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.     

Influence of dog ownership and high endotoxin on wheezing and atopy during infancy

BACKGROUND: Increased exposure to microbial products early in life may protect from development of atopic disorders in childhood. Few studies have examined the relationship of endotoxin exposure and pet ownership on atopy and wheezing during infancy. OBJECTIVE: Evaluate relationships among high endotoxin exposure, pet ownership, atopy, and wheezing in high-risk infants. METHODS: Infants (n = 532; mean age, 12.5 +/- 0.8 months) with at least 1 parent with confirmed atopy were recruited. A complete medical history and skin prick testing to foods and aeroallergens were performed at age 1 year. House dust samples were analyzed for endotoxin. RESULTS: Prevalences of wheezing were not independently associated with dog or cat ownership or endotoxin levels. Percutaneous reactivity to at least 1 allergen was observed in 28.6% of infants. Univariate analyses showed significant associations of any wheezing, recurrent wheezing, and recurrent wheezing with an event with daycare attendance, number of siblings, respiratory infections, maternal smoking, and history of parental asthma. Logistic regression adjusting for the latter variables showed that recurrent wheezing (odds ratio, 0.4; 95% CI, 0.1-0.9) as well as 2 other wheeze outcomes were significantly reduced in homes with high endotoxin exposure in the presence of 2 or more dogs. CONCLUSION: Pet ownership or endotoxin did not independently modify aeroallergen sensitization or wheezing during infancy. However, high endotoxin exposure in the presence of multiple dogs was associated with reduced wheezing in infants. CLINICAL IMPLICATIONS: A home environment with many dogs and high levels of endotoxin may be conducive to reduced wheezing in infancy.     

Endotoxin exposure, wheezing, and rash in infancy in a New Zealand birth cohort

BACKGROUND: Wheezing in infancy is common and is associated with small lungs, viral respiratory tract infection, and environmental tobacco smoke exposure. Recently, increased levels of endotoxin in the domestic environment have also been associated with infant wheezing, particularly among infants with a family history of atopic disease. OBJECTIVE: To explore associations between exposure to endotoxin at 3 months of age and reported symptoms of wheezing, rhinitis, itchy scaly rash, and atopy at 15 months in a birth cohort of 881 New Zealand children. METHODS: Using standardized methods, a 1-m(2) site from the bedroom floors of the 3-month-old infants was sampled and analyzed for endotoxin. RESULTS: Wheezing was significantly associated with higher endotoxin levels (odds ratio [OR], 1.54; 95% CI, 1.03-2.30), particularly among infants with a parental history of allergic disease (OR, 1.67; 95% CI, 1.07-2.60). Higher endotoxin concentrations were also strongly associated with recurrent itchy rashes (OR, 1.87; 95% CI, 1.14-3.05), particularly among infants who were atopic (OR, 4.64; 95% CI, 1.56-13.77) or had a parental history of allergic disease (OR, 2.10; 95% CI, 1.22-3.61). CONCLUSION: Domestic endotoxin was associated with reported airway and skin symptoms in this large group of New Zealand infants. The role of endotoxin in the development of respiratory and skin disease in infancy deserves further study. CLINICAL IMPLICATIONS: Reducing domestic endotoxin exposure might reduce infant wheezing and atopic dermatitis, but the long-term benefits of this remain unclear.     

