Early-life exposure to environmental microbial agents may be associated with development of wheezing and allergic diseases.
To assess the association of microbial exposure in rural homes with the risk of asthma, wheezing, atopic dermatitis and sensitization.
Birth cohorts of rural children (n = 1133), half from farmer families, were followed up from birth to 2 years of age by questionnaires in five European centres. Endotoxin and extracellular polysaccharides (EPS) of Penicillium and Aspergillus spp. were determined from living room floor and mother's mattress dust samples collected at 2 months of age. Specific IgE against 19 allergens was measured at 1 year of age. Discrete-time hazard models, generalized estimations equations (GEE) and logistic regression were used for statistical analyses.
The incidence of asthma was inversely associated with the amount of dust (adjusted odds ratio (aOR) 0.73, 95% CI 0.58-0.93) and the loads (units/m(2)) of EPS (aOR 0.75, 95% CI 0.55-1.04) and endotoxin (aOR 0.79, 95% CI 0.60-1.05) in the mother's mattress. Similar associations were seen with wheezing and with living room floor dust. The microbial markers were highly correlated and their effects could not be clearly separated. The inverse associations were seen especially among non-farmers. The risk of sensitization to inhalant allergens increased with increasing endotoxin exposure from mattress dust. No associations were observed with concentrations (units/g) or with atopic dermatitis.
The amount and microbial content of house dust were inversely associated with asthma and wheezing, but due to high correlations between microbial agents and amount of dust, it was not possible to disentangle their individual effects. New ways to better measure and represent exposure to environmental microbes, including indexes of biodiversity, are needed especially among farmers.
The association between exposure to ambient air nitrogen dioxide and cough was evaluated in a panel study among 162 children aged 3-6 y. The weekly average nitrogen dioxide exposure was assessed with Palmes-tube measurements in three ways: (1) personally, (2) outside day-care centers, and (3) inside day-care centers. Ambient air nitrogen dioxide concentrations were obtained from the local network that monitored air quality. The parents recorded cough episodes daily in a diary. The risk of cough increased significantly (relative risk = 3.63; 95% confidence interval = 1.41, 9.30) in the highest personal nitrogen dioxide exposure category in winter, and a nonsignificant positive trend was noted for the other assessment groups. In spring, risk increased nonsignificantly in all exposure-assessment groups, except for the fixed-site monitoring assessment. It is important that investigators select an exposure-assessment method sufficiently accurate to reflect the effective pollutant dose in subjects.
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.
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
Cross-sectional studies have shown an association between the farming environment and a decreased risk of atopic sensitization, mainly related to contact with farm animals in the childhood.
Investigate the association of a farming environment, especially farm animal contact, during infancy, with atopic sensitization and allergic diseases at the age of 31.
In a prospective birth cohort study, 5509 subjects born in northern Finland in 1966 were followed up at the age of 31. Prenatal exposure to the farming environment was documented before or at birth. At age 31, information on health status and childhood exposure to pets was collected by a questionnaire and skin prick tests were performed.
Being born to a family having farm animals decreased the risk of atopic sensitization [odds ratio (OR) 0.67; 95% confidence interval (CI) 0.56-0.80], atopic eczema ever (OR 0.77; 95% CI 0.66-0.91), doctor-diagnosed asthma ever (OR 0.74; 95% CI 0.55-1.00), allergic rhinitis at age 31 (OR 0.87; 95% CI 0.73-1.03) and allergic conjunctivitis (OR 0.86; 95% CI 0.72-1.02) at age 31. There was a suggestion that the reduced risk of allergic sensitization was particularly evident among the subjects whose mothers worked with farm animals during pregnancy, and that the reduced risk of the above diseases by farm animal exposure was largely explained by the reduced risk of atopy. Having cats and dogs in childhood revealed similar associations as farm animals with atopic sensitization.
Contact with farm animals in early childhood reduces the risk of atopic sensitization, doctor-diagnosed asthma and allergic diseases at age 31.
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.
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.
The short-term association of particulate air pollution with peak expiratory flow rate (PEF) and respiratory symptoms was examined. Forty-nine children with chronic respiratory symptoms aged 8-13 yrs were followed daily for six weeks in spring, 1995, in Kuopio, Finland. Daily concentrations of particulate material with a 50% cut-off aerodynamic diameter
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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During the winter of 1994, the association between daily changes in air pollution and in the respiratory health of children 7 to 12 yr of age were studied in Kuopio, Finland. Seventy-four children with asthmatic symptoms and 95 children with cough only, living either in urban or suburban areas, were followed for 3 mo. During the study period, the mean daily concentration of particulate air pollution (PM10) was 18 micrograms/m3 in the urban area and 13 micrograms/m3 in the suburban area. Lagged concentrations of PM10, black smoke, and NO2 were significantly associated with declines in morning peak expiratory flow (PEF) among asthmatic children. The regression coefficient (x10) for a 2-d lag of PM10 was -0.911 (SE, 0.386) in the urban and -1.05 (0.596), in the suburban area. Among children with cough only, PM10, black smoke, and NO2 were not significantly associated with PEF. In the urban area, there was a significant association between SO2 and morning and evening PEF and incidence of upper respiratory symptoms among children who cough only. No other associations between air pollution and evening PEF or respiratory symptoms were observed. This study suggests that particulate air pollution is associated with respiratory health, especially among children with asthmatic symptoms.
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.
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
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.
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 effect of labour and different labour-related factors on the cord blood (CB) cell cytokine production is still relatively unknown.
To study the relationships between the production of IL-5, IL-10 and IFN-? in CB samples and maternal, early neonatal and birth-related factors.
Whole-blood samples were collected after birth (n=423) and they were stimulated for 24 and 48 h with a combination of phorbol ester and ionomycin. Production of IL-5, IL-10 and IFN-? was determined using ELISA. Maternal, early neonatal and birth-related variables were recorded prospectively during pregnancy, and during and after delivery.
After multivariable adjustment for confounders, the strongest predictor of IL-5, IL-10 and IFN-? production in CB cell samples was the season of birth. Children born in the spring had significantly lower cytokine responses compared with those born in the fall. IL-5 production was inversely associated with female gender of the child and maternal smoking. If corrections for white blood cell (WBC) counts were not performed, IL-5 production was also significantly associated with the mode of delivery. Respectively, the production of IL-10 and IFN-? was inversely associated with prostaglandin induction before birth.
Environmental exposure to pollen and ultraviolet irradiation during gestation may have an effect on the cytokine profile of the offspring in CB because children born in the spring or winter showed the lowest IL-5, IL-10 and IFN-? responses. The production of IL-10 and IFN-? was also inversely associated with prostaglandin labour induction before birth. Other labour-related factors were not significantly associated with production of IL-5, IL-10 and IFN-? after WBC count correction.