Neonatal gut colonization by Staphylococcus aureus strains with certain adhesins and superantigens is negatively associated with subsequent development of atopic eczema.

BACKGROUND: Insufficient early immune stimulation may predispose to atopic disease. Staphylococcus aureus, a skin and gut colonizer, produces the B-cell mitogen protein A and T-cell-activating superantigens. Early gut colonization by S. aureus strains that possess the superantigens encoded by the enterotoxin gene (egc) cluster and elastin-binding protein is negatively associated with development of atopic eczema. OBJECTIVES: To investigate (i) whether these findings could be replicated in a second birth cohort, FARMFLORA, and (ii) whether nasal colonization by S. aureus also relates to subsequent atopic eczema development. METHODS: Faecal samples and nasal swabs from infants in the FARMFLORA birth cohort (n = 65) were cultured for S. aureus. Individual strains were distinguished by random amplified polymorphic DNA and assessed for adhesin and superantigen gene carriage by polymerase chain reaction. Atopic eczema at 18 months of age was related to nasal and gut S. aureus colonization patterns during the first 2 months of life (well before onset of eczema). RESULTS: Staphylococcus aureus colonization per se was unrelated to subsequent eczema development. However, gut S. aureus strains from the infants who subsequently developed atopic eczema less frequently carried the ebp gene, encoding elastin-binding protein, and superantigen genes encoded by egc, compared with strains from children who remained healthy. Nasal colonization by S. aureus was less clearly related to subsequent eczema development. CONCLUSIONS: The results precisely replicate our previous observations and may suggest that mucosal colonization by certain S. aureus strains provides immune stimulation that strengthens the epithelial barrier and counteracts the development of atopic eczema.

Late introduction of fish and eggs is associated with increased risk of allergy development - results from the FARMFLORA birth cohort.

The prevalence of allergy is markedly low in children growing up on farms. An increasing number of studies indicate that the timing of food introduction may affect allergy development. We aimed to investigate if protection against allergy in farm environments may be mediated through differences in food-introduction practices between farm and non-farm families, using an explorative approach. Twenty-eight farm and 37 non-farm children were included in the FARMFLORA birth cohort. Practices of breastfeeding and introduction of formulas and complementary foods were collected by questionnaires at 6, 12, and 18 months of age. Allergy was diagnosed by pediatricians at 3 years of age. The only difference in food-introduction practices observed between farm and non-farm children was an earlier introduction of nuts in farmers (median month: 11 [IQR: 8-6] in farmers, 15 [12-19] in non-farmers). One farm child (4%) and 10 non-farm children (27%) were allergic at 3 years of age. Lower risk of allergy development was associated with early exclusive breastfeeding (continuous variable; OR = 0.59, 95% CI: 0.39-0.89), but also having received eggs (OR = 0.08, 95% CI: 0.13-0.54) and fish (logistic regression not applicable, P = 0.01 in likelihood ratio testing [χ2]) at 10 months of age or earlier compared to later. Our results were not affected by reverse causation, as judged by a questionnaire sent to the families in retrospect. Timing of introduction of complementary foods is unlikely to contribute to the lower risk of allergy among farm children. Although early exclusive breastfeeding was associated with a lower rate of allergy development, postponed introduction of complementary foods might increase the risk of developing allergy. Owing to the limited sample size, our results are only indicative, but support prior findings.

Allergic disease in 8-year-old children is preceded by delayed B cell maturation.

