Th2抑制剂在儿童过敏免疫性疾病中的应用

基于Th2细胞因子在过敏性疾病中的作用，Th2抑制剂已被认为可应用于儿童过敏性哮喘和变应性鼻炎针对靶点的药物治疗。甲磺司特是一种新型选择性Th2细胞因子抑制剂，能选择性抑制Th细胞、减少炎症介质的产生，改善过敏性疾病的症状。在日本制定的儿童支气管哮喘指南与变应性鼻炎指南中均推荐可应用甲磺司特。甲磺司特是我国首个批准上市的Th2细胞因子抑制剂，2020年成人支气管哮喘防治指南推荐可应用甲磺司特治疗支气管哮喘，但该药在我国的应用尚处于起步阶段。该文就Th2抑制剂甲磺司特在儿童过敏免疫性疾病中的应用作一综述，以促进我国儿童Th2抑制剂的规范使用。     

Wheezing requiring hospitalization in early childhood: Predictive factors for asthma in a six-year follow-up

Although asthma is common after wheezing in early childhood, the risk factors for and the prevention of later asthma are poorly understood. During the present follow-up study, a range of possible predictive factors for school-age asthma was evaluated. The study group consisted of 82 children hospitalized for wheezing at age < 2 years in 1992–93. The baseline data were collected on entry to the study. In 1999, the children were re-examined at the median age of 7.2 years. A structured questionnaire was applied to chart the symptoms suggestive of asthma, and the children were examined clinically. An exercise challenge test, as well as skin prick tests (SPT) to common inhalant allergens, was performed. Asthma was present in 33 (40%) children, 30 (91%) having continuous medication for asthma. The significant asthma-predictive factors, present on entry to the study, were blood eosinophilia (p = 0.0008), atopic dermatitis (p = 0.0089), elevated total serum immunoglobulin E (IgE) (p = 0.0452), and a history of earlier episodes of wheezing in infancy (p = 0.0468). SPT positivity in early childhood was also associated with school-age asthma (p = 0.002). In contrast, respiratory syncytial virus (RSV) identification during the index episode of wheezing played a minor role as a predictive factor for asthma. In conclusion, if hospitalization for wheezing occurs in infancy, more than every third child will suffer from asthma at early school age; the risk is significantly increased with recurrent wheezing in infancy and the development of allergic manifestations.     

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

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

Creola bodies in wheezing infants predict the development of asthma

Creola bodies (CrBs) have been shown to be present specifically in the sputum of adults with asthma, and are clinically useful in the estimation of airway hyper-responsiveness through correlation with the levels of eosinophil cationic protein in the sputum. Our aim was to investigate whether CrBs can be detected in the sputum of wheezing infants, and the clinical significance of CrBs in wheezing infants in the development of asthma. Twenty-three wheezing infant patients, mean age 5.3 months, were studied. The presence of CrBs in the sputum was determined by Papanicolau's stain. The patients were divided into two groups: CrB positive [CrB(+)] and CrB negative [CrB(−)]. In addition, we examined the relationship between the presence of CrBs and the asthma symptom scores that occurred during a 1-month post-discharge period. The following results were obtained: (i) CrBs were detected in 15 of 23 (65%) wheezing infants; (ii) the asthma symptom scores after discharge was significantly higher in the CrB(+) group than in the CrB(−) group (p < 0.001); (iii) in the infants experiencing their first episode of wheezing, the asthma symptom scores during the post-discharge period was also significantly higher in the CrB(+) group than in the CrB(−) group (p < 0.05). Furthermore, infantile asthma was diagnosed in 12 (80.0%) infants in the CrB(+) group during the following 2-yr period, but none in the CrB(−) group. These findings suggest that CrBs detected in the sputum of wheezing infants may be used to identify the progression to infantile asthma.     

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

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

Total and allergen-specific IgE levels in serum reflect blood eosinophilia and fractional exhaled nitric oxide concentrations but not pulmonary functions in allergic asthmatic children sensitized to house dust mites

