Urinary eosinophil protein X in children: the relationship to asthma and atopy and normal values

BACKGROUND: In epidemiologic studies, it may be difficult to identify children with bronchial asthma. Since this is the most common chronic respiratory disease in childhood, and its prevalence is still increasing, reliable methods for identification of asthmatic children are required. This study evaluates the use of urinary eosinophil protein X (U-EPX) in epidemiologic studies in identifying atopic and asthmatic children. METHODS: U-EPX was measured in 877 Austrian schoolchildren. The skin prick test (SPT) was performed with eight common aeroallergens, and established questionnaires were used to assess respiratory symptoms. RESULTS: Of our cohort, 2.8% reported physician-diagnosed asthma, 5.1% reported wheezing within the last 12 months, and 24.1% were found to be atopic. In children with physician-diagnosed asthma, as well as in atopic children (positive SPT), median U-EPX levels were significantly higher than in healthy subjects (142.8 and 89.6 vs 63.9 microg/mmol creatinine, P<0.0001 and P<0.0001, respectively). In addition, perennial sensitization to inhalant allergens resulted in higher U-EPX levels than did seasonal sensitization. The odds ratio for U-EPX levels over the 90th percentile was significantly elevated for asthma, for wheezing, for nocturnal cough, and for breathlessness at exercise, as well as for seasonal and perennial sensitization. Pulmonary function was negatively related to U-EPX levels. CONCLUSIONS: Measurement of U-EPX, which can be obtained easily, may be helpful in diagnosing both asthma and atopy in children. However, there is a great overlap between controls and symptomatics, a fact which reduces the sensitivity of U-EPX in determination of the prevalence of asthma in epidemiologic studies.     

Prevalence of childhood asthma based on questionnaires and methacholine bronchial provocation test in Korea

Background In most epidemiological survey studies, only subjective symptoms and past medical history of asthma have been used as diagnostic criteria. Even though a questionnaire survey can be performed in a large population study at low cost, limitations such as lack of objectivity and poor predictability in non-specific bronchial hyperresponsiveness cannot be avoided. Objectives The purpose of this study was to elucidate the prevalence of current asthma based on questionnaires and methacholine bronchial provocation test, and the prevalence of atopy in Korea. Methods We performed modified ATS respiratory questionnaires and allergen skin-prick test with 10 common inhalant allergens among 3219 subjects aged 7–19 years in Seoul and a rural part of a small city, Chungju in Korea. Methacholine bronchial provocation tests were also performed among those who had asthma symptoms according to the questionnaire. The criteria of asthma was presence of both asthma symptoms and non-specific bronchial hyperresponsiveness. Atopy was defined as when an allergen induced weal size is same or larger than that caused by histamine. Results The prevalence of asthma based on questionnaires and methacholine bronchial provocation tests was 4.6%, while the prevalence of wheeze was 8.2% and 19.3% of total population complained of one or more respiratory symptoms related to asthma on the questionnaires. There was no significant difference according to age, sex and living area. The mean prevalence of atopy was 35.0% and the most common allergens were Dermatophagoides farinae (30.9%), Dermatophagoides pteronyssinus (27.5%), cat fur (20.4%) and cockroach (11.8%). The atopy prevalence in Chungju area was higher than that in Seoul and males showed a higher prevalence than females. The asthma prevalence was higher among atopies (6.8%) than among non-atopies (2.7%). None of questionnaire items were enough to predict the presence of bronchial hyperresponsiveness in terms of sensitivity, specificity and positive predictive value. Conclusion The prevalence rate of current asthma in Korea was 4.6% and the prevalence rate of atopy in Korea was 35.0%. Questionnaire-based surveys are not enough to predict the actual prevalence of asthma.     

