Non-allergic Children Research Articles

Differences in innate immune function between allergic and nonallergic children: New insights into immune ontogeny

Microbial products are of central interest in the modulation of allergic propensity. We sought to explore whether allergic children show differences in microbial Toll-like receptor (TLR)-mediated responses over their first 5 years of life. Mononuclear cells isolated from 35 allergic and 35 nonallergic children at birth and 1, 2.5, and 5 years of age were stimulated with TLR2-TLR9 ligands to study innate immune function and with allergens or mitogen to assess adaptive T-cell responses. Cytokine production was measured by using Luminex multiplexing technology. Nonallergic children show progressive and significant age-related increases in innate cytokine responses (IL-1β, IL-6, TNF-α, and IL-10) to virtually all TLR ligands. This innate maturation corresponds with a parallel increase in adaptive T(H)1 (IFN-γ) responses to allergens and mitogens. In contrast, allergic children show exaggerated innate responses at birth (P < .01) but a relative decrease with age thereafter, so that by age 5 years, TLR responses are attenuated compared with those seen in nonallergic subjects (P < .05). This early hyperresponsiveness in allergic subjects fails to translate to a corresponding maturation of T(H)1 function, which remains attenuated relative to that seen in nonallergic subjects but is associated with a characteristic age-dependent increase in allergen-specific T(H)2 responses (P < .01). Our findings suggest significant differences in the developmental trajectory of innate immune function in children with allergic disease that might contribute to the recognized differences in postnatal adaptive T-cell immunity.

Basophil activation test based on the expression of CD203c in the diagnostics of cow milk allergy in children

BackgroundDetection of allergen-induced basophil activation by flow cytometry has been shown to be a useful tool for allergy diagnosis.ObjectiveThe aim of this study was to assess the potential of this technique for the diagnosis of pediatric cow milk allergy.Material and methodsThe quantification of total and specific IgE and basophil activation test were performed to evaluate cow milk allergic (n = 9), and non-allergic children (n = 15).ResultsAllergen-induced basophil activation was detected as a CD203c up-regulation. The expression of CD203c antigen on basophils was measured with flow cytometry. The antigen CD203c was detected on 15.4 ± 10.2% basophils from allergic children after incubation with specific allergens in concentration 1:10, whereas in the control group there were 3.0 ± 1.5% of basophils positive for this molecule (P < 0.05). Stimulation with allergen diluted 1:500 resulted in activation of 15.3 ± 11.2% of basophils in allergic children and 3.8 ± 2.3% of cells in the control group (P < 0.05). Positive results of an allergenicity test (above the cut- off level of 10%) were obtained in 7 out of the 9 allergic children. In 5 cases, the cutoff level was reached with both dilution of allergens (1:10 and 1:500). In 1 patient, positive stimulation was observed after stimulation with allergen diluted 1:10 and in another case only 1:500 resulted in stimulation of more then 10% of basophils. In no child of the control group, stimulation above 10% was noted.ConclusionsThis study demonstrates that the analysis of allergen-induced CD203c up-regulation with flow cytometry is a reliable tool for the diagnosis of cow milk allergy in pediatric patients, with sensitivity similar to routine diagnostic tests and a higher specificity.

Diagnostic accuracy of the nasal obstruction index in detecting adenoid hypertrophy in children without allergy

Objective We have previously compared the capacity of the nasal obstruction index (NOI) and nasal fiberoptic endoscopy (NFE) to detect adenoid hypertrophy (AH) in children and found no agreement between them. However, the prevalence of false positive results was significantly higher in children with allergic rhinitis (AR), thus suggesting that AR may be a possible causative factor. The aim of this study was to verify the diagnostic accuracy of the NOI in detecting AH by comparing NOI scores with NFE findings in a selected series of non-allergic children affected by nasal obstruction. Methods This prospective study was carried out at the Outpatient Clinics of the Departments of Specialist Surgical Sciences and Maternal and Pediatric Sciences of the University of Milan, Italy, and involved 154 non-allergic children aged 3–12 years in whom otological diseases and/or perceived nasal obstruction led to the suspicion of adenoid obstruction. The diagnostic accuracy of NOI was tested at all of the thresholds obtained by combining all of the cut-off points of NFE and NOI. Results Sixty-two percent of the children had otological diseases. The choanal opening was completely blocked by the adenoids in 40% of the children, whereas NOI indicated severe clinical obstruction in only 16%. The analysis of diagnostic accuracy showed that sensitivity and specificity were respectively 17–96% and 15–91% depending on the threshold, with no simultaneously acceptable sensitivity and specificity values at any threshold and AUC values of ≤0.7 at all thresholds. Conclusions In comparison with NFE, the NOI seems to be inaccurate in detecting AH in non-allergic children with nasal obstruction.

