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 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.     

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.     

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.     

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.     

Bacterial and fungal components in house dust of farm children, Rudolf Steiner school children and reference children--the PARSIFAL Study

BACKGROUND: Growing up on a farm and an anthroposophic lifestyle are associated with a lower prevalence of allergic diseases in childhood. It has been suggested that the enhanced exposure to endotoxin is an important protective factor of farm environments. Little is known about exposure to other microbial components on farms and exposure in anthroposophic families. OBJECTIVE: To assess the levels and determinants of bacterial endotoxin, mould beta(1,3)-glucans and fungal extracellular polysaccharides (EPS) in house dust of farm children, Steiner school children and reference children. METHODS: Mattress and living room dust was collected in the homes of 229 farm children, 122 Steiner children and 60 and 67 of their respective reference children in five European countries. Stable dust was collected as well. All samples were analysed in one central laboratory. Determinants were assessed by questionnaire. RESULTS: Levels of endotoxin, EPS and glucans per gram of house dust in farm homes were 1.2- to 3.2-fold higher than levels in reference homes. For Steiner children, 1.1- to 1.6-fold higher levels were observed compared with their reference children. These differences were consistently found across countries, although mean levels varied considerably. Differences between groups and between countries were also significant after adjustment for home and family characteristics. CONCLUSION: Farm children are not only consistently exposed to higher levels of endotoxin, but also to higher levels of mould components. Steiner school children may also be exposed to higher levels of microbial agents, but differences with reference children are much less pronounced than for farm children. Further analyses are, however, required to assess the association between exposure to these various microbial agents and allergic and airway diseases in the PARSIFAL population.     

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.     

Asthma and allergic symptoms in relation to house dust endotoxin: Phase Two of the International Study on Asthma and Allergies in Childhood (ISAAC II)

Background Several studies have consistently reported inverse associations between exposure to endotoxin in house dust and atopy. With regard to the association between house dust endotoxin and asthma, the results are inconsistent. Objectives To study the association between house dust endotoxin levels and respiratory symptoms and atopy in populations from largely different countries. Methods Data were collected within the International Study on Asthma and Allergies in Childhood Phase Two, a multi‐centre cross‐sectional study of 840 children aged 9–12 years from six centres in the five countries of Albania, Italy, New Zealand, Sweden and the United Kingdom. Living room floor dust was collected and analysed for endotoxin. Health end‐points and demographics were assessed by standardized questionnaires. Atopy was assessed by measurements of allergen‐specific IgE against a panel of inhalant allergens. Associations between house dust endotoxin and health outcomes were analysed by logistic regression. Odds ratios (ORs) were presented for an overall interquartile range increase in exposure. Results Many associations between house dust endotoxin in living room floor dust and health outcomes varied between countries. Combined across countries, endotoxin levels were inversely associated with asthma ever [adjusted OR (95% confidence interval (CI)) 0.53 (0.29–0.96) for endotoxin levels per m² of living room floor] and current wheeze [adjusted OR (95% CI) 0.77 (0.64–0.93) for endotoxin levels per gram of living room floor dust]. There were inverse associations between endotoxin concentrations and atopy, which were statistically significant in unadjusted analyses, but not after adjustment for gender, parental allergies, cat and house dust mite allergens. No associations were found with dust quantity and between endotoxin exposure and hayfever. Conclusion These findings suggest an inverse association between endotoxin levels in living room floor dust and asthma in children.     

Prevalence and risk factors for allergic rhinitis and atopic eczema among schoolchildren in Israel: results from a national study.

