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

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

Farming environment and prevalence of atopy at age 31: prospective birth cohort study in Finland

Background 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. Objective Investigate the association of a farming environment, especially farm animal contact, during infancy, with atopic sensitization and allergic diseases at the age of 31. Methods 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. Results 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. Conclusion and Clinical Relevance Contact with farm animals in early childhood reduces the risk of atopic sensitization, doctor‐diagnosed asthma and allergic diseases at age 31. Cite this as: J. Lampi, D. Canoy, D. Jarvis, A.‐L. Hartikainen, L. Keski‐Nisula, M.‐R. Järvelin and J. Pekkanen, Clinical & Experimental Allergy, 2011 (41) 987–993.     

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.     

Infectious and uterus related complications during pregnancy and development of atopic and nonatopic asthma in children

BACKGROUND: It has been suggested that environmental factors early in life, particularly related to hygiene and infections, seem to be involved in the increase of asthma and allergic disease observed recently in developed countries. The possible effect of these factors also in utero have yet to be completely clarified. The aim of this study was to investigate the association between infective and uterus related complications during pregnancy, as well as related drug factors, with atopic and nonatopic asthma in children. METHODS: This was a case-controlled study enrolling 338 children with asthma and 467 controls, who had never suffered from wheeze or asthma. Fever episodes, flu episodes, threatened abortions and related drug factors were retrospectively assessed by parental report via a standardized questionnaire. Atopy was determined by skin-prick tests to 10 prevalent allergens at the time of examination. RESULTS: Flu episodes during pregnancy were significantly associated with development of asthma in children [adjusted odds ratio (aOR) 1.91; 95% confidence interval (95% CI) 1.1-3.2], mainly with nonatopic asthma. Fever episodes showed similar results (aOR 2.16; 95% CI 1.2-3.9), but were associated with both atopic and nonatopic asthma. The effect seems mainly due to flu and fever episodes contracted in the third trimester. Exposure to isoxsuprine was significantly associated with asthma (aOR 1.54; 95% CI 1.08-2.19) while threatened abortions were more frequent in the asthma group than in controls, although the difference was statistically significant only when such events occurred in the second trimester (aOR 2.06; 95% CI 1.07-3.94). Both threatened abortions and exposure to isoxsuprine were associated only with nonatopic asthma. CONCLUSIONS: This study confirms that prenatal infective complications may contribute to the development of asthma in children and show a possible role for a new risk factor for asthma, that is exposure to isoxsuprine. Therefore, larger prospective studies, capable of separating atopic and nonatopic asthma, would serve to confirm these results and to explain the possible mechanism through which these factors may act.     

House dust (1-3)-beta-D-glucan and wheezing in infants

BACKGROUND: (1-3)-Beta-D-glucan is a fungal cell wall component, suspected to cause respiratory symptoms in adults. However, very little is known on the possible health effects of (1-3)-beta-D-glucan during infancy. We examined the association between (1-3)-beta-D-glucan exposure and the prevalence of allergen sensitization and wheezing during the first year of life in a birth cohort of 574 infants born to atopic parents. Endotoxin exposure was included as a possible confounder. METHODS: (1-3)-Beta-D-glucan and endotoxin exposures were measured in settled dust collected from infants' primary activity rooms. The primary outcomes at approximately age one included parental reports of recurrent wheezing and allergen sensitization evaluated by skin prick testing to a panel of 15 aeroallergens as well as milk and egg white. RESULTS: Exposure to high (1-3)-beta-D-glucan concentration (within fourth quartile) was associated with reduced likelihood of both recurrent wheezing [adjusted OR (aOR) = 0.39, 95% CI = 0.16-0.93] and recurrent wheezing combined with allergen sensitization (aOR = 0.13, 95% CI = 0.03-0.61). Similar trends were found between (1-3)-beta-D-glucan concentrations and allergen sensitization (aOR = 0.57, 95% CI = 0.30-1.10). In contrast, recurrent wheezing with or without allergen sensitization was positively associated with low (1-3)-beta-D-glucan exposure within the first quartile (aOR = 3.04, 95% CI = 1.25-7.38; aOR = 4.89, 95% CI = 1.02-23.57). There were no significant associations between endotoxin exposure and the studied health outcomes. CONCLUSIONS: This is the first study to report that indoor exposure to high levels of (1-3)-beta-D-glucan (concentration >60 microg/g) is associated with decreased risk for recurrent wheezing among infants born to atopic parents. This effect was more pronounced in the subgroup of allergen-sensitized infants.     

