. The study included 175 children aged 5-24 months. The presence of RSV infection was identified by serum levels of IgA and IgG determined by ELISA. Bronchial hyperreactivity (BHR) has been defined as the existence of chronic bronchial disease and/or three or more previous suspected diagnosis of acute bronchial disease. Atopy was confirmed by detection of the specific serum IgE using quantitative multitest Phadiatop infant (cut off 0.35 kUA/L). The children with atopy were more frequently infected with RSV (43.3%) than those without atopy (22.8%; p = 0.02). The higher frequency of RSV infection was found in children with BHR in comparison with those without it but only in the group who also had atopy (77.8% vs. 28.6%, p = 0.018). In the female children, BHR and RSV infection were associated in 62.5% of cases, regardless the atopy. In the male children with atopy, RSV infection was associated with BHR in 83.3% of the cases, while in those without atopy, RSV infection with BHR was found in only 17.4% of the cases. Children up to two years of age with atopy are more frequently infected with RSV (43.3%) than nonatopic children. Every third child with atopy develops BHR and 77.8% of them also have RSV infection. Atopic children are at higher risk for development of BHR when infected with RSV also.

Estimation of serum immunoglobulin E levels as suggestive indicator of atopy in children having allergic rhinitis

Background: Atopy is the major factor predisposing for the development of allergic airway diseases. Immunoglobulin E (IgE) levels of children having atopy are elevated as compared with nonatopic children. Serum total IgE levels can be utilized as a surrogate marker for the presence of atopy. Objective: To study the presence of atopy by estimation of serum IgE levels in children having allergic rhinitis and to determine the proportion of concomitant allergic conditions in these children. Methods: From May 2012 to April 2013, 134 children aged 6-14 years having allergic rhinitis as diagnosed on the basis of their response to the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire were included in the study. Children were screened for concomitant atopic disorders, viz., asthma, atopic eczema, and conjunctivitis on the basis of their response to ISAAC questionnaire. Total serum IgE levels were determined for all subjects. Results: Total IgE levels of study subjects were found to be increased in 114 (85.07%) out of 134 children (cut-off value = 100 IU/mL). Mean serum IgE of the study subjects was 312.18 (95% confidence interval, 253.1-385.1) IU/mL. Children having persistent allergic rhinitis had higher mean IgE levels of 392.18 IU/mL as compared to 199.08 IU/mL (P

Cat Allergens in Homes of Cat Allergic Children without a Cat

Background: Cat allergy is very common among atopic children in Istanbul although most of them have never had a cat in their homes. Methods: Major cat allergen Fel d1 was measured in house dust samples of 25 atopic children and 15 non-atopic children. Results: Fel d1 levels in house dust samples were similar in both study and control groups (64.8 ± 72.8 ng/g vs 65.4 ± 69.8 ng/g, respectively). Conclusions: Cat allergens are common in the house dust samples of allergic and non-allergic children living in Istanbul. Presence of cat allergens at homes may be due to the presence of the stray cats in the city.

Atopic disease and cardiovascular risk factors in US children

Atopic disease and cardiovascular risk factors in US children

Association Between CD14 Polymorphism (-1145G/A) and Childhood Bronchial Asthma.

Polymorphisms in the promoter region of CD14 gene have been associated with asthma and atopy although the findings between cohorts have not been uniform. We aimed at investigating the association between CD14 gene (-1145G/A) polymorphism and bronchial asthma in Egyptian children. Genotyping of CD14 gene (-1145G/A) polymorphism was done by real-time PCR in 192 asthmatic children (atopic, n = 100 and non-atopic, n = 92) and 181 age- and gender-matched healthy children. Serum levels of total IgE were measured by ELISA. Skin prick test was performed on all patients. We found that the frequency of AA genotype was significantly higher in asthmatic children compared to healthy controls. Asthmatic children carrying GG genotype had a significantly lower prevalence of atopic asthma. Meanwhile, the "A" allele was significantly higher in atopic asthmatic children compared to healthy and non-atopic children. Moreover, atopic children carrying the "G" allele showed better asthma control. In conclusion, our findings represent an evidence for the role of CD14 gene (-1145G/A) polymorphism in childhood asthma and asthma control.

Prevalence and association of asthma and allergic sensitization with dietary factors in schoolchildren: data from the french six cities study

BackgroundThe prevalence of asthma and allergy has recently risen among children. This increase in prevalence might be related to various factors, particularly diet. The aim of this study is to assess the prevalence and association of asthma and allergic sensitization with dietary factors in the French Six Cities Study.MethodsCross-sectional studies were performed among 7432 schoolchildren aged 9–11 years in Bordeaux, Clermont-Ferrand, Créteil, Marseille, Reims, and Strasbourg. Parental questionnaires, based on the International Study on Asthma and Allergies in Childhood (ISAAC), were used to collect information on allergic diseases and potential exposure factors including a food frequency questionnaire to evaluate dietary habits. Skin prick testing to common allergens for allergic sensitization and bronchial hyper-responsiveness (BHR) testing to exercise were performed. Confounders control was performed with multiple logistic regressions.ResultsAsthma symptoms, asthma and allergic sensitization were more prevalent in boys than in girls and were more prevalent in the South than in the North of France. After adjustment for confounders, fruit juice intake was associated with a low prevalence of lifetime asthma (ORa [95 % CI]; 0.73 [0.56–0.97]), butter intake was positively associated with atopic wheeze (1.48 [1.07–2.05]) and having lunch at the canteen 1–2 times/week compared to never or occasionally was associated with a lower prevalence of past year wheeze (0.71 [0.52–0.96]), lifetime asthma (0.76 [0.60–0.96]) and allergic sensitization (0.80 [0.67–0.95]). Meat intake was inversely related to past year wheeze among atopic children (0.68 [0.50–0.98]) while fast food consumption and butter intake were associated with an increase prevalence of asthma (2.39 [1.47–3.93] and 1.51 [1.17–2.00] respectively). Fish intake was associated with a lower prevalence of asthma among non-atopic children (0.61 [0.43–0.87]. None of the dietary factors was associated with BHR.ConclusionsDiet is associated with wheeze, asthma and allergic sensitization but not with BHR in children. These results provide further evidence that adherence to a healthy diet including fruits, meat and fish seems to have a protective effect on asthma and allergy in childhood. However, prospective and experimental studies are needed to provide causal evidence concerning the effect of diet on asthma and atopy.