BACKGROUND: We previously reported that exposure to a farming environment is allergy-protective, while high proportions of neonatal immature/naïve CD5+ B cells and putative regulatory T cells (Tregs) are risk factors for development of allergic disease and sensitization up to 3 years of age. OBJECTIVE: To examine if B and T cell maturation are associated with allergic disease and farming environment over the first 8 years in life. METHODS: In the prospective FARMFLORA study, including both farming and non-farming families, 48 of 65 children took part in the 8-year follow-up study. Various B and T cell maturation variables were examined in blood samples obtained at several occasions from birth to 8 years of age and related to doctors' diagnosed allergic disease and sensitization, and to farming environment. RESULTS: We found that the incidence of allergic disease was lower among farmers' compared to non-farmers' children during the 8-year follow-up period, and that farmers' children had higher proportions of memory B cells at 8 years of age. Moreover, a high proportion of neonatal CD5+ B cells was a risk factor for and may predict development of allergic disease at 8 years of age. A high proportion of Tregs was not protective against development of these conditions. CONCLUSION AND CLINICAL RELEVANCE: High proportions of neonatal naïve B cells remained as a risk factor for allergic disease in school-aged children. Thus, the accelerated B cell maturation observed among farmers' children may be crucial for the allergy-protective effect of a farming environment.

Superantigens and adhesins of infant gut commensal Staphylococcus aureus strains and association with subsequent development of atopic eczema.

BACKGROUND: According to the hygiene hypothesis, insufficient immune activation by microbes increases the risk of allergy development. Staphylococcus aureus, which is part of the skin and gut microbiota of infants in Western countries, produces a variety of T-cell-activating enterotoxins, called superantigens. OBJECTIVES: To investigate whether early (0-2 months of age) gut colonization by S. aureus strains that carry specific superantigens and adhesins was related to subsequent development of atopic eczema in a Swedish birth cohort. METHODS: Staphylococcus aureus was isolated from rectal swabs and cultured quantitatively from faecal samples, with individual strains being tested for carriage of genes for superantigens and adhesins. Atopic eczema was diagnosed at onset of symptoms and at 18 months of age. RESULTS: Although the frequency of early gut colonization by S. aureus was not related to subsequent eczema development, the S. aureus strains that were found to colonize those infants who developed atopic eczema were less likely to carry the gene encoding the superantigen SElM (P = 0·008) and the gene for elastin-binding protein (P = 0·03), compared with strains that were isolated from infants who had not developed atopic eczema by 18 months of age. CONCLUSIONS: Gut colonization by S. aureus strains carrying a certain combination of superantigen and adhesin genes was negatively associated with subsequent development of atopic eczema. Such strains may provide stimulation and promote maturation of the infant immune system.

High proportions of FOXP3(+) CD25(high) T cells in neonates are positively associated with allergic sensitization later in childhood.

BACKGROUND: The role of FOXP3(+) regulatory T cells in the prevention against sensitization and allergy development is controversial. OBJECTIVE: We followed 65 newborn Swedish children from farming and non-farming families from birth to 3 years of age and investigated the relation between CD4(+) T cell subsets in blood samples and development of sensitization and allergic disease. METHODS: The proportions of FOXP3(+) CD25(high) , CTLA-4(+) CD25(+) , CD45RO(+) , HLA-DR(+) , CCR4(+) or α4ß7(+) within the CD4(+) T cell population were examined by flow cytometry of blood samples at several time-points. Mononuclear cells were isolated from blood and stimulated with birch allergen, ovalbumin or the mitogen PHA, and the levels of IL-1ß, IL-6, TNF, IFN-γ, IL-5 and IL-13 were measured. A clinical evaluation regarding the presence of allergen-specific IgE and allergy was performed at 18 and 36 months of age. RESULTS: Multivariate discriminant analysis revealed that children who were sensitized at 18 or 36 months of age had higher proportions of FOXP3(+) CD25(high) T cells at birth and at 3 days of life than children who remained non-sensitized, whereas allergy was unrelated to the neonatal proportions of these cells. The proportions of CTLA-4(+) CD25(+) T cells were unrelated to both sensitization and allergy. The association between higher proportions of FOXP3(+) CD25(high) T cells and sensitization persisted after exclusion of farmer's children. Finally, a farming environment was associated with lower proportions of FOXP3(+) CD25(high) T cells in early infancy and to a more prominent T cell memory conversion and cytokine production. CONCLUSION & CLINICAL RELEVANCE: Our results indicate that high proportions of FOXP3(+) CD25(high) T cells in neonates are not protective against later sensitization or development of allergy.

