Early-life exposure to environmental microbial agents may be associated with the development of allergies. The aim of the study was to identify better ways to characterize microbial exposure as a predictor of respiratory symptoms and allergies.
A birth cohort of 410 children was followed up until 6 years of age. Bacterial endotoxin, 3-hydroxy fatty acids, N-acetyl-muramic acid, fungal extracellular polysaccharides (EPS) from Penicillium and Aspergillus spp., ß-D-glucan, ergosterol, and bacterial or fungal quantitative polymerase chain reactions (qPCRs) were analyzed from dust samples collected at 2 months of age. Asthma, wheezing, cough, and atopic dermatitis were assessed using repeated questionnaires. Specific IgEs were determined at the age of 1 and 6 years.
Only few associations were found between single microbial markers and the studied outcomes. In contrast, a score for the total quantity of microbial exposure, that is, sum of indicators for fungi (ergosterol), Gram-positive (muramic acid) bacteria, and Gram-negative (endotoxin) bacteria, was significantly (inverted-U shape) associated with asthma incidence (P
Most previous studies on the association between moisture damage and asthma have been cross-sectional and relied on self-reported exposure and health. The present authors studied the association by carrying out careful home inspections among new, clinically determined cases of asthma and controls. New cases of asthma aged 12-84 months (n = 121) were recruited prospectively and matched for year of birth, sex and living area with two randomly selected population controls (n = 241). Trained engineers visited all homes. Both cases and controls had lived >or=75% of their lifetime or the past 2 yrs in their current home. Risk of asthma increased with severity of moisture damage and presence of visible mould in the main living quarters but not in other areas of the house. Cases more often had damage in their bedroom. Associations were comparable for atopic and nonatopic asthma and for children aged >30 months or
It has been suggested that main risk factors for development of allergic diseases operate already during pregnancy and in early childhood.
To study the association between gestational age, birth weight, parity and parental farming with the risk of atopy and asthma in young adults.
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.
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.
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.
The primary aim of the study was to evaluate the prevalences of allergic rhinitis and atopic dermatitis and their regional differences among Finnish children. The secondary objective was to determine whether the responses to the questions used are affected by the pollen season if asked during such a season. In 1994-5, the self-reported prevalence of allergic symptoms in four regions of Finland was studied among 11,607 schoolchildren aged 13-14 years, as part of the International Study of Asthma and Allergies in Childhood (ISAAC). The prevalence of rhinoconjunctivitis during the preceding year was 16% in eastern Finland (Kuopio County, n=2821), 23% in southern Finland (Helsinki area, n=2771), 15% in southwestern Finland (Turku and Pori County, n=2983), and 16% in northern Finland (Lapland, n=3032). The respective prevalences of flexural dermatitis were 15%, 19%, 16%, and 18%. The surveys were performed in winter, except in the Helsinki area where the survey was carried out mainly in the spring pollen season. Among the children studied in autumn in Helsinki, the prevalence of rhinoconjunctivitis was 19% and that of flexural dermatitis 17%. In multivariate analysis, flexural dermatitis was slightly more common in Lapland than in all other areas. In contrast, no significant differences were found in rhinoconjunctivitis. The prevalences of both disorders were twice as high in girls as in boys. In conclusion, regional differences in the prevalence of allergic rhinitis and atopic dermatitis were small in our country, and the prevalence figures were rather similar to those reported from other European countries. Almost half of the children had suffered from at least one atopic disorder, and over one-third had had symptoms in the past year. A clear season-of-response effect was observed; the prevalence of rhinoconjunctivitis was 25% when studied during the pollen seasons in the Helsinki area.
