Gestational age and occurrence of atopy at age 31—a prospective birth cohort study in Finland

BACKGROUND: It has been suggested that main risk factors for development of allergic diseases operate already during pregnancy and in early childhood. OBJECTIVE: To study the association between gestational age, birth weight, parity and parental farming with the risk of atopy and asthma in young adults. METHODS: In a prospective birth cohort study, 5192 subjects born in Northern Finland in 1966 were followed up at the age of 31. Skin prick tests were done to three of the most common allergens in Finland and to house dust mite. Data on doctor-diagnosed asthma was obtained from questionnaires. Perinatal data had already been collected during pregnancy. RESULTS: The risk of atopy increased linearly with increasing length of pregnancy among babies born in the 35th weak of gestation or later. Gestational age equal to, or over 40 weeks compared with less than 36 weeks was associated with an increased risk of atopy (multivariate odds ratio 1.65, 95% CI 1.16, 2.34). The association was stronger among farmers' children (P for interaction 0.01). High parity and being a farmer's child (multivariate odds ratio 0.50, 95% CI 0.42-0.60) was associated with decreased risk of atopy. In contrast, no associations were observed for doctor-diagnosed asthma. CONCLUSIONS: The results underline the importance of pregnancy and very early childhood in the development of atopy, and suggest that timing of the environmental exposure is of importance for the immune system. No association was observed for asthma, which may be due to the multifactorial origins of asthma.     

Early endotoxin exposure and atopy development in infants: results of a birth cohort study

BACKGROUND: Exposure to endotoxin in childhood is currently discussed to protect from the development of allergic diseases. OBJECTIVE: To study the effect of early endotoxin exposure on incidence of atopic sensitization, atopic dermatitis and wheezing until the age of 2 years in infants with different risk status in terms of parental atopy. METHODS: Data of 1942 infants of an ongoing birth cohort study were analysed by logistic regression. Endotoxin was measured in settled dust of the mothers' mattresses at infants' age of 3 months. Data on allergic symptoms and physicians' diagnoses were gathered by questionnaire. Sensitization to common food and inhalant allergens was assessed by specific serum IgE. RESULTS: High endotoxin levels increased the risk of repeated wheeze [adjusted odds ratio (OR) for 4th exposure quartile (Q4) 1.52, 95% confidence interval (CI) 1.08-2.14], but were associated with neither sensitization to food allergens nor atopic dermatitis. Stratification by parental atopy showed that there was an association of endotoxin exposure with incidence of repeated wheeze as well as with sensitization to inhalant allergens (P for trend = 0.008 and 0.044, respectively) only in infants with parental atopy, with the highest risk in the 4th exposure quartile (repeated wheeze: ORQ4 1.77, 95% CI 1.14-2.73; sensitization to inhalant allergens: ORQ4 1.69, 95% CI 0.70-4.11). CONCLUSION: Early endotoxin exposure in terms of mattress dust endotoxin levels seemed to increase the risk of atopic reactions to inhalant allergens at the age of 2 years, especially in infants at risk due to parental atopy. Our data disagree with an early protective effect of endotoxin on atopy development until the age of 2 years.     

Farming exposure in childhood, exposure to markers of infections and the development of atopy in rural subjects

BACKGROUND: Within the context of the hygiene hypothesis, we aimed to study the potential association between farming-related risk factors and Toxoplasma gondii (T. gondii) as well as Helicobacter pylori (H. pylori) seropositivity. METHODS: The study included questionnaire data and serum samples of 321 young adults living in a rural environment. Serum samples were analysed for specific IgE to a common panel of aeroallergens (SX1) as well as IgG against T. gondii and H. pylori. RESULTS: Regular contact with animal stables before the age of 3 years (odds ratio (OR) (95% confidence interval): 2.0 [1.0; 4.0]) and unpasteurized milk consumption at age 6 years (1.8 [1.0; 3.3]) were the strongest risk factors for T. gondii infection. None of the farming-related factors were significantly associated with H. pylori infection. Current consumption of raw farm milk was not significantly associated with H. pylori infection (2.1 [0.8; 5.3]). Regular contact with animal houses before the age of 7 years was the strongest predictor for atopy (0.49 [0.26-0.96]). The reduction in risk could not be further decreased by any other factor under consideration. After adjustment for animal house contact, the OR for atopy was decreased by raw milk consumption and H. pylori infection in an additive manner. CONCLUSION: Exposure to farming environments in childhood might predict T. gondii seropositivity in rural subjects. Nevertheless, the strongest predictor for atopy in rural subjects seems to be regular contact with farm animals. Whether T. gondii infection is an intermediate factor in the association between farm contact and atopy needs to be confirmed in larger studies.     