The association between persistent eosinophilia and asthma in childhood is independent of atopic status

BACKGROUND: Although peripheral blood eosinophilia is associated with risk of asthma, the relation with atopy has not been established. OBJECTIVE: To assess the relationship between eosinophils and chronic asthma in childhood, and to determine the factors associated with eosinophil levels over time. METHODS: Percent eosinophils/300 white blood cell (WBC) count ('eos') was measured at 9 months, 6 years and 11 years in subjects participating in the prospective Tucson Children's Respiratory Study. Children were classified based on the number of measurements in which they had low (< or = 2%) or high (>5%) eosinophils, as follows: (1) Persistently low eos (n = 130); (2) Low eos (intermittently low or consistently moderate, but never high, n = 317); (3) Intermittently high eos (n = 192); and (4) Persistently high eos (n = 17). Only children with > or = 2 eos measurements were included in the analysis. Chronic asthma was defined as medical doctor (MD)-diagnosed asthma with reports of wheezing during the previous year, on > or = 3 questionnaires completed between 2 and 13 years of age. Children with at least one positive skin prick test (SPT; > or = 3 mm) at age 6 or 11 were considered 'atopic'. RESULTS: Chronic asthma was linearly related to longitudinally ascertained eosinophils (trend chi2 P<0.001) with prevalence ranging from 5.8% among children with persistently low eos to 37.5% among children with persistently high eos. This relation was independent of atopy. Parental history of asthma was associated with both chronic asthma (P <0.001) and with longitudinal eosinophil status (P < 0.001). After adjusting for atopy and gender, there was a 70% increase in asthma risk with each increase in longitudinal eosinophil level. This stepwise increase was reduced to 48% when parental asthma was added to the model. CONCLUSION: Longitudinal eosinophil levels are linearly associated with chronic asthma in childhood, independent of atopy. The strong association between parental asthma and eosinophil status suggests that genetic background may be an important determinant of eosinophilic response.     

Clinical atopy and associated factors in primary-school pupils

To investigate potential risk factors for clinical atopy in childhood, we obtained cross-sectional data from a cohort of 1376 8-year-old pupils. Parental atopy (hay fever, asthma, eczema), gestational age, maternal smoking habits, and the child's history of asthma, hay fever, and eczema were ascertained by questionnaire. Combining the history and the result of a skin prick test using seven aeroallergens, we defined the child's atopic diseases. Of the population evaluated, 25.4% were categorized as atopic (10.2% allergic asthma, 17.3% eczema, 6.9% hay fever). As compared with the clear nonatopics (40.2%), parental atopic diseases were more prevalent in each of the atopic groups. Significant associations of the parents' and child's disease were obvious for eczema and hay fever. Low gestational age (LGA) was more frequent in children with any atopy or with an allergic asthma (odds ratio (OR) 1.7; 95% confidence interval (CI) 1.02-2.97; OR 2.8; 95% CI 1.5-5.4). Hay fever and allergic asthma occurred less frequently in girls (OR 0.5; 95% confidence interval 0.3-0.8; OR 0.6; 95% CI 0.4-0.9). In conclusion, our data underline the importance of parental atopy for the clinical outcome in the offspring. In addition, LGA appears to be a risk factor for allergic asthma and for general atopy in later life.     

The association between infant feeding practices and subsequent atopy among children with a family history of asthma

BACKGROUND: Although longer duration of breastfeeding and later introduction of solid foods are both recommended for the prevention of asthma and allergic disease, evidence to support these recommendations is controversial. OBJECTIVE: To examine the relation between infant feeding practices and the risk of asthma and allergic disease at age 5 years. METHODS: A cohort of children with a family history of asthma in Sydney, Australia, was followed from birth to age 5 years. Data on infant feeding practices and on early manifestations of eczema were collected prospectively. The presence of eczema, asthma and atopy (positive allergen skin prick tests) were determined at age 5 years. RESULTS: In 516 children evaluated at age 5 years, there was no significant association between the duration of breastfeeding or timing of introduction of solid foods and protection against asthma or other allergic disease, after adjustment for confounding factors. However, breastfeeding for 6 months or more and introduction of solid foods after 3 months were both associated with an increased risk of atopy at age 5 years (P=0.02 and 0.01, respectively). There was no significant association between the presence of eczema at 4 weeks and at 3 months and continued breastfeeding beyond those times. CONCLUSION: Longer duration of breastfeeding and later introduction of solid foods did not prevent the onset of asthma, eczema or atopy by age 5 years.     