Although elevated levels of serum immunoglobulin E (IgE) are considered the hallmark of atopic diseases, their clinical value in evaluating subjects with allergic disorders is under debate. To evaluate possible relationships between serum IgE levels and a variety of clinical parameters, 83 mild asthmatic children [10.98-year-old (2.95)], sensitized to house dust mites (HDM) Dermatophagoides pteronyssinus (Dp) or D. farinae (Df), were enrolled. As compared with normal control reference values detected in our laboratory, children with allergic asthma had higher blood eosinophil counts (expressed both as percentage and as absolute number) and higher fractional exhaled nitric oxide ( FeNO) levels but similar values in pulmonary function parameters. In the allergic asthmatic population, serum levels of total, Dp-specific or Df-specific IgE correlated positively with eosinophil counts (Rho ≥ 0.30, p < 0.01, each correlation) and FeNO levels (Rho ≥ 0.33, p < 0.01, each correlation) but not with pulmonary function parameters (p > 0.1, each correlation). Finally, significant correlations, although moderate, were found in the allergic asthmatic population between eosinophil counts and FeNO levels (Rho ≥ 0.42, p < 0.001, each correlation). Thus, in atopic children sensitized to HDM with mild intermittent asthma, IgE levels in blood appear to reflect systemic (blood eosinophils) and organ-specific (FeNO) markers of allergic inflammation but not pulmonary volumes or the degree of airflow limitation.     

喘息婴幼儿外周血气道炎症相关介质水平的研究

目的 通过检测喘息婴幼儿外周血相关炎症介质水平,从辅助性T细胞（Th）1/Th2失衡及气道炎症两个方面探讨婴幼儿喘息发生的可能机制。方法 选取急性喘息发作婴幼儿50例为喘息组,25例健康婴幼儿为健康对照组。喘息组患儿依据喘息发生次数分为首次喘息组（首发组）25例和反复喘息组（反复组,发作次数≥ 2次）25例;根据是否存在哮喘发生的高危因素分为有高危因素组22例和无高危因素组28例;根据病原学检测结果分为病原学阳性组23例和病原学阴性组27例。检测各组外周血Th1细胞因子白介素（IL）-2,Th2细胞因子IL-4、IL-5、IL-13、转化生长因子-β1（TGF-β1）,以及总IgE （TIgE）水平。喘息组患儿同时送检外周血嗜酸性粒细胞（EOS）计数,并采集标本进行呼吸道病原学检测。结果 喘息组外周血IL-4、IL-5、IL-13、TGF-β1及TIgE水平较健康对照组均明显升高（P < 0.05）;外周血IL-2、IL-4、IL-5、IL-13、TGF-β1及TIgE水平在首发组与反复组,有哮喘高危因素组与无哮喘高危因素组,以及病原学阳性组与病原学阴性组之间比较,差异均无统计学意义（P > 0.05）。相关性分析表明喘息组外周血EOS计数与IL-4水平呈正相关（P < 0.01）;IL-4水平与IL-5、IL-13水平呈正相关（P < 0.01）;IL-5水平与IL-13水平呈正相关（P < 0.01）;IL-2水平与TGF-β1水平呈正相关（P < 0.05）。结论 喘息婴幼儿存在Th1/Th2失衡,表现为Th2优势表达;IL-4、IL-5、IL-13、TGF-β1及IgE共同参与了婴幼儿喘息性疾病的发病过程。喘息婴幼儿存在气道炎症,与喘息发作次数、是否存在哮喘高危因素及病原学检测是否阳性无关。     

Increased eosinophil cationic protein levels in bronchoalveolar lavage from wheezy infants

Although studies examining the serum suggest a role for eosinophils in wheezing episodes in infants and toddlers, the presence of a chronic eosinophilic inflammation within their airways remains to be demonstrated. In this study we investigated whether eosinophil cationic protein (ECP) levels are increased in BAL fluid (BALF) from infants and toddlers with recurrent wheezing episodes, during an asymptomatic period. The levels of ECP in BALF were quantitated by radioimmunoassay in 61 children (36 with severe recurrent episodes of wheezing and 25 who were non-wheezy), aged 6–36 months, in whom flexible bronchoscopy was clinically indicated. BALF eosinophil counts were ≤ 1% in all patients and did not differ in wheezers, compared to non-wheezers. In contrast, ECP levels in BALF were ≥ 2.2 µg/l in 18 of 36 (50%) wheezy infants but in only three of 25 (12%) control infants (p < 0.01). Neutrophil counts were significantly higher in the wheezer group than in the non-wheezer group (8.1 × 10³ cells/ml vs. 3.0 × 10³ cells/ml). ECP levels in the BALF were not correlated with the absolute number of eosinophils ( r  = 0.03; p = 0.8) but were correlated with the absolute number of neutrophils ( r  = 0.54; p = 0.001). There was no association between high ECP levels in BALF and the atopic status of the wheezers. In conclusion, ECP levels are increased in BALF from young children with recurrent wheezing episodes, even during relatively quiescent periods, suggesting a chronic increased cell activation in the lower airways.     

