Filaggrin mutations in relation to skin barrier and atopic dermatitis in early infancy.

BACKGROUND: Loss-of-function mutations in the skin barrier gene filaggrin (FLG) increase the risk of atopic dermatitis (AD), but their role in skin barrier function, dry skin and eczema in infancy is unclear. OBJECTIVES: To determine the role of FLG mutations in impaired skin barrier function, dry skin, eczema and AD at 3 months of age and throughout infancy. METHODS: FLG mutations were analysed in 1836 infants in the Scandinavian population-based PreventADALL study. Transepidermal water loss (TEWL), dry skin, eczema and AD were assessed at 3, 6 and 12 months of age. RESULTS: FLG mutations were observed in 166 (9%) infants. At 3 months, carrying FLG mutations was not associated with impaired skin barrier function (TEWL > 11·3 g m-2  h-1 ) or dry skin, but was associated with eczema [odds ratio (OR) 2·89, 95% confidence interval (CI) 1·95-4·28; P < 0·001]. At 6 months, mutation carriers had significantly higher TEWL than nonmutation carriers [mean 9·68 (95% CI 8·69-10·68) vs. 8·24 (95% CI 7·97-8·15), P < 0·01], and at 3 and 6 months mutation carriers had an increased risk of dry skin on the trunk (OR 1·87, 95% CI 1·25-2·80; P = 0·002 and OR 2·44, 95% CI 1·51-3·95; P < 0·001) or extensor limb surfaces (OR 1·52, 95% CI 1·04-2·22; P = 0·028 and OR 1·74, 95% CI 1·17-2·57; P = 0·005). FLG mutations were associated with eczema and AD in infancy. CONCLUSIONS: FLG mutations were not associated with impaired skin barrier function or dry skin in general at 3 months of age, but increased the risk for eczema, and for dry skin on the trunk and extensor limb surfaces at 3 and 6 months.

Prenatal exposure to perfluoralkyl substances (PFASs) associated with respiratory tract infections but not allergy- and asthma-related health outcomes in childhood.

BACKGROUND: Prenatal exposure to perfluoralkyl substances (PFASs) has been reported to be associated with immunosuppression in early childhood, but with contradictory findings related to atopic and lung diseases. AIM: We aimed to determine if prenatal exposure to PFASs is associated with asthma or other allergic diseases or respiratory tract infections in childhood. METHODS: Nineteen PFASs were measured in cord blood available from 641 infants in the Environment and Childhood Asthma (ECA) prospective birth cohort study. The six most abundant PFASs were perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorooctanesulfonamide (PFOSA), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA), and perfluoroundecanoic acid (PFUnDA). Health outcomes were assessed at two and ten years of age, and included reported obstructive airways disease (wheeze by 10 years; asthma by 2 and 10 years; reduced lung function at birth; allergic rhinitis by 10 years), atopic dermatitis (AD) by 2 and 10 years, allergic sensitization by 10 years, and episodes of common respiratory tract infections (common cold by 2 years, lower respiratory tract infections (LRTI) by 10 years). The associations between exposure and health outcomes were examined using logistic and Poisson regression. RESULTS: The number of reported airways infections were significantly associated with cord blood concentrations of PFAS; common colds by two years with PFUnDA (ß = 0.11 (0.08-0.14)) and LRTIs from 0 to 10 years of age with PFOS (ß = 0.50 (0.42-0.57)), PFOA (ß = 0.28 (0.22-0.35)), PFOSA (ß = 0.10 (0.06-0.14)), PFNA (ß = 0.09 (0.03-0.14)) and PFUnDA (ß = 0.18 (0.13-0.23)) concentrations. Neither reduced lung function at birth, asthma, allergic rhinitis, AD nor allergic sensitization were significantly associated with any of the PFASs. CONCLUSION: Although prenatal exposure to PFASs was not associated with atopic or lung manifestations by 10 years of age, several PFASs were associated with an increased number of respiratory tract infections in the first 10 years of life, suggesting immunosuppressive effects of PFASs.

Food allergens in mattress dust in Norwegian homes - a potentially important source of allergen exposure.