Nasal nitric oxide in children with adenoidal hypertrophy: A preliminary study

Objective Nasal nitric oxide, a mediator involved in upper airway inflammation, is impaired in children with allergic rhinitis and rhinosinusitis. Normal values are 200–450 parts per billion, but no data are available concerning its levels in children with adenoidal obstruction, predisposing to chronic nasosinusal inflammation. This study aimed to: (1) measure nasal nitric oxide levels in non-allergic children with adenoidal hypertrophy and (2) assess its possible relationship with the degree of adenoidal hypertrophy and other variable (gender, age, body max index, passive smoking exposure, recurrent acute otitis media, recurrent respiratory infections, and hypertrophy of nasal turbinates). Methods Eighty-one children with suspected adenoidal hypertrophy underwent nasal fibroendoscopy to assess the degree of adenoidal hypertrophy, and nasal nitric oxide on-line measurements by means of a dedicated chemiluminescence analyser. Results Nasal nitric oxide was successfully measured in 35 patients, most of whom had levels >450 parts per billion; the values were significantly higher ( p = 0.031) in children with non-obstructive adenoids. There was no significant correlation with any other variable. Conclusions Preliminary data show above-normal nasal nitric oxide levels in children with adenoidal hypertrophy, especially those with non-obstructive adenoids. This suggests nitric oxide involvement in recurrent nasopharyngeal inflammation due to adenoidal hypertrophy.

Various effects of different probiotic strains in allergic disorders: an update from laboratory and clinical data

Epidemiological data show that allergic children have a different intestinal flora from healthy children with higher levels of Clostridia and lower levels of Bifidobacteria. Nonetheless, Bifidobacteria and Lactobacilli are found more commonly in the composition of the intestinal flora of non-allergic children. Probiotics are ingested live microbes that can modify intestinal microbial populations in a way that benefits the host and they are represented mainly by Lactobacilli. Enhanced presence of probiotic bacteria in the intestinal microbiota is found to correlate with protection against atopy. There is also very promising evidence to recommend the addition of probiotics to foods for the prevention and treatment of allergic diseases. Clinical improvement, especially in allergic rhinitis and immunoglobulin (Ig)E-sensitized (atopic) eczema, has been reported in most of the published studies. However, clinical benefit of probiotic therapy depends upon numerous factors, such as type of bacterium, dosing regimen, delivery method and other underlying host factors, e.g. the age and diet of the host. Selection of the most beneficial probiotic strain, the dose and the timing of supplementation still need to be determined. This review helps understanding of the role of probiotics in various allergic diseases, explaining laboratory and clinical data in light of recent literature.

T cell responses to major peanut allergens in children with and without peanut allergy

T cell responses involved in peanut allergy are poorly understood. To investigate T cell responses towards major peanut allergens in peanut-allergic (PA) subjects compared with peanut-sensitized (PS) non-allergic children and non-atopic (NA) controls. Eighteen PA children, seven non-allergic PS children and 11 NA adults were included. Peripheral blood mononuclear cells were stimulated with a crude peanut extract (CPE). Short-term T cell lines were generated and subsequently stimulated with CPE and purified Ara h 1, Ara h 2, Ara h 3 and Ara h 6. The proliferation and production of IL-13, IFN-gamma, IL-10 and TNF-alpha were analysed. Proliferation to CPE and major allergens was enhanced in PA subjects. The primary response to CPE was comparable with PS subjects, with increased production of IL-13 and IFN-gamma compared with NA. Production of IL-10 was not observed. In short-term T cell lines, the response to CPE was stronger in PA than in PS and NA subjects. Only PA children had a detectable response to major peanut allergens, characterized by IL-13 production. The response was the highest after Ara h 3 stimulation, and the lowest after Ara h 2 stimulation. No significant correlation was observed between peanut-specific IgE levels and T cell responses to CPE. T cell responses to CPE in PA and PS children were characterized by Th1 and Th2 cytokines. Only PA children showed enhanced Th2 responses to Ara h 1, Ara h 3 and Ara h 6.