Association between neopterin in cord blood, urinary neopterin in early childhood and the development of atopic dermatitis, asthma and hay fever.

It is generally accepted that the increased prevalence of atopic disease is due to a disturbed balance of T-helper (Th)1/Th2-type immunity. Upon stimulation by the Th1-type cytokine interferon (IFN)-gamma, human monocytes/macrophages release large amounts of neopterin. Thus, the determination of neopterin concentrations is an indirect measure of the levels of IFN-gamma and allows us to monitor Th1-type immune response. We evaluated whether neopterin concentrations in the neonatal cord blood could be a valuable marker predicting atopic disease in early childhood and whether there is a difference in actually determined urinary neopterin concentrations in children with and without atopic disease. Five hundred and five children born during 1997-1999 were enrolled, with cord blood neopterin data available at birth. The International study of asthma and allergies in childhood (ISAAC) questionnaire was used to assess the prevalence of wheezy bronchitis (asthma), atopic dermatitis and allergic rhinitis. Morning urinary samples were collected and urinary neopterin concentration was measured by high-pressure liquid chromatography. By the average age of 6 yr, the prevalence of atopic disease in the last 12 months was 31%. There was no significant correlation between cord blood and urinary neopterin concentrations at age 6 yr, and between cord blood neopterin and later atopic disease. Urinary neopterin concentrations were significant lower in children with a family history of atopic disease (p = 0.02). In this study, cord blood neopterin concentration was not a predictor for atopic disease in early childhood. Family history of atopic disease was associated with lower urinary neopterin levels at age 6 yr, which might mirror a Th1/Th2 imbalance.     

Cow's milk protein-specific T-helper type I/II cytokine responses in infants with necrotizing enterocolitis

Enteral feeding, in particular with formula feeds, is associated with necrotizing enterocolitis (NEC). In this study, we have examined, in the systemic and mucosal immune compartments, for evidence of bovine milk antigen sensitization in infants with NEC. Eleven newborns with Bell's staging 2–3 NEC [median post-conceptional age 31 wk (range 27–41 wk)], 21 neonatal controls [33 (28–40) wk] and 15 infants undergoing intestinal resection or mucosal biopsy for non-inflammatory conditions [39 (34–42) wk] were studied. Spontaneous and antigen or mitogen elicited interferon-γ (IFN-γ) [T-helper type I (Th1)], interleukin (IL)-4 and IL-5 [T-helper type II (Th2)] responses were enumerated using single-cell enzyme-linked immunospot (ELISPOT) assay in peripheral blood (PBMC) or lamina propria mononuclear cells. NEC infants, compared with controls, showed a significant elevation in baseline PBMC cytokine secreting cells, vigorous mitogen responses (20- to 120-fold increase) for IFN-γ, IL-4 and IL-5 (p < 0.001), strong responses to beta-lactoglobulin (βlg) (IFN-γ > IL-4/IL-5, p ≤ 0.001), and somewhat smaller casein responses. Similarly, in the lamina propria, a small but significant increase in spontaneous cytokine-secreting cells was detected in NEC infants (p < 0.01), with an IFN-γ/IL-4 predominant phytohemagglutinin (PHA)/concanavalin-A (ConA) response. Three of nine NEC infants (but no controls) also showed a positive ELISPOT response to βlg (IFN-γ only) but none to casein. We have thus demonstrated significant cow's milk protein (CMP) sensitization in NEC, at least in the systemic compartment (mixed Th1/Th2), with minimal mucosal activation in some cases. These novel findings provide a potential mechanism for a direct contributory role of CMP in the pathogenesis of NEC.     

A Prospective Study of the Clinical Manifestations of Atopic Disease in Infancy

ABSTRACT. We prospectively followed a group of infants with a family history of atopy, from birth for up to 20 months of age. All infants were seen every 4 months and a history, physical examination and skin tests obtained. Atopic dermatitis and rhinitis occurred in about half the infants at some time during the study, while wheezing occurred in about a quarter. Both atopic dermatitis and rhinitis were more common in the first 12 months whereas wheezing occurred later and increased in prevalence with age. Defining atopy by the presence of atopic dermatitis or positive skin tests, only immediate food reactions were significantly associated with atopic infants. In contrast, rhinitis, a single episode of wheezing, colic, vomiting and delayed food reactions were not associated with atopy and thus are unlikely to be due to IgE-related mechanisms during infancy.     