Allergen-specific sensitization in asthma and allergic diseases in children: the study on farmers'' and non-farmers'' children

BACKGROUND: Farmers' children are less frequently sensitized to common allergens than the non-farmers' children, but less is known about their sensitization to other allergens and its association with clinical diseases. OBJECTIVE: To examine the association of farm environment with atopic sensitization, allergic diseases, expression of allergen-induced symptoms, and the importance of specific sensitization against 'common' (timothy, dog, cat, birch, Dermatophagoides pteronyssimus, mugwort) and 'other' (cockroach, horse, Lepidoglyphus destructor, cow) allergens for asthma and allergic diseases in children. METHODS: A cross-sectional study including 344 farmers' and 366 non-farmers' children aged 6-13 years in eastern Finland, using a self-administered written questionnaire and skin prick tests against the above-mentioned allergens. RESULTS: Farmers' children had less asthma and allergic diseases and were less often sensitized against common allergens than the non-farmers' children. However, little difference was observed in sensitization against the other allergens between the farmers' (17.2%) and non-farmers (14.5%) children [adjusted odds ratios (aOR) 1.11 (0.71-1.72)]. Being sensitized against only other allergens, without sensitization against common allergens, was unrelated to asthma or allergic diseases. Among the single allergens, sensitization against pets or pollen, or against horse or cow, had the strongest association with asthma, hayfever, and atopic eczema; no such association was seen in D. pteronyssimus, mugwort, cockroach, or L. destructor. Farmers' children had significantly less often symptoms of allergic rhinitis in contact with dog (aOR 0.32%, 95% confidence interval (CI) 0.15-0.67), cat (aOR 0.45, 0.22-0.88), or pollen (aOR 0.58%, 95% CI 0.37-0.90) than the non-farmers' children. CONCLUSION: Farm environment reduces the occurrence of asthma, allergic diseases, and atopic sensitization in children, and also the occurrence of allergen-induced rhinitis. Remarkable differences were observed between single allergens in their association with allergic disease, stressing the importance of allergen selection when defining atopy in epidemiological studies.     

Family history, dust mite exposure in early childhood, and risk for pediatric atopy and asthma

BACKGROUND: Dust mite allergen exposure is considered a major determinant of sensitization to these allergens during childhood and a risk factor for pediatric asthma. OBJECTIVE: By using a birth cohort in a setting with a substantial burden of dust mite allergen, we evaluated exposure and risk for outcomes related to allergy and asthma. METHODS: We collected dust from the bedrooms of 428 children born from 1987 to 1989 and measured Der f 1 and Der p 1 (microg/g dust, combined). Follow-up at 6 to 7 years of age included clinical examination, skin prick testing, specific serum IgE measurement, and methacholine challenge. RESULTS: No overall association was evident for any outcome except bronchial hyperresponsiveness (adjusted odds ratio [OR], 0.62; 95% CI, 0.38-1.00; P <.050; and OR, 0.53; CI, 0.27-1.04; P <.065 for dust mite allergen levels > or =2 microg/g and >10 microg/g, respectively). With a parental history of allergy and asthma, there was an association between a positive dust mite skin test (OR, 2.09; CI, 0.93-4.73; P <.076) and dust mite allergen level >10 microg/g. The inverse was true for children without a parental history. Dust mite exposure of >10 microg/g was associated with a decreased risk of current atopic asthma among children with a parental history (OR, 0.39; CI, 0.05-3.13; P <.376), but with increased risk if without a parental history (OR, 1.52; CI, 0.22-10.6; P <.673). CONCLUSION: Parental history is an important independent variable in the relationship between early dust mite exposure and atopic outcomes. Increased exposure during infancy is associated with a higher risk for sensitization in the presence of a positive parental history, but is protective among children of parents without a history of atopic disease.     

