Season of Birth and Risk of Atopic Disease among Children and Adolescents

Background. Season of birth (SOB) has been regarded as a risk factor for atopy. The aim of this study was to explore the relationship between season of birth (SOB) and later development of atopic disease in children and adolescents. Methods. A total of 1,007 randomly selected subjects, 7 to 17 years of age, who were living in urban Copenhagen, Denmark were studied. All participants were interviewed about respiratory symptoms and possible risk factors for atopic disease. Skin test reactivity, serum total immunoglobulin E (IgE), and airway responsiveness were measured using standard techniques. Results. The overall risk of atopy, as judged by skin test reactivity and serum total IgE, was the same regardless of SOB. On the contrary, asthma was more common in subjects born in the autumn compared with subjects born during the remaining part of the year (12.4% vs. 5.6%), OR = 2.40, 95% CI (1.56–3.94), p < 0.001. This was observed both for atopic asthma OR = 2.41, 95% CI (1.25–4.64), p = 0.007, non-atopic asthma, OR = 2.35, 95% CI (1.14–4.83), p = 0.02, and house dust mite (HDM) sensitive airway hyperresponsiveness, OR = 3.00, 95% CI (1.44–6.24), p = 0.002. Rhinitis and pollen allergy were not significantly related to SOB. Conclusions. Atopy itself is independent of season of birth, whereas asthma is more prevalent among subjects born during the autumn. Regarding asthma, these results suggest that the first months of life enclose a period of particular vulnerability towards environmental risk factors, especially exposure to aeroallergens like HDM.     

Risk factors for asthma symptoms at school age: an 8-year prospective study.

Childhood recurrent wheezing is a very prevalent heterogeneous clinical entity. An 8-year prospective study was performed to correlate the clinical outcome of recurrent wheezing in the first years of life with prognostic risk factors. A cohort of 308 children with recurrent wheezing, aged <7 years, were enrolled in 1993, studied using a questionnaire, skin-prick tests, and serum total IgE. According to the study protocol, in 1996 and 2001, the cohort was assessed. In 2001, 81% of the initial sample was reevaluated (n=249); 61% remained symptomatic. Prevalence of atopy was 48% in 1993, 65% in 1996, and 75% in 2001. By logistic regression analysis, we identified the following as independent risk factors for asthma symptoms in the last year of the follow-up: personal history of rhinitis (odds ratio [OR] = 15.8, 95% confidence interval [CI], 6.1-40.8; p < 0.001), paternal asthma (OR =, 7.2; 95% CI = 1.7-29.7; p = 0.007), personal history of atopic dermatitis (OR = 5.9, 95% CI = 2.2-15.7; p < 0.001), maternal asthma (OR = 5.4, 95% CI = 1.7-17.1; p = 0.004), allergen sensitization (OR = 3.4, 95% CI = 1.2-10.4; p = 0.03), and onset of symptoms in the 2nd year or later in preschool-aged children (OR = 2.1, 95% CI = 1.1-4.8; p = 0.04). Kindergarten attendance before 12 months was identified as a protective factor (OR = 0.4, 95% CI = 0.2-0.9; p = 0.04). Among the 128 nonatopic children in 1993, 52% developed allergen sensitization. We identified as prognostic risk factors for asthma symptoms personal history of allergic disease, parental asthma, atopy, and late onset of symptoms. In a significant number of children clinical symptoms can occur years before allergen sensitization.     

Variants of endothelin-1 gene in atopic diseases.

BACKGROUND: Several studies suggest that the vasoactive peptide endothelin-1 (ET-1) could be involved in the pathophysiology of atopic asthma and allergic rhinitis. However, a possible involvement of polymorphisms of the corresponding gene in the origin of these conditions has so far not been subjected to a more comprehensive study. OBJECTIVE: This study investigates a possible association of two common polymorphisms in the ET-1 gene (TaqI in intron4 and BsiYI in position 138) with clinically manifested atopic diseases. The genetic linkage of these polymorphisms with the underlying phenotypes of asthma or parameters of atopy including total IgE level was examined, too. METHODS: The study included 456 subjects-270 Czech patients (Caucasians, Central Europe) with clinically manifested atopic diseases and 186 unrelated referent subjects with negative familial history of asthma/atopy. ET-1 genotypes were determined by PCR and restriction analysis by TaqI and BsiYI, respectively. RESULTS: No significant differences were found for the two polymorphisms between atopic patients and healthy subjects, or between subselected asthmatic patients and controls. However, the insertion exonic variant of ET-1 gene showed a significant association with signs of atopy, especially with total serum IgE levels (total IgE levels < or = 150 IU/ml turned out to be associated with DD genotypes, total IgE > 150 IU/ml with II and ID genotypes [OR = 3.76 (95% CI: 1.52-9.34), p = 0.003, Pc = 0.0061). CONCLUSIONS: These findings suggest that ET-1 may participate in the pathogenesis of high total serum IgE level in clinically manifested atopic diseases in our population.     