Health impacts of second-hand exposure to cat allergen Fel d 1 in infants

BACKGROUND: Recent cross-sectional studies suggested that highest sensitization prevalences occur with moderate cat allergen exposures. We aimed to assess the impact of moderate levels of second-hand cat allergen exposure on the incidence of specific sensitization and wheezing in the framework of a birth cohort study. Therefore we restricted our analysis to infants without a cat at home since birth. METHODS: At infant's age 3 months, cat allergen levels were measured in the mattress dust of 1840 families without cats. At age 2 years, serum IgE specific to Fel d 1 was analyzed. Incidence of wheezing apart from respiratory infection was assessed by questionnaire. Logistic regression models were used to calculate adjusted odds ratios (OR) for the association between second-hand cat allergen exposure and health outcomes. RESULTS: Until age 2 years, 13 of 1301 infants (1%) were sensitized to cat allergen and 56 of 1492 infants (4%) had ever-wheezing without infection. Early exposure to second-hand cat allergen levels >or= 1 microg/g dust increased substantially the risk for specific sensitization to Fel d 1 (OR 10.9, 95% CI 3.4-35.0) and ever-wheeze without infection (OR 2.0, 95% CI 1.1-3.9) at age 2 years. CONCLUSIONS: Second-hand exposure to cat allergen in homes without cats is detrimental in terms of allergy development in infants.     

Perinatal influences on the development of asthma and atopy in childhood

BackgroundIn most children with asthma and atopy, onset of disease occurs early in life, indicating a crucial role of in utero and early childhood environment. However, only a small part of this burden of disease established early in life has been explained.ObjectiveTo examine the effects of early environmental exposures on the development of asthma and atopy within the setting of an affluent urban population.MethodsThe authors followed 526 German children from birth to 5 years of age. Parental interviews in pregnancy and then yearly assessed the health of the child and environmental characteristics. Endotoxin and allergens in house dust were measured at 3 months. Atopic sensitization was assessed at 1 and 5 years.ResultsIn atopic mothers, acute atopic symptoms during pregnancy were associated with increased risk of early atopic dermatitis (adjusted odds ratio [aOR] 1.74, 95% confidence interval [CI] 1.00–3.02) and allergic rhinitis at 5 years (aOR 2.11, 95% CI 1.01–4.41). Further, maternal illnesses during pregnancy (ie, repeated common colds) increased the risk of asthma at 5 years (aOR 2.31, 95% CI 1.12–4.78). Endotoxin in the child's mattress was inversely associated with atopic sensitization (aOR 0.79, 95% CI 0.64–0.97) and asthma (aOR 0.71, 95% CI 0.55–0.93). A contrasting effect of early endotoxin and mite exposure was observed for mite sensitization: mite exposure increased the risk of mite sensitization at 5 years (aOR 1.30, 95% CI 1.11–1.53), whereas endotoxin exposure was inversely associated with mite sensitization (aOR 0.73, 95% CI 0.57–0.95).ConclusionFactors affecting the in utero environment, such as maternal atopy and infections, and bacterial exposure in pregnancy or early life may act as immunomodulators enhancing or inhibiting the development of asthma and atopy in childhood.     

Environmental determinants of atopic eczema phenotypes in relation to asthma and atopic sensitization

BACKGROUND: There is still uncertainty about the determinants of atopic eczema (AE). To explain the heterogeneity of the disease, different phenotypes of AE have been suggested. METHODS: The cross-sectional PARSIFAL study included 14 893 school-age children of farmers or children attending Steiner schools and their respective reference groups. A detailed questionnaire was completed, and house dust was collected for the measurement of endotoxin and glucans. Atopic sensitization was defined by allergen-specific IgE levels in the serum. RESULTS: In multivariate analyses, helping with haying was the only variable related to a farming environment having a consistent inverse association with both current symptoms and a doctor's diagnosis of AE [aOR = 0.65 (95% CI: 0.46-0.93) and 0.73 (0.51-1.05)], respectively. Severe lower respiratory tract infections (LRTI) in the first 2 years of life and usage of antibiotics ever were found to be positively related only to asthma-associated AE, whereas the effect of LRTI on AE without asthma had an opposite effect. Levels of beta(1-->3)-glucans in mattress dust were inversely related to a doctor's diagnosis of asthma-associated AE [aOR = 0.75 (0.57-0.98)], and endotoxin levels to current symptoms of asthma-associated AE [aOR = 0.73 (0.57-0.94)]. CONCLUSIONS: The analyses of the PARSIFAL study revealed two different phenotypes of AE, depending on the association with asthma and wheezing ever. With regard to the hygiene hypothesis, help with haying, exposure to beta(1-->3)-glucans and endotoxin were found to be inversely associated with the AE phenotype associated with asthma and wheezing.     