BACKGROUND: There is growing evidence that the prevalence rates of asthma and allergic diseases are increasing, especially among children. Several risk factors are under investigation. OBJECTIVE: To evaluate the prevalence and risk factors for allergic diseases, including allergic rhinitis (AR) and atopic eczema (AE), among 13- to 14-year-old schoolchildren in Israel. METHODS: A modified version of the International Study of Asthma and Allergies in Childhood written questionnaire was administered to a national sample of schoolchildren 13 to 14 years old in Israel. The questionnaire was completed by the schoolchildren themselves. RESULTS: There were 10,057 complete questionnaires available for analysis. The prevalence of AR symptoms ever and current AR were 41.6% and 9.4%, respectively. Allergic rhinoconjunctivitis symptoms ever were reported by 15.8% of the children. The prevalence rates of 6 months of itchy rash ever and AE were 5.9% and 7.8%, respectively. After adjustment for demographic and environmental factors, current asthma, parental history of asthma, and population group were the most significant risk factors for current AR (odds ratio [OR], 4.47; 95% confidence interval [CI], 3.70-5.40; OR, 1.30; 95% CI, 1.02-1.66; and OR, 1.75; 95% CI 1.45-2.13; respectively) and AE (OR, 2.30; 95% CI, 1.80-2.90; OR, 1.80; 95% CI, 1.40-2.30; and OR, 1.70; 95% CI, 1.40-2.00; respectively). CONCLUSIONS: Israeli children have a low prevalence rate of current AR and a midrange rate of AE. Arabs have lower prevalence rates of allergic diseases than Jews, and the prominent risk factors for those diseases are current asthma and parental history of asthma.     

Allergen provocation augments endotoxin-induced nasal inflammation in subjects with atopic asthma

BACKGROUND: Recent epidemiologic and in vivo studies have suggested that inhaled endotoxin plays an important role in asthma pathogenesis. OBJECTIVE: The present study examines the effect of nasal allergen provocation on subsequent endotoxin challenge in subjects with atopic asthma. METHODS: By using a split-nose randomized crossover design, individual nares of 12 asthmatic subjects underwent challenge and lavage as follows. Immediately after a baseline nasal lavage, one nares received normal saline, and the other received dust mite antigen. Four hours later, both nares were exposed to either saline or endotoxin. Dust mite antigen (Dermatophagoides farinae) and endotoxin (Escherichia coli 026:B6) doses were 100 AU and 1000 ng, respectively. Postchallenge lavages were done at 8 and 24 hours after the initial challenge. The subjects then returned a minimum of 3 weeks later for crossover to the study arm. Nasal lavage fluid was analyzed for total and differential cell counts, IL-8, IL-6, intercellular adhesion molecule 1, GM-CSF, eosinophil cationic protein, myeloperoxidase, and soluble CD14. RESULTS: A significant increase in the total inflammatory cell count was seen at 8 hours for the dust mite/endotoxin exposure compared with the saline/saline and saline/endotoxin exposures. Differential cell counts revealed a similar neutrophilic and eosinophilic inflammation for the dust mite/endotoxin exposure at 8 hours. CONCLUSIONS: These data demonstrate an interaction between allergen and endotoxin exposure in asthmatic subjects, suggesting that a prior allergen challenge significantly augments the endotoxin-induced inflammation. Moreover, these data provide further evidence that concomitant exposure to allergen and endotoxin may be an important factor in asthma pathogenesis.     

Validation of a new questionnaire on asthma, allergic rhinitis, and conjunctivitis in young adults

BACKGROUND: Epidemiologic data on asthma and allergies among adults are mainly based on questionnaires: this study validates the questions on asthma, allergic rhinitis, and conjunctivitis of a new Finnish questionnaire. METHODS: To validate questions used in a country-wide study among university students aged 18-25 years, we examined 150 subjects who had ever reported asthma or wheezing, and 140 without asthma symptoms. Questions were validated in relation to current diseases including 1) symptoms detected during the preceding year at the physician's interview 2) objective measurements, such as methacholine challenge, skin prick tests, and specific IgE. Data were adjusted for original proportions of "asthmatics" and"nonasthmatics" in the questionnaire study. RESULTS: Questions on "reported asthma" and "doctor-diagnosed asthma" had good positive predictive value (PPV) and specificity in diagnosing current asthma. The question on "attacks of shortness of breath with wheezing", and especially the question on "cough with wheezing" were most sensitive. Questions on "allergic nasal symptoms" and "allergic eye symptoms" that were "related to pollen or animals" were sensitive, but a further question on doctor's diagnosis yielded higher specificity and PPV. CONCLUSION: Diagnosis-based questions were found suitable for risk-factor studies, because of their good specificity and PPV, and symptom-based questions for screening, because they were highest in sensitivity.     