BACKGROUND: Sensitization to food allergens and food allergic reactions are mostly caused by ingesting the allergen, but can also occur from exposure via the respiratory tract or the skin. Little is known about exposure to food allergens in the home environment. OBJECTIVE: The objective of this study was firstly to describe the frequency of detection of allergens from fish, egg, milk, and peanut in mattress dust collected from homes of 13-year-old adolescents and secondly to identify home characteristics associated with the presence of food allergen contamination in dust. METHODS: Food allergens were measured by dot blot analysis in mattress dust from 143 homes in Oslo, Norway. We analysed associations between home characteristics (collected by parental questionnaires and study technicians) and food allergens by multivariate regression models. RESULTS: Fish allergen was detected in 46%, peanut in 41%, milk in 39%, and egg allergen in 22% of the mattress dust samples; only three samples contained none of these allergens. All four food allergens were more frequently detected in mattresses in small dwellings (< 100 m(2)) than larger dwellings (≥ 130 m(2)); 63-71% of the small dwellings (n = 24) had milk, peanut, and fish allergens in the samples compared with 33-44% of the larger dwellings (n = 95). Milk, peanut, and egg allergens were more frequently detected in homes with bedroom and kitchen on the same floor as compared with different floors, with odds ratios of 2.5 (95% confidence interval (CI): 1.1, 5.6) for milk, 2.4 (95% CI: 1.0, 6.1) for peanut, and 3.1 (95% CI: 1.3, 7.5) for egg allergens. CONCLUSIONS AND CLINICAL RELEVANCE: Food allergens occurred frequently in beds in Norwegian homes, with dwelling size and proximity of kitchen and bedroom as the most important determinants. Due to the amount of time children spent in the bedroom, mattress dust may be an important source of exposure to food allergens.

Transcriptomic fingerprints in human peripheral blood mononuclear cells indicative of genotoxic and non-genotoxic carcinogenic exposure.

For evaluating genotoxic exposure in human populations a number of biomarkers has been successfully applied over the last 30 years to determine early biological effects due to exposure to carcinogens. Despite their success, these early biological effect markers provide limited mechanistic insight, and do not allow detection of exposure to non-genotoxic carcinogens. Gene expression profiling forms a promising tool for the development of new biomarkers in blood cells to overcome these limitations. The aim of our research was to identify novel genomics-based candidate markers for genotoxic and non-genotoxic carcinogen exposure in human peripheral blood cells (PBMC). Whole genome gene expression changes were investigated following 20 h of in vitro exposure to a high and low concentration of eight genotoxic and three non-genotoxic carcinogenic compounds using whole genome microarrays. Per condition, PBMC of five independent donors were exposed, all in the presence of human liver S9. Sets of genes, as well as biological pathways indicative of genotoxic exposure and of non-genotoxic carcinogenic exposure were identified. Furthermore, networks were built using the genotoxic and non-genotoxic gene sets, showing the majority of the genes to be interlinked and revealing distinctive transcription factors for both classes. The identification of these potential candidate marker genes might contribute to the development of genomic based biomarkers of carcinogen exposure.

Can childhood asthma be predicted at birth?

BACKGROUND: Early life appears optimal for prevention of asthma, but interventions require a relevant target population, to date not clearly identified at birth. OBJECTIVE: We therefore aimed to identify the predicting capacity of factors known around birth for asthma and rhinitis at 10 years. METHODS: The included 614 healthy term babies with lung function measured at birth in the 1992/1993 Environment and Childhood Asthma study in Oslo attended a 10-year follow-up visit including a structured interview and skin prick test (SPT) for allergies. The logistic regression analyses included 37 general variables from an extensive birth questionnaire; lung function; cord blood total immunoglobulin E and soluble CD14. A history of asthma, current asthma, history of rhinitis and 'healthy' (no history of asthma, rhinitis and negative SPT) was predicted on a group level and individual predicted probabilities were calculated. RESULTS: The predictability of the models [area under the curve (95% confidence intervals)] was 0.74 (0.69, 0.79), 0.72 (0.64, 0.78), 0.69 (0.54, 0.72) and 0.67 (0.62, 0.71) for a history of asthma, current asthma, rhinitis and 'healthy', respectively. The best model predicted a history of asthma correctly in 93/124 (75%), and incorrectly in 176/490 (36%) children without asthma. The positive predictive values for all outcomes were low (19-61), the highest predicting healthy. CONCLUSION: Although at best 75% of children with a history of asthma could be predicted at birth, an intervention applied to our predicted high-risk children would be started more often in children without than with future disease. Parental allergic disease alone appears insufficient to identify high-risk populations in future studies of asthma and allergic disease.