Does early indoor microbial exposure reduce the risk of asthma? The Prevention and Incidence of Asthma and Mite Allergy birth cohort study

BACKGROUND: Exposure to microbial agents might inhibit the development of atopy and asthma. OBJECTIVE: We measured the association between microbial exposure assessed at 3 months and the development of atopic sensitization and doctor-diagnosed (DD) asthma and wheeze in the first 4 years in a birth cohort study of children with atopic mothers. METHODS: Endotoxin, fungal (1-->3)-beta-D-glucans, extracellular polysaccharides from the genera Penicillium and Aspergillus (EPS-Pen/Asp), and dust on living room floors were measured at 3 months of age. Serum IgE levels against common allergens were determined at 1 and 4 years, and questionnaire information about respiratory morbidity was collected yearly. RESULTS: Microbial levels in mattresses were low and not associated with serum IgE levels, DD asthma, and wheeze. Floor levels of biocontaminants and dust, on the other hand, were inversely associated with DD asthma, being most pronounced for endotoxin (odds ratio [OR], 0.40; 95% CI, 0.21-0.77) and EPS-Pen/Asp (OR, 0.42; 95% CI, 0.18-0.99). Mutual adjustment for other exposures did not significantly alter the results for endotoxin and only moderately affected the results for EPS-Pen/Asp. Persistent wheeze was also consistently less common in the high-exposure group, being significant only for EPS-Pen/Asp (OR, 0.37; 95% CI, 0.15-0.96). Transient wheeze and wheeze in the past 12 months were also reduced, but effects were smaller and not significant. Relationships with serum-specific IgE levels, which could only be assessed in 41% at age 4 years, were less pronounced and statistically significant only for EPS-Pen/Asp. CONCLUSIONS: Early exposure to common microbial contaminants, including fungal agents, might protect against asthma. CLINICAL IMPLICATIONS: Microbial exposure in early life might protect against asthma and might constitute a novel target for prevention.     

The pattern of atopic sensitization is associated with the development of asthma in childhood.

BACKGROUND: Even though atopic sensitization has been shown to be strongly associated with childhood asthma, asthma eventually develops in only one third of atopic children. OBJECTIVE: The aim of this study was to prospectively investigate the pattern of atopic sensitization typically associated with the development of asthma in childhood. METHODS: The German Multicenter Allergy Study followed 1314 children from birth to the age of 7 years. Parental questionnaires on asthma and asthmatic symptoms were completed 6 times up to the age of 2 years and from then on yearly. Determination of specific IgE to 9 food and inhalant allergens was performed yearly, and at the age of 7 years, a bronchial histamine challenge was conducted. RESULTS: Onset of atopic sensitization in atopic children with current asthma at the age of 7 years was significantly earlier than in atopic children without current asthma (39.4% before age 1 year vs 21.0%, P =.015). Early atopic sensitization without any sensitization to inhalant allergens at the age of 7 years conferred no increased risk for asthma at this age. Only those children sensitized to any allergen early in life and sensitized to inhalant allergens by the age of 7 years were at a significantly increased risk of being asthmatic at this age (odds ratio, 10.12; 95% CI, 3.81-26.88). However, even in this group of persistently sensitized children, the risk of being asthmatic at the age of 7 years was only increased if a positive parental history of asthma or atopy was present (odds ratio, 15.56; 95% CI, 5.78-41.83), with the effect being strongest for maternal asthma. CONCLUSION: Our results indicate that an underlying factor pertaining to asthma and maternal transmission may determine both a certain pattern of sensitization and the expression of asthma.     

Lymphoproliferative responses in cord blood and at one year: no evidence for the effect of in utero exposure to dust mite allergens

