Endotoxin In Early Life Research Articles

Exposure to House Dust Mite Allergen and Endotoxin in Early Life and Sensitization and Allergic Rhinitis: The JECS.

The association between endotoxin and allergic rhinitis (AR) is not conclusive. The aim of this study was to determine the association between endotoxin and house dust mite (HDM) allergens in dust, and HDM sensitization and AR among Japanese infants. This study included 4188 participants in the Sub-Cohort Study of the Japan Environment and Children's Study. Dust was collected from children's mattresses at age 18 months and endotoxin and HDM allergen levels were measured. A logistic regression model was used to analyze the association between endotoxin or HDM allergen and the sensitization to HDM (specific-IgE) at age 2 and AR at age 3. The median (interquartile range) endotoxin level was 375.1(186.9-826.5) EU/m2 and the Der 1 (Der p 1 + Der f 1) level was 51.2 (14.8-168.6) ng/m2. There were significant positive associations between endotoxin and HDM sensitization (Der f 1, adjusted odds ratio [aOR] quartile [Q] 4 vs. Q1, 1.44, 95% CI, 1.04-2.00; Der p 1, aOR Q4 vs. Q1, 1.56, 95% CI, 1.12-2.16). There were also significant positive associations between Der 1 exposure and HDM sensitization (Der f 1, aOR Q3 vs. Q1, 1.75, 95% CI, 1.26-2.44; aOR Q4 vs. Q1, 2.98, 95% CI, 2.15-4.13; Der p 1, aOR Q3 vs. Q1, 1.91, 95% CI, 1.37-2.66; aOR Q4 vs. Q1, 2.91, 95% CI, 2.09-4.05). There were, however, no associations between endotoxin or Der 1 and AR. In the population residing mostly in non-farming settings, both endotoxin and HDM allergens in dust were associated with an increased risk of HDM allergen sensitization, but not with AR.

Endotoxin inhalation alters lung development in neonatal mice.

Childhood asthma is a significant public health problem. Epidemiologic evidence suggests an association between childhood asthma exacerbations and early life exposure to environmental endotoxin. Although the pathogenesis of endotoxin-induced adult asthma is well studied, questions remain about the impact of environmental endotoxin on pulmonary responsiveness in early life. We developed a murine model of neonatal/juvenile endotoxin exposures approximating those in young children and evaluated the lungs inflammatory and remodeling responses. Persistent lung inflammation induced by the inhalation of endotoxin in early life was demonstrated by the influx of inflammatory cells and pro-inflammatory mediators to the airways and resulted in abnormal alveolarization. Results of this study advance the understanding of the impact early life endotoxin inhalation has on the lower airways, and demonstrates the importance of an experimental design that approximates environmental exposures as they occur in young children.

Prenatal endotoxin exposure alters behavioural pain responses to lipopolysaccharide in adult offspring

Evidence suggests that exposure to bacterial endotoxin in early life can alter the production of pro-inflammatory cytokines in later life. This phenomenon may have significant consequences for pain and pain related behaviours as pro-inflammatory cytokines heighten pain sensitivity. This association has yet to be examined. As such, the aim of the present study was to characterize pain behaviours in adult rat offspring following prenatal endotoxin (PE) exposure. Pregnant F344 rats received endotoxin (200 µg/kg, s.c.) or saline on gestational days 16, 18 and 20. Pain thresholds were assessed in the adult PE offspring ( n = 23) and control offspring ( n = 24) prior to and 4 h following administration of lipopolysaccharide (LPS; 100 µg/kg, s.c.). Three assays of pain were employed — the hot plate, tail immersion and von Frey tests. Results demonstrated sex-specific effects of prenatal endotoxin on the offspring, with PE males displaying unaltered pain thresholds on the von Frey test post-LPS administration ( p < 0.01), while male control offspring ( n = 24) displayed the expected hyperalgesia. Male PE offspring also displayed increased pain thresholds on the tail immersion test ( p < 0.01), while no change in pain sensitivity was observed in control males following LPS exposure. No difference in response was observed between the female PE and control offspring on the von Frey test, however PE female offspring displayed increased thresholds on the tail immersion test compared to baseline — an effect not observed in the control female offspring. Pain sensitivity on the hot plate test was unaffected by prenatal exposure to endotoxin. These data suggest that prenatal exposure to products associated with bacterial infection have the capacity to alter pain responses, which are evident in the adult offspring.