Effect of lifestyle factors on Staphylococcus aureus gut colonization in Swedish and Italian infants.

In recent years, Staphylococcus aureus has become a common bowel colonizer in Swedish infants. We aimed to identify host factors that determine such colonization. Stool samples from 100 Italian and 100 Swedish infants were obtained on seven occasions during the first year of life and cultured quantitatively for S. aureus. In a subgroup of infants in each cohort, individual strains were identified by random amplified polymorphic DNA analysis. Colonization at each time-point was related to delivery mode, siblings in family and antibiotic treatment. In total, 66% of the Italian and 78% of the Swedish infants had S. aureus in their stools on at least one time-point (p 0.08) and 4% of Italian and 27% of Swedish infants were positive on at least six of the seven time-points investigated (p 0.0001). Most infants analysed regarding strain carriage harboured a single strain in their microbiota for several months. The S. aureus stool populations in colonized infants decreased from 10(7) to 10(4) colony-forming units/g between 1 week and 1 year of age in both cohorts. In multivariate analysis, the strongest predictor for S. aureus colonization was being born in Sweden (OR 3.4 at 1 week of age, p 0.002). Having (an) elder sibling(s) increased colonization at peak phase (OR 1.8 at 6 months, p 0.047). Antibiotic treatment was more prevalent among Italian infants and correlated negatively with S. aureus colonization at 6 months of age (OR 0.3, p 0.01). To conclude, S. aureus is a more common gut colonizer in Swedish than Italian infants, a fact that could not be attributed to feeding or delivery mode.

Early fish introduction is associated with less eczema, but not sensitization, in infants.

OBJECTIVE: To investigate if the development of allergic diseases during the child's first 18 months of life is influenced by the time at which different food items were introduced into the child's diet. METHOD: A birth cohort of 184 children was followed to 18 months of age. Diaries were used to document feeding practices, and parental interviews were performed at 6 and 12 months of age, probing for symptoms suggesting allergic disease, general health-related issues and food introduction regimes. Symptoms promoted prompt clinical examination, and all children were examined clinically, and tested for sensitization to common airborne and food allergens at 18 months of age. RESULTS: The earlier the fish was introduced into the child's diet the lower was the frequency of eczema. This association remained after control for confounding factors. The timing of fish introduction and asthma development showed a similar pattern, but did not reach statistical significance. Sensitization was not influenced by the timing of fish introduction. Other food items or feeding practices did not seem to influence allergy development. CONCLUSION: Early introduction of fish into the child's diet was associated with less eczema development, and a tendency to less asthma. Sensitization was not associated with the timing of fish introduction.

Infection of infants with human herpesvirus type 6 may be associated with reduced allergic sensitization and T-helper type 2 development.

BACKGROUND: Epidemiological studies point to an inverse relationship between microbial exposure and the prevalence of allergic diseases. The underlying mechanism for this observation remains largely unknown, as well as the nature of the microbes involved. OBJECTIVE: To investigate the effects of early infection with human herpesviruses (HHVs) on IgE formation and T-helper type 2 (Th2) development in infants. METHODS: Serum was collected from children aged 18 months and assessed for IgE to common allergens and IgG to five common herpesviruses. Cord blood plasmacytoid dendritic cells (pDC) were exposed to HHV type 6 in vitro and mixed with allogeneic cord blood CD4(+) T cells. Cytokine levels were determined by ELISA and by flow cytometry. RESULTS: We found that children seropositive at 18 months of age to HHV type 6 were significantly less often IgE sensitized than seronegative children [odds ratio (OR): 0.08, 95% confidence interval (CI): 0.009-0.68]. HHV type 6 also decreased the production of the Th2-associated cytokines IL-5 and IL-13 by CD4(+) T cells when co-cultured with allogeneic cord blood pDC. This was associated with an increased production of IFN-alpha by pDC exposed to HHV type 6. CONCLUSION: These data indicate that an early childhood infection with HHV type 6 could down-regulate Th2 responses and reduce IgE formation to common allergens in a young child.