Any benefits of probiotics in allergic disorders?

Development of the child's immune system tends to be directed toward a T-helper 2 (Th2) phenotype in infants. To prevent development of childhood allergic/atopic diseases, immature Th2-dominant neonatal responses must undergo environment-driven maturation via microbial contact in the early postnatal period. Lactic acid bacteria and bifidobacteria are found more commonly in the composition of the intestinal flora of nonallergic children. Epidemiological data also showed that atopic children have a different intestinal flora from healthy children. Probiotics are ingested live health-promoting microbes that can modify intestinal microbial populations in a way that benefits the host; and enhanced presence of probiotic bacteria in the intestinal microbiota is found to correlate with protection against atopy. There is insufficient but very promising evidence to recommend the addition of probiotics to foods for prevention and treatment of allergic diseases, especially atopic dermatitis. Clinical improvement especially in allergic rhinitis and IgE-sensitized (atopic) eczema has been reported too. Literature data for food allergy/hypersensitivity and asthma are not adequate for this guaranteed conclusion; however, clinical benefit of probiotic therapy depends on numerous factors, such as type of bacterium, dosing regimen, delivery method, and other underlying host factors, e.g., the age and diet of the host. The selection of the most beneficial probiotic strain, the dose, and the timing of supplementation still need to be determined. Accordingly, probiotics can not be recommended generally for primary prevention of atopic disease; and if probiotics are used in atopic infants/children for any reason, such as therapy or prevention, cautionary approach ought to be taken.

Clinical assessment of adenoidal obstruction based on the nasal obstruction index is no longer useful in children

Objective To evaluate the accuracy of clinical assessment of adenoidal obstruction based on a standardized score of the degree of mouth breathing and speech hyponasality (nasal obstruction index [NOI]) in comparison to nasal fiberoptic endoscopy. Study Design Cross-sectional study with planned data collection. Setting Outpatient clinics of the Departments of Maternal and Pediatric Sciences and Specialized Surgical Sciences, University of Milan, Italy. Subjects and Methods Children aged three to 12 years with adenoidal obstruction suspected on the grounds of persistent/recurrent otitis media or perceived obstructive nasal breathing were eligible. Ear, nose, and throat examination, allergy testing, NOI measurement, and nasal fiberoptic endoscopy to assess the degree of adenoidal hypertrophy were performed. Agreement between the NOI and adenoidal hypertrophy grade was assessed in the patients as a whole and by clinical subgroups. Results A total of 202 children were enrolled: 54.9 percent had otological diseases and 45.1 percent had perceived obstructive nasal breathing. Most of the children (79.2%) showed mild or moderate clinical nasal obstruction. Adenoidal hypertrophy ranged from no obstruction (18%) to severe obstruction (38%). There was no substantial agreement between the NOI and the degree of adenoidal obstruction in the population as a whole and in all the clinical subgroups. False positive findings were significantly more frequent among allergic children (50%) than non-allergic children (22.4%, P = 0.009). Conclusion Clinical assessment based on the NOI is incapable of accurately predicting the degree of adenoidal obstruction. In children with clinical nasal obstruction not explainable by adenoidal size, the clinician should consider, among causes of more anterior obstruction, nasal allergy.

Allergy from infancy to adolescence. A population-based 18-year follow-up cohort

BackgroundAnxious parents have many concerns about the future health of their atopic infants. Paediatricians and primary care practitioners need to seek knowledge on long-term outcomes in order to cope with the increasing caseload of suspected allergy and the concerns of parents. The aim of the study was to assess suspected and diagnosed allergy in infancy as predictors of allergy and asthma in adolescence.MethodsFamilies expecting their first baby and making their first visit to a maternity health care clinic in 1986 were selected as the study population in a random sample. There were 1278 eligible study families. The data were provided of the children at the ages of 9 and 18 months and 3, 5, 12, 15 and 18 years by health care professionals, parents, and adolescents (themselves).ResultsAt the age of 9 months, the prevalence of allergy suspicions was distinctly higher than that of allergy diagnoses. At the age of five years suspected allergy approaches were nil, and the prevalence of diagnosed allergy was about 9%. During the adolescence, the prevalence of self-reported allergy increases steadily up to the age of 18 years, and that of asthma remains at approximately 5%. Suspected allergy at the age of 9 or 18 months and at the 5 years of age does not predict allergy at adolescence. Compared with non-allergic children, children with definite allergy at the age of 5 were over 8 times more likely to have allergy and nearly 7 times more likely to have asthma in adolescence.ConclusionAn early ascertained diagnosis of allergy, but not suspicions of allergy, predicts prevailing allergy in adolescence. Efforts need to be focused on accurate diagnosis of early childhood allergies.