Early life exposures and risk of atopy among Danish children.

A large proportion of atopy develops in childhood and early life exposures are suspected to play a considerable role in the inception. The aim of this study was to examine the association between early life exposures and development of atopic disease in children. We performed a case-cohort study of a random population-based sample of children (n = 480) 7-17 years of age, living in urban Copenhagen, Denmark. Information on breast-feeding, supplementation, wheezy bronchitis, use of antibiotics, and parental smoking during pregnancy and in early life was obtained retrospectively by questionnaire. Skin test reactivity to 10 common aeroallergens was measured using standard techniques. Atopic disease was defined as a history of hayfever and/or asthma concomitantly with a positive skin-prick test. Logistic regression showed that parental atopy (odds ratio [OR] = 1.98; 95% confidence interval [CI], 1.12, 3.49; p = 0.019) and wheezy bronchitis before the age of 2 years (OR = 3.13; 95% CI, 1.63, 6.01; p < 0.001) were predictors of atopic disease, the latter especially when predisposition to atopy was present (OR = 8.63; 95% CI, 3.64, 20.44; p < 0.001). Duration of breast-feeding was longer in subjects with atopic heredity (p = 0.017), whereas smoking exposure during pregnancy (p = 0.019) and in the 1st year of life (p = 0.018) was less prevalent. Wheezy bronchitis was equally frequent among subjects with and without atopic predisposition (p = 0.893). Wheezy bronchitis before the age of 2 years seems to be independent of familial predisposition to atopic disease and significantly increases the likelihood for development of atopy in genetically susceptible individuals. Parental knowledge of atopic heredity significantly influences smoking and breast-feeding habits.     

Cigarette Smoking, But Not Sensitization to Alternaria, Is Associated with Severe Asthma in Urban Patients

Hereditary susceptibility and allergen exposure have been identified as general risk factors for asthma. However, risk factors for severe asthma still remain to be identified. To further assess and quantify risk factors associated with severe asthma in adult patients apart from clinical exacerbations, 306 randomly selected subjects (mean age 40 ± 17 years, 46% males) presenting to an inner city pulmonary practice between 1995 and 1996 were retrospectively investigated. Of these, 117 patients were atopic, 112 had current asthma, and 22 asthmatics had severe asthma. Risk factors associated with atopy were family history of atopy and any domestic pet ownership (OR: 3.1, 95% CI: 1.6-6.1). Asthma was generally associated with atopy (OR: 4.2, CI: 2.4-7.4) and pet ownership (OR: 2.4, CI: 1.2-4.6). Severe asthma was strongly associated with current smoking (OR: 4.8, CI: 1.3-18.3), and lung function was negatively correlated with the amount of consumed cigarettes per day (r = -0.61, p = 0.04). However, no association with sensitization to Alternaria was found in severe asthma. Cigarette smoking is an independent risk factor associated with severe asthma in urban patients, whereas sensitization to Alternaria is of less importance in these patients.     