IL15 gene variants are not associated with asthma and atopy

Background:  Interleukin 15 (IL15) promotes activation and proliferation of CD8+ T cells and enhances the differentiation into Th2 cells. A previous study described five polymorphisms in the IL15 gene to be associated with asthma in a haplotype analysis.
Aim:  We selected HapMap tagging single nucleotide polymorphisms (SNPs) from IL15 to systematically investigate these IL15 associations in a large population-based sample.
Methods:  Genotyping of seven IL15 SNPs was performed using MALDI-TOF MS in a cross-sectional study population of 3099 children from Dresden or Munich (age 9–11 years). All children were phenotyped by standardized and validated protocols for atopic phenotypes. Effects of single SNPs and haplotypes were studied using sas 9.1.3 and haploview . Equivalence tests were performed to prove the significance of negative results.
Results:  Neither single IL15 polymorphisms nor haplotype analyses showed associations with asthma or atopy after correction for multiple testing.
Conclusion:  These results do not confirm previous case–control studies and suggest that IL15 gene variants do not play an important role in the development for asthma or other atopic disorders.     

The cysteinyl-leukotriene type 1 receptor polymorphism 927T/C is associated with atopy severity but not with asthma

BACKGROUND: The cysteinyl-leukotriene receptor type 1 (CysLT1) mediates the bronchoconstrictor and pro-inflammatory actions of cysteinyl-leukotrienes (LTC4, LTD4, LTE4) in asthma and is the molecular target of the lukast class of oral anti-leukotriene drugs. We screened the CYSLTR1 gene on chromosome Xq13-21 for coding region polymorphisms, and investigated their associations with allergy and asthma. METHODS: Solid-phase chemical cleavage was used to screen polymorphisms in the coding region of CYSLTR1. A TaqMan allelic discrimination assay was used to genotype a 927T/C SNP and oligonucleotide ligation assays were used to genotype the previously reported 617T/C and 898G/A SNPs of CYSLTR1 in 341 asthmatic families from the UK. Associations with asthma diagnosis, atopic status, serum-specific IgE and severity of allergy and asthma were examined. RESULTS: Family-based association tests showed that the 927 T allele was associated with atopy severity, especially in female subjects, but not with asthma diagnosis or severity, atopic status, bronchial hyper-responsiveness to methacholine or forced expiratory volume in 1 s. CONCLUSION: Mutation screening identified only one polymorphism, 927T/C, in the coding region of the CysLT1 receptor. This polymorphsim is predictive of atopy severity, but not associated with asthma.     

Establishing the incidence and prevalence of clinician-diagnosed allergic conditions in children and adolescents using routinely collected data from general practices

Background There remains a need to better characterize the epidemiology of allergic disorders, particularly in relation to describing the incidence, natural history and co‐morbidity of allergic conditions. Objectives To estimate the incidence and prevalence of clinician‐diagnosed eczema, asthma and rhinitis, alone and in combination, in children and adolescents in the United Kingdom. Methods Using the national General Practice Research Database (GPRD) – one of the largest validated databases of routinely collected healthcare data in the world aggregating 3.6 million individuals – we constructed a retrospective birth cohort of 43 473 children born in the year 1990 and registered with a UK general practice within a year of birth. The cohort was followed until 2008 or the longest available follow‐up period to determine the cumulative and age‐specific incidence and prevalence rates of clinician‐diagnosed eczema, asthma and rhinitis, and an 18‐year prevalence of these conditions, alone and in combination. Results Eczema had the highest incidence density of 226.9 per 10 000 person‐years [95% confidence interval (CI): 225.8–228.0] followed by asthma [136.6;(95% CI: 135.7–137.5)] and rhinitis [61.4;(95% CI: 60.8–62.0)], by the age of 18 years. The incidence densities of suffering from one, two or all three allergic conditions were 323.2 (95% CI: 322.0–324.4), 206.4 (95% CI: 205.7–207.1) and 141.9 (95% CI: 141.4–142.4) per 10 000 person‐years, respectively. Among the 24 112 children with a complete 18‐year follow‐up, eczema had the highest 18‐year prevalence of clinician‐diagnosed condition at 36.5% (95% CI: 35.9–37.2%) followed by asthma [22.9;(95% CI: 22.3–23.4%)] and rhinitis[11.4;(95% CI: 11.0–11.8%)]. The 18‐year prevalence of more than one and all three conditions was 16.1% (95% CI: 15.6–16.6%) and 2.5% (95% CI: 2.4–2.8%), respectively. Conclusions This is one of the first studies to provide national estimates on the age‐specific incidence and age‐specific prevalence of the major allergic disorders showing clinician‐diagnosed eczema, asthma and rhinitis to have high incidence rates in early childhood. A significant proportion of children experience and are diagnosed with multiple allergic conditions in early childhood.     