Altered early infant gut microbiota in children developing allergy up to 5 years of age

Early colonization with bifidobacteria and lactobacilli is postulated to protect children from allergy, while Clostridium (C.) difficile colonization might be associated with allergic disease. Previous studies of infant gut microbiota in relation to subsequent allergy development have mostly employed culture-dependent techniques, studied genera of bacteria and the follow-up period was limited to 2 years. To relate gut microbiota in early infancy, notably bifidobacteria and lactobacilli at species level, to allergy development during the first 5 years of life and study if environmental factors influence the early infant gut microbiota. Fecal samples were collected at 1 week, 1 month and 2 months after birth from 47 Swedish infants, followed prospectively to 5 years of age. Bacterial DNA was analysed with real-time PCR and related to allergy development, family size as well as endotoxin and Fel d 1 levels in house dust samples. Primers binding to C. difficile, four species of bifidobacteria, two lactobacilli groups and Bacteroides fragilis were used. Children regarded as allergic manifested allergic symptoms and were skin prick test positive during their first 5 years while non-allergic children were neither. Children who developed allergy were significantly less often colonized with lactobacilli group I (Lactobacillus (L.) rhamnosus, L. casei, L. paracasei), Bifidobacterium adolescentis and C. difficile during their first 2 months. Infants colonized with several Bifidobacterium species had been exposed to higher amounts of endotoxin and grew up in larger families than infants harbouring few species. A more diverse gut microbiota early in life might prevent allergy development and may be related to the previously suggested inverse relationship between allergy, family size and endotoxin exposure.

Impaired Toll-like receptor 2 signalling in monocytes from 5-year-old allergic children

The relative composition of the two major monocytic subsets CD14(+)CD16(-) and CD14(+)CD16(+) is altered in some allergic diseases. These two subsets display different patterns of Toll-like receptor levels, which could have implications for activation of innate immunity leading to reduced immunoglobulin E-specific adaptive immune responses. This study aimed to investigate if allergic status at the age of 5 years is linked to differences in monocytic subset composition and their Toll-like receptor levels, and further, to determine if Toll-like receptor regulation and cytokine production upon microbial stimuli is influenced by the allergic phenotype. Peripheral blood mononuclear cells from 5-year-old allergic and non-allergic children were stimulated in vitro with lipopolysaccharide and peptidoglycan. Cells were analysed with flow cytometry for expression of CD14, Toll-like receptors 2 and 4 and p38-mitogen-activated protein kinase (MAPK). The release of cytokines and chemokines [tumour necrosis factor, interleukin (IL)-1 beta, IL-6, IL-8, IL-10, IL-12p70] into culture supernatants was measured with cytometric bead array. For unstimulated cells there were no differences in frequency of the monocytic subsets or their Toll-like receptor levels between allergic and non-allergic children. However, monocytes from allergic children had a significantly lower up-regulation of Toll-like receptor 2 upon peptidoglycan stimulation. Further, monocytes from allergic children had a higher spontaneous production of IL-6, but there were no differences between the two groups regarding p38-MAPK activity or cytokine and chemokine production upon stimulation. The allergic subjects in this study have a monocytic population that seems to display a hyporesponsive state as implicated by impaired regulation of Toll-like receptor 2 upon peptidoglycan stimulation.

Potential association between allergic diseases and pertussis infection in schoolchildren: Results of two cross-sectional studies seven years apart

BackgroundIn this study, we aimed to investigate the relationship between pertussis infections and allergic diseases in two cross-sectional questionnaire-based surveys carried out in 1997 and 2004. We also measured serum level of antibody to B. pertussis. Material and MethodsTwo cross-sectional, questionnaire-based surveys were carried out in 1997 (n=3164) and 2004 (n=3728). 361 cases and 465 controls were recruited from both surveys. The skin tests were performed using standardised extracts. The level of pertussis specific IgG was measured in 136 allergic and 168 non-allergic children. ResultsWe found that allergic diseases prevalence was significantly higher in the children suffering from pertussis infections (22.3 % first and 8.8 % second survey) compared to children who did not suffer from pertussis infections (6.6 % first and 4.5 % second survey) (p=0.001 and p=0.035, respectively). Asthma prevalence was also significantly higher in children suffering from pertussis infection (37.6 % first and 26.2 % second survey) compared to children who did not suffer from pertussis (7.4 % first and 5.0 % second survey) (p=0.001 and p=0.001, respectively). However, the mean serum levels of anti-pertussis IgG were similar in allergic and non-allergic groups (p>0.05). ConclusionAlthough pertussis antibody levels in atopic and non-atopic children were similar to each other, pertussis infection still seemed to have a significant effect on the development of atopic diseases.