广州城市青少年特应性与支气管哮喘的关系调查

目的了解广州城市青少年特应性的流行情况，探讨特应性与支气管哮喘（简称哮喘）的关系，明确主要的吸人性变应原。方法2002年4至5月在广州市参加儿童哮喘和变应性疾病的国际性对比研究（简称ISAAC）第三阶段调查的10所学校学生中，每所学校以班级为单位进行随机整群抽样调查。采用5组9种吸人性变应原（屋尘螨、粉尘螨、猫毛、美洲大镰、德国小镰、混合草花粉、混合树木花粉、链格孢属真菌、混合霉菌）对1187名学生进行皮肤点刺试验。哮喘定义为：既往或近12个月胸部有喘息声、胸闷或曾被医生诊断为哮喘，有哮喘、鼻炎、湿疹中的任1种疾病视为有变应性疾病史。变应原皮试反应的风团直径大于阴性对照3mm以上为阳性，有1个或以上变应原反应阳性视为特应性。特应性程度及变应原阳性反应强度分别以特应性指数（AI）及皮肤指数（SI）分级表示。结果随机抽取1543人参加调查，实际应答率为77．0％（1187／1543），其中男性为51．6％（613／1187），女性为48．4％（574／1187），年龄12～17岁（中位数14岁）。哮喘的患病率为9．4％（111／1187），其中合并鼻炎率为81．1％（90／111），合并湿疹率为24．3％（27／111）。686例有鼻炎史患者合并哮喘率为[13．1％（90／686）]，高于无鼻炎史者[4．2％（21／501），OR值为3．444，95％可信区间（CI）为2．110～5．622，P〈0．01]；200例有湿疹史患者合并哮喘率为[13．5％（27／200）]，也高于无湿疹史者[8．5％（84／987），OR值为1．676，95％CI为1．055～2．663，P〈0．05]。特应性阳性率为46．3％（549／1187），其中尘螨（屋尘螨、粉尘螨）皮试反应阳性率最高[分别为41．8％（496／1187）、42．7％（507／1187）]。哮喘患者特应性阳性率为[71．2％（79／111）]，高于无变应性疾病者[26．4％（112／425），OR值为6．812，95％CI为4．276～10．853，P〈0．01]，且随着合并其他疾病种类的增加而升高。与特应性阴性者比较，特应性阳性是哮喘的危险因素（OR值为3．183，95％CI为2．075～4．883，P〈0．01），且哮喘的患病风险随着特应性程度的增加而升高。单因素Logistic回归分析结果表明，哮喘的危险因素有屋尘螨（SI≥2）、粉尘螨（SI=3～4）、美洲大蠊、德国小蠊、猫毛、链格孢属、混合草花粉。多因素Logistic回归分析结果表明，屋尘螨（SI=3～4）、链格孢属阳性仍是哮喘独立的危险因素。结论广州城市青少年哮喘患者大多属尘螨变应性的，哮喘的患病风险随着特应性程度及屋尘螨皮试反应强度增加而升高。     

Markers of impaired growth of pulmonary function in children and adolescents.

Our knowledge about the age-related growth of pulmonary function is incomplete. The purpose of this study was to describe the relation of various factors to the growth of pulmonary function in children and adolescents. A population sample comprising 408 children and adolescents (7-17 yr of age at enrollment) was reexamined after a 6-yr interval. Case history was obtained by interview and questionnaire. Pulmonary function, skin prick test reactivity to common allergens, and airway responsiveness (AR) were measured using standard techniques; airway hyperresponsiveness (AHR) was defined as a concentration of histamine causing a 20% decline in FEV1 < 8 mg/ml. The cross-sectional analyses of data from the two surveys showed that the presence of asthma (p < 0.02), atopy to house dust mite (HDM) (p = 0.03), and increasing degree of AR (p < 0.002) were associated with a lower level of FEV1 %pred. The longitudinal analysis revealed that asthma (p = 0.0001) and a lower level of FEV1 (p < 0.0001) at enrollment were associated with a lower level of FEV1 at follow-up. Further, an increase in the degree of AR (p = 0. 0001), new asthma (p = 0.0002), and new atopy to HDM (p = 0.03) also predicted a lower level of FEV1 at the end of the observation period. Confining the analysis to subjects without asthma and without evidence of AHR (n = 271) showed that both persistent (p = 0.04) and new (p = 0.03) atopy to HDM predicted a lower level of FEV1 at follow-up; compared with subjects with a negative skin reaction to HDM, those subjects who were sensitized to HDM had on average a 5%pred lower level of FEV1. The growth of FEV1 in children and adolescents appears to be impaired not only by symptomatic asthma but also by an increase in the degree of AR and atopy to HDM; sensitization to HDM appears to have a negative impact on the age-related growth in FEV1 even in nonasthmatic subjects without evidence of AHR.     

Early life risk factors for current wheeze, asthma, and bronchial hyperresponsiveness at 10 years of age