Allergen and Endotoxin Exposure, Infection, and Breastfeeding in Early Life, and Persistent Wheezing in Children: 60-month Follow-up of a Cohort Study

RATIONALE: Exposure to environmental factors early in life may have a critical role in subsequent development of sensitization and asthmaMETHODS: One-hundred and four newborns were enrolled at birth in this cohort study. Children belonged to low-income families and were at high risk for asthma. Persistent wheezing was defined as ever wheezing treated with inhaled corticosteroids and beta-2 agonists in the past year. Infection of the upper or lower respiratory tract requiring antibiotics was recorded. Dust samples were collected from bedding and floor of the infants' bedroom within six months after birth. Endotoxin content was determined by Limulus Amebocyte Lysate assay, and major allergens from mites, cockroach, cat, dog, mouse and rat were quantitated by ELISA in dust extracts. Serum IgE antibodies were quantitated by ImmunoCAP.RESULTS: At age 60 months, 18/95(18.9%) children presented with persistent wheezing. Multivariate analysis revealed that respiratory infection in the first 12 months of life was associated with persistent wheezing, OR(95% CI) 7.83(0.95-64.16), p = 0.05, whereas allergen exposure, exclusive breast feeding for six months, male gender, and exposure to endotoxin had no effect. Sensitization to D. pteronyssinus (CAP score>2) was found in 25/90(27%) children, with no association with persistent wheezing.CONCLUSIONS: Respiratory infection in the first 12 months of life was associated with persistent wheezing at age 5, whereas exposure to allergen and endotoxin in early life and exclusive breastfeeding for six months showed no effect in development of asthma. RATIONALE: Exposure to environmental factors early in life may have a critical role in subsequent development of sensitization and asthma METHODS: One-hundred and four newborns were enrolled at birth in this cohort study. Children belonged to low-income families and were at high risk for asthma. Persistent wheezing was defined as ever wheezing treated with inhaled corticosteroids and beta-2 agonists in the past year. Infection of the upper or lower respiratory tract requiring antibiotics was recorded. Dust samples were collected from bedding and floor of the infants' bedroom within six months after birth. Endotoxin content was determined by Limulus Amebocyte Lysate assay, and major allergens from mites, cockroach, cat, dog, mouse and rat were quantitated by ELISA in dust extracts. Serum IgE antibodies were quantitated by ImmunoCAP. RESULTS: At age 60 months, 18/95(18.9%) children presented with persistent wheezing. Multivariate analysis revealed that respiratory infection in the first 12 months of life was associated with persistent wheezing, OR(95% CI) 7.83(0.95-64.16), p = 0.05, whereas allergen exposure, exclusive breast feeding for six months, male gender, and exposure to endotoxin had no effect. Sensitization to D. pteronyssinus (CAP score>2) was found in 25/90(27%) children, with no association with persistent wheezing. CONCLUSIONS: Respiratory infection in the first 12 months of life was associated with persistent wheezing at age 5, whereas exposure to allergen and endotoxin in early life and exclusive breastfeeding for six months showed no effect in development of asthma.

Allergen and Endotoxin Exposure, Infection, and Breastfeeding in Early Life, and Recurrent Wheezing in Children: 48-month Follow-up of a Cohort Study

RATIONALE: Exposure to environmental factors early in life may have a critical role in subsequent development of sensitization and asthma.METHODS: One-hundred and four newborns were enrolled at birth in this cohort study. Children belonged to low-income families and were at high risk for asthma. Recurrent wheezing was defined as three or more wheezing episodes in the past year. Infection of the upper or lower respiratory tract requiring antibiotics was recorded. Dust samples were collected from bedding and floor of the infants' bedroom within six months after birth. Endotoxin content was determined by Limulus Amebocyte Lysate assay, and major allergens from mites, cockroach, cat, dog, mouse and rat were quantitated by ELISA in dust extracts. Serum IgE antibodies were quantitated by ImmunoCAP.RESULTS: At age 48 months, 35/98 (35.7%) children presented with recurrent wheezing. Multivariate analysis revealed that respiratory infection in the first 12 months of life was associated with recurrent wheezing, OR (95% CI) 3.94 (1.29-11.98), p = 0.016, whereas allergen exposure, exclusive breast feeding for at least four months, male gender, and high levels of exposure to endotoxin had no effect. Sensitization to D. pteronyssinus (CAP score≥2) was found in 25/90 (27%) children, with no association with recurrent wheezing.CONCLUSIONS: Respiratory infection in the first 12 months of life was associated with recurrent wheezing at age 4, whereas exposure to allergen and high levels of endotoxin in early life and exclusive breastfeeding for at least four months showed no effect in development of asthma. RATIONALE: Exposure to environmental factors early in life may have a critical role in subsequent development of sensitization and asthma. METHODS: One-hundred and four newborns were enrolled at birth in this cohort study. Children belonged to low-income families and were at high risk for asthma. Recurrent wheezing was defined as three or more wheezing episodes in the past year. Infection of the upper or lower respiratory tract requiring antibiotics was recorded. Dust samples were collected from bedding and floor of the infants' bedroom within six months after birth. Endotoxin content was determined by Limulus Amebocyte Lysate assay, and major allergens from mites, cockroach, cat, dog, mouse and rat were quantitated by ELISA in dust extracts. Serum IgE antibodies were quantitated by ImmunoCAP. RESULTS: At age 48 months, 35/98 (35.7%) children presented with recurrent wheezing. Multivariate analysis revealed that respiratory infection in the first 12 months of life was associated with recurrent wheezing, OR (95% CI) 3.94 (1.29-11.98), p = 0.016, whereas allergen exposure, exclusive breast feeding for at least four months, male gender, and high levels of exposure to endotoxin had no effect. Sensitization to D. pteronyssinus (CAP score≥2) was found in 25/90 (27%) children, with no association with recurrent wheezing. CONCLUSIONS: Respiratory infection in the first 12 months of life was associated with recurrent wheezing at age 4, whereas exposure to allergen and high levels of endotoxin in early life and exclusive breastfeeding for at least four months showed no effect in development of asthma.