Characterization of wheezing phenotypes in the first 10 years of life

BACKGROUND: Childhood wheezing illnesses are characterized into different phenotypes. However, severity of the disease associated with these phenotypes has not been extensively studied. OBJECTIVES: To determine characteristics of childhood wheezing phenotypes in the first decade of life using health outcomes plus measurements of atopy, lung function and bronchial hyper-responsiveness. METHODS: A whole population birth cohort (n = 1456) was prospectively studied to examine the natural history of childhood wheezing. Children were seen at 1, 2, 4 and 10 years for questionnaire completion and prospectively collected data used to define wheezing phenotypes. Assessment was made of adverse health outcomes plus spirometry, bronchial hyper-responsiveness, serum IgE measurement at 10 years and skin test sensitization at both 4 and 10 years for wheezing phenotypes. RESULTS: Phenotypic analysis identified that 37% early life wheezers (symptom onset by age 4 years) still wheezed at 10 years. These persistent wheezers showed significantly more physician-diagnosed asthma in early life (P < 0.005 at 2 years) than early transient wheezers (wheezing transiently with onset by age 4 years). Overall they experienced greater multiple hospital admissions (P = 0.024), specialist referral (P = 0.009) and use of inhaled (P < 0.001) and oral steroids (P < 0.001) than early transient wheezers. They also demonstrated enhanced bronchial hyper-responsiveness compared with early transient wheezers (P < 0.001). However, both groups of early life wheezers showed impairment of baseline lung function at 10 years in comparison with non-wheezers: FEV1 (P < 0.029) and FEV1/FVC ratio (P < 0.001) with persistent wheeze and PEF (P = 0.036) with early transient wheeze. Late-onset wheezers (onset from 5 years onwards) had similar BHR to persistent wheezers but maintained normal lung function at age 10 and had lower cumulative prevalence of adverse health outcomes than persistent wheezers. CONCLUSIONS: Persistent wheezing with early childhood onset is associated with substantial morbidity in the first decade of life in association with high levels of atopy, bronchial hyper-responsiveness and impaired lung function at 10 years of age. Late-onset wheezing in the first decade of life could harbour potential for similarly significant disease subsequently.     

The protective effect of rural living against atopy in Mongolia

BACKGROUND: Farm environment in childhood protects against atopy. We investigated in a population-based study in Mongolia the effects of rural living and migration from rural to urban areas on the risk of atopy. METHODS: The screening study data of 9453 subjects, aged 10-60 years, were used for taking the sample for the clinical study in which 869 subjects were examined. Asthma, allergic rhinoconjunctivitis and sensitization were clinically defined and their risk factors analysed by logistic regression. RESULTS: The risks of allergic rhinoconjunctivitis [adjusted odds ratio (OR) 0.43, 95% confidence interval (CI) 0.19-0.98] and allergic sensitization (OR 0.26, 95% CI 0.13-0.55) were the lowest in subjects living in a village from birth and intermediate in subjects who had relocated from a village to a town (OR for rhinoconjunctivitis 0.68, 95% CI 0.36-1.27, OR for sensitization 0.62, 95% CI 0.35-1.12) compared with subjects living in a town from birth. Simultaneous exposure to herd animals and dung heating decreased the risk of atopy. Keeping animals was a risk-factor for asthma only in Ulaanbaatar city. CONCLUSIONS: Continuing farm exposure after childhood may be important in reducing the risk of atopy.     