The development and prediction of atopy in high-risk children: Follow-up at age seven years in a prospective randomized study of combined maternal and infant food allergen avoidance

Background: The natural history of allergic disease and its potential for prevention merit close examination because of the explosive worldwide increase in the prevalence and morbidity of atopic disorders. This study examines the development of atopy at age 7 years in 165 children in a high-risk cohort, previously reported from birth to age 4 years. Methods: In this prospective, randomized, controlled study of food allergen avoidance in infancy, the prophylactic-treated group consisted of infants whose mothers avoided cow's milk, egg, and peanut during the last trimester of pregnancy and lactation and who, themselves, avoided cow's milk until age 1 year (casein hydrolysate supplementation before age 1), egg until age 2 years, and peanut and fish until age 3 years. The control group consisted of maternal/infant pairs who followed standard feeding practices. Results: Despite a significant reduction in food allergy and milk sensitization before age 2 years, none of the following differed between the groups at age 7 years: food allergy, atopic dermatitis, allergic rhinitis, asthma, any atopic disease, lung function, food or aeroallergen sensitization, serum IgE level, or presence of nasal eosinophils or nasal basophilic cells. Children with food allergy by 4 years evidenced higher 7-year (current) prevalences of allergic rhinitis and asthma (p < 0.01). Atopic diseases/parameters at age 7 years were shown, by multivariate analysis (p < 0.05), to be associated with several genetic and environmental risk factors (male gender, maternal nonwhite ethnicity and asthma, and household smoking), as well as predictive atopic markers during infancy (elevated serum IgE level; egg, cow's milk, and peanut sensitization; and nasal eosinophils and nasal basophilic cells). Conclusions: These findings help to: (1) elucidate the natural history of atopic disease in high-risk children; (2) document the progression of allergy from atopic dermatitis, food allergy, and food sensitization to respiratory allergy and aeroallergen sensitization despite food allergy prevention in infancy; (3) identify allergy predictive markers; and (4) expand our appreciation of the interactions of genetic and environmental factors in the development of atopy. (J ALLERGY CLIN IMMUNOL 1995;95:1179-90.)     

Neuropsychologic status at the age 4 years and atopy in a population-based birth cohort

Background:  Mental health has been reported to be associated with allergy, but only a few cohort studies have assessed if neurodevelopment predicts atopy.
Objective:  To investigate if neurobehavioral status of healthy 4-year-old children was associated with specific immunoglobulin E (IgE) at the same age and skin prick test results 2 years later.
Methods:  A population-based birth cohort enrolled 482 children, 422 of them (87%) provided neurobehavioral data, 341 (71%) had specific IgE measured at the age of 4 years; and 395 (82%) had skin prick tests completed at the age of 6 years. Atopy was defined as IgE levels higher than 0.35 kU/l to any of the three tested allergens at the age of 4 or as a positive skin prick test to any of the six tested allergens at the age of 6. McCarthy Scales of Child Abilities and California Preschool Social Competence Scale were the psychometric instruments used.
Results:  Twelve percent of children at the age of 4 and 17% at the age of 6 were atopic. Neurobehavioral scores were negatively associated with 6-year-old atopy after adjustment for socio-demographic and allergic factors, A relative risk of 3.06 (95% CI: 1.30–7.24) was associated with the lowest tertile (scorings ≤90 points) of the general cognitive scale. Similar results were found for verbal abilities, executive functions, and social competence. Asthma, wheezing, rhinitis, and eczema at the age of 6, but not at the age of 4, were associated with neurodevelopment at the age of 4.
Conclusions:  Neuropsychologic functioning and later atopy are negatively associated in preschool age children.     

The association of early life exposure to antibiotics and the development of asthma,eczema and atopy in a birth cohort: confounding or causality?