STUDY OBJECTIVES: We sought to identify early life factors (ie, first 4 years) associated with wheeze, asthma, and bronchial hyperresponsiveness (BHR) at age 10 years, comparing their relative influence for these conditions. METHODS: Children were seen at birth, and at 1, 2, 4, and 10 years of age in a whole-population birth cohort study (1,456 subjects). Information was collected prospectively on genetic and environmental risk factors. Skin-prick testing was performed at 4 years of age. Current wheeze (in the last 12 months) and currently diagnosed asthma (CDA) [ie, current wheeze and ever-diagnosed asthmatic subject] were recorded at 10 years of age when BHR was measured at bronchial challenge. Independent significant risk factors for these outcomes were identified by logistic regression. RESULTS: Independent significance for current wheeze occurred with maternal asthma (odds ratio [OR], 2.08; 95% confidence interval [CI], 1.27 to 3.41) and paternal asthma (OR, 2.12; 95% CI 1.29 to 3.51), recurrent chest infections at 2 years (OR, 3.98; 95% CI, 2.36 to 6.70), atopy at 4 years of age (OR, 3.69; 95% CI, 2.36 to 5.76), eczema at 4 years of age (OR, 2.15; 95% CI, 1.24 to 3.73), and parental smoking at 4 years of age (OR, 2.18; 95% CI, 1.25 to 3.81). For CDA, significant factors were maternal asthma (OR, 2.26; 95% CI, 1.24 to 3.73), paternal asthma (OR, 2.30; 95% CI, 1.17 to 4.52), and sibling asthma (OR, 2.00; 95% CI, 1.16 to 3.43), recurrent chest infections at 1 year of age (OR, 2.67; 95% CI, 1.12 to 6.40) and 2 years of age (OR, 4.11; 95% CI, 2.06 to 8.18), atopy at 4 years of age (OR, 7.22; 95% CI, 4.13 to 12.62), parental smoking at 1 year of age (OR, 1.99; 95% CI, 1.15 to 3.45), and male gender (OR, 1.72; 95% CI, 1.01 to 2.95). For BHR, atopy at 4 years of age (OR, 5.38; 95% CI, 3.06 to 9.47) and high social class at birth (OR, 2.03; 95% CI, 1.16 to 3.53) proved to be significant. CONCLUSIONS: Asthmatic heredity, predisposition to early life atopy, plus early passive smoke exposure and recurrent chest infections are important influences for the occurrence of wheeze and asthma at 10 years of age. BHR at 10 years of age has a narrower risk profile, suggesting that factors influencing wheezing symptom expression may differ from those predisposing the patient to BHR.     

G-Protein-coupled receptor polymorphisms are associated with asthma in a large German population

RATIONALE: Recently, a new asthma susceptibility gene, GPRA (G-protein-related receptor for asthma), has been identified by positional cloning. Initial association studies in a Finnish and Canadian population suggested an association with asthma and elevated serum IgE levels. OBJECTIVE: In a large, nested case-control study, associations between GPRA polymorphisms, asthma, and serum IgE levels were analyzed. Methods: Using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) technology, 1,872 German children aged 9 to 11 years (including 624 children with asthma and/or bronchial hyperresponsiveness) were genotyped for seven polymorphisms in the GPRA gene. MEASUREMENTS: Hardy-Weinberg equilibrium was assessed, and association studies with single nucleotide polymorphisms (SNPs) and haplotypes were performed. MAIN RESULTS: SNP 546333 increased the risk for asthma (odds ratio [OR], 1.40; 95% confidence interval [CI], 1.04-1.88; p = 0.025) and concomitant asthma and bronchial hyperresponsiveness (BHR; OR, 2.38; 95% CI, 1.22-4.66; p = 0.009). Also, SNP 585883 was associated with asthma (OR, 1.34; 95% CI, 1.04-1.72; p = 0.022) and asthma in combination with BHR (OR, 2.71; 95% CI, 1.45-5.09; p = 0.001). Furthermore, SNP 585883 was associated with elevated serum IgE levels (OR, 1.63; 95% CI, 1.10-2.42; p = 0.015). Haplotype combinations of risk alleles increased the OR for asthma to 1.83 (95% CI, 1.08-3.08; p = 0.024) and for asthma and concomitant BHR to OR 3.51 (95% CI, 1.08-11.37; p = 0.036). CONCLUSIONS: These results indicate that GPRA polymorphisms increase the susceptibility for asthma and BHR, and to a lesser degree for the elevation of serum IgE, in a German population, confirming initial observations in other white populations.     

Allergic rhinitis, asthma, and atopy among grape farmers in a rural population in Crete, Greece