BACKGROUND: Maternal allergen exposure beyond the 22nd week of pregnancy may be important in foetal T cell priming. Allergen-specific cord blood mononuclear cell (CBMC) immunoproliferative responses without corresponding bacterial antigen responses (tetanus toxoid), have been suggested as evidence of in utero sensitization. OBJECTIVES: To investigate the relationship between lymphoproliferative responses at birth and at 1 year with maternal and 1-year infants house dust mite allergen exposure. METHODS: Home visits and dust sampling were performed by the 20th week of pregnancy, immediately after birth, and then at 1 years of age. Der p 1 was assayed using a two-site immunometric ELISA. CBMC immunoproliferative responses (AIM V serum-free medium; 1 x 105 cells/well) were measured for 225 neonates (171 had a high risk of atopy (HR)--both parents skin test positive; 59 had a low risk of atopy (LR) - both parents skin test negative, no history of atopy) by 3H-Thymidine (1microCi/well) incorporation after stimulation in primary culture with phytohaemagglutinin (PHA) (1 microg/mL), house dust mite [HDM] extract (30 microg/mL), immunopurified Der p 1 (30 microg/mL), Tetanus toxoid (TT) (aluma free, 30 Lf/mL) or vehicle. Blood was collected from 144 infants at the age of 1 years and stimulated proliferative responses were assessed using the same procedure. RESULTS: PHA-stimulated lymphoproliferative response was significantly lower in HR compared to LR neonates (mean difference 38%, 95% CI 15%-54%; P = 0.003); significantly lower proportion of positive CBMC responses to HDM occurred in LR than in HR neonates (30.4% vs. 46.6%; P = 0.034). There was no relationship between Der p 1 levels in maternal bed and CBMC immunoproliferative responses, despite the 21 000-fold range of maternal Der p 1 exposure. No significant differences in magnitude, or in proportion of positive responses to any stimulant were observed between the neonates at low, medium or high tertile of allergen exposure. Immunoproliferative responses at birth were not predictive of 1-year PBMC responses. There was no relationship between maternal allergen exposure in pregnancy and 1-year PBMC proliferative responses. However, the proportion of positive proliferative responses at 1 years significantly increased with increasing infant Der p 1 exposure at 1 years. CONCLUSION: These results indicate that the magnitude of immunoproliferative responses are unrelated to maternal mite allergen exposure and cannot be used as evidence for in utero sensitization to inhalant allergens. The immunoproliferative responses at 1 year seem to shift away from the genetically influenced responses at birth towards responses to specific stimulants which correlate with environmental exposure to those specific stimulants. These data support the concept of sensitization to inhalant allergens occurring in early life, but not in utero.     

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.     

Respiratory illnesses in early life and asthma and atopy in childhood

BACKGROUND: The relation between respiratory illnesses in early life and the development of asthma and atopy in childhood is incompletely understood. OBJECTIVE: We sought to examine the relationship between respiratory illnesses in early life and atopic diseases at school age. METHODS: We performed a prospective birth cohort study of the relationship between respiratory illnesses in the first year of life and asthma, atopy (sensitization to >or=1 allergen), and allergic rhinitis at school age in 440 children with a parental history of atopy. Logistic regression was used to examine the relationship between respiratory illnesses and asthma, atopy, and allergic rhinitis. The relationship between respiratory illnesses in early life and repeated measures of wheezing between the ages of 1 and 7 years was investigated by using a proportional hazards models. RESULTS: Physician-diagnosed croup (adjusted odds ratio [OR], 0.30; 95% CI, 0.12-0.72) and having 2 or more physician-diagnosed ear infections (adjusted OR, 0.58; 95% CI, 0.35-0.98) in the first year of life were inversely associated with atopy at school age. Physician-diagnosed bronchiolitis before age 1 year was significantly associated with asthma at age 7 years (adjusted OR, 2.77; 95% CI, 1.23-6.22). Recurrent nasal catarrh (>or=3 episodes of a runny nose) in the first year of life was associated with allergic rhinitis at age 7 years (adjusted OR, 2.99; 95% CI, 1.03-8.67). CONCLUSION: The relationship between early-life respiratory illnesses and asthma and atopy is complex and likely dependent on the type of infection and immune response it initiates. CLINICAL IMPLICATIONS: Certain respiratory illnesses in early life modify the risk of atopy and asthma at school age.     

NAC Manchester Asthma and Allergy Study (NACMAAS): risk factors for asthma and allergic disorders in adults