Interleukin-4 receptor polymorphisms in asthma and allergy: relation to different disease phenotypes.

AIM: Inheritance and genetic factors are supposed to influence susceptibility to asthma and allergy. We tested if single nucleotide polymorphisms (SNPs) in the IL4R gene were associated with susceptibility to such diseases, or if they were related to the phenotypic presentation of asthma and allergic rhinoconjunctivitis (ARC). METHODS: Three hundred and nine 12- to 13-year-old children were included. Six SNPs in the IL4R were analysed in response to current allergic disease, and to presentation of specific asthma and ARC phenotypes. Questionnaires were used to determine allergic disease status, and skin prick tests to evaluate sensitization to common airborne allergens. RESULTS: Less eczema was seen in individuals with the AA-genotype of rs2057768, and less ARC among those with the AA-genotype of rs2107356, especially ARC associated with sensitization to pollen. The AA-genotype of rs2057768 and the TT genotype of rs3024632 were associated with a specific asthma phenotype. CONCLUSION: Variations within the IL4R gene are associated with allergic diseases in children, preferably with eczema and disease phenotypes of ARC and asthma.

Primary ciliary dyskinesia: a consensus statement on diagnostic and treatment approaches in children.

Primary ciliary dyskinesia (PCD) is associated with abnormal ciliary structure and function, which results in retention of mucus and bacteria in the respiratory tract, leading to chronic oto-sino-pulmonary disease, situs abnormalities and abnormal sperm motility. The diagnosis of PCD requires the presence of the characteristic clinical phenotype and either specific ultrastructural ciliary defects identified by transmission electron microscopy or evidence of abnormal ciliary function. Although the management of children affected with PCD remains uncertain and evidence is limited, it remains important to follow-up these patients with an adequate and shared care system in order to prevent future lung damage. This European Respiratory Society consensus statement on the management of children with PCD formulates recommendations regarding diagnostic and therapeutic approaches in order to permit a more accurate approach in these patients. Large well-designed randomised controlled trials, with clear description of patients, are required in order to improve these recommendations on diagnostic and treatment approaches in this disease.

High circulating immunoglobulin A levels in infants are associated with intestinal toxigenic Staphylococcus aureus and a lower frequency of eczema.

BACKGROUND: Intestinal bacteria trigger IgA production and delayed maturation of mucosal IgA response is linked to allergy development. OBJECTIVE: Our aim was to investigate if plasma levels of IgA or APRIL (a proliferation inducing ligand), an important factor for IgA class switch recombination, in infancy correlates with intestinal colonization by any specific bacteria or yeast. We also examined if plasma IgA or APRIL levels are related to sensitization and the development of eczema. METHODS: IgA was quantified in plasma obtained from infants at birth and at 4 and 18 months of age and APRIL was measured at 4 months of age. Colonization by major bacterial groups and yeast was followed in the first 8 weeks of life by quantitative culture of stool samples. A clinical evaluation regarding the presence of allergen-specific IgE or eczema and eosinophil counts in blood was performed at 18 months of age. RESULTS: In multiple linear regression analysis, only colonization by Staphylococcus aureus strains producing toxins with superantigen function (SEA-D or TSST-1) made an independent contribution to plasma IgA levels at 4 months of age. Further, increased levels of APRIL in plasma at 4 months were negatively associated with sensitization while IgA plasma levels were inversely correlated to eczema development and blood eosinophil counts at 18 months of age. CONCLUSION: Early intestinal colonization by toxigenic S. aureus strains seems to promote systemic IgA responses. Furthermore, high levels of APRIL and IgA in the circulation at 4 months of age seem to correlate negatively with allergy development.