STUDY OBJECTIVE: To measure the prevalence of allergic rhinitis, atopy, and asthma among grape farmers, and to compare the respiratory and atopic status in grape farmers with those of nonexposed control subjects. DESIGN: Cross-sectional study. SETTING: Malevisi region in northern Crete, Greece. SUBJECTS AND METHODS: One hundred twenty grape farmers and 100 control subjects living in the Malevisi region were examined. The protocol comprised a questionnaire, skin prick tests for 16 common allergens, measurement of specific IgE antibodies against 8 allergens, and spirometry before and after bronchodilation. RESULTS: Grape farmers were found to have an excess of respiratory symptoms. The comparison with the control group, after adjusting for age, sex, and smoking status, showed that the differences were statistically significant for rhinorrhea (odds ratio [OR], 2.7; 95% confidence interval [CI], 1.5 to 5.1; p < 0.001), sneezing (OR, 2.2; 95% CI, 1.2 to 4.0; p < 0.01), and nasal itching (OR, 1.9; 95% CI, 1.0 to 3.6; p < 0.05), but were nonsignificant for asthma-related symptoms. In the multiple logistic regression model, grape farmers were found to have increased work-related symptoms, such as sneezing (OR, 2.9; 95% CI, 1.3 to 6.6; p < 01), rhinorrhea (OR, 2.9; 95% CI, 1.3 to 6.6; p < 0.01), cough (OR, 3.7; 95% CI, 1.2 to 11.4; p < 0.05), and dyspnea (OR, 3.8; 95% CI, 1.1 to 1.3; p < 0.05). The prevalence of allergic rhinitis was 40.8% in grape farmers and 26% in control subjects (OR, 2.0; 95% CI, 1.1 to 3.5; p < 0.02). Increased but statistically nonsignificant values of asthma prevalence were found in grape farmers (6.7%) compared with the control group (2.0%). The prevalence of atopy was 64.2% in grape farmers and 38.0% in the control group (OR, 2.2; 95% CI, 1.2 to 3.5; p < 0.01). Mean FEV1 was significantly lower in grape farmers than in control subjects (p < 0.05), after adjusting for age, sex, and smoking status. Bronchial obstruction was reversible in 23 grape farmers (19.2%) and in 6 control subjects (6%; p < 0.01). CONCLUSIONS: The study mainly demonstrated the high prevalence of allergic rhinitis and work-related respiratory symptoms in grape farmers compared to control subjects. It also suggested that grape farming is possibly associated with increased allergic sensitization to specific pollens, low baseline FEV1, and increased bronchial hyper-responsiveness. Further studies are needed to determine the potential risk factors for these disorders among the farming population.     

Obesity is not Associated with Mild Asthma Diagnosis in a Population of Spanish Adults

Background. Several studies have suggested a relationship between asthma and obesity. Moreover, atopy is an important risk factor for asthma, but the relationship between obesity and atopy is uncertain. Methods. A cross-sectional multicenter study was conducted in a population of Spanish adults between November 2007 and July 2008. The subjects included had experienced asthma symptoms in the last year but had a forced expiratory volume in 1 second (FEV₁)/forced vital capacity (FVC) > 70%. Mild asthma diagnosis was confirmed by measuring airway hyperresponsiveness to methacholine. Body mass index in kg/m² was used as measure of obesity. Subjects were considered atopic when they had at least one positive skin prick test to common aeroallergens. Adjusted odd ratios (OR) were obtained by logistic regression. Results. A total of 662 subjects were included and 234 subjects (35.3%) were diagnosed with asthma (consistent symptoms and positive methacholine test). After adjusting the model for age, gender, atopy, baseline FEV₁, and FEV₁/FVC ratio, there was no association between overweight or obesity with asthma diagnosis, with OR of 0.889 (95% CI, 0.60–1.38) and 0.925 (95% CI, 0.577–1.48), respectively. A multivariable logistic regression analysis confirmed that atopy increases the risk of asthma (p = 0.008). The non-atopic obese group had an increased risk of asthma compared to the non-atopic group with normal weight or overweight (p = 0.0032). Conclusions. In this study obesity was not associated with a diagnosis of asthma. The presence of atopy was a risk factor for asthma, independent of obesity. Obesity, however, may be a risk factor for the development of asthma among non-atopic subjects.     

Gut microbiota composition and development of atopic manifestations in infancy: the KOALA Birth Cohort Study

