Additive effect of eosinophilia and atopy on exhaled nitric oxide levels in children with or without a history of respiratory symptoms

Although atopy and blood eosinophilia both influence exhaled nitric oxide (eNO) measurements, no study has quantified their single or combined effect. We assessed the combined effect of atopy and blood eosinophilia on eNO in unselected schoolchildren. In 356 schoolchildren (boys/girls: 168/188) aged 9.0-11.5 yr, we determined eNO, total serum IgE, blood eosinophil counts and did skin prick tests (SPT) and spirometry. Parents completed a questionnaire on their children's current or past respiratory symptoms. Atopy was defined by a SPT >3 mm and eosinophilia by a blood cell count above the 80th percentile (>310 cells/ml). eNO levels were about twofold higher in atopic-eosinophilic subjects than in atopic subjects with low blood eosinophils [24.3 p.p.b. (parts per billion) vs. 14.1 p.p.b.] and than non-atopic subjects with high or low blood eosinophils (24.3 p.p.b. vs. 12.2 p.p.b. and 10.9 p.p.b.) (p <0.001 for both comparisons). The additive effect of atopy and high eosinophil count on eNO levels remained unchanged when subjects were analyzed separately by sex or by a positive history of wheeze (n=60), respiratory symptoms other than wheeze (n=107) or without respiratory symptoms (n=189). The frequency of sensitization to Dermatophagoides (Dpt or Dpf) was similar in atopic children with and without eosinophilia (66.2% and 67.4%, respectively); eosinophilia significantly increased eNO levels in Dp-sensitized children as well in children sensitized to other allergens. In a multiple linear regression analysis, eNO levels were mainly explained by the sum of positive SPT wheals and a high blood eosinophil count (t=4.8 and 4.3, p=0.000), but also by the presence of respiratory symptoms (especially wheeze) and male sex (t=2.6 and 2.0, p=0.009 and 0.045, respectively). Measuring eNO could be a simple, non-invasive method for identifying subjects at risk of asthma in unselected school populations.     

Local production of total IgE and specific antibodies to the house dust mite in adenoid tissue

Adenoids are known as immunosecretory organs and those in atopic children present cellular and cytokine profiles different from those of non‐atopic children. We hypothesized that locally produced total IgE and allergen‐specific antibodies could be involved in the inflammatory responses in adenoid tissue. Local productions of total IgE and Dermatophagoides pteronyssinus (DP)‐specific IgE, IgA, IgG1, and IgG4 antibodies were evaluated, as well as their relationships with the markers of allergic inflammation within adenoid tissue. Eighteen atopic subjects, who were sensitized to more than one common aeroallergen, and 22 non‐atopic subjects undergoing adenotonsillectomy, were recruited. Immunoassays using adenoid tissue homogenate were performed to quantify the levels of total IgE, eosinophil cationic protein (ECP), and mast cell tryptase. DP‐specific IgE, IgA, IgG1, and IgG4 antibodies, soluble IL‐2 receptors (sIL‐2R), soluble CD23 (sCD23), and IL‐6 were measured by ELISA. All parameters measured in adenoid tissue homogenate were presented as a ratio to the albumin level found in the adenoid. Median level of total IgE in adenoid tissue homogenate was significantly higher in atopic individuals than in non‐atopic individuals. Median values of DP‐specific IgE and IgA antibodies were significantly higher in atopics than in non‐atopics (p = 0.001, p = 0.006, respectively), while no differences were seen in DP‐specific IgG1 and IgG4 antibodies. ECP and sCD23 levels in adenoid homogenate were significantly higher in atopics than in non‐atopics (p = 0.026, p = 0.048, respectively), while no significant differences were noted in tryptase, sIL‐2R, and IL‐6 levels. The levels of DP‐specific IgE, IgA, IgG1, and IgG4 antibodies in adenoid homogenate correlated significantly with ECP levels, but not with those of sIL‐2R, sCD23, and IL‐6. The presence of total IgE and DP‐specific antibodies in adenoid tissue was confirmed to be more prominent in atopics. In conclusion, locally‐produced total IgE and DP‐specific antibodies may contribute to eosinophilic inflammation in adenoid tissue in atopic children.     