Urticaria is associated with birch-pollen sensitization.

Urticaria is a common condition, seldom of allergic origin. It is however not always possible to find the provoking allergen. The aim of the present study was to analyze if there was a relationship between urticaria and sensitization to common airborne allergens. A representative sample of 402 12 to 13-yr-old children answered a questionnaire on allergic diseases, 397 were interviewed by the study nurse and 371 underwent skin prick tests to cat, dog, horse, birch, timothy-grass, house dust mites and Cladosporium mould. Specific IgE-antibodies were analyzed to birch pollen and cat dander. Urticaria was more common in sensitized children, but the relationship between urticaria and sensitization was only statistically significant for birch pollen sensitization (OR 1.99, 95% CL 1.04-3.83), when tested in a multiple logistic regression model with the specified allergens as independent variables. A similar pattern was seen for birch-specific IgE-antibody levels, which was higher in children reporting urticaria than in those without. IgE-levels to cat dander did not show such a difference. Urticaria was statistically significantly associated with sensitization to birch-pollen, but not to other common inhalant allergens. We propose that intake of birch-pollen cross-reactive food-stuffs may be a neglected cause of urticaria and relapsing urticaria, in birch-pollen sensitized subjects.

Increased levels of circulating soluble CD14 but not CD83 in infants are associated with early intestinal colonization with Staphylococcus aureus.

BACKGROUND: Soluble forms of the monocyte marker CD14 and the mature dendritic cell marker CD83 are plasma proteins with immunoregulatory functions. The physiological stimulus for their production is unclear and their possible role in allergy development is unknown. METHODS: We measured the plasma levels of soluble CD14 (sCD14) and soluble CD83 (sCD83) in 64 Swedish children in relation to intestinal bacterial colonization pattern in a prospective birth cohort. Soluble CD14 and sCD83 levels were quantified by enzyme linked immunosorbent assay in plasma obtained at birth and at 4, 18 and 36 months of age. All major aerobic and anaerobic bacteria were quantified in faecal samples obtained regularly over the first 8 weeks of life. Clinical allergy and IgE levels were evaluated at 18 months of age. RESULTS: Soluble CD14 in plasma increased during the first 18 months of life while sCD83 peaked at 4 months of age. Children who were perinatally colonized with Staphylococcus aureus had significantly higher levels of sCD14 in plasma at 4 months of age relative to non-colonized children. The levels of sCD14 were unrelated to colonization with Escherichia coli, other enterobacteria, enterococci, clostridia, Bacteroides, bifidobacteria or lactobacilli. Further, children with food allergy by 18 months tended to have lower levels of sCD14 than healthy children. Plasma levels of sCD83 were not related to either bacterial colonization pattern or allergy development. CONCLUSIONS: Perinatal colonization with S. aureus may trigger the occurrence of sCD14 in plasma, which may influence development of the infantile immune system and risk of allergy development.

High-dose exposure to cat is associated with clinical tolerance--a modified Th2 immune response?

BACKGROUND: Allergen-specific IgG4 antibodies, it is suggested, may be protecting against allergy development by blocking responses. Levels are proposed as a marker of modified Th2 response. OBJECTIVES: To assess the levels of IgE, IgG1 and IgG4 antibodies to cat in relation to cat exposure, asthma and allergic diseases. METHODS: We studied a population-based sample of 412 schoolchildren of 12-13 years of age. Parents of 402 children completed a questionnaire covering their child's medical history, the keeping of cats and other background data. Skin prick tests (SPTs) to common aeroallergens were performed in 371 of the children. Blood samples for the analyses of IgE, IgG1 and IgG4 antibodies were obtained from 309 of them. RESULTS: All children had an immune response to cat, predominantly of the IgG1 subclass. The levels of cat-specific IgG1 and IgG4, but not IgE, were high in children currently keeping a cat. Children with asthma had increased levels of cat-specific IgE and IgG1, and children with a positive SPT to cat also had increased IgG4. The presence of IgG4 was not associated with asthma or sensitization, unless there was a simultaneous production of IgE. Twenty-five percent of the children had an immune response with only IgG4, and no IgE antibodies to cat. This group of children had the highest frequency of cat-keeping, but a similar prevalence of asthma and allergy as those with neither IgE nor IgG4 antibodies to cat. CONCLUSION: Cat-keeping was associated with a modified Th2 response, producing IgG4 but not IgE antibodies. This immune response was not associated with an increased risk of asthma or allergy. However, the IgG4 antibodies did not directly mediate any protective effect.