The aim of this study was to determine whether there are regional differences in the prevalence of childhood asthma in Finland. A secondary objective was to assess the concordance between a written and a video questionnaire on asthma symptoms. In 1994-1995, the self-reported prevalence of asthma symptoms in four regions of Finland was studied among 11,607 schoolchildren aged 13-14 yrs, as part of the International Study of Asthma and Allergies in Childhood (ISAAC). The ISAAC written and video (AVQ 3,0) questionnaires were administered in the school setting. The prevalences of any wheezing during the previous 12 months in the ISAAC video questionnaire were 10% in East Finland (Kuopio County, n=2,821), 12% in South Finland (Helsinki area, n=2,771), 12% in Southwest Finland (Turku and Pori County, n=2,983), and 11% in North Finland (Lapland, n=3,032). The prevalences in the ISAAC written questionnaire were 13, 20, 15, and 16%, respectively. The surveys were performed during winter, except in Helsinki where the survey was carried out mainly during the spring pollen season. During autumn, the prevalence in the written questionnaire in Helsinki was 16%. In multivariate analysis, boys had a lower prevalence than girls, and smokers a threefold higher prevalence than nonsmokers. In conclusion, the prevalence of childhood asthma is lower in Finland than in other European countries, and may be even lower in the eastern part of the country. In contrast to the results from some other European countries, prevalences were lower in the video than in the written questionnaire, which suggests that translating the word "wheezing" into other languages, including Finnish, may produce results that cannot be compared. The strong association of smoking with wheeze both in the video and written questionnaires should be considered in further analysis of the ISAAC study.
BACKGROUND: The high and increasing prevalence of childhood asthma is a major public health issue. Various risk factors have been proposed in local studies with different designs. METHODS: We have made a questionnaire study of the prevalence of childhood asthma, potential risk factors and their relations in four regions in Scandinavia (Umeå and Malmö in Sweden, Kuopio in eastern Finland and Oslo, Norway). One urban and one less urbanized area were selected in each region, and a study group of 15962 children aged 6-12 years was recruited. RESULTS: The prevalence of symptoms suggestive of asthma varied considerably between different areas (dry cough 8-19%, asthma attacks 4-8%, physician-diagnosed asthma 4-9%), as did the potential risk factors. Urban residency was generally not a risk factor. However, dry cough was common in the most traffic polluted area. Exposure to some of the risk factors. such as smoking indoors and moisture stains or moulds at home during the first 2 years of life, resulted in an increased risk. However, current exposure was associated with odds ratios less than one. CONCLUSIONS: Our findings were probably due to a combination of early impact and later avoidance of these risk factors. The effects of some risk factors were found to differ significantly between regions. No overall pattern between air pollution and asthma was seen, but air pollution differed less than expected between the areas.
Studies have shown that perinatal factors are associated with childhood asthma. The current analyses examined the association between obstetric complications and risk of asthma at the age of 7 years using a prospectively population-based birth cohort in northern Finland. Results indicated that obstetric complications were associated with a higher risk of asthma among children. Those children who were administered special procedures at birth, i.e., cesarean section, vacuum extraction, and other procedures, including use of forceps, manual auxiliary, and extraction breech, had an adjusted odds ratio (OR) for asthma of 1.38 (95% confidence interval [CI] 1.00-1.92), 1.32 (95% CI 0.80-2.19), and 2.14 (95% CI 1.06-4.33), respectively, as compared to children who were delivered normally. Children who had a lower Apgar score at the first and the fifth minute after birth also had a higher risk as compared to those who had an Apgar score of 9-10. The results encourage further evaluation of the association between obstetric complications and risk of asthma among children in other populations, and further exploration of possible mechanisms underlying the association.
The association of serum cholesterol with cause-specific and all-cause mortality was assessed in a cohort of 1,426 men aged 40-59 years who were free of clinically evident heart disease at baseline (1959). A total of 748 deaths (53 percent of the participants) occurred during the 25-year follow-up period. Men with high serum cholesterol levels at baseline had high mortality due to coronary heart disease during both the early and later parts of the follow-up period. In contrast, the association of serum cholesterol with mortality due to causes other than coronary heart disease changed during follow-up (interaction of cholesterol with follow-up period: p = 0.004). During the first 10 years of follow-up, despite their high coronary mortality, men with high cholesterol levels had lower all-cause mortality (age-adjusted relative risk = 0.71 for serum cholesterol above 5.79 mmol/liter vs. below 5.80 mmol/liter; p = 0.03) because of their low cancer mortality (relative risk = 0.55, p = 0.03) and residual mortality (relative risk = 0.49, p less than 0.01). During the last 15 years of follow-up, cholesterol at baseline was no longer associated with mortality due to causes other than coronary heart disease, and consequently, because of their high coronary mortality, men with high cholesterol levels also had higher all-cause mortality (relative risk = 1.22, p = 0.05). The results suggest that to fully analyze the association of serum cholesterol with all-cause mortality, the follow-up period should be sufficiently long--possibly more than 10 years--and the possibility of a change in the direction of the association studied should always be considered.