Background In general, studies reporting positive associations between antibiotic exposure and respiratory and allergic disease have been unable to determine the nature of this association.
Objective To examine the association between antibiotic exposure in infancy and the development of asthma, eczema and atopy in early childhood.
Methods In a birth cohort study, we collected reported antibiotic exposure before 3 months and before 15 months along with outcomes (wheeze, asthma, eczema, rash, inhaler use) at 15 months ( n =1011) and 4 years ( n =986). Atopy was measured using skin prick tests at 15 months.
Results We found significant univariate associations of antibiotic exposure before 3 months with asthma developing between birth and 15 months [OR 2.32 (95% CI 1.45–3.69)]. After adjustment for chest infections, this association reduced (OR=1.58, 95% CI 0.96–2.60) becoming marginally significant ( P =0.07). A marginally significant association of antibiotics with atopy (OR=1.44, 95% CI 0.96–2.14) in the univariate analysis also reduced after adjustment for chest infections (OR=1.36, 95% CI 0.91–2.05). There was no effect of antibiotic exposure before 15 months on asthma developing after 15 months and present between 3 and 4 years (OR=1.35 95% CI 0.85–2.14). Antibiotic exposure before 3 months was not associated with eczema and rash developing between birth and 15 months but exposure before 15 months was related to eczema [OR 1.83 (95% CI 1.10–3.05)] and rash [OR 1.61 (95% CI 1.02–2.53)] developing after 15 months and remaining present at 4 years. These effects reduced in the multivariate analysis.
Conclusions Our findings suggest that the effect of antibiotics on respiratory disease may be due to confounding by chest infections at an early age when asthma may be indistinguishable from infection.     

Serum IgE levels, atopy, and asthma in young adults: results from a longitudinal cohort study

To explore the natural history of asthma and its relation to allergic responses, we examined the relation between total serum IgE in early adulthood and a history of respiratory symptoms, airway hyperresponsiveness (AHR), and atopy during childhood. We studied 180 subjects aged 18–20 years who had been studied since the age of 8–10 years. We measured wheeze in the previous year by questionnaire, AHR by histamine inhalation test, atopy by skin prick tests, and serum IgE levels by immunoassay. Subjects with AHR in early adulthood had higher IgE levels (mean 257.0 IU/ml) than subjects with past AHR (mean 93.3 IU/ml) or with lifelong normal responsiveness (mean 67.6 lU/ml) ( P< 0.001). Subjects who had symptoms had higher IgE levels (mean 125.9 IU/ml) than those who were lifelong asymptomatic (mean 63.1 IU/ml) ( P< 0.001). Recent wheeze, AHR, and allergic sensitization all had a positive relation to serum IgE, but IgE was not more predictive of AHR than skin prick tests. The finding that young adults who are sensitized to common allergens are highly likely to have AHR even in the absence of symptoms is further evidence of the fundamental role of IgE-mediated responses in the natural history of AHR throughout childhood and into adulthood.     

Indoor survey of moulds and prevalence of mould atopy in Israel

BACKGROUND: Moulds are ubiquitous indoor as well as outdoor allergens and therefore potential candidates for indoor environmental control measures. However, very few studies have been performed to examine the significance of indoor moulds in allergic diseases and the effectiveness of measures to reduce the quantity of indoor moulds has not been established. OBJECTIVE: To determine the significance and the contribution of moulds to allergic manifestations. METHODS: Prevalence of allergic rhinitis and asthma in 395 members of a rural community were examined by questionnaire and examination of medical files. The atopic status in general and allergy to moulds was determined by skin-prick tests (SPTs) to a panel of aeroallergens including Aspergillus, Penicillium, Alternaria and Cladosporium. A study of indoor mould levels was performed by placing SDA plates in 59 houses. The type of fungi and the number of colonies from each species were recorded. RESULTS: Forty-two subjects, comprising 10.9% of the study group had positive SPT to moulds, 61.9% of those were classified as symptomatic. When taking into account individuals with a borderline positive SPT to moulds, an additional 23 had positive results. Of the 65 mould-positive subjects, 48% were symptomatic and of the 13 who were allergic to moulds alone, only two had allergic symptoms. Viable moulds were recovered from all 59 houses examined. The most common isolated genus was Aspergillus, followed by Penicillium, Alternaria and Cladosporium. Aspergillus was also the most abundant mould in houses. There was no significant correlation between the abundance of moulds, positive SPT to that mould and symptomatology. CONCLUSIONS: Viable moulds are common in houses in temperate climates. Allergy to moulds itself has a low predictive value to development of allergic symptoms, but allergy to moulds in otherwise atopic subjects increases the risk of symptomatic allergic disease.     