Clostridium difficile,atopy and wheeze during the first year of life

Differences have been suggested to occur in the composition of intestinal microflora from allergic and non‐allergic children. In this study we used a semi‐quantitative enzyme‐linked immunosorbent assay (ELISA) for the measurement of Clostridium difficile‐specific immunoglobulin G (IgG) (CDIgG). CDIgG was excellent in differentiating between adults with or without Cl. difficile colitis (absorbance levels, positive vs. negative controls: geometric mean (GM) 0.301, 95% CI: 0.289–0.314 vs. GM 0.167, 95% CI: 0.155–0.181; mean difference 1.8‐fold, 95% CI: 1.65–1.95; p < 0.0001). We used this technique to investigate whether there are any differences between atopic wheezy infants and non‐atopic non‐wheezy controls. In a prospective cohort study (n = 390) 10 patients were identified at 1 year of age (atopic, history of recurrent wheeze) and matched (gender, month of birth, exposure to Der p 1, Fel d 1 and Can f 1) with a control group of infants (non‐atopic, no history of wheeze). The patients had significantly higher Cl. difficile‐specific IgG absorbance levels (GM 0.298, 95% CI: 0.249–0.358) compared with controls (GM 0.235, 95% CI: 0.201–0.274; mean difference 1.27‐fold, 95% CI: 1.07–1.50; p = 0.01). These results suggest that there may be differences in the composition of intestinal microflora between allergic and non‐allergic infants at 1 year of age, with allergic children having higher Cl. difficile IgG antibody levels.     

Wheeze in children: the impact of parental education on atopic and non‐atopic symptoms

de Meer G, Reijneveld SA, Brunekreef B. Wheeze in children: the impact of parental education on atopic and non‐atopic symptoms.
Pediatr Allergy Immunol 2010: 21: 823–830.
© 2009 John Wiley & Sons A/S There is conflicting evidence for the relationship between parental socioeconomic position and their children’s asthma. The aim of this study was to investigate relationships between parental education and respiratory symptoms in their children, distinguishing atopic and non‐atopic symptoms. A cross‐sectional survey among 3262 elementary school children (age 8–13) was performed; data on parental education were obtained for 3213 children. Parents completed a questionnaire on their child’s allergic and respiratory symptoms, and potential explanatory variables including family history, indoor environment, and the child’s medical history. Subsets of children were tested for atopy (n = 1983), lung function (n = 2325), and airway hyperresponsiveness (AHR) (n = 880). Logistic regression was used to assess relationships of health outcomes with parental education. A high parental education was associated with an increased risk of atopic sensitization to indoor allergens (OR 1.31, 95% CI 1.02; 1.69). Studied explanatory variables did not influence the relationship. In contrast, a high parental education protected children from wheeze (OR 0.77, 95% CI 0.61; 0.97). This only applied to non‐atopic wheeze (OR 0.65, 95% CI 0.43; 0.99) and not to atopic wheeze (OR 0.89, 95% CI 0.60; 1.31). The protection from non‐atopic wheeze in children of highly educated parents declined after adjustment for household smoking and breastfeeding (OR 0.96, 95% CI 0.58; 1.57). Similar results were observed for non‐atopic and atopic rhinitis. We conclude that children from highly educated parents are protected from non‐atopic respiratory symptoms, which is largely explained by a lower rate of household smoking and a higher rate of breastfeeding.     

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 μg/ml mite extract. Analysis of the data obtained with 1.6 μg/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 μg/ml allergen extract and a sensitivity and specificity of 100%. The same threshold and specificity values were obtained with 1.6 μg/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.     

Aeroallergen sensitization in childhood asthmatics in Northern India

Abstract

To determine the prevalence of sensitization to common aeroallergens in asthmatic children and study the differences in characteristics of atopics and non atopics.

Design

Analysis of data from a prospective cohort study.

Setting

Pediatric Chest Clinic of tertiary care center in Northern India

Patients

Asthmatic children from 5–18 year of age.

Main outcome measures

Prevalence of sensitization to common aeroallergens.

Results

Skin prick testing (SPT) was performed on 180 children above 5 years of age, with a mean (SD) age of 111.4 (34.2) months. 100 children (55.6%) were sensitized to at least one aeroallergen, suggesting atopy; 68 (37.8%) were sensitized to more than one allergen. 36.7% children were sensitized to housefly antigen; 31.1% to rice grain dust, 18.3% to cockroach, and 7.8% to house dust mite antigens. Atopic children had significantly higher median FENO during follow up than nonatopic children (17.5 ppb vs 13 ppb, P=0.002). There was a positive correlation between age and the number of allergens that an individual was sensitized to (r= 0.21; P=0.0049).

Conclusions

More than half of asthmatic children in our cohort had sensitization to one or more aeroallergens suggesting atopy; sensitization was most commonly seen to housefly antigen and rice grain dust. Atopic children had significantly higher FENO measurements during follow up as compared to non-atopic children.     