Duodenal Intraepithelial Lymphocytes of Children with Cow Milk Allergy Preferentially Bind the Glycan-Binding Protein Galectin-3

A breakdown in intestinal homeostasis results in inflammatory bowel diseases including coeliac disease and allergy. Galectins, evolutionarily conserved beta-galactoside-binding proteins, can modulate immune-epithelial cell interactions by influencing immune cell fate and cytokine secretion. In this study we investigated the glycosylation signature, as well as the regulated expression of galectin-1 and -3 in human duodenal samples of allergic and non-allergic children. Whereas galectin-1 was predominantly localized in the epithelial compartment (epithelial cells and intraepithelial lymphocytes) and the underlying lamina propria (T cells, macrophages and plasma cells), galectin-3 was mainly expressed by crypt epithelial cells and macrophages in the lamina propria. Remarkably, expression of these galectins was not significantly altered in allergic versus non-allergic patients. Investigation of the glycophenotype of the duodenal inflammatory microenvironment revealed substantial alpha2-6-linked sialic acid bound to galactose in lamina propria plasma cells, macrophages and intraepithelial lymphocytes and significant levels of asialo core 1 O-glycans in CD68+ macrophages and enterocytes. Galectin-1 preferentially bound to neutrophils, plasma cells and enterocytes, while galectin-3 binding sites were mainly distributed on macrophages and intraepithelial lymphocytes. Notably, galectin-3, but not galectin-1 binding, was substantially increased in intraepithelial gut lymphocytes of allergic patients compared to non-allergic subjects, suggesting a potential role of galectin-3-glycan interactions in shaping epithelial-immune cell connections during allergic inflammatory processes.

Is caesarean delivery associated with sensitization to food allergens and IgE‐mediated food allergy: A systematic review

Several studies have shown differences in the composition of the gastrointestinal flora of children who develop sensitization to food allergens compared with non-allergic children. It has been hypothesized that changes in the gut microbiota resulting from caesarean section delivery could increase a child's risk of developing food allergy; however, studies examining the relationship between mode of delivery and food allergy have produced conflicting results. The objective of this review was to determine whether there is sufficient evidence to support an association between delivery by caesarean section and the development of sensitization to food allergens and immunoglobulin E (IgE) mediated food allergy. Using predefined inclusion and exclusion criteria, MEDLINE and PubMed were searched for studies investigating the relationship between caesarean section delivery and food allergy. The information on the quality of the studies and results were extracted and analysed systematically. The search identified four relevant studies as per our protocol. Symptomatic food allergy was used as the outcome in two studies and was found to occur more frequently in children born by caesarean section in one study while the second study found no association between food allergy diagnoses and mode of delivery. The other two studies measured levels of food antigen-specific IgE, with both studies showing an increase in sensitization to food allergens among children born by caesarean section. Overall, there is evidence that the risk of developing IgE-mediated sensitization to food allergens is increased among children delivered by caesarean section, however further studies using objectively diagnosed food allergy as the outcome are needed to verify whether this equates to an increase in confirmed food allergy. Future birth cohort studies should control for the effects of mode of delivery when investigating environmental modifiers of food allergy.

Peanut‐specific B and T cell responses are correlated in peanut‐allergic but not in non‐allergic individuals