Exposure to endotoxin decreases the risk of atopic eczema in infancy: a cohort study.

BACKGROUND: Previous studies have shown a protective effect of early exposure to cats and dogs on the development of atopic eczema, asthma, allergic rhinitis, and atopic sensitization in later life. In particular, a higher microbial exposure to endotoxin in early childhood might contribute to this effect. OBJECTIVE: We examined the associations between bacterial endotoxin in house dust and atopic eczema, infections, and wheezing during the first year of life in an ongoing birth cohort study (LISA). METHODS: Data of 1884 term and normal-weight neonates with complete information on exposure to biocontaminants and confounding variables were analyzed. House dust from the mothers' and the children's mattresses was sampled 3 months after birth. Endotoxin content was quantified by using a chromogenic kinetic limulus amoebocyte lysate test. RESULTS: During the first 6 months of life, the risk of atopic eczema was significantly decreased by endotoxin exposure in dust from mothers' mattresses in the fifth quintile (odds ratio [OR], 0.50; 95% CI, 0.28-0.88), whereas the risk was increased for respiratory infections (OR, 1.69; 95% CI, 1.25-2.28) and cough with respiratory infection, bronchitis, or both (OR, 1.73; 95% CI, 1.28-2.33). The risk of wheezing was also significantly increased during the first 6 months of life (OR, 2.37; 95% CI, 1.40-4.03). For the entire first year of life, these associations attenuated, except for the risk of wheezing, which remained significant (OR, 1.60; 95% CI, 1.10-2.30). CONCLUSION: Our findings support the hygiene hypothesis that exposure to high concentrations of endotoxin very early in life might protect against the development of atopic eczema within the first 6 months of life, along with an increased prevalence of nonspecific respiratory diseases.     

Exposure to house dust endotoxin and allergic sensitization in adults

BACKGROUND: It has been suggested that exposure to elevated levels of endotoxin decreases the risk of allergic sensitization. OBJECTIVE: To examine the associations between current exposure to bacterial endotoxin in house dust and allergic sensitization in adults. METHODS: In 1995-1996, we conducted a nested case-control study following a cross-sectional study performed within the European Community Respiratory Health Survey (ECRHS). Data of 350 adults aged 25-50 years was analysed. Allergic sensitization was assessed by measurement of specific immunoglobulin E (IgE) against several inhalant allergens. Living room floor dust samples were taken. The endotoxin content was quantified using a chromogenic kinetic Limulus amoebocyte lysate test. RESULTS: Multiple logistic regression analysis showed a negative association between exposure to house dust endotoxin and severe allergic sensitization. Odds ratios (95% CI) adjusted for place of residence, gender, age, and 'caseness' were 0.80 (0.64-1.00) for sensitization to >/=1 allergen and 0.72 (0.56, 0.92) for sensitization to >/=2 allergens using 3.5 kU/l as a cut-off value for sensitization. With regard to single allergens, the protective effect of endotoxin was strongest for pollen sensitization [aOR (95% CI) = 0.74 (0.58, 0.93)]. CONCLUSION: Our results indicate that current exposure to higher levels of house dust endotoxin might be associated with a decreased odds of allergic sensitization in adults.     

Mold damage in homes and wheezing in infants.