Asthma and atopic disorders are the most common chronic diseases in the developed countries. Knowledge of the risk factors for these disorders may facilitate the development of preventive strategies aimed at reducing prevalence rates. To investigate the risk factors for asthma and allergic diseases in a large number of adults who are the parents of children in the National Asthma Campaign Manchester Asthma and Allergy Study. All pregnant women and their partners attending "Booking" antenatal clinics were invited to take part in the study. Questionnaire data were collected including the history of asthma and other atopic diseases, pet ownership and smoking habits, and skin prick tests were performed. The prevalence of atopy and the risk factors for asthma and allergic disorders were investigated in all subjects who completed the questionnaire and underwent skin testing. Statistical analysis was carried out using logistic regression. Initially, risk factors were assessed by univariate analysis to see how each potential explanatory variable affected the probability of having allergic disease. Variables were then tested in a forward stepwise multivariate analysis. In 5687 adult subjects there was a very high (48.2%) prevalence of atopy, and 9.7% of subjects had a diagnosis of asthma. In a multivariate regression analysis sensitization to dust mite, cat, dog and mixed grasses were all independently associated with asthma. The odds ratios for current asthma increased with the increasing number of positive skin tests (any two allergens - OR 4.3, 95% CI 3.3-5.5; any three allergens - OR 7.0 95% CI 5.3-9.3; all four allergens - OR 10.4, 95% CI 7.7-14; P < 0.00001). Dog ownership (OR 1.31, 95% CI 1.10-1.57; P = 0.003) and current smoking (OR 1.36, 95% CI 1.15-1.62; P = 0.0004) were significantly and directly associated with "asthma ever". Thirteen per cent of participants reported a history of eczema. In the multivariate analysis the strongest independent associate of eczema was sensitization to dog (OR 1.37, 95% CI 1.14-1.63, P < 0.0001). Apart from dog, the strength of the association between sensitization to common allergens and eczema appeared to be much lower than in the case of asthma. The prevalence of hay fever was high (20.6%), and in the multivariate analysis the association between sensitization to pollen and hay fever was extremely strong (OR 13.6, 95% CI 11.3-16.3; P < 0.0001). The results of the current study emphasize the importance of sensitization to indoor allergens in asthma. However, evidence of a possible direct role of allergen exposure in asthma causation remains unclear.     

Multiple microbial exposures in the home may protect against asthma or allergy in childhood

Background Experimental animal data on the gram‐negative bacterial (GNB) biomarker endotoxin suggest that persistence, dose, and timing of exposure are likely to influence its effects on allergy and wheeze. In epidemiologic studies, endotoxin may be a sentinel marker for a microbial milieu, including gram‐positive bacteria (GPB) as well as GNB, that may influence allergy and asthma through components (pathogen‐associated molecular patterns) that signal through innate Toll‐like receptor pathways. Objective To determine the influence of current GNB and GPB exposures on asthma and allergic sensitization in school‐aged children. Methods We examined the relationship between bacterial biomarkers and current asthma and allergic sensitization in 377 school‐aged children in a birth cohort study. We then evaluated the effects of school‐aged endotoxin, after controlling for exposure in early life. Results Exposure to GNB was inversely associated with asthma and allergic sensitization at school age [for >median endotoxin: prevalence odds ratio (POR)=0.34, 95% CI=0.2–0.7, for current asthma and prevalence ratio=0.77, 95% CI=0.6–0.97, for allergic sensitization]. In contrast, elevated GPB in the bed was inversely associated with current asthma (POR=0.41, 95% CI=0.2–0.9) but not with allergic sensitization (POR=1.07, 95% CI=0.8–1.4). School‐aged endotoxin exposure remained protective in models for allergic disease adjusted for early‐life endotoxin. Conclusion Both GNB and GPB exposures are associated with decreased asthma symptoms, but may act through different mechanisms to confer protection. Endotoxin exposure in later childhood is not simply a surrogate of early‐life exposure; it has independent protective effects on allergic disease.     

Prenatal farm exposure is related to the expression of receptors of the innate immunity and to atopic sensitization in school-age children