We aim to find what is the relationship between B cell antibody responses and specific T cell help in the specific cases of allergy and tolerance to peanuts. B cell antibody responses to foreign proteins usually depend upon antigen-specific T cell help. However, specific antibody levels can sometimes be maintained lifelong after infections or vaccination. We measured peanut-specific proliferation and antibody levels in peanut-allergic and non-allergic children using tritiated thymidine incorporation and UniCAP, respectively. We also investigated the corresponding tetanus toxoid specific responses in both groups. We found that tetanus-specific IgG did not correlate with lymphocyte proliferation (Spearman rank correlation coefficient r'=0.08, P=0.74) nor with tetanus-specific cytokine production (IFN-gamma: r'=0.198, P=0.285; TNF-alpha: r'=0.274, P=0.146; IL-4: r'=-0.007, P=0.96; P=0.221; IL-13: r'=0.363, P=0.056). Conversely, in peanut-allergic donors, peanut-specific IgE (average 21 kU/L, median 2.27 kU/L, range 0.34-100 kU/L) but not peanut-specific IgG was positively correlated with proliferation (r'=0.751, P=0.003). In these donors, specific IgE was positively correlated with peanut-specific Th2 cytokines production: r'=0.635, P=0.02 for IL-4 and r'=0.641, P=0.025 for IL-13 and negatively correlated with Th1 cytokines (r'=-0.71, P=0.007 for IFN-gamma and r'=-0.746, P=0.005 for TNF-alpha, respectively). However, peanut-specific IgE was not correlated with T cell proliferation or cytokine production in non-allergic individuals. In conclusion, in allergic individuals, B and T cell responses to peanut antigens are correlated whereas normal immune responses B and T cell responses are uncoupled. Our results support the view that B cell responses to allergens but not those to non-allergenic proteins are correlated with specific T cell responses and therefore specific immunotherapy targeting of such T cells would inhibit allergen-specific B cells.

Children with egg allergy have evidence of reduced neonatal CD4 +CD25 +CD127 lo/− regulatory T cell function

The role of regulatory T (Treg) cells in allergic predisposition is not known. This study compared the frequency and function of cord blood Treg cells from nonallergic children (n = 18) with those from children who have egg allergy (n = 15) in the first year of life. CD4(+) effector T cells and autologous antigen-presenting cells isolated from cord blood mononuclear cells were cocultured with or without CD4(+)CD25(+)CD127(lo/-) Treg cells, and cytokine responses to staphylococcal endotoxin B were assessed after 48 hours. The addition of Treg cell populations to cord blood mononuclear cell cultures resulted in significant reduction in IL-10 (P = .002), IL-13 (P = .012), and IFN-gamma (P < .001) production. Consistent with other reports, effector CD4(+) T-cell responses (IFN-gamma and IL-13) tended to be lower in the allergic group. These neonates showed less significant Treg cell-associated suppression of IFN-gamma (P = .015) compared with that seen in the nonallergic group (P = .001). The allergic group was also less likely (44%) to show Treg cell-associated suppression of IFN-gamma effector responses compared with that seen in the nonallergic group (78%, P = .015). The magnitude of suppression (change in IFN-gamma level when CD4(+)CD25(+)CD127(lo/-) Treg cells were added to responding effector T-cell cultures) was significantly lower in the allergic group (P = .004). There were no between-group differences in the circulating CD4(+)CD25(+)CD127(lo/-) Treg cells (as a percentage of cord blood T cells) or in the FOXP3 expression of these cells. This study confirms the presence and activity of Treg cells in cord blood and provides preliminary evidence of differences in neonates who progress to allergic disease in the first year of life.

Analysis of basophil activation by flow cytometry in pediatric house dust mite allergy

Detection of allergen-induced basophil activation by flow cytometry has been shown to be a useful tool for allergy diagnosis. The aim of this study was to assess the potential of this technique for the diagnosis of pediatric house dust mite allergy. Quantification of total and specific IgE and basophil activation test were performed to evaluate mite allergic (n = 24), atopic (n = 23), and non-allergic children (n = 9). Allergen-induced basophil activation was detected as a CD63-upregulation. Receiver operating characteristics (ROC) curve analysis was performed to calculate the optimal cut-off value of activated basophils discriminating mite allergic and non-allergic children. ROC curve analysis yielded a threshold value of 18% activated basophils when mite-sensitized and atopic children were studied [area under the curve (AUC) = 0.99, 95% confidence interval (CI) = 0.97-1.01, p < 0.001] with a sensitivity and specificity of 96% for 16 microg/ml mite extract. Analysis of the data obtained with 1.6 microg/ml mite extract defined a cut-off value of 8% activated basophils (AUC = 0.96, 95% CI = 0.91-1.01; p < 0.001) with a sensitivity of 82% and specificity of 100%. Comparison between mite allergic and non-allergic children produced a cut-off of 8% activated basophils (AUC = 1.0) with 16 microg/ml allergen extract and a sensitivity and specificity of 100%. The same threshold and specificity values were obtained with 1.6 microg/ml extract (AUC = 97%, 95% CI = 0.92-1.02; p < 0.001) but sensitivity decreased to 83%. Two atopic children showed negative skin prick and basophil activation tests and high specific IgE (>43 kU/l) values for Dermatophagoides pteronyssinus allergen. They also showed positive prick (wheal diameter >1.0 cm) and basophil activation (>87%) tests and high specific IgE (>100 kU/l) with shrimp allergen. Shrimp sensitization was demonstrated by high levels of Pen a 1-specific IgE (>100 kU/l). Cross-reactivity between mite and shrimp was confirmed by fluorescence enzyme immunoassay (FEIA-CAP) inhibition study in these two cases. This study demonstrated that the analysis of allergen-induced CD63 upregulation by flow cytometry is a reliable tool for diagnosis of mite allergy in pediatric patients, with sensitivity similar to routine diagnostic tests and a higher specificity. Furthermore, this method can provide additional information in case of disagreement between in vivo and in vitro test results.