The association of baseline serum total cholesterol, systolic blood pressure, smoking and body mass index with coronary heart disease (CHD) mortality was analyzed among 1,619 men aged 40-59 at baseline. Analyses were made separately for the first, second and third decade of follow-up. Serum cholesterol and smoking more than 9 cigarettes daily were strong predictors of risk of CHD death (n = 450) occurring early and late during the 30-year follow-up. After 20 years of follow-up, systolic blood pressure was no longer associated with CHD risk. In contrast, highest tertile of body mass index (over 24.7 kg/m2) was only then associated with increased CHD risk. The correlations between the baseline and the 30-year risk factor values were 0.42 for serum cholesterol (n = 444), 0.28 for systolic blood pressure (n = 444) and 0.57 for body mass index (n = 429). Our results showed large differences in the long-term predictive power of the classical coronary risk factors. The reasons for these differences are discussed.
In the retrospective cohort study based on record linkage, the authors studied a cohort of persons born in 1900-1930 (n = 144,627), who had lived in the same rural location at least from 1967 to 1980. Estimates for fluoride concentrations (median, 0.1 mg/liter; maximum, 2.4 mg/liter) in well water in each member of the cohort were obtained by a weighted median smoothing method based on ground water measurements. Information on hip fractures was obtained from the Hospital Discharge Registry for 1981-1994. No association was observed between hip fractures and estimated fluoride concentration in the well water in either men or women when all age groups were analyzed together. However, the association was modified by age and sex so that among younger women, those aged 50-64 years, higher fluoride levels increased the risk of hip fractures. Among older men and women and younger men, no consistent association was seen. The adjusted rate ratio was 2.09 (95% confidence interval: 1.16, 3.76) for younger women who were the most exposed (>1.5 mg/liter) when compared with those who were the least exposed (
It has recently been suggested that an atopic phenotype may already be programmed in utero. We examine here the association between prenatal factors and the subsequent development of allergic rhinitis and eczema among offspring.
The analyses were based on 8088 children in a population-based prospective birth cohort started in northern Finland in 1985-6.
The prevalences of allergic rhinitis and allergic eczema by the age of 7 years among 8088 children were 3.3% and 6.7%, respectively. The results indicate that low parity, febrile infections in pregnancy, and the use of contraceptives before pregnancy increased the risk of allergic disorders among children. Bleeding in the first trimester and a greater weight gain during pregnancy appeared to be risk factors for rhinitis only. Children whose mothers experienced infections in the first trimester had ORs of 2.65 (95% CI 1.50-4.69) for rhinitis and 1.63 (95% CI 1.00-2.69) for eczema after adjustment for potential confounders.
Obstetric complications and infection in pregnancy may increase the risk of allergic disorders among the offspring.
Previous studies have suggested that asthma phenotype could probably be programmed before birth. The current study examined the impact of maternal vaginitis and febrile infections during pregnancy on the subsequent development of asthma among children.
The analyses were based on 8088 children from the northern Finland birth cohort, 1985-1986.