High levels of urinary eosinophil protein X in young asthmatic children predict persistent atopic asthma

Levels of urinary eosinophil protein X (U-EPX) and eosinophil counts were measured in 32 children (12–36 months of age) who were hospitalized for acute asthma, and the U-EPX levels were measured in 20 healthy children of the same age. The ability of these parameters to predict persistent asthma (at least one wheezing episode during the last 6 months) and atopic asthma (a positive skin-prick test [SPT]), was evaluated at a follow-up 2 years later. On admission, levels of U-EPX were higher in children with asthma (median: 120 µg/mmol of creatinine; quartiles: 67–123 µg/mmol of creatinine) than in controls (60 µg/mmol of creatinine, 38–74 µg/mmol of creatinine; p< 0.001). The U-EPX level was higher in those with persistent atopic asthma at follow-up (173 µg/mmol of creatinine, 123–196 µg/mmol of creatinine, n = 16), than in those with persistent non-atopic asthma (73 µg/mmol creatinine, 46–105 µg/mmol of creatinine, n = 8; p< 0.05), and higher than in those with transient asthma (no symptoms at follow-up) (106 µg/mmol creatinine; 42–167 µg/mmol of creatinine, n = 8; p< 0.05). By multiple logistic regression analysis, U-EPX was the only parameter able to predict persistent atopic asthma; eosinophil counts, parental atopy, age or gender could not. Parental atopy was the only parameter predictive for persistent asthma, regardless of atopic status. In conclusion, levels of U-EPX, but not eosinophil counts, measured in young children hospitalized with acute asthma can predict the persistence of atopic asthma 2 years later.     

Cutaneous lymphocyte‐associated antigen expression in children with atopic dermatitis and non‐atopic healthy children

Cutaneous lymphocyte‐associated antigen (CLA) is a cell surface glycoprotein which has been implicated in the homing of lymphocytes to cutaneous sites. It is postulated to play an important role in T‐cell migration to skin in atopic dermatitis; however, the expression of CLA in both normal children and children with atopic dermatitis has not been extensively studied. If CLA expression on T cells were important in the traffic of lymphocytes to atopic dermatitis skin lesions, it might be expected that the proportion of CLA⁺ T cells in unstimulated peripheral blood from children with atopic dermatitis would be elevated. We have examined the proportion of CLA⁺ T cells in children with atopic dermatitis and non‐atopic age‐matched controls. The proportion of CLA⁺ T cells in non‐atopic children was highly associated with and increased with increasing age ( r  = 0.88, p < 0.001). There was no difference between the proportion of T cells expressing CLA in the unstimulated PBMC from children with severe or mild/moderate atopic dermatitis and age‐matched non‐atopic controls (p = 0.18, p = 0.3, respectively). Despite this, children with atopic dermatitis did show evidence of perturbation of CLA expression, as unlike the non‐atopic children the proportion of CLA⁺ T cells in the atopic children did not correlate with age. These findings suggest that while CLA expression may play a role in atopic dermatitis, other as yet undefined surface markers are likely to principally determine the migration of T cells to skin in atopic dermatitis.     

Obesity and the prevalence of allergic diseases in schoolchildren

Although the association between obesity and bronchial asthma (BA) has been gaining more attention, few studies have been conducted concerning the relationship between obesity and other allergic diseases. The objective of this study was to determine whether and how childhood obesity is associated with allergic diseases other than BA, such as atopic dermatitis (AD), allergic rhinitis (AR), allergic conjunctivitis (AC), and either AR or AC (AR/AC). A questionnaire was administered to the parents of 50,086 Japanese schoolchildren. Associations between childhood obesity and the various allergic diseases were evaluated by univariate and multivariate logistic models. Significant associations were found between higher body mass index (BMI) and AD (p = 0.03), and lower BMI and AC (p < 0.0001), and AR/AC (p < 0.0001). There was a significantly higher prevalence of BA in girls with obesity (p = 0.009) than in those without obesity. Significantly lower prevalence of AC (p = 0.01) and AR/AC (p = 0.002) among children with obesity, and AR (p = 0.04) and AR/AC (p = 0.0004) among boys with obesity were observed than those without obesity. Those who were obese and had AD were significantly more likely to have severe symptoms (p = 0.01). Overall, childhood obesity has positive associations with BA prevalence and AD severity, whereas it has negative associations with AR and AC prevalence, especially among boys. Changes in the immunologic balance accompanied by obesity might have different effects on each type of allergic disease. Exploring the mechanisms by which childhood obesity affects allergic status should lead to new management options for childhood allergy.     