Not all farming environments protect against the development of asthma and wheeze in children

BACKGROUND: In recent years, studies have shown a protective effect of being raised in a farm environment on the development of hay fever and atopic sensitization. Inconsistent data on the relation of farming to asthma and wheeze have raised some doubt about a true protective effect. OBJECTIVE: We sought to study the differential effects of farm-associated exposures on specific asthma-related health outcomes. METHODS: The cross-sectional Prevention of Allergy Risk Factors for Sensitization in Children Related to Farming and Anthroposophic Lifestyle study included 8263 school-age children from rural areas in 5 European countries. Information on farm-related exposures and health outcomes was obtained by using questionnaires. In subsamples allergen-specific IgE and RNA expression of CD14 and Toll-like receptor genes were measured, and dust from children's mattresses was evaluated for microbial components. RESULTS: Inverse relations with a diagnosis of asthma were found for pig keeping (odds ratio [OR], 0.57; 95% CI, 0.38-0.86), farm milk consumption (OR, 0.77; 95% CI, 0.60-0.99), frequent stay in animal sheds (OR, 0.71; 95% CI, 0.54-0.95), child's involvement in haying (OR, 0.56; 95% CI, 0.38-0.81), and use of silage (OR, 0.55; 95% CI, 0.31-0.98; for nonatopic asthma) and in Germany for agriculture (OR, 0.34; 95% CI, 0.22-0.53). Protective factors were related with higher expression levels of genes of the innate immunity. Potential risk factors for asthma and wheeze were also identified in the farm milieu. Levels of endotoxin and extracellular polysaccharides were related to the health outcomes independently of the farm exposures. CONCLUSIONS: The protective effect of being raised in a farm environment was ascribed to distinct exposures. CLINICAL IMPLICATIONS: The development of atopic sensitization and atopic and nonatopic asthma is most likely determined by different environmental factors, possibly reflecting distinct pathomechanisms.     

Bacterial and fungal agents in house dust and wheeze in children: the PARSIFAL study

BACKGROUND: Growing up on a farm and an anthroposophic lifestyle are associated with a lower prevalence of allergic diseases in childhood. This might be related to increased inhalatory exposure to microbial agents. OBJECTIVE: To assess the association between microbial agents in house dust and atopic wheeze in farm children, Steiner school children and reference children. METHODS: Levels of bacterial endotoxin, fungal beta(1,3)-glucans and fungal extracellular polysaccharides (EPS) in mattress and living room floor dust were measured in a population of 270 atopic (=Phadiatop-positive) children with self-reported wheezing, including 168 current atopic wheezers, and 441 non-atopic, non-symptomatic controls. These children were selected from a cross-sectional study in five European countries. RESULTS: In the study population as a whole, average levels of mattress dust endotoxin, EPS and glucans were slightly (1.1-1.2-fold; P<0.10) higher in control children than in atopic wheezers. Atopic wheeze was related to mattress levels of endotoxin, EPS and glucans in farm and farm-reference children. However, when adjusting for group (farm vs. farm-reference children), the associations became non-significant whereas the group effect remained. No associations between atopic wheeze and microbial agents were observed in Steiner and Steiner-reference children. For current atopic wheeze, the farm effect became non-significant after adjustment for microbial agent levels. CONCLUSION: Not only bacterial endotoxin but also mould components might offer some protection against atopic wheeze in children. However, the protective effect of being raised on a farm was largely unexplained by the mattress microbial agent levels measured in this study.     