Relevance of examination and treatment of the most common gastrointestinal disorders in children in Lithuania during the last decade

In the last decade, scientific studies in the field of children's gastroenterology performed in Lithuania explored different problems: pathology of Helicobacter pylori infection and food allergy. Our studies revealed that children with atopic dermatitis had gastrointestinal complaints (abdominal pain, diarrhea, distension and unstable stool, which appeared with the exacerbation of skin rash) more often as compared to nonallergic children of the control group. Abdominal pain in children with atopic dermatitis with local rash was more frequent and lasted longer than in control group children, whereas children with extended rash had stools more frequently. Gastrointestinal disorders in children with atopic dermatitis statistically significantly did not depend on the extent of skin rash and severity of atopic dermatitis. In our scientific research on the importance of H. pylori infection on children's gastrointestinal system, children with chronic dyspepsia were examined. Endoscopy, rapid urease test, biopsies from antrum and corpus of stomach and their histological examination as well as serologic tests were done. According to the results obtained, we recommend to examine children with chronic dyspepsia in a complex way: not only endoscopic examination, but H. pylori diagnostic tests should be performed as well. Serologic test is not suitable for screening H. pylori infection in children. Considering this, we recommend to use no fewer than two different methods to diagnose this infection. The highest frequency of H. pylori infection was found in children with duodenal ulcer; histological changes in their gastric pylorus and corpus mucosa were greatest. More than half of children with nonulcer dyspepsia were infected with H. pylori. After eradication of H. pylori infection, the prevalence of dyspepsia in children with duodenal ulcer decreased.

Mixed-up Nuts: Identification of Peanuts and Tree Nuts by Children

Ferdman RM, Church JA. Ann Allergy Asthma Immunol. 2006;97:73–77 PURPOSE OF THE STUDY. To determine the age at which nut-allergic and nonallergic children can accurately identify various nuts. STUDY POPULATION. Thirty-seven children who were allergic to peanut or tree nuts (TNs) and 63 nonallergic children. METHODS. A “nut box” was constructed with peanuts (shelled and unshelled) and 9 different TNs fastened to its base in separate compartments. The box was covered with a clear top for easy viewing and to prevent accidental exposure. Children were asked to identify any peanuts they saw in the box. They then were asked to identify each TN in the box. Children were asked to identify which nuts they could not eat. RESULTS. Twenty-three children were allergic only to peanut, 5 were allergic to peanut and at least 1 TN, 5 were allergic to all TNs and peanut, 3 were allergic to ≤2 TNs, and 1 was allergic to ≥3 TNs. On average, children identified 2.7 nuts, with no difference between allergic and nonallergic children. Among allergic and nonallergic children, older children identified more nuts correctly. There was a better correlation of age with number of nuts identified correctly in the allergic (r = 0.82) than in the nonallergic (r = 0.52) group (P &amp;lt; .001 for each group). Ten children (9 &amp;lt;5 years old) did not identify any nuts correctly. Twenty-eight children identified only peanut in the shell. An additional 21 children identified only 2 nuts correctly, 13 of whom only identified shelled and unshelled peanut. Eighty-nine percent of those who correctly identified a nut recognized peanut in the shell, and 52% recognized shelled peanut. Although there were few differences between allergic and nonallergic children, the allergic children were less likely to recognize peanut either in the shell (81.1% vs 93.7%; P = .052) or shelled (29.7% vs 65.1%; P &amp;lt; .001). Of the 37 allergic children, 12 (32%) correctly identified the nut(s) to which they were allergic. Another 15 children (41%) said they would eat none of the nuts, and 10 (27%) indicated that they would eat ≥1 nut to which they were allergic. CONCLUSIONS. Peanut- and TN-allergic children can identify few nuts, which places them at increased risk of accidental ingestion of a food to which they are allergic. Avoidance and correct identification of the nuts to which a child is allergic should be part of an overall educational plan. REVIEWER COMMENTS. Most allergists instruct strict avoidance of all TNs to their sensitive patients to decrease the risk of accidental ingestion of the offending nuts(s). Because of the high rate of TN sensitization in peanut-allergic patients and vice versa, many also recommend avoidance of TNs and peanut in both groups. Considering the high rate of misidentification of peanut and TNs in this study, that advice seems prudent. Furthermore, nuts are frequently present in small pieces in baked products, etc, and cannot easily be identified. Most patients are satisfied with the safety of complete avoidance. If a patient is intent on eating TNs to which he or she is not known to be sensitive, I recommend waiting until he or she is mature enough to correctly identify TNs proven to be safe by a thorough allergy evaluation. Even then, I recommend eating the “safe” TN from the shell.