BACKGROUND: In most studies that investigate the association of mold or water damage and respiratory disorders in infants, the analysis is not adjusted for exposure to house dust mite (HDM), which is also a known cause of respiratory illnesses. OBJECTIVE: To investigate the relationship between visually observable mold or water damage and HDM (Der f 1) levels and the prevalence of lower respiratory tract symptoms and allergen sensitization in infants of atopic parents as part of a prospective birth cohort study. METHODS: On-site home visits (at the infants' age of 8 months) were performed to evaluate observable mold or water damage and HDM exposure. At a clinic visit near the infant's first birthday, medical histories, including parent-reported wheezing episodes, and a skin prick test to food and 15 common aeroallergens were conducted in 640 infants. RESULTS: More than half of the homes were found to have mold or water damage, and 5% had major mold or water damage with visible mold at 0.2 m2 or more. Only 16% of homes had a HDM allergen (Der f 1) concentration of more than 2 microg/g. Major mold or water damage increased the risk of recurrent wheezing nearly 2 times in infants, 5 times in food or aeroallergen-sensitized infants, and 6 times in aeroallergen-sensitized infants. Neither visible mold or water damage nor HDM exposure was associated with sensitization to either mold or aeroallergens. CONCLUSIONS: Visible mold was shown to be a significant risk factor for recurrent wheezing in infants at high risk of developing atopic disorders, whereas HDM exposure did not significantly increase the risk.     

Exposure to dust mite allergen and endotoxin in early life and asthma and atopy in childhood

BACKGROUND: There has been no longitudinal study of the relation between concurrent exposure to dust mite allergen and endotoxin in early life and asthma and atopy at school age. OBJECTIVES: To examine the relation between exposure to dust mite allergen and endotoxin at age 2 to 3 months and asthma, wheeze, and atopy in high-risk children. METHODS: Birth cohort study of 440 children with parental history of atopy in the Boston metropolitan area. RESULTS: In multivariate analyses, early exposure to high levels of dust mite allergen (> or =10 microg/g) was associated with increased risks of asthma at age 7 years (odds ratio [OR], 3.0; 95% CI, 1.1-7.9) and late-onset wheeze (OR, 5.0; 95% CI, 1.5-16.4). Exposure to endotoxin levels above the lowest quartile at age 2 to 3 months was associated with reduced odds of atopy at school age (OR, 0.5; 95% CI, 0.2-0.9). In contrast with its inverse association with atopy, endotoxin exposure in early life was associated with an increased risk of any wheeze between ages 1 and 7 years that did not change significantly with time (hazard ratio for each quartile increment in endotoxin levels, 1.23; 95% CI, 1.07-1.43). CONCLUSION: Among children at risk of atopy, early exposure to high levels of dust mite allergen is associated with increased risks of asthma and late-onset wheeze. In these children, endotoxin exposure is associated with a reduced risk of atopy but an increased risk of wheeze. CLINICAL IMPLICATIONS: Early endotoxin exposure may be a protective factor against atopy but a risk factor for wheeze in high-risk children.     

Different effects of endotoxin versus mite and cat allergen exposure on T-cell differentiation in infants

BACKGROUND: Early exposure to bacterial endotoxin has been proposed to protect against allergy development in children. Whether endotoxin is able to direct T-cell differentiation into a predominance of type 1 immunity is still unresolved. OBJECTIVE: We sought to compare the effects of endotoxin and mite and cat allergens on T-cell differentiation in infants. METHODS: In a random population sample of 135 2-year-old children of an ongoing birth-cohort study, peripheral blood CD4+ and CD8+ T-cell subsets were defined by the expression of the chemokine receptors CCR5 and CCR3 as surrogate markers for type 1 and type 2 T cells, respectively. Endotoxin and mite and cat allergens were measured in house dust collected from the mother's mattress at the child's age of 3 months to assess early exposure. RESULTS: In the CD4+ T-cell subset, endotoxin levels were positively associated with high proportions of type 1 CCR5+ cells (odds ratio for fourth exposure quartile [OR(Q4)], 7.68; 95% CI, 1.35-43.75), whereas cat allergen levels were associated with increased proportions of type 2 CCR3+ cells (OR(Q4), 4.07; 95% CI, 1.05-15.85). In contrast to endotoxin, allergen levels were associated with CD8+ T cells, showing an inverse relationship between mite allergen concentrations and high proportions of CCR5+ or CCR3+ cells (CCR5+ cells: OR(Q4), 0.14; 95% CI, 0.03-0.74; CCR3+ cells: OR(Q4), 0.16; 95% CI, 0.03-0.89) and a positive association of cat allergen levels with increased proportions of CCR5+ cells (OR(Q4), 9.24, 95% CI, 1.61-53.10), as well as CCR3+ cells (OR(Q3), 6.64; 95% CI, 1.21-36.51). CONCLUSION: Our results indicate that endotoxin has the potential to promote the development of type 1 CD4+ T cells, whereas mite and cat allergens primarily modify the proportion of CD8+ cells of both types.     