BACKGROUND AND AIMS: Perturbations in intestinal microbiota composition due to lifestyle changes may be involved in the development of atopic diseases. We examined gut microbiota composition in early infancy and the subsequent development of atopic manifestations and sensitisation. METHODS: The faeces of 957 infants aged 1 month and participating in the KOALA Birth Cohort Study were analysed using quantitative real-time PCR. Information on atopic symptoms (eczema, wheeze) and potential confounders was acquired through repeated questionnaires. Total and specific IgE were measured in venous blood samples collected during home visits when the infant was 2 years old. During these home visits a clinical diagnosis of atopic dermatitis was made according to the UK-Working Party criteria. RESULTS: The presence of Escherichia coli was associated with a higher risk of developing eczema (OR(adj) = 1.87; 95% CI 1.15 to 3.04), this risk being increased with increasing numbers of E coli (p(for trend) = 0.016). Infants colonised with Clostridium difficile were at higher risk of developing eczema (OR(adj) = 1.40; 95% CI 1.02 to 1.91), recurrent wheeze (OR(adj) = 1.75; 95% CI 1.09 to 2.80) and allergic sensitisation (OR(adj) = 1.54; 95% CI 1.02 to 2.31). Furthermore, the presence of C difficile was also associated with a higher risk of a diagnosis of atopic dermatitis during the home visit (OR(adj) = 1.73; 95% CI 1.08 to 2.78). CONCLUSION: This study demonstrates that differences in gut microbiota composition precede the development of atopy. Since E coli was only associated with eczema and C difficile was associated with all atopic outcomes, the underlying mechanisms explaining these association may be different.     

Factors Associated with Severe Disease in a Population of Asthmatic Children of Bogota, Colombia

Background. There is evidence that prevalence and severity of asthma in children has risen. Risk factors for severe asthma have been studied extensively in children living in developed countries, but little is known about factors determining the severity of asthma in Latin American countries. The aim of this study was to investigate the role of suspected, potential risk factors for asthma severity in a population of children living in urban Bogota. Methods. We studied 175 children, 2 to 16 years old, with asthma attending an asthma clinic. Severe cases and nonsevere asthmatic subjects were compared regarding suspected, potential pre-, peri-, and postnatal risk factors. Results. After controlling for asthma duration, we found that children never breast fed (OR, 11.53; 95% CI, 2.35-56.50; p = 0.003), mothers 30 years or younger at the child's birth (OR, 3.44; 95% CI, 1.23-9.63; p = 0.019), usual use of acetaminophen for fever in the child in the 12 months previous to the survey application (OR, 3.13; 95% CI, 1.14-8.56; p = 0.026), older siblings at birth (OR, 3.81; 95% CI, 1.28-11.32; p = 0.016), and primary or secondary school as the highest level of education attained by mother (OR, 3.20; 95% CI, 1.01-10.07; p = 0.046) were all independent predictors of severe asthma. Conclusion. No breastfeeding, maternal age at child's birth of less than 30 years, routine use of acetaminophen for fever in the child in the 12 months previous to the survey application, older siblings at birth, and primary or secondary school as the highest level of education attained by mother were independent predictors of severe asthma. Some of these risk factors are clearly modifiable. Further prospective, population-based studies with a bigger sample size and a more representative sample of the general population residing in the city are needed to retest and clarify these associations.     

Home exposures, parental atopy, and occurrence of asthma symptoms in adulthood in southern Taiwan

OBJECTIVE: Parental atopy and environmental exposures at home have been recognized risk factors for adulthood asthma. However, the relative contributions of specific risk factors and the overall contributions of heredity or home exposure remain unexplored. The purpose of this study was to identify predictors and estimate the population attributable risk (PAR) of each exposure for typical asthma symptoms among 26- to 50-year-old Taiwanese. We also investigated whether an interactive effect existed between parental atopy and home exposures on the occurrence of asthma symptoms in adulthood. DESIGN: A cross-sectional study with retrospective components. SETTING: Elementary and middle schools in Southern Taiwan. SUBJECTS: Between March and October 2004, we conducted a cross-sectional survey among schoolchildren's parents from 94 elementary and middle schools in Southern Taiwan. The main outcome measure was typical asthma-like symptoms occurring within the preceding 5 years. Information on hereditary and home exposures was collected by using a self-administered questionnaire. RESULTS: After excluding unqualified questionnaires, data from 24,784 subjects were left for analysis. New-onset asthma was reported for 0.83% of male (n = 80 of 9,662) and 1.36% of female subjects (n = 206 of 15,122). Besides parental atopic factors, environmental tobacco smoke or pet avoidance and visible mold on walls at home were independently associated with the occurrence of asthma symptoms. Mutually adjusted models produced statistically significant associations between any home exposure (odds ratio [OR], 1.80; 95% confidence interval [CI], 1.08 to 3.23; PAR, 28.04%), parental atopy (OR, 4.47; 95% CI, 3.47 to 5.75; PAR, 31.38%), and new-onset asthma. However, there was no interaction between parental atopy and home exposures. CONCLUSIONS: Home exposures and parental atopy both increased the risks of new-onset asthma in adulthood but did not show an interactive effect. These two exposure categories approximately contributed equally to the adulthood asthma.     