Urinary eosinophil protein X in children with asthma: Influence of atopy and airway infections

It has been suggested that urinary eosinophil protein X (U‐EPX) can be used to monitor bronchial inflammation in childhood asthma. However, the influence of atopy and airway infections is not well elucidated. To determine the clinical value of measuring U‐EPX in children with asthma and to evaluate the influence of atopy and airway infections, U‐EPX was measured in 170 children with asthma (mean age 69 months, range 12–179 months), in 79 children with lower or upper respiratory tract infections (mean age 41 months, range 1–165 months), and in 64 controls. U‐EPX was elevated in children with acute asthma (median 132 µg/mmol of creatinine, quartiles 77–195 µg/mmol of creatinine, n = 51, p < 0.001) and chronic asthma (median 93 µg/mmol of creatinine; quartiles 46–149 µg/mmol of creatinine, n = 119, p < 0.01) compared with controls (median 54 µg/mmol of creatinine; quartiles 40–89 µg/mmol of creatinine, n = 39). Atopic children had higher levels of U‐EPX than non‐atopics with acute asthma (median 155 µg/mmol of creatinine, quartiles 113–253 µg/mmol of creatinine, n = 27, vs. median 102 µg/mmol of creatinine, quartiles 56–168 µg/mmol of creatinine, n = 24, p < 0.05), as well as with chronic asthma (median 110 µg/mmol of creatinine, quartiles 65–162 µg/mmol of creatinine, n = 63, vs. median 60 µg/mmol of creatinine, quartiles 39–123 µg/mmol of creatinine, n = 56, p < 0.01). In chronic asthma, children without atopy had levels of U‐EPX similar to values of controls; levels were similar in symptomatic and asymptomatic patients, and not influenced by treatment with inhaled corticosteroids. Moreover, U‐EPX levels were higher in children with pneumonia (median 207 µg/mmol of creatinine, quartiles 111–280 µg/mmol of creatinine, n = 35, p < 0.001), laryngitis (median 109 µg/mmol of creatinine, quartiles 65–161 µg/mmol of creatinine, n = 24, p < 0.01), and rhinitis (median 172 µg/mmol of creatinine, quartiles 123–254 µg/mmol of creatinine, n = 19, p < 0.001) than in controls (median 62 µg/mmol of creatinine, quartiles 41–93 µg/mmol of creatinine, n = 64). There was significant overlap among all groups of children with disease, as well as between children with disease and controls. Hence, U‐EPX may reflect differences in eosinophil involvement and activation between children with atopic and non‐atopic asthma, but the individual spread within groups and the influence of airway infections limits the clinical value of U‐EPX in childhood asthma.     

Skin‐prick test findings in atopic asthmatic children: A follow‐up study from childhood to puberty

In a prospective cohort study we investigated the course of allergic sensitization from childhood to puberty in a group of children with atopic asthma. An attempt was made to correlate the findings with the persistence of asthma. A total of 150 children with atopic asthma established at 7 years of age were evaluated when 8–10 years of age. A battery of skin‐prick tests (SPTs) to common environmental allergens, a detailed clinical history for asthma severity classification, and spirometric analyses, were performed. In 127 of these children a re‐evaluation was performed at puberty. A variety of statistical methods were used to analyze the results regarding changes in skin test reactivity to individual aeroallergens and atopic index (degree of atopy), as well as to determine any correlation between these changes and the persistence of asthma in puberty. A wide spectrum of modification in skin reactivity to common environmental allergens was observed, including the complete loss of sensitization to some allergens or the development of a new one to others. Specifically, 34% of asthmatic children sensitive to Dermatophagoides pteronyssinus and 52.7% sensitive to cat lost their sensitivity in puberty, while only 7.5% and 11.1%, respectively, became sensitized (p = 0.03 and p = 0.001, respectively). In contrast, regarding pollen sensitivity, 30.2% and 24% of asthmatic children became sensitive in puberty to olive pollen and grasses mix, respectively, and only 11.7% and 12.5%, respectively, lost their sensitivity to these allergens (p = 0.04). No correlation was shown between the skin test reactivity changes to individual allergens and the persistence of asthma, but a significant correlation was found between atopic index to indoor allergens in childhood and the persistence of asthma at puberty (p = 0.04). Interestingly, multi‐sensitivity to allergens (≥ 4 allergens) in childhood was also found to correlate with the persistence of asthma at puberty [p = 0.05, odds ratio (OR) = 2.65, 95% confidence interval (CI) 1.2–7.2]. Our findings indicate that significant modification of skin reactivity to common environmental allergens in atopic children with asthma in puberty can occur. However, no association between these changes and the persistence of asthma could be demonstrated, although children with indoor allergic sensitization and multi‐reactivity were found to have a higher probability of maintaining their asthma in puberty.     