Exposure to pets, and the association with hay fever, asthma, and atopic sensitization in rural children

BACKGROUND: An increasing number of studies report pet exposure to be associated with lower risk of asthma and allergies. This 'protective pet effect' has been suggested to result from a modified T-helper (Th)2-cell response, or because of increased microbial load in homes where pets are kept. We examined the associations between pet contact and the occurrence of asthma and allergies in children of the rural Allergy and Endotoxin (ALEX) population, taking farm animal contact, endotoxin and cat allergen levels in mattress dust into account. METHODS: Information about contact with pets and farm animals, asthma and allergy were collected for 812 children by a standardized parents' questionnaire and an interview. Mattress dust endotoxin and cat allergen levels as well as specific IgE and IgG4 antibodies to Fel d1 were determined. RESULTS: Current contact with dogs was inversely associated with diagnosed hay fever (OR 0.26, 95% CI 0.11-0.57), diagnosed asthma (OR 0.29, 95% CI 0.12-0.71), sensitization to cat allergen (OR 0.48, 95% CI 0.23-0.99) and to grass pollen (OR 0.55, 95% CI 0.33-0.94), but not with increased IgG4 levels. Early and current contact with cats were associated with reduced risk of wheezing (OR 0.48, 95% CI 0.23-1.00, and OR 0.49, 95% CI 0.26-0.92, respectively) and grass pollen sensitization. Adjustment for farm animal contact but not for endotoxin and cat allergen exposure attenuated these associations and the effect of pet was stronger among farmers' children. CONCLUSION: Although pet exposure was very frequent in this rural population, the inverse relation between current dog contact, asthma and allergy was mostly explained by simultaneously occurring exposure to stable animals or was restricted to farm children. In addition, a subtle form of pet avoidance may contribute to the protective effect of pet.     

Perinatal risk factors for sensitization, atopic dermatitis and wheezing during the first year of life (PIPO study)

Objective To evaluate the influence of perinatal environmental factors on early sensitization, atopic dermatitis and wheezing during the first year. Methods Information on pregnancy‐related factors, parental atopic history, environmental factors and the clinical course of the infant until age one was gathered by questionnaires, as part of a prospective birth cohort study (Prospective study on the Influence of Perinatal factors on the Occurrence of asthma and allergies [PIPO‐study]). Quantification of total and specific IgE was performed in 810 children and their parents. Results Early sensitization was found in 107/810 (13%) of the infants. Multiple regression analysis showed that specific IgE in fathers was a risk factor for early sensitization in their daughters (adjusted odds ratios (OR_adj) 2.21 (95% confidence interval (CI) 1.10–4.49); P=0.03), whereas in boys, day care attendance was shown to be protective for early sensitization (OR_adj 0.38 (95% CI 0.20–0.71); P=0.001). Atopic dermatitis occurred in 195/792 infants (25%). Specific IgE in the mother (OR_adj 1.52 (95% CI 1.06–2.19); P=0.02) and in the infant (OR_adj 4.20 (95% CI 2.63–6.68); P<0.001) were both risk factors for the occurence of atopic dermatitis, whereas postnatal exposure to cats was negatively associated with atopic dermatitis (OR_adj 0.68 (0.47–0.97); P=0.03). Postnatal exposure to cigarette smoke (OR_adj 3.31 (95% CI 1.79–6.09); P<0.001) and day care attendance (OR_adj 1.96 (95% CI 1.18–3.23); P=0.009) were significantly associated with early wheezing, which occurred in 25% (197/795) of the infants. Conclusion The effect of paternal sensitization and day care attendance on sensitization is gender dependent. Maternal sensitization predisposes for atopic dermatitis, whereas postnatal exposure to cats had a protective effect.     