Elevated exhaled nitric oxide in newborns of atopic mothers precedes respiratory symptoms

RATIONALE: Exhaled nitric oxide (NO) is a well-known marker of established airway inflammation in asthma. Its role in the disease process before the onset of respiratory symptoms remains unclear. Objectives: To examine whether elevated NO in newborns with clinically naive airways is associated with subsequent respiratory symptoms in infancy. METHODS: We measured exhaled NO concentration and output after birth and prospectively assessed respiratory symptoms during infancy in a birth cohort of 164 unselected healthy neonates. We examined a possible association between NO and respiratory symptoms using Poisson regression analysis. RESULTS: In infants of atopic mothers, elevated NO levels after birth were associated with increased risk of subsequent respiratory symptoms (risk ratio [RR], 7.5; 95% confidence interval [CI], 1.7-32.4 for each nl/s increase in NO output; p = 0.007). Similarly, a positive association between NO and symptoms was seen in infants of smoking mothers (RR, 6.6; 95% CI, 2.3-19.3; p = 0.001), with the strongest association in infants whose mothers had both risk factors (RR, 21.8; 95% CI, 5.8-81.3; p < 0.001). CONCLUSIONS: The interaction of NO with maternal atopy and smoking on subsequent respiratory symptoms is present early in life. Clinically, noninvasive NO measurements in newborns may prove useful as a new means to identify high-risk infants. Future confirmation of a role for NO metabolism in the evolution of respiratory disease may provide an avenue for preventative strategies.     

Airway responsiveness: associated features in infants with recurrent respiratory symptoms.

Increased airway responsiveness (AR) is one of the main pathophysiological manifestations of asthma. The present study aimed to define the clinical features associated with increased AR in infants with recurrent lower respiratory tract symptoms. AR was evaluated by performing a novel dosimetric methacholine challenge test. Increased AR to methacholine, defined as a methacholine dose of < or =0.90 mg producing a 40% fall (PD(40)) in the maximal flow at functional residual capacity (V'(max,FRC)), was associated with atopy (odds ratio (OR) 4.1; 95% confidence interval (CI) 1.3-13.3), a history of physician-confirmed wheezing with respiratory syncytial virus (OR 32.9; 95% CI 2.5-428.8) or of a nonspecified aetiology (OR 4.9; 95% CI 1.1-22.5), functional residual capacity z-score > or =2 (OR 36.8; 95% CI 2.9-472.6), and V'(max,FRC) z-score (OR 0.5; 95% CI 0.2-0.9) at baseline, when compared with infants with only mild or no responsiveness to methacholine (PD(40) V'(max,FRC) >0.90 mg). In conclusion, in recurrently symptomatic infants, increased airway responsiveness is associated with reduced baseline lung function, an atopic trait of the child, a history of physician-confirmed wheeze and viral aetiology of wheeze. Future intervention studies are needed to confirm the role of airway responsiveness in respiratory morbidity during infancy.     

The effects of respiratory infections, atopy, and breastfeeding on childhood asthma.

The objectives of the present study were to quantify the association of atopy and respiratory infections with asthma, and exclusive breastfeeding with respiratory illness, atopy and asthma in children. A cohort study of 2,602 children enrolled prior to birth and followed prospectively, provided data on respiratory illness, the method of feeding in the first year of life, as reported on a prospective diary card, and current asthma at the age of 6 yrs (defined as doctor-diagnosed asthma with wheeze in the last year or cough without a cold, and currently taking either preventer or reliever asthma medication), as reported by parental questionnaire. Atopy was defined by a positive skin-prick test assessed at the age of 6 yrs. Wheezing lower respiratory illness (LRI) in the first year of life, particularly multiple episodes of wheezing LRI, increased the risk for current asthma in both nonatopic (odds ratio (OR) 4.10, p< or =0.0005) and atopic children (OR 9.00, p< or =0.0005), but did not increase the risk for atopy. In contrast, up to three upper respiratory tract infections demonstrated a negative association and four or more a positive risk for current asthma in unadjusted (p=0.006) and adjusted (p=0.057) analysis. Following adjustment, exclusive breastfeeding for <4 months was associated with an increased risk for current asthma (OR 1.36, 95% confidence interval 1.00-1.85, p=0.047). Wheezing lower respiratory illness in the first year of life and atopy are independently associated with increased risk for current asthma at the age of 6 yrs, suggesting that their effects are mediated via different causal pathways and that these risk factors are multiplicative when they operate concomitantly within individual children. Exclusive breastfeeding protects against asthma via effects on both these pathways, as well as through other as yet undefined mechanisms.     