Gender differences in indoor allergen exposure and association with current rhinitis.

BACKGROUND: Differences between boys and girls in allergic manifestations are well known, and this difference is possibly not attributed to physiological differences alone. OBJECTIVE: We, therefore, investigated whether boys and girls could be exposed to different allergen levels at home and whether indoor allergen levels could be differently associated with rhinitis in boys and girls at 10 years of age. METHODS: Cat, dog and house dust mite (HDM) allergen levels in mattress dust and interview data regarding current allergic disease were available for 797 10-year-old children (360 girls) in The Environment and Childhood Asthma Study in Oslo. RESULTS: Girls had higher concentrations of cat and dog allergens in their mattresses compared with boys, also in homes without cats [geometric mean 95% confidence intervals (95% CI): 0.37 (0.31, 0.44) for girls and 0.26 (0.23, 0.30) microg cat allergen/g dust for boys, P=0.002], and without dogs [girls: 0.74 (0.63, 0.86) and boys: 0.55 (0.48, 0.62) microg dog allergen/g dust, P=0.003]. No difference was observed for HDM allergen (Der p 1) levels. Of the 190 (23.8%) children reporting current rhinitis, 144 (75.8%) were sensitized to at least one allergen. The adjusted odds ratio for current rhinitis increased with 1.20 (95% CI: 1.01, 1.42) per 1 microg/g dust increase in Der p 1 for girls (P=0.037), but not for boys (P=0.91). CONCLUSION: Girls had higher levels of cat and dog allergens in mattress dust compared with boys, whereas no difference was observed for Der p 1 allergen. Nevertheless, only increasing levels of Der p 1 and not cat and dog allergens significantly increased the risk of current rhinitis in girls, whereas no significant association was observed for boys.

Childhood asthma and early life exposure to indoor allergens, endotoxin and beta(1,3)-glucans.

BACKGROUND: Divergent results have been reported regarding early life exposure to indoor environmental agents and the risk of asthma and allergic sensitization later in life. OBJECTIVE: To assess whether early exposure to indoor allergens, beta(1,3)-glucans and endotoxin modifies the risk of allergic diseases at 10 years of age. METHODS: The concentrations of mite, cat and dog allergens, endotoxin and beta(1,3)-glucans were determined in dust from the homes of 260 two-year-old children with lung function measured at birth (tidal flow volume loops) in the Environment and Childhood Asthma study in Oslo. At 10 years, the health status was assessed in a follow-up study including a structured interview of the parents and an extended clinical examination. RESULTS: Cat and dog keeping at 2 years of age was reported in 6.5% and 5.5% of the families, respectively. Mite allergens were detected in only 4/260 dust samples. The adjusted odds ratio for asthma at age 10 was 1.20 (95% confidence interval: 1.01-1.43) and 1.22 (1.02-1.46) for bronchial hyperresponsiveness (BHR) per 10 microg/g dust increase in cat allergen exposure at 2 years of age. No association was seen with allergic sensitization. Moreover, endotoxin and beta(1,3)-glucan exposure did not modify the risk of asthma or allergic sensitization. None of the measured environmental factors were associated with lung function at 10 years of age or a relative change in lung function from birth. CONCLUSION: In a community with a low prevalence of pet keeping and low mite allergen levels, exposure to cat allergens early in life increased the risk of late childhood asthma and BHR, but not the risk of allergic sensitization. No risk modification was seen for dog allergens, endotoxin and beta(1,3)-glucans.

Do allergic families avoid keeping furry pets?