Eosinophil counts and urinary eosinophil protein X in children hospitalized for wheezing during the first year of life: prediction of recurrent wheezing

Early identification of wheezing children with an increased risk of recurrent wheezing or subsequent asthma is important. The aim of the study was to determine the role of markers of eosinophil activation, along with other parameters, in the prediction of recurrent wheezing and allergic sensitization in children with early and severe wheezing. We examined 105 children without atopic dermatitis, hospitalized for wheezing during the first year of life. At a 20-mo follow-up, 101 of the children were assessed for the occurrence of recurrent wheezing (at least 3 episodes, including 1 in the previous 6 mo) and allergic sensitization (positive skin-prick test). By univariate analysis, levels of eosinophil counts at the time of hospitalization (p = 0.005, OR = 18.9), age in months (p < 0.0001, OR = 1.5), respiratory syncytial virus (RSV)-negative disease (p < 0.0001, OR = 8.8), parental atopy (p = 0.006, OR = 3.3) and male sex (0.02, OR = 2.7) were all predictive factors for recurrent wheezing at follow-up. With all parameters included in a multiple regression analysis, RSV-negative disease was not a predictive factor for recurrent wheezing. A simple model including eosinophil counts > or = 0.1 x 10(9)/L and age had a predictive accuracy of 79%, with only a 6% chance of a child being wrongly predicted as symptomatic. Urinary protein X (U-EPX) was not a predictive factor for recurrent wheezing. When included in a multiple logistic regression analysis, a level of U-EPX > or = 100 microg/mmol creatinine was the only parameter with a positive predictive value for allergic sensitization (p = 0.007, OR = 18.9), whereas age, parental allergy or parental asthma were not. CONCLUSION: Children with severe wheezing during the first year of life and subsequent recurrent wheezing are characterized by a normal or high eosinophil count in response to viral infections.     

Recurrent wheezing in preterm infants: Prevalence and risk factors

ObjectiveTo evaluate the prevalence and risk factors associated with progression to recurrent wheezing in preterm infants.MethodsThe cross-sectional study was carried out in 2014 and 2015 and analyzed preterm infants born between 2011 and 2012. The search for these children was performed in a university maternity hospital and a Special Immunobiological Reference Center. The evaluation was performed through a questionnaire applied during a telephone interview.ResultsThe study included 445 children aged 39 (18–54) months. In the univariate analysis, the risk factors with the greatest chance of recurrent wheezing were birth weight <1000 g, gestational age <28 weeks, living with two or more siblings, food allergy, and atopic dermatitis in the child, as well as food allergy and asthma in the parents. In the multivariate analysis, there was a significant association between recurrent wheezing and gestational age at birth <28 weeks, food allergy and atopic dermatitis in the child, and living with two or more children. Of the 445 analyzed subjects, 194 received passive immunization against the respiratory syncytial virus, and 251 preterm infants were not immunized. There was a difference between the gestational age of these subgroups (p < 0.001). The overall prevalence of recurrent wheezing was 27.4% (95% CI: 23.42–31.70), whereas in the children who received passive immunization it was 36.1% (95% CI: 29.55–43.03).ConclusionsPersonal history of atopy, lower gestational age, and living with two or more children had a significant association with recurrent wheezing. Children with lower gestational age who received passive immunization against the respiratory syncytial virus had a higher prevalence of recurrent wheezing than the group with higher gestational age.     

Increased serum IL-10/IL-12 ratio in wheezing infants

To investigate the association between various serum markers and atopic symptoms in the first year of life, and to evaluate the prognostic value of these markers for the development of wheezing and skin rash in the second year of life. Data of 86 children on the development of wheezing and skin rash in the first 2 years of life were collected prospectively, making use of parental completed questionnaires, weekly symptom cards, structured interview and physical examination. Serum markers (IL-10, IL-12, IL-13, eotaxin, sE-selectin, sICAM-1, sIL-2R) and total and specific IgE were determined at age 1. Children who developed wheezing in the first year of life had lower serum levels of IL-12 than children without symptoms (median 40.3 pg/ml vs. 49.0 pg/ml, p = 0.01) and a higher serum IL-10/IL-12 ratio (0.41 vs. 0.31, p = 0.001) at age 1. The IL-10/IL-12 ratio increased with an increasing number of wheezing episodes. Levels of sE-selectin in children with wheezing and in children with itchy skin rash in the first year of life were higher than in symptom free children (6.1 ng/ml and 5.9 ng/ml vs. 4.9 ng/ml, p = 0.01 and p = 0.03, respectively). Children who developed wheezing in the second year of life already had increased sICAM-1 levels at age 1. Children who developed wheezing in the first year of life showed a serum cytokine response that is skewed towards a T-helper 2 profile, with lower IL-12 levels and an increased IL-10/IL-12 ratio. Children who developed wheezing in the second year of life had elevated sICAM-1 levels at age 1. Follow-up of the children is needed to evaluate the prognostic value of various serum markers for the development of allergic disease in later childhood.     