Increased serum‐soluble interleukin‐5 receptor alpha level precedes the development of eczema in children

Semic‐Jusufagic A, Gevaert P, Bachert C, Murray C, Simpson A, Custovic A. Increased serum‐soluble interleukin‐5 receptor alpha level precedes the development of eczema in children.
Pediatr Allergy Immunol 2010: 21: 1052–1058.
© 2010 John Wiley & Sons A/S Interleukin‐5 receptor α‐subunit expression may be implicated in the development of allergic diseases. In a population‐based birth cohort, we investigated the relationship between IL‐5Rα and the development of allergic phenotypes in childhood, using soluble IL‐5Rα (s‐IL‐5Rα) as a marker. Children (n = 510) were followed from birth and assessed at age 3, 5 and 8. Based on the onset and resolution of symptoms, we assigned children into the following wheeze and eczema phenotypes: never, transient, persistent, intermittent and late‐onset. Specific IgE to common allergens, s‐IL‐5Rα (ELISA) and urinary eosinophilic protein X (U‐EPX) levels was measured at age 5. s‐IL‐5Rα was significantly higher among atopic compared to non‐atopic children (pg/ml, geometric means [95% CI], 152.4 [126.0–184.5] vs. 103.4 [94.0–113.9], p < 0.0001). While we found no association between s‐IL‐5Rα and current eczema at age 5, there was a significant association between eczema phenotypes and s‐IL‐5Rα (multiple anova model adjusted for gender and atopy, F = 2.56, p = 0.04). After adjustment for multiple comparisons, we found that children with late‐onset eczema had significantly higher s‐IL‐5Rα compared to those who have never had eczema (mean difference [95% CI], 2.41 [1.03–5.62], p = 0.04) and those with intermittent eczema (2.63 [1.08–6.41], p = 0.02), with no difference between children who have never had eczema and other eczema phenotypes. We found no such association for wheeze phenotypes. There was a weak correlation between s‐IL‐5Rα and U‐EPX (r = 0.16, p < 0.0001). Increased serum s‐IL‐5Rα level at age 5 was associated with contemporaneous atopic sensitization and with subsequent development of eczema by age 8.     

Comparison between serial skin-prick tests and specific serum immunoglobulin E to mite allergens

Sensitization to dust mite allergens can be determined by means of a skin-prick test (SPT) or by measurement of specific IgE antibodies in serum (sIgE). In our study, concordance of the results of both methods was analyzed on the basis of reproducible SPT results. Three consecutive SPTs were performed on 138 school children (age 6–8 years) at one-year intervals. SIgE was determined at the end of a two-year observation period. Seven common inhalant allergens (Dpt, Df, birch pollens, hazel pollens, grass pollens and cat and dog dander) were analyzed. The majority of subjects with positive SPT reactions to the respective allergen also showed sIgE (Dpt: 82/86; Df: 53/53; cat dander: 31/32; dog dander: 6/9; birch pollens: 29/31; hazel pollens: 22/22; grass pollens: 37/37). A significant correlation between the SPT [weal diameter (P₁) or allergen/histamine ratio (P₂)] and sIgE was found for Dpt (P₁ = 0.004/P₂ = 0.016), birch pollens (P₁ = 0.002/P₂ = 0.0001) and grass pollens (P₁ = 0.0005/P₂ = 0.0001). There was also a significant correlation between sIgE to Dpt and to either Der p 1 (p = 0.0001) or Der p 2 (p = 0.0001), as well as between sIgE of both major allergens (p = 0.0001). In the analysis of co-sensitization of Dpt and Df, most subjects sensitized to Dpt were also sensitized to Df (57/91). Children with sIgE to Dpt (n = 87) usually showed sIgE to Df (n = 83). In this study, SPT and sIgE results are concordant and appear equivalent when using reproducible SPTs. Therefore, in the case of a positive Dpt result, additional testing for sensitization to Df can be regarded as redundant when Dpt and Df are the major contributors to the allergen content of house dust.     

Serum carotenoids and atopy among children of different ethnic origin living in Germany