Born small for gestational age: relation to future allergy and asthma.

AIM: To evaluate whether intrauterine growth retardation (IUGR) protects against the development of allergy. METHODS: A case-control study of 1515 subjects (15-25 y), of whom 430 were cases (birthweight/length below -2 SD for gestational age). Birth data were from the national birth register. The frequencies of allergic diseases were evaluated by questionnaire. RESULTS: For the 950 who replied, the frequencies of allergic diseases were similar in cases and controls. CONCLUSION: IUGR does not protect against the development of allergy.

Allergic rhinoconjunctivitis, eczema, and sensitization in two areas with differing climates.

In this 5-year follow-up study we compared the prevalence of allergic rhinoconjunctivitis, eczema, and sensitization, in relation to several background factors, in two Swedish regions (Göteborg and Kiruna). In Göteborg, a city on the southwest coast, the climate is mild and humid. Kiruna is a town north of the Arctic Circle. Questionnaire replies and results of interviews were collected from all 412 7-8-year-old children of a population-based sample (203 in Göteborg and 209 in Kiruna); in addition, 192 children from Göteborg and 205 from Kiruna were skin-prick tested for sensitization to common aero-allergens. After 5 years, at 12-13 years of age, almost all of the initial study cohort were re-investigated. At follow-up the prevalence of allergic rhinoconjunctivitis was 17%, eczema 23%, and sensitization 32%. Allergic rhinoconjunctivitis and eczema were as common in Göteborg as in Kiruna, whereas sensitization was far more common in Kiruna. Children born during the pollen season had allergic rhinoconjunctivitis less often -- and were sensitized to pollen and animal protein less often -- than those born during the rest of the year. Sensitization to birch pollen, cat protein, and horse protein was less common in children living in Göteborg, the region with the highest frequency of cat ownership and horseback riding, and with the longest birch-pollen season. The girls were more commonly horseback riders but the boys were more often sensitized to horses. The results reinforce our previous findings: indoor climate may affect the development of sensitization and allergic diseases, to some extent independently; and if exposure to antigen is unavoidable, high doses might be better than low doses.

Inhalation of corticosteroids after hospital care for respiratory syncytial virus infection diminishes development of asthma in infants.

UNLABELLED: The aim of the study was to assess the effect of inhaled corticosteroids on subsequent respiratory symptoms and asthma in infants hospitalized for respiratory syncytial virus infection (RSV). The study included 188 children below 12 mo of age, hospitalized because of RSV infection. During the winter of 1994/95 only selected children (13%) were given inhaled corticosteroids following discharge from the hospital. The following winter (1995/96), almost all children (86%) were given this treatment for 6-8 wk. Outcomes of the two different treatment regimens were compared by questionnaire 19-24 mo after discharge. Children hospitalized and treated during the winter of 1995/96 developed asthma (12% vs. 24%) and other severe symptoms of the respiratory tract less often than infants treated the year before. The frequency of children with less severe symptoms did not differ between the two treatment periods. CONCLUSION: The results indicate that inhalation of corticosteroids for 6-8 wk may reduce subsequent asthma and severe respiratory morbidity in infants hospitalized for RSV infection.