Inverse association of farm milk consumption with asthma and allergy in rural and suburban populations across Europe

BACKGROUND: Dietary interventions as a means for atopy prevention attract great interest. Some studies in rural environments claimed an inverse association between consumption of farm-produced dairy products and the prevalence of allergic diseases, but current evidence is controversial. OBJECTIVE: To investigate whether consumption of farm-produced products is associated with a lower prevalence of asthma and allergy when compared with shop-purchased products. METHODS: Cross sectional multi-centre study (PARSIFAL) including 14,893 children aged 5-13 years from five European countries (2823 from farm families and 4606 attending Steiner Schools as well as 5440 farm reference and 2024 Steiner reference children). A detailed questionnaire including a dietary component was completed and allergen-specific IgE was measured in serum. RESULTS: Farm milk consumption ever in life showed a statistically significant inverse association with asthma: covariate adjusted odds ratio (aOR) 0.74 [95% confidence interval (CI) 0.61-0.88], rhinoconjunctivitis: aOR 0.56 (0.43-0.73) and sensitization to pollen and the food mix fx5 (cut-off level of >or=3.5 kU/L): aOR 0.67 (0.47-0.96) and aOR 0.42 (0.19-0.92), respectively, and sensitization to horse dander: aOR 0.50 (95% CI 0.28-0.87). The associations were observed in all four subpopulations and independent of farm-related co-exposures. Other farm-produced products were not independently related to any allergy-related health outcome. CONCLUSION: Our results indicate that consumption of farm milk may offer protection against asthma and allergy. A deepened understanding of the relevant protective components of farm milk and a better insight into the biological mechanisms underlying this association are warranted as a basis for the development of a safe product for prevention.     

A longitudinal analysis of wheezing in young children: the independent effects of early life exposure to house dust endotoxin,allergens, and pets

BACKGROUND: It has been postulated that exposure to bacterial endotoxins and animals early in life might confer protection against the development of asthma and allergies. OBJECTIVE: We investigated the longitudinal effects of exposure to house dust endotoxin (HDE), allergen levels, and the presence of a dog in the home on wheezing in young children over a 4-year period. METHODS: Two hundred twenty-six children younger than 5 years were followed for 4 years. Endotoxin and allergen levels were measured from house dust collected at baseline. Longitudinal associations were investigated by using a proportional hazards technique that allowed for multiple outcomes per subject. RESULTS: Exposure to high concentrations of HDE of greater than the median level was associated with an increased risk for wheezing over the period of observation (multivariate relative risk, 1.52; 95 % CI, 1.07-2.14), but this risk rapidly decreased over time (P for trend =.005). Exposure to cockroach allergen was associated with increased risk for wheezing, whereas exposure to cat allergen and the presence of a dog in the home were both associated with decreased risk for wheezing. The risks associated with cockroach allergen, cat allergen, and dog did not change over the period of observation. CONCLUSION: The negative associations between exposures to dogs and cat allergen and wheeze appear to be independent of the effects of endotoxin and suggest that separate mechanisms might mediate the effects of HDE exposure and pet exposure on the developing immune system.     

Better maternal quality of life in pregnancy yields better offspring respiratory outcomes: A birth cohort