Rühl R, Taner C, Schweigert FJ, Wahn U, Grüber C. Serum carotenoids and atopy among children of different ethnic origin living in Germany.
Pediatr Allergy Immunol 2010: 21: 1072–1075.
© 2010 John Wiley & Sons A/S
Journal compilation © 2010 Blackwell Munksgaard The manifestation of atopy in early life is thought to be influenced by the diet. We hypothesized that the previously reported lower prevalence of atopy among Turkish immigrant children in Germany might be related to a different pattern of serum carotenoids. Serum carotenoid concentrations were measured in pre‐school children of different ethnic origin from Berlin, D. German children (D, N = 49) were compared to Turkish children with well (TR‐D, N = 32) or weak cultural adaptation (TR‐TR, N = 41). Serum levels of pro‐vitamin A carotenoids (α‐ and β‐carotene, β‐cryptoxanthin) and non‐pro‐vitamin A carotenoids (lutein, zeaxanthin, lycopene) were measured by high performance liquid chromatography. Serum IgE to common inhalant allergens was measured by immunoassay. Median levels of pro‐vitamin A carotenoids were lower in Turkish children if compared to German children: D 135μg/L, TR‐D 100μg/L (p = 0.025), TR‐TR 82μg/L (p = 0.001). By contrast, median levels of non‐pro‐vitamin A carotenoids were not higher in German children. The ratio of pro‐vitamin A to non‐pro‐vitamin A carotenoid median levels was highest among D (2.05), lower among TR‐D (1.32; p = 0.001) and lowest among TR‐TR (1.26; p < 0.001)). A higher ratio was not significantly associated with atopy (atopic 1.79, non‐atopic 1.36; p = 0.067). Pro‐vitamin A carotenoids are higher in children originating from a cultural population with a higher prevalence of atopy, but atopy seems not to be directly related to the current carotenoid serum levels in children at school age. The distinct pattern of carotenoid levels among Turkish migrant and German children indicates changed nutrition patterns with acculturation.     

Discrepancy between sensitization to inhaled allergens and respiratory symptoms in pediatric patients with type 1 diabetes mellitus

According to the ‘Th₁/Th₂ paradigm’, children with type 1 diabetes mellitus (T1DM) should have a lower risk of developing allergic sensitization and, because of the involvement of insulin in modulating airway inflammation, different frequency or severity in allergy‐related respiratory manifestations. This article aims at evaluating the frequency and type of allergic sensitization and its respiratory manifestation, asthma and/or rhinitis, in a group of pediatric patients with T1DM. Patients (112) with T1DM, 7.8–16.9 yr of age (63 males and 49 females) were evaluated. Skin prick test (SPT) reactivity to the most common classes of aeroallergens were performed and compared with data obtained in 709 school‐aged children. The frequency of sensitization was not different in the T1DM and in the control subjects (43.7% and 40.8%, respectively; p = 0.55), with similar proportions of individuals sensitized to one allergen (32.7% and 38.1%, respectively; p = 0.47). In both groups, sensitization to house dust mite allergens was the most frequently detected (69.4% and 65.4%, respectively; p = 0.59), with a higher proportions of individuals sensitized to Graminae (+Cynodon dactylon; p < 0.0001) and a lower, but weakly significant, proportion sensitized to Parietaria (p = 0.03) in the T1DM group, as compared with controls. No differences were found between T1DM and control groups in the proportion of individuals reporting rhinitis (26.8% and 29.2%; p = 0.60). However, comparing separately sensitized and non‐sensitized subjects, a lower proportion of rhinitis subjects was detected in the non‐sensitized T1DM patients, when compared with the non‐sensitized control subjects (p = 0.01). In addition, no differences were detected between T1DM and control groups in frequency of symptoms related to ‘lifetime asthma’, i.e., asthma episodes during life (14.3% and 16.5%, respectively: p = 0.55), also when sensitized and non‐sensitized subjects were evaluated separately (p = 0.12 and p = 1.00, respectively). However, no T1DM patient had ‘actual asthma’, i.e., asthma episodes in the last year, vs. 5.8% of the individuals in the control group (p = 0.009), the difference being mostly ascribed to sensitized subjects (p = 0.012). Finally, out of the 16 T1DM patients with ‘lifetime asthma’, 15 had mild intermittent disease and only one mild persistent disease. T1DM does not seem to play a downregulating role on the development of allergic sensitization to aeroallergens, but may lower the frequency or the severity of its clinical manifestations at respiratory level.     

IL13 variants are associated with total serum IgE and early sensitization to food allergens in children with atopic dermatitis

Increased total and specific serum immunoglobulin E (IgE) levels are common characteristics of atopic diseases and their basal production is proposed to be under strong genetic control. Interleukin 13 (IL13) variants have been consistently associated with total serum IgE levels in white populations with a strongest association in non‐atopics. The aim of this study was to test the IL13 p.R130Q and c.1‐1111C>T variants in children with atopic dermatitis (AD) for associations with total serum IgE and early sensitization to common food and inhalant allergens and with asthma. We included 453 children with AD [participants of the Early Treatment of the Atopic Child (ETAC) study] that were followed from the age of 12–24 months for 3 yr. Total and specific IgE were determined at four time points. We genotyped the IL13 p.R130Q and c.1‐1111C>T variants by melting curve analysis. In children up to 4 yr of age, the 130Q allele was related to slightly higher total IgE levels compared to heterozygotes and 130R homozygotes. More importantly, both IL13 variants were significantly associated with sensitization to food allergens, with most significant results for sensitization to egg (p = 0.0001). Although early sensitization to hen’s egg represents a strong risk factor for subsequent sensitization to inhalant allergens and asthma, the investigated IL13 variants were not associated with these phenotypes at the age of 48–60 months. In summary IL13 variants contribute to elevated levels of total serum IgE in young atopic children and are strongly associated with sensitization to food allergens, particularly to hen’s egg. These findings suggest that IL13 variants play a major role not only in non‐cognate but also in allergen specific IgE synthesis.     