Time trends of the prevalence of asthma and allergic disease in Austrian children

After a substantial increase in the prevalence of atopic disease in Europe, recent studies indicate that a plateau has been reached. However, variation across countries and age groups exists. We studied the prevalence and time trends of asthma and allergic disease among schoolchildren in Austria, a country with traditionally low rates of asthma, hay fever, and eczema. As part of the International Study of Asthma and Allergies in Childhood (ISAAC), symptoms and physician diagnoses of asthma and allergic disease of 13,399 Austrian children aged 6–7 yr and 1516 children aged 12–14 yr were surveyed between 1995 and 1997. A similar survey was conducted between 2001 and 2003. Among children aged 6–7 yr, significant increases were seen in the prevalence of physician-diagnosed asthma (+16%; p = 0.013), hay fever (+22%; p < 0.001), and eczema (+37%; p < 0.001) between 1995 and 2003. These changes were paralleled by an increase in the prevalence of symptoms typical for hay fever (itchy eyes and runny nose), but not by an increase in wheeze. Among children aged 12–14 yr, the lifetime prevalence of diagnosed asthma increased by 32%, of hay fever by 19%, and of eczema by 28% (all, p < 0.001). These changes were paralleled by increases in the prevalence of wheezing as documented by both questions before and after a video showing wheezing children but not by symptoms typical for hay fever such as itchy eyes and runny nose. In conclusion, in Austria, contrary to other European countries, the prevalence of asthma and allergic disease increased among schoolchildren. Additional studies are needed to continue monitoring the dynamics of the prevalence of asthma and allergic disease in Austria and to explore trends in their risk factors.     

What lessons can be learned about asthma phenotypes in children from cohort studies?

‘Phenotyping’ asthma by multivariate analyses and more recently by unsupervised analysis has been performed in children cohorts. We describe the key findings that have emerged from these cohorts. It would appear that there are three wheeze phenotypes in children of preschool age: the mild episodic viral wheeze phenotype; the multitrigger atopic wheeze; and, less often encountered, the severe non‐atopic wheeze. Early onset of allergy in asthma (more prevalent in boys) is associated with poor prognosis unlike the severe non‐atopic wheeze phenotype which has a female predominance. The prognosis of the severe non‐atopic wheeze depends on time of onset (early or late) of allergic expression. At school age, the risk of severe asthmatic exacerbations is associated with eosinophil predominant inflammation frequently related to allergic asthma, whereas neutrophil inflammation is associated with moderate‐to‐severe asthma with poorer lung function. Nevertheless, allergic asthma is also a heterogeneous disease with a severe allergic phenotype strongly associated with atopic dermatitis and very high eosinophil‐driven inflammatory markers. Further studies are required to find non‐invasive biological markers in very young children to better define wheezing phenotypes associated with an elevated risk of developing severe asthma with a view to personalizing treatment.     

Food allergy: When and how to perform oral food challenges

In many situations, the diagnosis of food allergy rests simply upon a history of an acute onset of typical symptoms, such as hives and wheezing, following the isolated ingestion of a suspected food, with confirmatory laboratory studies of positive prick skin tests or RASTs. However, the diagnosis is more complicated when multiple foods are implicated or when chronic diseases, such as asthma or atopic dermatitis, are evaluated. The diagnosis of food allergy and identification of the particular foods responsible is also more difficult when reactions are not mediated by IgE antibody, as is the case with a number of gastrointestinal food allergies. In these latter circumstances, well‐devised elimination diets followed by physician‐supervised oral food challenges are critical in the identification and proper treatment of these disorders. Since childhood food allergies to common allergenic foods such as milk, egg, wheat and soy are usually outgrown, oral food challenges are also an integral part of the long‐term management of these children.