BackgroundIt is suggested that maternal mental health during pregnancy may affect offspring immune and respiratory features, based on the developmental origins of health and disease hypothesis.ObjectiveTo evaluate whether maternal quality of life (QoL) and depression during pregnancy leads to wheezing, asthma, and food allergy of the offspring at 3 years of age.MethodsWe conducted a nationwide, multicenter, prospective birth cohort study, Japan Environment and Children’s Study. All variables were collected from questionnaires. Health-related QoL was measured using the Medical Outcomes Survey Short Form–8 questionnaire with a physical component summary and a mental component summary score. We conducted logistic regression analyses to evaluate the associations of offspring’s wheezing, asthma, and food allergy with maternal QoL and depression.ResultsThere were 72,685 participants with no missing variables. Maternal physical component summary scores of the Medical Outcomes Survey Short Form–8 questionnaire were negatively associated with offspring’s asthma (adjusted odds ratio [aOR], 0.99; 95% confidence interval [CI], 0.99-1.00), current wheezing (aOR, 0.99; 95% CI, 0.99-0.99), and food allergy diagnoses (aOR, 0.99; 95% CI, 0.98-0.99) in children. Offspring’s wheezing and asthma were also associated with maternal depression and anxiety during pregnancy.ConclusionPoor maternal prenatal QoL increased the risk of wheezing, asthma, and food allergy in offspring. In addition, maternal depression and anxiety increased the risk of offspring’s wheezing, asthma, and food allergy.     

Cat and dust mite sensitivity and tolerance in relation to wheezing among children raised with high exposure to both allergens

BACKGROUND: Recent evidence has suggested that high exposure to cat allergens is associated with decreased prevalence of sensitization to cat and, in some studies, decreased asthma. OBJECTIVE: Our objective was to study antibodies to cat and mite allergens and their relationship to wheezing in a country with high exposure to both allergens. METHODS: Sera from 112 wheezing and 112 control children aged 10 to 11 years in a nested case-control study in New Zealand were assayed for specific IgE antibody, as well as IgG antibody and IgG4 antibody, to Der p 1 and Fel d 1. RESULTS: IgE antibody to both mite (99/224) and cat (41/224) were strongly associated with wheezing (odds ratios, 5.2 and 6.5, respectively). Children who had ever lived with a cat were less likely to have IgE antibody to cat (20/141 vs 21/83, P < .04); however, cat ownership had no effect on IgE antibody to mite (67/141 vs 32/83, P = .23). Among sensitized children, cat ownership was associated with a lower prevalence of IgE antibody to cat (28% vs 66%, P < .001), and this analysis remained significant after exclusion of children whose families had chosen not to own a cat. Among sensitized subjects, the mean titer of IgE antibody to cat (1.7 IU/mL) was 10-fold lower than for mite (22.1 IU/mL). A cat in the home had no significant effect on endotoxin or mite allergen in house dust, whereas cat allergen was much higher (40.8 vs 3.3 microg/g). CONCLUSION: The response to these 2 allergens was distinct on the basis of the prevalence of sensitization, the titer of IgE antibody, and the effect of cat ownership. The results suggest that induction of tolerance to cat allergen is an allergen-specific phenomenon that cannot be attributed to endotoxin or family choice. The strength of the IgE antibody response to dust mite in humid climates could contribute to the increased prevalence and severity of asthma.     

IL-13 genetic polymorphism identifies children with late wheezing after respiratory syncytial virus infection

BACKGROUND: The nature of wheezing after respiratory syncytial virus lower respiratory tract infection (RSV LRTI) is usually transient. However, some children will develop persistent or late wheezing. OBJECTIVE: We hypothesized that early and late postbronchiolitis wheezing are determined by distinct clinical, immunologic, and genetic variables. METHODS: A cohort of 101 children hospitalized for RSV LRTI was prospectively followed for 6 years. During RSV LRTI, cytokine studies were performed and genetic polymorphisms were determined. Parents performed daily log registration of respiratory symptoms during the first 3 years of follow-up and again at age 6 years during the winter season. RESULTS: Distinctive associations for early and late postbronchiolitis wheezing were found. We previously showed that airflow limitation during RSV LRTI as well as convalescent monocyte IL-10 production are associated with early wheezing. These variables were not associated with late wheezing. On the other hand, atopic family history was not associated with early wheezing, but it was associated with late wheezing. Most importantly, the IL-13 Gln allele was associated with late wheezing (odds ratio 3.27, 95% confidence interval 1.32-8.06), but it was not associated with early wheezing. CONCLUSION: This study revealed distinct clinical, immunologic, and genetic determinants of early and late wheezing after RSV LRTI, indicating distinct pathophysiological mechanisms. We conclude that late wheezing at age 6 years, but not early postbronchiolitis wheezing, is an asthmatic phenomenon and genetically related to a functional IL-13 polymorphism. CLINICAL IMPLICATIONS: After RSV LRTI, wheezing at age 6 years is not related to early postbronchiolitis wheezing and represents a distinct disease entity.     