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??Objective To explore the change of exhaled nitric oxide ??eNO?? in children from community and its importance in asthma management. Methods The study was conducted from October 2011 to December 2011. Totally 133 non-asthmatic children and 94 asthmatic children aged 7~12 years old from elementary schools in Beijing Xicheng District were included in the study. The eNO?? skin prick test ??SPT???? lung function and physical examination were carried out and information of medical history was collected in all children. The eNO level between non-asthmatic children and asthmatic children?? and its association with atopy?? rhinitis?? lung function and asthma control were analyzed. Results eNO levels of non-asthmatic children and asthmatic children were 11.63±1.88 ppb?? and 19.68±2.31 ppb respectively and the difference between them was statistically significant ??P<0.01??. In non-asthmatic children?? the level of eNO in children with rhinitis was significantly higher than in children without rhinitis ???17.49±2.02??×10-9 vs. ??10.42±1.76??×10-9?? P<0.01?? and eNO level in atopic children was higher than non-atopic children ???23.06±2.18??×10-9 vs. ??9.60±1.66??×10-9?? P<0.01??. In asthmatic children?? the difference in eNO level was not significant in children with rhinitis and without rhinitis ???19.58±2.34??×10-9 vs. ??20.09±2.25??×10-9??? but the eNO levels in atopic children ??23.06±2.18??×10-9 was significantly higher than non-atopic children ???8.75±1.86??×10-9?? P<0.01??. The level of eNO of uncontrolled asthmatic children was significantly higher than controlled asthmatic children ???25.09±2.31??×10-9 vs. ??17.21±2.22??×10-9?? P<0.05??. There was no significant difference in eNO level between children who used and those who did not use inhaled corticosteroid. The eNO level was not related to lung function parameters either in non-asthmatic or in asthmatic children. Conclusion The eNO level increases significantly in children with asthma or rhinitis and is associated with asthma control status. Atopy is an important factor on eNO level as well. Measuring eNO level would help improve the diagnosis of asthma and atopy and management of asthma and rhinitis in children from community.     

Accuracy of ImmunoCAP® Rapid in the diagnosis of allergic sensitization in children between 1 and 14 years with recurrent wheezing: The IReNE study

It is estimated that at least one out of three children with recurrent wheezing is atopic. Reliable diagnostic tools are needed in primary care that allow for adequate identification of these children. The purpose of this study was to assess the value of ImmunoCAP^® Rapid (ICR) Wheeze‐Rhinitis Child in the identification of atopy with the use of 10 selected allergens in children with recurrent episodes of wheezing. A multicenter population study is based on primary care. It included children managed consecutively at the health center, who had three or more episodes of wheezing, at least one of them in the last 12 months. Each child completed a physical examination, an epidemiological survey, one capillary blood sampling (110 μl) for ICR, and one venous blood sampling for determination of Phadiatop Infant, total IgE and 10 specific IgE measurements. The children were identified as atopic, based on their clinical signs and symptoms and at least one positive specific IgE (0.35 kU_A/l or higher), before knowing the results of ICR, Phadiatop Infant and total IgE. ICR was read by two independent observers. Six classes were evaluated, negative without any color and five positive degrees of pink‐red color. Two hundred and fifteen children aged between 1 and 14 years were studied (138 boys); 50.7% were identified as atopic, 39.1% were sensitized only to inhalant allergens, 6.5% to food allergens and 5.1% to both. The predominant allergen was the dust mite (39.3%). For ICR, there were 2134 valid double observations. The Kappa index, comparing the negative results vs. any positive result, was 0.91 (95% CI: 0.88–0.94). The intraclass correlation coefficient was 0.98 (95% CI: 0.98–0.99). In the identification of a child as atopic, the positive post‐test probability of ICR depended on the color degrees considered: 88.4% for any positive and 97.6% for the most intense tones. The positive post‐test probability of Phadiatop Infant and total IgE was 95.6% and 68.2% respectively. ICR showed good reliability for the most prevalent allergen, the dust mite, with a sensitivity of 90.5% (95% CI: 82.1–95.8) and specificity of 88.5% (95% CI: 81.7–93.4). The analysis of the other allergens was limited by the small number of sensitized children. The analysis of receiver operating characteristic curves revealed an area under the curve of 0.84 (95% CI 0.80–0.88) for the cut‐off point of specific IgE of 0.35 kU_A/l and of 0.94(CI 0.91–0.97) for 2 kU_A/l. A greater intensity of color of the lines of ICR was related to higher levels of specific IgE in blood. ICR is a reliable test for the identification of atopy in children, which identifies most children as atopic, and shows a good correlation in allergen‐by‐allergen identification. This suggests that it should be regarded as a first‐rate tool, in the primary care clinic, for the evaluation of children with recurrent wheezing.     