The association between contextual socioeconomic factors and prevalent asthma in a cohort of Southern California school children

Spatial variation in childhood asthma and a recent increase in prevalence indicate that environmental factors play a significant role in the etiology of this important disease. Socioeconomic position (SEP) has been associated inversely and positively with childhood asthma. These contradictory results indicate a need for systematic research about SEP and asthma. Pathways have been suggested for effects of SEP on asthma at both the individual and community level. We examined the relationship of prevalent asthma to community-level indicators of SEP among 5762 children in 12 Southern California communities, using a multilevel random effects model. Estimates of community-level SEP were derived by summarizing census block group-level data using a novel method of weighting by the proportion of the block groups included in a community-specific bounding rectangle that contained 95% of local study subjects. Community characteristics included measures of male unemployment, household income, low education (i.e., no high school diploma) and poverty. There was a consistent inverse association between male unemployment and asthma across the inter-quartile range of community unemployment rates, indicating that asthma rates increase as community SEP increases. The results were robust to individual-level confounding, methods for summarizing census block group data to the community level, scale of analysis (i.e., community-level vs. neighborhood-level) and the modeling algorithm. The positive association between SEP and prevalent childhood asthma might be explained by differential access to medical care that remains unmeasured, by the hygiene hypothesis (e.g., lower SES may associate with higher protective exposures to endotoxin in early life), or by SEP acting as a proxy for unmeasured neighborhood characteristics.

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

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. 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. Birth cohort study of 440 children with parental history of atopy in the Boston metropolitan area. 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). 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. Early endotoxin exposure may be a protective factor against atopy but a risk factor for wheeze in high-risk children.

Exposure to Allergens and Endotoxin in Early Life and Recurrent Wheezing in Infants: a Cohort Study

Exposure to Allergens and Endotoxin in Early Life and Recurrent Wheezing in Infants: a Cohort Study

A profile of the immediate endocrine, metabolic and behavioural responses following a dual exposure to endotoxin in early life

Dual exposure to endotoxin on postnatal days (PNDs) 3 and 5 is increasingly being used to model the impact of bacterial challenge, in early life, on long-term health outcomes. Currently, however, little is known about how exposure to endotoxin using this model disrupts systems known to program physiological alterations in later life. The aim of the current study was to define, in Fischer 344 rat pups, a framework of the immediate endocrine, metabolic, and behavioural consequences following challenge with 0.05 mg/kg of endotoxin ( Salmonella enteritidis) on PNDs 3 and 5. Circulating corticosterone in endotoxin challenged neonates was significantly elevated at all time points assessed on PND 3 ( P<0.05), however, by PND 5 this response was attenuated showing a significant elevation only at 4-h post-injection. In these same pups, glucose levels were significantly reduced by 8-h post-injection on PND 3 and remained significantly lower until 8-h post-injection on PND 5 ( P<0.05). Finally, the dams of endotoxin challenged pups, exhibited significantly less arched back nursing ( P<0.05) but increased levels of off-nest time across the challenge period ( P<0.05). These findings demonstrate that postnatal endotoxin exposure impacts on both endocrine and metabolic activity and that alterations in these two systems may in part be mediated by the impact of endotoxin exposure on maternal behaviour.

Endotoxin exposure and eczema in the first year of life.