Mediterranean diet is associated with reduced asthma and rhinitis in Mexican children

Background: Diet during pregnancy and childhood has been suggested to play an important role in children’s asthma risk. We assessed whether the adherence to a Mediterranean dietary pattern, for children in the last 12 months and their mothers during pregnancy, was associated with both childhood asthma and allergic rhinitis. Methods: A cross‐sectional study was conducted in 2004 using a random sample of 1476 children (6‐ to 7‐year old) from the Mexicali region, Mexico. Dietary data of children’s intake in the last 12 months and their mothers’ intake during pregnancy was collected, through a parental food frequency questionnaire. A Mediterranean diet score was computed [Trichopoulou et al., N Engl J Med 348 (2003), 2599]. Data on seven asthma and rhinitis‐related outcomes were obtained from the International Study of Asthma and Allergies in Childhood questionnaire. Results: Adherence to a Mediterranean dietary pattern was inversely associated with asthma ever (OR = 0.60, 95% CI = 0.40–0.91), wheezing ever (0.64, 0.47–0.87), rhinitis ever (0.41, 0.22–0.77), sneezing ever (0.79, 0.59–1.07), current sneezing (0.71, 0.52–0.96) and current itchy‐watery eyes (0.63, 0.42–0.95). No associations were found using the mothers’ pregnancy diet score, except for current sneezing (0.71, 0.53–0.97). Conclusions: Our findings suggest a protective effect of following a healthy dietary pattern on asthma and allergic rhinitis in Mexican children.     

Mode of delivery is not associated with asthma or atopy in childhood

BACKGROUND: Caesarean-section delivery has been associated with the subsequent development of atopy and wheezing in childhood. OBJECTIVE: To examine the association between mode of delivery (vaginal vs. caesarean section) and development of atopy, asthma and wheezing disorders in a population-based cohort of children. METHODS: The Avon Longitudinal Study of Parents and Children is a longitudinal birth cohort of children born 1 April 1991 to 31 December 1992. Mode of delivery was categorized as vaginal (including forceps and ventouse extractions) or caesarean section (elective and emergency). Primary outcomes were parental report of asthma or wheezing between 69 and 81 months of age, physician-diagnosed asthma (PDA) at 91 months of age and atopy at 7 years by skin prick testing. Possible confounding factors were considered in a multivariable logistic regression model. RESULTS: Total livebirths were 14,062, from which were selected 12 367 born to mothers resident in a defined area and delivered in one of two major obstetric hospitals. Of these infants, 10,980 (88.8%) were delivered vaginally and 1387 (11.2%) by caesarean section. Outcome data were available for 7495 (61%) subjects (asthma 69-81 months); 7389 (60%) (wheeze 69-81 months); 7196 (58%) (PDA 91 months) and 5916 (48%) (atopy 7 years). Adjusted odds ratios [95%confidence interval] for caesarean section compared with vaginal delivery were not statistically significant for any outcome we considered: asthma 69-81 months 1.16 [0.9, 1.5]; wheeze 69-81 months 0.95 [0.7, 1.3]; PDA 1.14 [0.9, 1.4]; atopy 1.04 [0.8, 1.3]. CONCLUSION: Delivery by caesarean section was not associated with the subsequent development of asthma, wheezing or atopy in later childhood in this population.     