在社区儿童哮喘诊断与管理中呼出气一氧化氮测定应用研究

目的 探讨呼出气一氧化氮（exhaled nitric oxide, eNO）体积分数在社区儿童的改变及对哮喘诊断与管理的价值。方法 2011年10月至2011年12月对来自北京西城区小学的7~12岁132例非哮喘儿童和93例哮喘儿童进行eNO测定、肺功能检测、过敏原皮肤点刺检查（skin prick test, SPT）以及病史询问和常规体检,观察eNO在社区非哮喘儿童和哮喘儿童的改变、影响因素及与临床情况的相关性。结果 非哮喘儿童与哮喘儿童eNO体积分数分别为（11.63±1.88）×10-9和（19.68±2.31）×10-9,其差异有统计学意义（P < 0.01）。在非哮喘儿童中,有鼻炎儿童的eNO为（17.49±2.02）×10-9,显著高于无鼻炎儿童（10.42±1.76）×10-9;特应性儿童的eNO为（16.12±1.98）×10-9,显著高于非特应性儿童（9.60±1.66）×10-9,差异均有统计学意义（P均 < 0.01）。在哮喘儿童中,伴有鼻炎与不伴有鼻炎儿童,其eNO水平分别为（19.54±2.31）×10-9、（20.09±2.25）×10-9,差异无统计学意义;但特应性儿童eNO水平显著高于非特应性儿童［分别为（23.06±2.18）×10-9、（8.75±1.86）×10-9,P < 0.01］;哮喘未控制儿童eNO为（25.09±2.31）×10-9,显著高于哮喘控制儿童［（17.21±2.22）×10-9,P < 0.05］;曾使用吸入激素与未曾使用吸入激素儿童,其eNO水平差异无统计学意义。无论是非哮喘儿童,还是哮喘儿童,其eNO水平与肺功能各参数间均无相关性。结论 eNO在社区特应性哮喘儿童中显著升高,并与哮喘控制与否有关。特应性是影响eNO水平的突出因素。在社区儿童中测定eNO有利于对儿童哮喘的进行早期诊断和分型,全面了解其过敏情况,从而改善哮喘的管理。     

Thromboxane A2 receptor gene polymorphism is associated with the serum concentration of cat-specific immunoglobulin E as well as the development and severity of asthma in Chinese children

Thromboxane A2 and its receptor (TBXA2R) are involved in the constriction of vascular and respiratory smooth muscles. The T924C polymorphism in the TBXA2R gene was recently found to be associated with asthma in Japanese adults but not in children. Its relationship with atopy or asthma severity in children has not been defined. To investigate this further, we first assessed the severity of asthma in Chinese children using a standardized questionnaire modified from the Disease Severity Score and spirometric evaluation. Then, peripheral blood was analyzed for serum total and aeroallergen‐specific immunoglobulin E (IgE) levels, and TBXA2R T924C genotypes were determined by restriction fragment length polymorphism (RFLP) analysis. One‐hundred and fifty three asthmatic patients and 57 control children were recruited, of respective mean ages 9.9 and 11.0 years (p = 0.07). The mean logarithmic serum total IgE concentration was 2.57 and 2.09, respectively, for the asthmatic group and control group (p < 0.0001). Atopy was detected in 132 (86%) asthmatics and 33 (58%) controls. A significant association was observed between T924C and the diagnosis of atopic asthma (p = 0.044; odds ratio: 1.84). In addition, those asthmatics homozygous for the mutant allele in T924C had a lower forced expiratory volume in 1 s (FEV₁) and forced vital capacity (FVC) (p = 0.032 and 0.002, respectively). Among our asthmatic patients, the TBXA2R T924C polymorphism correlated with the concentration of cat‐specific IgE in serum (p = 0.046). Nonetheless, this gene marker did not show an association with the serum total IgE concentration or any clinical indicator of asthma severity. In conclusion, our results suggest that the T924C marker in the TBXA2R gene is associated, in Chinese children, with an increased susceptibility of developing atopic asthma. This marker is also associated with the extent of allergic sensitization to cat, as well as with reduced FEV₁ and FVC values.     