The complexities of defining atopy in severe childhood asthma

Background Defining atopy in children with severe, therapy‐resistant asthma is complex. There is currently no gold standard test; both skin prick testing (SPT) and allergen‐specific IgE (sIgE) are used. Furthermore, atopy is increasingly considered to be a spectrum, not an all‐or‐none phenomenon. Hypothesis SPTs and sIgE cannot be used interchangeably, and if both tests are not performed, opportunities for intervention will be missed. Furthermore, the severity of atopy will be defined differently by the two tests. Methods Cross‐sectional study of 47 children with severe, therapy‐resistant asthma, mean age 11.8 years, range 5.3–16.6 years, who underwent SPT, and measurement of total and sIgE as part of their clinical work‐up. Results Overall, 42/47 (89%) were atopic (defined as either one positive SPT or sIgE). There was 98% concordance between the two tests in classifying atopy. When each allergen was considered individually, in 40/200 (20%), the SPT and sIgE results were discordant, most commonly in 25/200 (12.5%), the SPT was negative and the sIgE was positive. House dust mite and cat sensitization were more likely detected by sIgE, but dog sensitization by SPT. When atopy was quantified, the sum of sIgEs compared with the sum of SPT weal diameter showed a moderate correlation (r²=0.44, P<0.001). Total IgE increased with an increasing number of positive sIgEs (P=0.028), but not significantly with increasing numbers of positive SPTs. Conclusion and Clinical Relevance SPT and sIgE identify group prevalence of atopy equally well; however, for individual allergens, concordance is poor, and when used to quantify atopy, SPTs and sIgE were only moderately correlated. In a clinical setting, if allergen avoidance is contemplated in children with severe, therapy‐resistant asthma, both tests should be performed in order to detect sensitization. Cite this as: J. Frith, L. Fleming, C. Bossley, N. Ullmann and A. Bush, Clinical & Experimental Allergy, 2011 (41) 948–953.     

Microbial content of drinking water in Finnish and Russian Karelia - implications for atopy prevalence

Background and aim: The influence of microbial quality of drinking water from different sources on the occurrence of atopy has been poorly examined. This study was undertaken to clarify the association between the overall microbial content in drinking water and the occurrence of atopy among schoolchildren from two neighbouring areas with profound differences in living conditions and lifestyles. Methods: Drinking water samples were obtained from kitchens of nine schools in North Karelia, Finland and of nine schools from Pitkäranta, the Republic of Karelia, Russia. The pupils of these schools were participants of the Karelian Allergy Study. Occurrence of atopy, determined by skin prick test positivity (one or more) to 14 common airborne and food allergens, was measured in all 563 children, aged 7–16 years, from these 18 schools. Water samples were analysed using standard methods for drinking water analyses including viable counts for Escherichia coli, intestinal enterococci, coliform bacteria and heterotrophic bacteria. In addition, total cell counts including both viable and nonviable bacteria, algae and protozoans were assessed using epifluorescence microscope with 4′‐6‐diamidino‐2‐phenylindole (DAPI) staining. Results: In Finland, 29% of the children were sensitized to birch when compared with 2% of the Russian children (P < 0.0001). Overall, sensitization rates for any of the pollens were 39% and 8% (P < 0.0001), and for any of the allergens 48% and 16%, respectively (P < 0.0001). Because of substantial differences in raw water sources and treatment practices, the total numbers of microbial cells in drinking water were many‐fold higher in Russia than in Finland. A dose–response relationship was found for occurrence of atopy and the DAPI value indicative of microbial cell content in the water (P < 0.0001). Further, multivariate logistic regression analysis revealed that high (>10⁶ cells/ml) and intermediate (10⁵–10⁶ cells/ml) DAPI values were associated with reduced risk of atopy (odds ratio 0.34, 95% confidence interval 0.20–0.57 and 0.39, 0.23–0.69, respectively), independently from other factors. Conclusion: High overall content of micro‐organisms in drinking water may be associated with reduced risk of atopy, independently from other determinants.