Outcome of Endoscopic Sinus Surgery in Children With Allergic Rhinitis

Ramadan HH, Hinerman RA. Am J Rhinol. 2006;20:438–440 PURPOSE OF THE STUDY. To compare results of endoscopic sinus surgery for treatment of chronic rhinosinusitis in children with and without documented allergy. STUDY POPULATION. One hundred forty-one children (aged 3–13 years) with chronic rhinosinusitis who were followed for at least 12 months after endoscopic sinus surgery and had symptoms assessed by caregiver questionnaire were included in this study. All children were evaluated for allergy, immunoglobulin deficiency, and cystic fibrosis before surgery. A total of 77 children had documented allergy, and 64 had negative allergy evaluations. The allergic and nonallergic children were similar with regard to gender distribution, tobacco exposure, and disease severity, but asthma was more than twice as prevalent in the allergic group (56% vs 23%). Children with cystic fibrosis, immunodeficiency, fungal infection, or previous sinus surgery were excluded from the study. Surgery usually consisted of middle meatal antrostomy and anterior ethmoidectomy. METHODS. Symptoms were evaluated by the caregiver using a nonvalidated questionnaire before surgery and every 3 months for at least 12 months after surgery. The results of the questionnaire 12 months after surgery were used to create 2 groups: (1) cured or improved subjects were categorized as successful, and (2) subjects with unchanged or worsened symptoms and those who required additional surgery were categorized as treatment failures. Medical treatment for sinusitis included long-term antibiotics, intranasal steroids, decongestants, antireflux treatment, systemic steroids, and allergy management. Allergy management consisted of antihistamines and intranasal steroids in all allergic children and immunotherapy in 25%. One third of allergic patients underwent endoscopic sinus surgery before initiation of allergy treatment. RESULTS. The overall success rate for endoscopic sinus surgery was 80%. The allergic group had a 77% success rate after sinus surgery, whereas the nonallergic group had an 84% success rate, a difference that was not statistically significant. Multivariate analysis was performed, and the presence of allergy did not predict a poorer outcome. Allergic children who underwent sinus surgery without preoperative allergy treatment had a 62% success rate, compared with a success rate of 84% for children who were treated for allergy before surgery. CONCLUSIONS. The presence of allergy does not predict poorer outcomes after sinus surgery in children. Preoperative treatment of such allergy improves surgical results. REVIEWER COMMENTS. This article demonstrated that endoscopic sinus surgery can effectively treat refractory sinusitis in children even when allergy is documented. The standard practice of allergy evaluation and treatment before sinus surgery in children was also supported, although the details of such evaluation were not addressed in this article. Because this was a cohort study, not a randomized, controlled trial, we cannot assess the effects of allergy management alone on children with chronic sinusitis. It is curious that the group of children who had allergy treatment before surgery had better surgical results at a 12-month follow-up than the others with allergy, because we would suspect that all children diagnosed with allergy would be treated for allergy at some point before or after surgery. The indications for endoscopic sinus surgery in children, and the extent of such surgery, remain debated. This article adds to evidence that such surgery is effective for refractory sinusitis, even in allergic children.