Exposure to cockroach allergen in the home is associated with incident doctor-diagnosed asthma and recurrent wheezing

BACKGROUND: Indoor inhaled allergens have been repeatedly demonstrated to worsen asthma in sensitized individuals, but their role in incident asthma is more controversial. OBJECTIVE: We investigated the relationship between exposure to allergens (dust mite, cat, and cockroach) measured in the home and incident doctor-diagnosed asthma and recurrent wheezing in children born to parents with asthma, allergies, or both. METHODS: From an ongoing longitudinal family and birth cohort study, we identified 222 siblings (median age, 2.87 years) of the index children. Allergen levels in the home were measured from dust samples obtained at the beginning of the study. Incident doctor-diagnosed asthma and recurrent wheezing were determined from questionnaires administered at 14 months and 22 months after the initial questionnaire. RESULTS: Thirteen (5.9%) children were reported to have incident asthma, twenty (9.0%) children had recurrent asthmatic wheezing, and 18 (8.1%) had recurrent wheezing without asthma. Compared with children living in homes with Bla g 1 or 2 levels of less than 0.05 U/g, children exposed to Bla g 1 or 2 levels of 0.05 to less than 2 U/g had a relative risk for incident asthma of 8.27 (95% confidence interval, 1.04-66.04), whereas children exposed to Bla g 1 or 2 levels of 2 U/g or greater had a relative risk for incident asthma of 35.87 (95% confidence interval, 4.49-286.62). Cockroach allergen exposure was likewise a significant predictor for recurrent asthmatic wheezing. Neither dust mite nor cat allergen levels were significantly associated with either outcome. These findings remained after control for several covariates. CONCLUSION: Exposure to cockroach allergen early in life may contribute to the development of asthma in susceptible children.     

Endotoxin exposure in inner-city schools and homes of children with asthma

BackgroundEndotoxins are stimulators of the immune system and, despite their potential to protect against allergy, have been associated with early wheezing and asthma morbidity.ObjectiveTo compare inner-city school endotoxin exposure with home endotoxin exposure in children with asthma.MethodsStudents with asthma were recruited from 12 urban elementary schools. Settled and airborne dust samples, linked to enrolled students, were collected from school classrooms, gymnasiums, and cafeterias twice during the academic year. For comparison, settled dust was collected once from the bedrooms of students with asthma.ResultsTwo hundred twenty-nine school settled dust samples and 118 bedroom settled dust samples were collected and analyzed for endotoxin. The median endotoxin concentration for school samples was 13.4 EU/mg (range, 0.7–360.7 EU/mg) and for home samples was 7.0 EU/mg (range = LLOD–843.0 EU/mg). The median concentration within each individual school varied from 6.6 EU/mg to 24.0 EU/mg. One hundred four students with asthma had matched classroom and bedroom endotoxin exposure measurements performed in the same season and demonstrated significantly higher concentrations of endotoxin in the students' classrooms (mean log value, 1.13 vs 0.99, P = .04). The median of the classrooms was 12.5 EU/mg compared with their bedrooms, with a median of 7.0 EU/mg. Within the school environment, no significant difference was seen between the fall and spring samples (mean log value 1.14 vs 1.09; P = .35).ConclusionInner-city children with asthma were exposed to higher concentrations of endotoxin in their classrooms as compared with their bedrooms. Further studies are needed to evaluate school endotoxin exposure as a factor in asthma morbidity.