Mouse exposure and wheeze in the first year of life.

BACKGROUND: Studies have found that exposure to mice is highly prevalent among children with asthma living in urban areas. OBJECTIVE: To examine the relationship between exposure to mice and wheeze in the first year of life. METHODS: We conducted an ongoing prospective birth cohort study of 498 children with a history of allergy or asthma in at least 1 parent living in metropolitan Boston (the Home Allergens and Asthma Study). RESULTS: In a multivariate analysis, infants whose parents reported exposure to mice in the household had nearly twice the odds of developing any wheeze in the first year of life as children without exposure (odds ratio [OR], 1.83; 95% confidence interval [CI], 1.14-2.95; P = .01). Other variables associated with wheeze in the first year of life included low birth weight (OR, 1.77; 95% CI, 1.06-2.95; P = .03), having at least 1 lower respiratory tract illness (OR, 5.59; 95% CI, 3.46-9.04; P < .001), exposure to high levels of endotoxin at age 2 to 3 months (fourth quartile compared with first quartile: OR, 2.32; 95% CI, 1.19-4.54; P = .01), and exposure to cockroach allergen of 0.05 U/g of dust or more at age 2 to 3 months (OR, 1.83; 95% CI, 1.09-3.08; P = .02). CONCLUSION: Among children with a parental history of asthma or allergies, exposure to mice is associated with wheeze in the first year of life, independent of other factors.     

Microbial exposure of rural school children, as assessed by levels of N-acetyl-muramic acid in mattress dust, and its association with respiratory health

BACKGROUND: Endotoxin exposure has been shown to be associated with a decreased prevalence of atopic sensitization and symptoms. Yet endotoxin represents only a part of the indoor microbial exposure. Muramic acid, a constituent of peptidoglycan, is present in gram-negative and gram-positive bacteria in the environment and may therefore serve as an additional marker of microbial exposure. OBJECTIVE: To study the factors determining the level of indoor exposure to muramic acid/peptidoglycan, as well as its potential association with respiratory health. METHODS: In 553 farm and nonfarm school children from Austria, Switzerland, and Germany, mattress dust muramic acid concentrations were determined, and health was assessed by using IgE measurements and questionnaire information. RESULTS: The muramic acid concentration was found to be significantly higher in dust from farm children's mattresses than in dust from nonfarm children's mattresses (157 vs 131 ng/mg). Children with higher mattress dust muramic acid concentrations had a significantly lower prevalence of wheezing (odds ratio of highest vs lowest tertile of muramic acid concentration, 0.3; 95% CI, 0.1-0.9), regardless of farming status and endotoxin exposure. The association for asthma was similar, and no association was found with atopic sensitization. CONCLUSION: Next to endotoxin, muramic acid provides us with an independent marker of microbial exposure. Unlike endotoxin, muramic acid was inversely associated with wheezing rather than with atopic sensitization.     

Exposure to birch pollen in infancy and development of atopic disease in childhood