The prevalence of asthma at age 7 was 3.5%. Children had a higher risk of asthma if their mothers experienced vaginitis and febrile infections during pregnancy, odds ratio (OR) = 1.41, (95% CI: 1.08-1.84) and 1.65 (95% CI: 1.25-2.18), respectively, after adjusting for other covariates. There was a clear time trend in risk of childhood asthma corresponding to the timing of maternal febrile infections in pregnancy. The adjusted OR for the first, second and third trimesters were 2.08 (95% CI: 1.13-3.82), 1.73 (95% CI: 1.09-2.75) and 1.44 (95% CI: 0.97-2.15), respectively. Maternal history of allergic diseases, birthweight
We assessed the levels of arsenic in drilled wells in Finland and studied the association of arsenic exposure with the risk of bladder and kidney cancers. The study persons were selected from a register-based cohort of all Finns who had lived at an address outside the municipal drinking-water system during 1967-1980 (n = 144,627). The final study population consisted of 61 bladder cancer cases and 49 kidney cancer cases diagnosed between 1981 and 1995, as well as an age- and sex-balanced random sample of 275 subjects (reference cohort). Water samples were obtained from the wells used by the study population at least during 1967-1980. The total arsenic concentrations in the wells of the reference cohort were low (median = 0.1 microg/L; maximum = 64 microg/L), and 1% exceeded 10 microg/L. Arsenic exposure was estimated as arsenic concentration in the well, daily dose, and cumulative dose of arsenic. None of the exposure indicators was statistically significantly associated with the risk of kidney cancer. Bladder cancer tended to be associated with arsenic concentration and daily dose during the third to ninth years prior to the cancer diagnosis; the risk ratios for arsenic concentration categories 0.1-0.5 and [Greater/equal to] 0.5 microg/L relative to the category with
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Nitrogen dioxide is known as a deep lung irritant. The aim of this study was to find out whether the relatively low ambient air NO2 concentrations in the northern city of Helsinki had an impact on the respiratory health of children. The association between personal exposure to ambient air NO2 and respiratory health was investigated in a 13-week follow-up study among 163 preschool children aged 3-6 yrs. Personal weekly average exposure to NO2 was measured by passive diffusion samplers attached to the outer garments. Symptoms were recorded daily in a diary by the parents. Among 53 children, peak expiratory flow (PEF) was measured at home in the mornings and evenings. The association between NO2 exposure and respiratory symptoms was examined with Poisson regression. The median personal NO2 exposure was 21.1 microg x m(-3) (range 4-99 microg x m(-3)). An increased risk of cough was associated with increasing NO2 exposure (risk ratio = 1.52; 95% confidence interval 1.00-2.31). There was no such association between personal weekly NO2 exposure and nasal symptoms, but a nonsignificant negative association was found between the exposure and the weekly average deviation in PEF. In conclusion, even low ambient air NO2 concentrations can increase the risk of respiratory symptoms among preschool children.
Western lifestyle is associated with high prevalence of allergy, asthma and other chronic inflammatory disorders. To explain this association, we tested the 'biodiversity hypothesis', which posits that reduced contact of children with environmental biodiversity, including environmental microbiota in natural habitats, has adverse consequences on the assembly of human commensal microbiota and its contribution to immune tolerance.
We analysed four study cohorts from Finland and Estonia (n = 1044) comprising children and adolescents aged 0.5-20 years. The prevalence of atopic sensitization was assessed by measuring serum IgE specific to inhalant allergens. We calculated the proportion of five land-use types--forest, agricultural land, built areas, wetlands and water bodies--in the landscape around the homes using the CORINE2006 classification.
The cover of forest and agricultural land within 2-5 km from the home was inversely and significantly associated with atopic sensitization. This relationship was observed for children 6 years of age and older. Land-use pattern explained 20% of the variation in the relative abundance of Proteobacteria on the skin of healthy individuals, supporting the hypothesis of a strong environmental effect on the commensal microbiota.
The amount of green environment (forest and agricultural land) around homes was inversely associated with the risk of atopic sensitization in children. The results indicate that early-life exposure to green environments is especially important. The environmental effect may be mediated via the effect of environmental microbiota on the commensal microbiota influencing immunotolerance.
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Perinatal factors during delivery might modulate fetal immunological development and thereby be associated with the development of allergic diseases and asthma later.
Perinatal data was recorded during pregnancy and at the time of delivery in regard to 5823 children who were born in Northern Finland in 1985-1986. Data from self-administered questionnaires were available at the ages of 7 and 15-16 years and skin prick tests for four main allergens were carried out at the age of 15-16 years. Only singletons delivered by the vaginal route were analyzed.