Prevalence of Bronchial Asthma and Respiratory Symptoms in Schoolchildren in Oslo

During the school year 1980-81 a survey questionnaire was carried out among schoolchildren aged 7 to 15 years in Oslo. The survey population comprised 39,162 children attending compulsory primary school. The questionnaire was distributed to a random sample of 1772 children in 81 classes, forms 1 to 9, and the response rate was 95%. The prevalence of physician-diagnosis of current and cumulative asthma was 1.6% and 3.1%, respectively. Of those with current asthma 68% used asthma drugs regularly. Occasional wheezing and attacks of breathlessness were reported by 9% and 4%, respectively. Wheezing and breathlessness on exposure to pollen (4.5%), animals (3.1%) and exercise (5.5%) was reported more frequently than physician-diagnosis of asthma. The cumulative prevalence of either hay fever, eczema, urticaria or asthma was 17%. More boys than girls under the age of 12 had a physician-diagnosis of asthma.     

Clonorchis sinensis infection is positively associated with atopy in endemic area

Background Epidemiologic studies have suggested that helminth infections play a protective role against allergy; this inverse association, however, has not been consistent. Clonorchis sinensis, the liver fluke of human, is prevalent in the Far East. The association between C. sinensis infection and allergy has not yet been reported. Objective We evaluated the association between clonorchiasis and atopy or allergic diseases in adults in endemic areas of clonorchiasis. Methods A total of 1116 subjects (males 419, females 697; age range, 30–86; mean age=61 years) were recruited from two endemic areas of C. sinensis in Korea. Clonorchiasis was confirmed by stool examination. Allergic symptoms were evaluated with a modified ISAAC questionnaire, and atopy was defined by skin prick test for common inhalant allergens. Total serum IgE and C. sinensis‐specific IgE level was measured by ELISA and methacholine bronchial provocation test was performed to evaluate airway hyperresponsiveness (AHR). Results Clonorchiasis was positively associated with atopy [odds ratio (OR), 1.856; 95% confidence interval (CI), 1.199–2.873] and high levels of total serum IgE (OR, 1.455; 95% CI, 1.050–2.016). Higher association with clonorchiasis was shown in subjects who showed both atopy and high total serum IgE levels (OR, 2.540; 95% CI, 1.448–4.455). Clonorchiasis had no association with wheezing, AHR, asthma or allergic rhinitis. Conclusion and Clinical Relevance Clonorchiasis was positively associated with atopy in adults in endemic area. Cite this as: M‐H Choi, Y‐S Chang, M. K. Lim, Y. M. Bae, S‐T Hong, J‐K Oh, E. H. Yun, M‐J Bae, H‐S Kwon, S‐M Lee, H‐W Park, K‐U Min, Y‐Y Kim and S‐H Cho, Clinical & Experimental Allergy, 2011 (41) 697–705.     

Sibling effect on atopy in children of patients with asthma.

BACKGROUND: Multiple population studies have shown the presence of a sibling effect on atopic disease. However, it is unclear if the sibling effect is also of importance in subjects who are genetically at high risk for the development of atopy. OBJECTIVE: To study the presence of a sibling effect on markers of atopy (serum total IgE, specific IgE, skin tests) and asthma (bronchial hyper-responsiveness to histamine) in families ascertained through a parent with asthma. METHODS: First-degree offspring in 200 asthma families were studied (n = 541). Mixed effects regression models were used to account for the dependence of the observations within a family, and to adjust for possible confounding variables. RESULTS: Multiple regression analysis showed that having older siblings was inversely related to atopy, defined as >/= 2, >/= 3, >/= 4, or >/= 5 skin tests (P = 0.07-0.009). In addition, family size (number of siblings) had a significant protective effect on the presence of specific IgE to common aeroallergens (P = 0.03). Exposure to cigarette smoke in the first 3 years of life significantly increased the risk of having specific IgE to common aeroallergens (P = 0.04). No sibling effect was detected for serum total IgE or bronchial hyper-responsiveness to histamine. CONCLUSIONS: This study shows a protective sibling effect on the presence and severity of atopy but not on bronchial hyper-responsiveness in children who are genetically at risk. The identification of the sibling effect in high-risk families stresses the need to understand the basis of this effect, in order to design future prevention programmes.