BACKGROUND: There is increasing evidence that environmental exposures determining childhood illnesses operate early in life. Prenatal exposure to a farming environment through the mother might also play an important role. OBJECTIVE: We sought to investigate the role of maternal exposures to environments rich in microbial compounds for the development of atopic sensitization, asthma, and corresponding alterations in the innate immune system in offspring. METHODS: In the children of the cross-sectional Prevention of Allergy Risk Factors for Sensitization in Children Related to Farming and Anthroposophic Life Style study, asthma and atopy were assessed by means of standardized questionnaires (n = 8263) and serum IgE measurements (n = 2086). In a subsample (n = 322) gene expression of Toll-like receptors (TLR2 and TLR4) and CD14 was assessed. Maternal exposures were defined through questionnaire information. RESULTS: Both atopic sensitization (adjusted odds ratio, 0.58; 95% CI, 0.39-0.86) and the gene expression of receptors of innate immunity were strongly determined by maternal exposure to stables during pregnancy, whereas current exposures had much weaker or no effects. A dose-response relation was found between the extent of upregulation of these genes and the number of different farm animal species the mother had encountered in her pregnancy. Each additional farm animal species increased the expression of TLR2, TLR4, and CD14 by a factor of 1.16 (95% CI, 1.07-1.26), 1.12 (95% CI, 1.04-1.2), and 1.10 (95% CI, 1.03-1.23), respectively. CONCLUSION: Maternal exposure to an environment rich in microbial compounds might protect against the development of atopic sensitization and lead to upregulation of receptors of the innate immune system. The underlying mechanisms potentially operating through the intrauterine milieu or epigenetic inheritance await further elucidation. CLINICAL IMPLICATIONS: When assessing risk factors of allergies in an infant's medical history, attention must also be paid to environmental exposures affecting the mother.     

Early childhood environment related to microbial exposure and the occurrence of atopic disease at school age

BACKGROUND: There is a growing body of evidence that the early childhood environment with respect to day care attendance, older siblings, pet ownership, and early life airway infections may protect from developing atopic disease. Few studies have distinguished between atopic sensitization and symptoms, and none have evaluated independent contributions for all of these different environmental conditions. OBJECTIVE: Examine independent effects on atopic sensitization and symptoms of day care attendance, older siblings, pet ownership, and early infancy's airway disease. METHODS: A cross-sectional survey among 8-13-year-old school children with complete data for 1555 children. RESULTS: After adjustment for confounders, atopic sensitization occurred less frequently in children that had attended a day care centre (OR: 0.73, 95% CI: 0.55-0.98) or had a cat or dog before 2 years of age (OR: 0.78, 95% CI: 0.61-0.99). Having older siblings yielded a nonsignificant trend towards protection (OR: 0.88, 95% CI: 0.70-1.11). For symptoms, there was no relation with having older sibs, day care attendance and pet ownership, although there was a trend towards protection for the combination of atopy and symptoms. In contrast, children with doctors' treated airway disease before age 2, more frequently reported recent symptoms of wheeze, asthma, rhinitis, or dermatitis (all P < 0.05). CONCLUSION: Early life environmental exposure to day care, or pets may protect against atopic sensitization. Protection against symptoms only occurred if atopic sensitization was present as well.     

Maternal fish intake during pregnancy and atopy and asthma in infancy

BACKGROUND: There is growing evidence that n-3 fatty acids have anti-inflammatory properties and may modulate immune response. Dietary intake of these nutrients during pregnancy could play a role in the risk of asthma and atopy in the offspring. METHODS: Using data from a cohort of women (n=462) enrolled during pregnancy and whose offspring were followed up to 6 years, we evaluated the impact of fish consumption during pregnancy on the incidence of atopy and asthma. Dietary intake was assessed by food frequency questionnaire (42 items) applied by an interviewer. RESULTS: Thirty-four percent of infants had a medical diagnosis of eczema at age 1 year, 14.3% of the children were atopic [based on skin prick test (SPT) at 6 years], and 5.7% had atopic wheeze at age 6 years. After adjusting for potential confounding factors, fish intake during pregnancy was protective against the risk of eczema at age 1 year, a positive SPT for house dust mite at age 6 years and atopic wheeze at age 6 years [odds ratio (OR)=0.73 95% confidence interval (CI) 0.55-0.98, OR=0.68, 95% CI 0.46-1.01 and OR=0.55, 95% CI 0.31-0.96, respectively]. For an increase in fish intake from once per week to 2.5 times per week, the risk of eczema at age 1 year decreased by 37%, and the risk of positive SPT at age 6 years by 35%. Stratification by breastfeeding showed that fish intake was significantly related to a decrease risk in persistent wheeze among non-breastfed children (P for interaction<0.05). No protective effect was observed among breastfed children. CONCLUSION: Our data suggest a protective effect of fish intake during pregnancy on the risk of atopy-related outcomes.     