There was a higher prevalence of doctor-diagnosed asthma at any time of life among children who were delivered by vacuum extraction (RR 1.80, 95% CI 1.27-2.56; P
In similarity to many other western countries, the burden of allergic diseases in Finland is high. Studies worldwide have shown that an environment rich in microbes in early life reduces the subsequent risk of developing allergic diseases. Along with urbanization, such exposure has dramatically reduced, both in terms of diversity and quantity. Continuous stimulation of the immune system by environmental saprophytes via the skin, respiratory tract and gut appears to be necessary for activation of the regulatory network including regulatory T-cells and dendritic cells. Substantial evidence now shows that the balance between allergy and tolerance is dependent on regulatory T-cells. Tolerance induced by allergen-specific regulatory T-cells appears to be the normal immunological response to allergens in non atopic healthy individuals. Healthy subjects have an intact functional allergen-specific regulatory T-cell response, which in allergic subjects is impaired. Evidence on this exists with respect to atopic dermatitis, contact dermatitis, allergic rhinitis and asthma. Restoration of impaired allergen-specific regulatory T-cell response and tolerance induction has furthermore been demonstrated during allergen-specific subcutaneous and sublingual immunotherapy and is crucial for good therapeutic outcome. However, tolerance can also be strengthened unspecifically by simple means, e.g. by consuming farm milk and spending time in nature. Results so far obtained from animal models indicate that it is possible to restore tolerance by administering the allergen in certain circumstances both locally and systemically. It has become increasingly clear that continuous exposure to microbial antigens as well as allergens in foodstuffs and the environment is decisive, and excessive antigen avoidance can be harmful and weaken or even prevent the development of regulatory mechanisms. Success in the Finnish Asthma Programme was an encouraging example of how it is possible to reduce both the costs and morbidity of asthma. The time, in the wake of the Asthma Programme, is now opportune for a national allergy programme, particularly as in the past few years, fundamentally more essential data on tolerance and its mechanisms have been published. In this review, the scientific rationale for the Finnish Allergy Programme 2008-2018 is outlined. The focus is on tolerance and how to endorse tolerance at the population level.
A total of 630 randomly selected dwellings were surveyed for visible signs of moisture damage by civil engineers, and questionnaire responses were collected from the occupants (a total of 1,017 adults) to analyse the association between moisture damage and occupant health. A three-level grading system was developed, which took into account the number of damage sites in buildings and estimated the severity of the damage. In the present study, this grading system was tested as an improved model of moisture damage-related exposure in comparison to a conventional two-category system: based on independent, technical criteria it also allowed dose-response to be estimated. The questionnaire probed 28 individual health symptoms, based on earlier reported associations with building moisture and mould-related exposure. Criteria in evaluating the goodness of the selected exposure model were (1) dose-responsiveness and (2) higher risk compared to a two-level classification. Dose-responsiveness was observed with the three-level classification in 7, higher risk in 10, and both criteria in 5 out of 28 health symptoms. Two-level classification had higher risk in 4 health symptoms. Dose-dependent risk increases for respiratory infections and lower respiratory symptoms, and recurrent irritative and skin symptoms were observed with the three-level classification using symptom score variables. Although the results did not unambiguously support the three-level model, they underline the importance of developing more accurate exposure models in assessing the severity of moisture damage.
Certain housing characteristics increase the risk for moisture damage, which has been associated with increased risk for asthma in children. Modeling moisture damage as a function of these characteristics could therefore provide a simple tool to estimate building-related risk for asthma. This study aimed to find out specific associations between asthma case-control status of children and moisture damage and housing characteristics. The data consisted of information on 121 asthmatic children and predominately two age-, gender- and place of residence-matched control children for every case, and information on moisture damage and housing characteristics in the homes of the children. In a previous study, we found a statistically significant association between moisture damage observations in main living areas and asthma in children. Using logistic regression, five models were formulated to predict moisture damage status of the homes and moisture damage status of living areas. The models were able to classify the damage status correctly in 65.0-87.7% of the homes (kappa values 0.10-0.47) as functions of housing characteristics. None of the models qualified as a significant determinant of the case-control status of the children.
It can be hypothesized that building-related risk for asthma could be roughly estimated using models predicting moisture damage status of buildings as a function of easily obtainable housing characteristics. The results of this study indicated that, with a moderate certainty, it is possible to model moisture damage status of buildings using housing characteristics. However, the models developed did not associate with asthma in children. In conclusion, it was not possible to estimate the risk for asthma by studying housing characteristics only, but detailed information on moisture damage (e.g. location of damage) was crucial for such estimation.