Asthma in children: prevalence, treatment, and sensitization.

This study compares the prevalence of asthma and sensitization in children from two Swedish regions with different climates: Göteborg on the southwest coast and Kiruna in the northern inland, north of the Arctic Circle. The 412 children of a population-based sample, 203 in Göteborg and 209 in Kiruna, were investigated at age 7-8 and 12-13 years. Questionnaire reports and interviews were obtained from all children at 7-8 years of age, and 192 children were skin-prick tested for common aeroallergens in Göteborg and 205 in Kiruna. At the follow-up, 5 years later, almost all the children were re-investigated. The prevalence of asthma, wheeze, and sensitization had increased with increasing age during the follow-up period. The questionnaire reports revealed that the prevalence of asthma was 8.5% at 12-13 years of age. All children who in the questionnaire reported current asthma, were using asthma medication. The interviews indicated that the prevalence of a clinically significant asthma might be even higher, reaching approximately 12%. Asthma and wheeze were as common in Göteborg as in Kiruna despite large differences in prevalence of sensitization. Sensitization, and especially sensitization to animals, was far more common in Kiruna than in Göteborg. This study shows that asthma and wheeze are increasingly prevalent even in school age children and that sensitization does not necessarily reflect the prevalence of asthma in a population.

Does early exposure to cat or dog protect against later allergy development?

BACKGROUND: It is unknown which factors in modern western society that have caused the current increase in prevalence of allergic diseases. Improved hygiene, smaller families, altered exposure to allergens have been suggested. OBJECTIVES: To assess the relationship between exposure to pets in early life, family size, allergic manifestations and allergic sensitization at 7-9 and 12-13 years of age. METHODS: The prevalence of allergic diseases and various background factors were assessed in 1991 and 1996 by questionnaire studies. In 1991, the study comprised representative samples of children from the Göteborg area on the Swedish west coast (7 years old, n = 1649) and the inland town Kiruna in northern Sweden (7-9 years old, n = 832). In 1992, a validation interview and skin prick test (SPT) were performed in a stratified sub-sample of 412 children. In 1996, this subgroup was followed up with identical questions about clinical symptoms as in 1991, detailed questions about early pet exposure were added and SPT performed. RESULTS: Children exposed to pets during the first year of life had a lower frequency of allergic rhinitis at 7-9 years of age and of asthma at 12-13 years. Children exposed to cat during the first year of life were less often SPT positive to cat at 12-13 years. The results were similar when those children were excluded, whose parents had actively decided against pet keeping during infancy because of allergy in the family. There was a negative correlation between the number of siblings and development of asthma and allergic rhinitis. CONCLUSION: Pet exposure during the first year of life and increasing number of siblings were both associated with a lower prevalence of allergic rhinitis and asthma in school children.

Prevalence of allergic diseases in schoolchildren in relation to family history, upper respiratory infections, and residential characteristics.

The prevalences of asthma, allergic rhinitis (AR), and eczema were analyzed in relation to retrospective risk factors from birth in a questionnaire study of schoolchildren in two areas covering the whole climatic span of Sweden: the Göteborg area on the southwestern coast (7-year-olds, n = 1649) and Kiruna, a mining town in the northernmost inland mountains (7-9-year-olds, n = 832). The strongest background factor, a family history of the diseases, was more common in children with another strong risk factor, particularly for asthma: high frequency of upper respiratory tract infection (URTI). Other significant risk factors related to high indoor humidity caused an increased prevalence of both allergic diseases and URTI. Active mechanical ventilation of the homes caused a slight reduction of the prevalence of allergic diseases, and repainting or new wallpaper in the bedroom of the child after birth caused a moderately increased risk of allergic disease. This study illustrates the interaction between genetic and environmental risk factors with special emphasis on factors related to an unventilated indoor climate, which may have substantially contributed to the current increase of the diseases in the country.