BACKGROUND: The relationship between early allergen exposure, sensitization, and development of atopic disease remains controversial. In 1993, extremely high levels of birch pollen were recorded in Stockholm, Sweden, creating the unique opportunity to study children with different exposures during infancy. OBJECTIVE: We sought to assess the influence of early high-dose exposure to an inhalant allergen (birch pollen) on sensitization and development of atopic disease in children. METHODS: A total of 583 children with atopic heredity born in Stockholm in February through April 1992, 1993, or 1994 were investigated at age 4.5 to 5 years. The children were examined and underwent skin prick testing with inhalant and food allergens. IgE antibodies (RAST) against birch pollen and recombinant birch pollen allergen (rBet v 1) were analyzed in serum. RESULTS: The children born in 1993 (high-dose exposure at 0-3 months) were more often sensitized (ie, positive skin prick test response) to birch pollen than the children born in 1994 (low-dose exposure; 17.8% and 8.8%, respectively; odds ratio [OR], 2.4; 95% CI, 1.2-4.6). A tendency in the same direction was seen for children born in 1992 (high-dose exposure at 12-15 months; OR, 1.7; 95% CI, 0.9-3.2). The results were supported by the RAST analyses. The prevalence of bronchial asthma, allergic rhinoconjunctivitis, and atopic dermatitis did not differ between the birth-year groups. However, the prevalence of pollen- and animal dander-induced allergic asthma was increased in the children born in 1993 (OR, 2.6; 95% CI, 1.2-5.6). An interaction between early high-dose exposure to birch pollen and cat in the household was suggested for sensitization to cat (P =.06). CONCLUSION: Exposure to high levels of birch pollen in infancy increases the risk of sensitization to the same allergen, as well as the risk of allergic asthma.     

Prevention of allergic disease during childhood by allergen avoidance: the Isle of Wight prevention study

BACKGROUND: Early life allergen exposure may increase the risk of childhood allergy, but the protective effect of reduction in allergen exposure remains uncertain. OBJECTIVE: To evaluate the effect of reduction in food and house dust mite (HDM) allergen exposure in infancy in preventing asthma and allergy. METHODS: Infants, at higher risk because of family predisposition, were recruited prenatally and randomized to prophylactic (n = 58) and control (n = 62) groups. Prophylactic group infants were either breast-fed with mother on a low allergen diet or given an extensively hydrolyzed formula. Exposure to HDM was reduced by the use of an acaricide and mattress covers. The control group followed standard advice. Development of allergic diseases and sensitization to common allergens (atopy) was assessed blindly at ages 1, 2, 4, and 8 years in all 120 children. RESULTS: Repeated measurement analysis, adjusted for all relevant confounding variables, confirmed a preventive effect on asthma: adjusted odds ratio (OR), 0.24; 95% CI, 0.09-0.66; P = .005; atopic dermatitis, OR, 0.23; CI, 0.08-0.64; P = .005; rhinitis, OR, 0.42; CI, 0.19-0.92; P = .03; and atopy, OR, 0.13; CI, 0.05-0.32; P < .001. The protective effect was primarily observed in the subgroup of children with persistent disease (symptoms at all visits) and in those with evidence of allergic sensitization. CONCLUSION: Allergic diseases can be reduced, for at least the first 8 years of life, by combined food and HDM allergen avoidance in infancy. CLINICAL IMPLICATIONS: Strict food and HDM allergen avoidance should be considered for prevention of allergy in high-risk infants.     

Endotoxin exposure and atopic sensitization in adult pig farmers

BACKGROUND: Recent studies have reported a low prevalence of atopic sensitization and respiratory allergy in children growing up on farms. OBJECTIVES: We sought to evaluate the dose-response relationship between endotoxin and atopic sensitization in adult farmers and to assess the effect on respiratory health outcomes. METHODS: Data on endotoxin exposure and serum IgE levels were available for 162 pig farmers from a cross-sectional case-control study, with case selection on the basis of respiratory symptoms. Exposure to endotoxin was modeled in detail, and respiratory health effects were assessed during a medical examination. Exploratory analysis was done by using nonparametric modeling and was followed by classical parametric regression. RESULTS: IgE to one or more common allergens was detected in sera from 28 (17%) farmers. The average (geometric mean) total serum IgE levels was 37 IU/mL (geometric SD, 4 IU/mL). A strong inverse relationship was found between endotoxin and sensitization to common allergens for exposures of 75 ng/m 3 or less, with an odds ratio of 0.03 (95% CI, 0.0-0.34) for a 2-fold increase in endotoxin. For endotoxin exposure of greater than 75 ng/m 3 , the association was weak (odds ratio, 1.2 [95% CI, 0.38-3.6]). No association was found between endotoxin exposure and total serum IgE levels. Endotoxin was associated with increased airway hyperresponsiveness to histamine and lower lung function in sensitized farmers, without evidence of a nonlinear relationship. CONCLUSIONS: The prevalence of atopic sensitization in adult pig farmers is low. Endotoxin or related exposures might protect from sensitization, even in an adult working population exposed to high levels of endotoxin, but is a risk factor for increased airway hyperresponsiveness and low lung function.     