Asthma and sensitization in a community with low indoor allergen levels and low pet-keeping frequency

BACKGROUND: Little is known about causes of asthma and sensitization in desert countries. OBJECTIVE: To investigate risk factors associated with asthma and sensitization in Kuwait. METHODS: One hundred sixty children (9-16 years) with physician-diagnosed asthma were recruited and matched (age, sex) with 303 healthy controls. Risk factors were assessed by questionnaires, determination of sensitization status (skin tests and IgE), and home allergen exposure (mite, cat, dog, cockroach; ELISA). RESULTS: Home allergen levels and frequency of pet ownership were very low (cat, 4.1%; dog, 1.5%). The risk of cat sensitization increased significantly among cat owners (odds ratio [OR], 3.53; 95% CI, 1.33-9.41; P = .01), and in children with reported contact with cats during the first year of life (OR, 2.60; 95% CI, 1.17-5.80; P = .019). In the multivariate analysis, maternal atopy (OR, 1.77; 95% CI, 1.13-2.75; P = .01) and cat ownership (OR, 3.32; 95% CI, 1.19-9.25; P = .02) remained significant associates of cat sensitization. Current dog ownership significantly increased the risk of sensitization to dog (OR, 6.05; 95% CI, 1.33-27.54; P = .02). In the multivariate analysis, dog ownership remained the only significant associate of dog sensitization (OR, 6.02; 95% CI, 1.30-27.96; P = .02). Sensitization to Alternaria was the strongest independent associate of the asthma group. Family history of asthma, history of whooping cough, current cat ownership, and breast-feeding <2 months were other significant and independent risk factors for asthma. CONCLUSIONS: Pet ownership markedly increased the risk of sensitization to pets. Despite low allergen exposure, the pattern of childhood asthma in Kuwait follows that described in Western communities (strong association with sensitization).     

Breastfeeding Might Have Protective Effects on Atopy in Children With the CD14C-159T CT/CC Genotype

Breastfeeding is widely recommended to reduce risk of sensitization, eczema and asthma. However, the role of breastfeeding in prevention of allergic diseases is uncertain. We aimed to investigate whether the relationship between breastfeeding and sensitization to aeroallergens is modified by cluster of differentiation 14 (CD14) genotype. This study included 1,828 school children aged 9-12. We administered a detailed questionnaire and genotyped the CD14C-159T polymorphism. Skin prick tests for 12 aeroallergens were performed. School children who had been breastfed were less likely sensitized to aeroallergens (adjusted odds ratio [aOR] 0.712, 95% confidence interval [CI]: 0.555-0.914). There was no significant association between CD14C-159T genotype and atopy. Breastfeeding was associated with a decreased risk of atopic sensitization in children with CT/CC genotype (aOR 0.667, 95% CI: 0.463-0.960). Our data might identify the gene-environment interaction between the CD14C-159T polymorphism and breastfeeding in relation to aeroallergen sensitization.     

Allergen exposure in infancy and the development of sensitization, wheeze, and asthma at 4 years

BACKGROUND: The relationship between mite and pet allergen exposure in infancy and the subsequent development of sensitization and asthma is complex. OBJECTIVE: We prospectively investigated the effect of allergen exposure at 3 months of age on the development of sensitization, wheeze, and physician-diagnosed asthma in the first 4 years of life in a birth cohort of children with and without an atopic mother. METHODS: Children participated in the Prevention and Incidence of Asthma and Mite Allergy study. Allergen exposure at 3 months of age was determined from mattress dust samples. Specific IgE to inhalant allergens was measured at 4 years of age, and information about wheeze and physician-diagnosed asthma was collected with yearly questionnaires. RESULTS: Mite and cat allergen exposure in infancy were associated with an increased risk of specific sensitization to house dust mite and cat, respectively, at 4 years of age. There were borderline significant associations between cat allergen exposure and persistent wheeze in the total study population and between dog allergen exposure and persistent wheeze in children with a nonatopic mother. In children with an atopic mother, there was some indication of a positive association between mite allergen exposure and physician-diagnosed asthma. CONCLUSION: Early house dust mite and cat allergen exposure might lead to sensitization and, in case of cat allergen exposure, to persistent wheeze. Early mite and dog allergen exposure might lead to asthma and persistent wheeze, respectively, but only in subgroups defined by maternal atopy.