Effects of montelukast on symptoms and eNO in children with mild to moderate asthma

BACKGROUND: Asthma is a chronic inflammatory airway disease. Exhaled nitric oxide (eNO) is a marker reflecting airway inflammation. This study was conducted to investigate whether montelukast, a leukotriene receptor antagonist, could be used for the management of asthma and how fast the montelukast sodium decreased airway inflammation as demonstrated by eNO levels. METHODS: Twenty children aged 6-14 years (mean age: 9.2 +/- 2.4 years; mean weight 30 +/- 4.6 kg) with mild to moderate asthma were recruited for the study. They received montelukast plus an inhaled short-acting beta2 agonist as open and uncontrolled therapy. Asthma score (AS) and peak expiratory flow rate (PEFR) and eNO concentrations were measured at pretreatment (0 week) and post-treatment (1 and 2 weeks) as well as 2 weeks after withdrawal of therapy. RESULTS: In one week, the eNO levels (33.3 +/- 15.5 p.p.b. vs 14.8 +/- 8.6 p.p.b.; P < 0.05), and AS (4.2 +/- 1.3 vs 1.8 +/- 1.3; P < 0.05) decreased rapidly, and PEFR (206.9 +/- 69.7 L/min vs 236.2 +/- 69.8 L/min; P < 0.05) increased. Concurrent beta2 agonist use decreased from a mean +/- SD of 2.2 +/- 0.4-1.3 +/- 0.3 puffs per weeks (P < 0.05). After the withdrawal of treatment for 2 weeks, the eNO levels (29.2 +/- 16.1 p.p.b) rebounded again, although the improvements in AS (1.1 +/- 1.3) and PEFR (245.0 +/- 91.3 L/min) persisted. CONCLUSION: Oral montelukast sodium treatment of these children with mild to moderate asthma effectively improved asthmatic symptoms and suppressed airway inflammation in 1 week, suggesting that this leukotriene antagonist combined with short-acting beta2 agonists may provide effective treatment option in mild to moderate childhood asthma. Larger, controlled, and double-blinded studies are needed to confirm these preliminary open uncontrolled observations.     

Exhaled nitric oxide, total serum IgE and allergic sensitization in childhood asthma and allergic rhinitis

Exhaled nitric oxide (eNO) levels are correlated with several markers of atopy and inflammatory activity in the airways, but the relationship between eNO and total serum IgE has not been fully elucidated in the context of allergic sensitization. The aim of this study was to investigate the relationship between eNO, total serum IgE and allergic sensitization in childhood asthma and allergic rhinitis. eNO levels, lung function, skin prick tests and total serum IgE were determined in 109 children (mean age, 10.4 yr) with mild intermittent asthma and in 41 children (mean age, 10.1 yr) with allergic rhinitis; 25 healthy non-atopic children were recruited as controls. eNO levels (median) were significantly higher in patients with asthma (22.7 p.p.b.) and in those with allergic rhinitis (15.3 p.p.b.) than in healthy controls (5.9 p.p.b.). Children with allergic asthma had higher eNO levels than children with allergic rhinitis. A significant positive correlation was found between eNO and total serum IgE (asthma, r = 0.42, p < 0.0001; allergic rhinitis, r = 0.31, p < 0.01), and between eNO and the number of positive skin prick tests (asthma, r = 0.31, p < 0.0001; allergic rhinitis, r = 0.39, p < 0.01). eNO levels were better correlated with total IgE than with the number of positive skin prick tests. This correlation was independent of allergic sensitization. High total serum IgE represents a specific and predictive marker of eNO increase in children with asthma or allergic rhinitis. This finding adds further support to the hypothesis that increased serum IgE could be a marker itself of airway inflammation in patients with allergic disease.     

Consistently high levels of exhaled nitric oxide in children with asthma

Background: Exhaled nitric oxide (eNO) levels in children are unstable because they are regulated by many potent factors. The purpose of the current study was to evaluate the reliability of eNO levels between a long interval and other lung functions in normal and asthmatic children. Methods: Eighty‐three elementary school children (aged 11–12 years; male : female, 39 : 44) participated in this study. Lung function, airway resistance and eNO levels were measured twice: the first measurement was in autumn 2007, and the second was one year later. Results: There were 62 non‐asthmatic control children (male : female, 31 : 31) and 21 asthmatic children (male : female, 8 : 13). In both the first and the second examination, the levels of eNO in children with asthma were higher than those in children without asthma. The parameters of lung function and the respiratory resistance in children without asthma showed a good correlation between the results of the first and second examinations. The eNO level in non‐asthmatic children showed a good correlation between the two. On the other hand, the peripheral airway parameters of lung function and the respiratory resistance in children with asthma were not correlated between the first and the second examinations. The eNO level in these patients was well correlated between the two examinations. Conclusions: These data suggest that the eNO level showed good reproducibility in children with and without asthma. The eNO level is therefore considered to be a useful marker for reproducibly evaluating a subject's airway condition.