Allergic diseases and atopic sensitization in children related to farming and anthroposophic lifestyle--the PARSIFAL study

BACKGROUND: The prevalence of allergic diseases has increased rapidly in recent decades, particularly in children. For adequate prevention it is important not only to identify risk factors, but also possible protective factors. The aim of this study was to compare the prevalence of allergic diseases and sensitization between farm children, children in anthroposophic families, and reference children, with the aim to identify factors that may protect against allergic disease. METHODS: The study was of cross-sectional design and included 14,893 children, aged 5-13 years, from farm families, anthroposophic families (recruited from Steiner schools) and reference children in Austria, Germany, The Netherlands, Sweden and Switzerland. A detailed questionnaire was completed and allergen-specific IgE was measured in blood. RESULTS: Growing up on a farm was found to have a protective effect against all outcomes studied, both self-reported, such as rhinoconjunctivitis, wheezing, atopic eczema and asthma and sensitization (allergen specific IgE > or = 0.35 kU/l). The adjusted odds ratio (OR) for current rhinoconjunctivitis symptoms was 0.50 (95% confidence interval (CI) 0.38-0.65) and for atopic sensitization 0.53 (95% CI 0.42-0.67) for the farm children compared to their references. The prevalence of allergic symptoms and sensitization was also lower among Steiner school children compared to reference children, but the difference was less pronounced and not as consistent between countries, adjusted OR for current rhinoconjunctivitis symptoms was 0.69 (95% CI 0.56-0.86) and for atopic sensitization 0.73 (95% CI 0.58-0.92). CONCLUSIONS: This study indicates that growing up on a farm, and to a lesser extent leading an anthroposophic life style may confer protection from both sensitization and allergic diseases in childhood.     

Predictors of indoor exposure to mouse allergen in urban and suburban homes in Boston

BACKGROUND: Mouse allergen exposure is prevalent among urban children with asthma. Little is known about mouse allergen exposure in children at risk for the development of allergic diseases. AIMS OF THE STUDY: To assess indoor mouse allergen exposure in early life among children with parental history of asthma or allergies. METHODS: Prospective birth cohort study of 498 children with a history of allergy or asthma in at least one parent living in metropolitan Boston. RESULTS: Of the 498 participating children, 357 (71.7%) resided outside the city of Boston and 439 (90.7%) lived in households with incomes > 30,000 dollars. Mouse allergen was detected in 42% of the homes of study participants. In a multivariate analysis adjusting for sex, income, and endotoxin, black race [odds ratio (OR) = 3.0; 95% confidence interval (CI) = 1.3-6.6, P = 0.009], signs of mice in the home at age 2-3 months (OR = 3.0; 95% CI = 1.6-5.6, P = 0.0006), and kitchen cockroach allergen levels > or = 0.05 to < 2 U/g (OR = 1.8; 95% CI = 1.1-3.2, P = 0.02) were associated with detectable mouse allergen in the kitchen. In this model, living in a single detached house was inversely associated with detectable kitchen mouse allergen levels (OR = 0.4; 95% CI = 0.2-0.6, P = 0.0001). CONCLUSION: Infants with a parental history of asthma or allergies are commonly exposed to mouse allergen in their homes. Among infants at high risk for atopy, predictors of increased mouse allergen levels included black race, reported mice exposure, and moderate levels of cockroach allergen.