UNLABELLED: Studies addressing the relationship between pet keeping and development of asthma and allergies may be influenced by pet avoidance in families with a history of allergic disease. Following a cohort of 1019 children in Oslo till 10 years of age, we studied the association of pet keeping with socio-economic factors and allergic disease in the family. A family history of asthma and rhinoconjunctivitis was not significantly associated with pet ownership at birth or with pet removal by 10 years. Acquiring cats and dogs was less likely if the child had allergic rhinoconjunctivitis, whereas no association was seen with asthma (in any family member). Single parenthood increased the likelihood of acquiring a cat, smoking parents more often had cats or dogs, and having older siblings was associated with keeping dogs and other furry pets. Among 319 families reporting pet avoidance, 70% never had pets, 8% had given up pets, and 22% avoided a particular type of pet only. Twenty-four per cent of the parents failed to retrospectively report pet keeping during the child's first year of life. Overall, allergic rhinitis, but not asthma was associated with actual pet avoidance, whereas the strongest predictors for keeping pets were found to be socio-economic factors. PRACTICAL IMPLICATIONS: Allergic disease in a child most often does not lead to the removal of the family's furry pet. Pet avoidance is associated with allergic symptoms, but not asthma. Socio-economic factors like parental education, single parenthood and smoking affects the families' decisions on pet keeping, including the type of pets the families will avoid or acquire. The large recall error demonstrated points to the need for prospective data regarding pet keeping.

Perfluoroalkyl substances, airways infections, allergy and asthma related health outcomes - implications of gender, exposure period and study design.

INTRODUCTION: Exposure to perfluoroalkyl substances (PFASs) has been inconsistently associated with asthma, allergic diseases and airways infections in early childhood. The aim of the study was, therefore, to investigate the effect of childhood exposure to PFASs on asthma and allergy related outcomes and on airways infections before and during puberty using the prospective birth cohort Environment and Childhood Asthma (ECA) Study. Aspects of gender, exposure period and study design (cross-sectional and longitudinal) were also taken into consideration. MATERIAL AND METHODS: Included in the study was 378 participants with PFAS measurements at age 10 years and follow-up data at ages 10 years (cross sectional data) and 16 years (longitudinal data). Eight PFASs with at least 70% of measurements above the limit of quantification (LOQ) in the child's serum were included in the present study: perfluoroheptanoate (PFHpA), perfluorooctanoate (PFOA), perfluourononanoate (PFNA), perfluorodecanoate (PFDA), perfluoroundecanoate (PFUnDA), perfluorohexane sulfonate (PFHxS), perfluoroheptane sulfonate (PFHpS) and perfluorooctane sulfonate (PFOS). The PFAS levels were converted into interquartile range (IQR). In addition, perfluorooctane sulfonamide (PFOSA) detected in 60% of the samples, was recoded into "not detected /detected". Binomial, multinomial and linear regression were used, followed by Bonferroni adjustment to correct for multiple comparisons. Sensitivity analyses evaluating the effect of extreme PFAS values and gender were performed. RESULTS: In the cross sectional data at 10 years a positive statistically significant association was seen between PFHpA and asthma in girls. In the longitudinal data, PFNA, PFDA and PFUnDA were inversely associated with atopic dermatitis (AD) in girls and with PFHxS in all participants and in boys. Further, PFNA and PFHpS were positively associated with rhinitis in girls and with PFOA in all participants. There seems to be a suggestive pattern of increased risk of allergic sensitisation in all participants and a decreased risk in boys, but due to different results in main and sensitivity analyses these findings should be interpreted with caution. No associations were found between PFASs and lung function. For airways infections and longitudinal data, PFDA was inversely associated with common cold, while positive association was found for PFHpA, PFOA, PFHpS and PFOS and lower respiratory tract infections (LRTI). DISCUSSION AND CONCLUSION: Our results lend further support for an immunosuppressive effect of PFASs on AD and LRTI. Gender seems to be important for some exposure-health associations. No clear pattern in exposure-health associations was observed with regard to exposure period or study design, with the exception of asthma where significant findings have mostly been reported in cross-sectional studies.

Maternal levels of perfluoroalkyl substances (PFASs) during pregnancy and childhood allergy and asthma related outcomes and infections in the Norwegian Mother and Child (MoBa) cohort.