Day care attendance in early life,maternal history of asthma,and asthma at the age of 6 years

Among children not selected on the basis of a parental history of atopy, day care attendance in early life is inversely associated with asthma at school age. We examined the relation between day care in the first year of life and asthma, recurrent wheezing, and eczema at the age of 6 years and wheezing in the first 6 years of life among 453 children with parental history of atopy followed from birth. Among all study participants, day care in the first year of life was inversely associated with eczema (odds ratio [OR] = 0.3, 95% confidence interval [CI] = 0.1-0.8). Day care attendance in early life was associated with a decreased risk of asthma (OR = 0.3, 95% CI = 0.1-0.7) and recurrent wheezing (OR = 0.3, 95% CI = 0.1-0.9) at the age of 6 years and with a decreased risk of any wheezing after the age of 4 years only among children without maternal history of asthma. Among children with maternal history of asthma, day care in early life had no protective effect on asthma or recurrent wheezing at the age of 6 years but was instead associated with an increased risk of wheezing in the first 6 years of life. Our findings suggest that maternal history of asthma influences the relation between day care-related exposures and childhood asthma.     

Acetaminophen intake and risk of asthma, hay fever and eczema in early adolescence

A positive association between acetaminophen intake and allergic diseases has recently been reported in developed countries with impaired oxidant/antioxidant balance and promotion of atopy as proposed underlying mechanisms. The aim of the study was to explore the relationship between acetaminophen intake and asthma, hay fever, and eczema in The Republic of Macedonia as a country with acetaminophen intake not physician-controlled, high passive smoke exposure and dietary antioxidant intake, and moderately low prevalence of allergic diseases. Self-reported data obtained through the standardized International Study of Asthma and Allergies in Childhood Phase Three written questionnaires of 3026 adolescents aged 13/14 years from randomly selected schools in Skopje, the capital of Macedonia, were used. The frequency of current acetaminophen intake--both unadjusted and adjusted for confounding factors--was correlated to current and ever-diagnosed asthma, hay fever and eczema by odds ratios (OR, 95% CI) in binary logistic regression. Use of acetaminophen at least once monthly increased the risk of current wheeze (adjusted OR 2.04, 1.31-3.20 p = 0.002), asthma 'ever' (adjusted OR 2.77, 1.06-7.26 p=0.039), current allergic rhinoconjunctivitis (adjusted OR 2.95, 1.79-4.88 p=0.000) and hay fever 'ever' (adjusted OR 2.25, 1.36-3.70 p=0.002). A significant association between frequent acetaminophen intake and atopic eczema and also between infrequent acetaminophen intake and investigated allergic diseases was not established. The findings suggest an increased risk of asthma and hay fever, but not atopic eczema associated with frequent acetaminophen use in a developing country.     

Respiratory symptoms and lung function in relation to atopy in children born preterm

Respiratory morbidity is a major health problem among children. The aim of this study was to compare the background of respiratory problems of children born preterm with that of children born full-term, with special reference to atopy. The study comprised two cohorts of 10-year-old children: a group of 72 children born preterm with birth weights of less than 1,501 g, and a group of 65 children born full-term with birth weights of over 2,500 g. Histories of respiratory and atopic symptoms, and of risk factors for atopy, were collected with a questionnaire. Predisposition to atopy was verified by skin-prick testing and by measuring serum total and antigen-specific IgEs. Lung function was evaluated by spirometry testing. Children born preterm had significantly more wheezing. In them, the lifetime prevalence of wheezing was 43%, vs. 17% in children born full-term (P = 0.001; odds ratio, 3.71; 95% confidence interval, 1.67-8.25). In the full-term group, wheezing was associated with atopy: 64% of wheezers were atopic; in the preterm group, 23% of wheezers were atopic (difference between groups, P = 0.024). Children born preterm expired significantly lower spirometry values of forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1), FEV1/FVC ratio, forced expiratory flow after 50% of vital capacity has been exhaled (FEF50), and forced expiratory flow during middle half of FVC (FEF25-75). In the preterm group, wheezing, asthma, and low gestational age, but not atopy, were significantly associated with lower lung function values. Wheezers of the preterm group who still wheezed at age 10 were significantly more often atopic than those who no longer wheezed (62% vs. 9%, P = 0.006). In conclusion, we demonstrated a significant difference between groups in the association of atopy with respiratory problems. However, although atopy was not associated with a lifetime prevalence of respiratory symptoms in prematurely born children, an atopic predisposition in them was found to associate with persistence of wheezing.