Short-term ibuprofen treatment and pulmonary function in children with asthma.

To investigate the association between ibuprofen use and pulmonary function in children with Asthma. Ninety 9- to 10-year-old children were classified into 3 groups: Study group, mild to moderate stable asthmatic children with self-reported aspirin allergy and no history of anaphylaxis; Allergy control group: atopic children (allergic rhinitis/atopic dermatitis); Healthy control group: non-atopic healthy children. None of the participants in the atopic and healthy control groups had a history of aspirin allergy. All received ibuprofen 4 times a day for 3 consecutive days. Forced expiratory volume in the first second (FeV1) and fractional exhaled nitric oxide (FeNO) measurements were performed before and after ingestion of ibuprofen daily for 3 days. In the study group, a decrease in FeV1 and increase in FeNO levels were observed after taking ibuprofen for 2 days. The atopic control group showed only an increase in FeNO but not FEV1. In the healthy control group, both FeV1 and FeNO were unchanged from baseline. The results showed that cross-reactive non-steroidal anti-inflammatory drug hypersensitivity may exist between ibuprofen and aspirin. This raises the possibility that asthma exacerbation could be mediated by ibuprofen ingestion.

The association of intrafamilial violence against children with symptoms of atopic and non-atopic asthma: A cross-sectional study in Salvador, Brazil

This study aims to describe the types of intrafamilial violence perpetrated against children according to living conditions, family factors, and child characteristics, and to identify the association between types of intrafamilial violence and asthma symptoms in atopic and non-atopic children. A cross-sectional study was carried out with 1,370 caregivers as part of the Social Changes, Asthma and Allergy in Latin America (SCAALA) study, conducted in 2006 in Brazil. The study population was selected by random sampling. The main outcome measures were atopic and non-atopic asthma. We investigate the association between intrafamilial violence and asthma symptoms in atopic and non-atopic children. A backward multivariate logistic polytomous regression was performed to verify the main association. Nonviolent discipline (NVD) and maltreatment nonviolent discipline (MNVD) were positively associated with non-atopic asthma symptoms (NVD: odds ratio (OR)=1.95/95% confidence interval (CI)=1.17–3.25; MNVD: OR=1.95/95% CI=1.19–3.20). However, for the most severe intrafamilial violence, this association was not found after control of potential confounders. This study demonstrates the effect of types of intrafamilial violence on non-atopic asthma. Intrafamilial violence against children represents one more component in the determination of non-atopic asthma in Latin America.

Pro-inflammatory interleukins in middle ear effusions from atopic and non-atopic children with chronic otitis media with effusion.

Chronic otitis media with effusion (OME) is associated with irreversible changes in the middle ear, sometimes leading to hearing loss and abnormal language development in children. While the pathogenesis of OME is not fully understood, inflammatory and allergic factors are thought to be involved. The study aimed to investigate the role of cytokines in the local development of chronic OME, and assess differences in the cytokine profiles between atopic and non-atopic children. 84 atopic and non-atopic children with chronic OME (mean age of 6years 7months) were studied. Age-matched children with hypertrophy of the adenoids and Eustachian tube dysfunction served as the control group. The number of past acute otitis media (AOM) episodes, their age, and the type of effusion were recorded for all children. Pro-inflammatory cytokine concentrations (TNF-α, IL-1β, IL-6 and IL-8) were determined and the presence of pathogenic bacteria in the patients' effusions was examined. High concentrations of TNF-α, IL-1β, IL-6 and IL-8 were found in the effusions in all children with chronic OME, with the highest levels observed in the non-atopic group. The atopic group showed persistently high IL-1β levels, while in the non-atopic children, IL-1β and TNF-α levels positively correlated with the patient's age and the number of past AOM episodes. Pathogenic bacteria were more frequently isolated from effusions in non-atopic children. In both atopic and non-atopic children, pro-inflammatory cytokines are found at high concentrations. This argues in favor of instituting anti-inflammatory management for treating OME, regardless of atopy.

Similar Occurrence of Febrile Episodes Reported in Non-Atopic Children at Three to Five Years of Age after Prebiotics Supplemented Infant Formula.

This is a follow up study of a multicenter randomised placebo-controlled trial in seven centres in five West European countries. The RCT assessed the effect of infant formula supplemented with a mixture of prebiotics (with neutral short-chain and long-chain oligosaccharides and pectin-derived acidic oligosaccharides) during infancy in term-born children (n=1130). In the follow-up study 672 children (60% of the study population) participated: 232 (56%) from the prebiotics group (PG), 243 (58%) from the control group (CG), and 197 (66%) from the non-randomised breast-fed group (BG). The primary outcome was the occurrence of febrile episodes at three to five years of age prospectively documented by the parents: in the PG 1.17 (interquartile range 0.50-2.08) episodes per year versus 1.20 (0.52-2.57) in the CG; and 1.48 (0.65-2.60) in the BG. This specific prebiotics mixture given during infancy in healthy non-atopic subjects does not decrease febrile episodes and therefore seems not to prevent infection between their third and fifth birthday.