INTRODUCTION: Prenatal exposure to perfluoroalkyl substances (PFASs) has been inconsistently associated with asthma and allergic diseases and increased number of infections in early childhood. We examined the association of PFASs measured in pregnancy with childhood asthma, allergies and common infectious diseases in a prospective pregnancy cohort followed to age 7 years. MATERIAL AND METHODS: Six PFASs (out of 19 measured) with at least 80% of measurements above the limit of quantification (LOQ) in maternal plasma during pregnancy in two subcohorts of the Norwegian Mother and Child Cohort Study (MoBa) were analyzed in relation to health outcomes: perfluorooctane sulfonic acid (PFOS), acid (PFOA), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA), perfluoroundecanoic acid (PFUnDA), and perfluoroheptane sulfonic acid (PFHpS). Follow-up questionnaires were completed at 3 years by 1270 women and at 7 years by 972 women among the 1943 with pregnancy questionnaire and PFAS measures. Health outcomes included parent reports of child's symptoms or doctor diagnosed asthma and allergic conditions at age 7 years and parent-reported frequency of various infections at 3 and 7 years of age. Logistic and Poisson regression were used. The false discovery rate was controlled at 5%. Sensitivity analyses on gender were performed. RESULTS: Among the allergy and asthma outcomes, a statistically significant inverse association was seen between PFUnDA concentrations and ever having atopic eczema in girls. PFUnDA also tended to be inversely associated with both wheeze and asthma. For infections from 0 to 3 and 6 to 7 years, 11 significant positive associations were seen between PFASs and airways infections (bronchitis/pneumonia, throat infection, pseudocroup), ear infection and gastric flu/diarrhea; whereas 6 inverse associations were seen for pseudocroup, ear infections and urinary tract infections. The majority of the findings with respect to infectious diseases were found in girls only. DISCUSSION: With the exception of an inverse association between PFUnDA and eczema, and a tendency of a similar association for wheeze and asthma, maternal PFAS levels during pregnancy showed little association with asthma or allergy related outcomes. Findings from the present study suggest immunosuppressive effects of PFASs on airways infections, such as bronchitis/pneumonia and throat infections, as well as diarrhea/gastric flu. Our results indicate a possible role of gender in the PFAS-health outcome associations.

Mould-specific immunoglobulin antibodies quantified by flow cytometry reflect mould exposure in Norwegian children.

BACKGROUND: Studies from many countries have shown an association between dampness in buildings and airway symptoms. Little is known about the role of mould-specific IgG antibodies in this context. Objective To examine the IgG antibody response to mould applying a new flow cytometric assay, compare the results with the standardized ImmunoCap method, and evaluate the association of IgG to IgE antibodies, dampness in buildings, and airway symptoms like wheeze and asthma. METHODS: A population of 3713 children 9-11 years of age living in Northern Norway was investigated for airway symptoms and dampness at homes by a parental questionnaire, using protocols of the International study of Asthma and Allergy in Childhood (ISAAC). Among these, a case-control study of 100 wheezers and 100 non-wheezers was established that included home inspection, a parental structured interview, and serum samples analysed for mould-specific IgG and IgE antibodies, total IgE, and specific IgE to an allergen panel (Phadiatop). RESULTS: Self-reported visible signs of mould or moisture at home during the child's first year of life were a significant risk factor for both wheeze and asthma. The levels of mould-specific IgG antibodies were associated with mould and moisture findings, but only when IgG antibodies were measured by flow cytometry. CONCLUSIONS: The results support that dampness at home can increase the risk of airway symptoms. IgG antibodies determined by flow cytometry reflect mould exposure better than antibodies measured by the conventional method. IgG antibodies measured by flow cytometry may be used as an indicator of mould exposure.

Adjuvant activity of particulate pollutants in different mouse models.

Particulate air pollutants may play a role in the increasing prevalence of respiratory allergy by acting as adjuvants for a T helper 2 (Th2) mediated immune response to common allergens. The immunomodulating capacity of well-defined polystyrene particles as well as different particles as present in our environment (diesel exhaust, carbon black, and silica particles) was investigated in different models. Polystyrene particles were injected intraperitoneally or installed intratracheally, while the environmentally relevant particles were injected subcutaneously. From these studies, it becomes clear that all particles exert an adjuvant effect on the immune response to the co-administered antigen. The particle core rather than attached chemical factors seems to be mainly responsible for this effect. The different particles, however, stimulate different types of immune responses, indicating that physicochemical properties of particles may be of importance in steering the response towards a T helper 1 (Th1) or a Th2-like response.

IgE adjuvant effect caused by particles - immediate and delayed effects.