Exposure to endotoxin in early life has been proposed as a factor that may protect against the development of allergic diseases such as eczema. The objective of this study was to examine the relation between endotoxin exposure in early life and eczema in the first year of life in children with parental history of asthma or allergies. This study used a prospective birth cohort study of 498 children who had a history of allergy or asthma in at least 1 parent and lived in metropolitan Boston. A subset of 401 living rooms had house dust samples adequate for analysis of endotoxin. In multivariate analyses adjusting for gender, income, and season of birth, endotoxin levels in the living room at 2 to 3 months of age was inversely associated with physician- or nurse-diagnosed eczema in the first year of life (odds ratio [OR] for each quartile increment: 0.76; 95% confidence interval [CI]: 0.61-0.96). Exposure to a dog in the home at age 2 to 3 months was also inversely associated with eczema in the first year of life, but the CI widened when endotoxin was included in the multivariate model (OR: 0.54; 95% CI: 0.27-1.09). Other variables associated with eczema in the first year of life included paternal history of eczema (OR: 1.91; 95% CI: 1.03-3.55) and maternal specific immunoglobulin E positivity to > or =1 allergen (OR: 1.61; 95% CI: 1.01-2.56). Among children with parental history of asthma or allergies, exposure to high levels of endotoxin in early life may be protective against eczema in the first year of life. In these children, paternal history of eczema and maternal sensitization to at least 1 allergen are associated with an increased risk of eczema in the first year of life.

Hygiene hypothesis and endotoxin: what is the evidence?

The hygiene hypothesis has gained strong support over the past few years. Exposure to microbial products in early life could be an underlying factor in this hypothesis, but the mechanisms that lead from a less clean and more crowded environment to a lower prevalence of asthma and allergies are not known. Among the variety of potential microbial molecules that may confer protection against the development of asthma and allergies, endotoxin, a component of Gram-negative bacteria, has incited lively as well as controversial discussions. This review focuses on recent studies on endotoxin and its role in the context of the hygiene hypothesis. Results from cross-sectional surveys, prospective cohorts, and experimental studies in vitro and in rodents suggest that exposure to house dust endotoxin in early life protects from atopic sensitization and IgE-mediated diseases, but is a risk factor for wheezing in infancy. Numerous studies have supported the hygiene hypothesis, but whether endotoxin by itself confers the protection or whether it acts as a marker for another environmental exposure is still unclear. The challenge for the future will be to identify those factors that confer the protection proposed by the hygiene hypothesis, and to find strategies to modify the environment without causing harm to susceptible individuals.

Endotoxin exposure and eczema in the first year of life

Rationale Early life exposure to endotoxin may protect against the development of allergic diseases. Our objective was to examine the relation between endotoxin exposure and eczema in the first year of life in children with parental history of asthma or allergies. Methods Prospective birth cohort study. Results In multivariate analyses adjusting for sex, household income, and season of birth, endotoxin level in the household at age 2 to 3 months was inversely associated with physician or nurse diagnosed eczema in the first year of life (odds ratio [OR] for each quartile increment=0.76; 95% confidence interval [CI]: 0.61–0.96: P=0.02). Exposure to a dog in the home at age 2–3 months was also inversely associated with eczema in the first year of life, but the confidence interval for the estimate of the association between dog exposure and eczema became wider when endotoxin was included in the multivariate model (OR=0.54, 95% CI=0.27–1.09: P=0.09). Other variables associated with eczema in the first year of life included paternal history of eczema (OR=1.91, 95% CI=1.03–3.55, P=0.04) and maternal specific IgE positive to =1 allergen (OR=1.61, 95% CI=1.01–2.56, P=0.05). Conclusions Among children with parental history of asthma or allergies, exposure to high levels of endotoxin in early life may be protective against eczema in the first year of life. In these children, paternal history of eczema and maternal sensitization to at least one allergen are associated with an increased risk of eczema in the first year of life.

Role of lipopolysaccharide (LPS) in asthma and other pulmonary conditions.

Endotoxin significantly contaminates house dust and is an enhancing factor for asthma severity. Natural exposure to endotoxin in early life could influence immune development and protect from the risk of developing atopy. This article will focus on published data showing that home environmental contamination by endotoxin can participate in chronic airways diseases, in particular asthma.

Role of lipopolysaccharide (LPS) in asthma and other pulmonary conditions

Endotoxin significantly contaminates house dust and is an enhancing factor for asthma severity. Natural exposure to endotoxin in early life could influence immune development and protect from the risk of developing atopy. This article will focus on published data showing that home environmental contamination by endotoxin can participate in chronic airways diseases, in particular asthma.