Diesel exhaust particles are reported to increase the specific IgE response to ovalbumin (OVA) and pollen. Evidence has been provided that the particle core contributes to this adjuvant activity. The purpose of our study was to investigate the effect of well-defined simple particles, polystyrene particles (PSP), on the production of allergen-specific IgE in a mouse model. The IgE adjuvant effect of PSP was investigated in experiments using intranasal (i.n.) instillation, intratracheal (i.t.) instillation or intraperitoneal (i.p.) injection. Delayed and cumulative adjuvant effects were investigated by giving mice i.p. injections with PSP 1-3 days, or on 4 consecutive days before OVA, respectively. The levels of allergen-specific and total IgE were measured. Irrespectively of immunisation route and protocol, OVA in combination with PSP elicited increased levels of both allergen-specific and total IgE when compared with OVA alone. Therefore, in the experimental model, particles were found to augment the specific IgE response to an allergen even when the allergen was introduced several days after the particles. These findings imply that individuals exposed to particulate air pollution at one point of time may develop an increased reaction towards allergens inhaled later that day or even several days after the particle exposure.

Fine particles of widely different composition have an adjuvant effect on the production of allergen-specific antibodies.

Diesel exhaust particles (DEP) are reported to increase the specific IgE response to allergens, and results from our laboratory suggest that the particle core of DEP contribute to this adjuvant activity. The purpose of the present study was to explore further the adjuvant effect of particles per se, that is particles by themselves. NIH/Ola mice were given two intraperitoneal injections with ovalbumin (OVA; 10 microg) alone or OVA in combination with PSP, polytetrafluoroethylene (teflon), titanium dioxide (TiO(2)) or amorphous silica particles (2.8x10(10)-2.8x10(12)). Blood samples were drawn 7 days after the last injection, and serum levels of allergen-specific and total IgE and IgG2a were measured. All types of particles gave increased levels of allergen-specific IgE and IgG2a. Similar results were obtained after intranasal or intratracheal instillation with OVA plus PSP or silica. Our results indicate that fine particles of widely different composition may have an adjuvant effect on the production of allergen-specific antibodies.

Toxicogenomic profiles in relation to maternal immunotoxic exposure and immune functionality in newborns.

A crucial period for the development of the immune system occurs in utero. This results in a high fetal vulnerability to immunotoxic exposure, and indeed, immunotoxic effects have been reported, demonstrating negative effects on immune-related health outcomes and immune functionality. Within the NewGeneris cohort BraMat, a subcohort of the Norwegian Mother and Child Cohort Study (MoBa), immunotoxicity was demonstrated for polychlorinated biphenyls and dioxins, showing associations between estimated maternal intake levels and reduced measles vaccination responses in the offspring at the age of 3. The present study aimed to investigate this link at the transcriptomic level within the same BraMat cohort. To this end, whole-genome gene expression in cord blood was investigated and found to be associated with maternal Food Frequency Questionnaires-derived exposure estimates and with vaccination responses in children at 3 years of age. Because the literature reports gender specificity in the innate, humoral, and cell-mediated responses to viral vaccines, separate analysis for males and females was conducted. Separate gene sets for male and female neonates were identified, comprising genes significantly correlating with both 2,3,7,8-tetrachlorodibenzodioxin (TCDD) and polychlorinated biphenyls (PCB) exposure and with measles vaccination response. Noteworthy, genes correlating negatively with exposure in general show positive correlations with antibody levels and vice versa. For both sexes, these included immune-related genes, suggesting immunosuppressive effects of maternal exposure to TCDD and PCB at the transcriptomic level in neonates in relation to measles vaccination response 3 years later.

In vitro cytokine release from human peripheral blood mononuclear cells in the assessment of the immunotoxic potential of chemicals.

Alternative methods to the use of animals in testing of chemicals are needed. We investigated if the immunotoxic potential of 12 dietary toxicants could be predicted from effects on cytokine release from human peripheral blood mononuclear cells (PBMC) after in vitro exposure. Nine cytokines were selected to reflect different types of immune responses. The toxicants were classified as immunotoxic or non-immunotoxic substances according to the published in vivo data. Isolated human PBMC were exposed for 20 h to three concentrations of each of the 12 substances in the presence of human liver S9 fraction. After further incubation of PBMC in fresh medium containing the mitogen phytohemagglutinin (PHA, 10 µg/ml) for 48 h, release of the nine selected cytokines into the supernatant as well as cell proliferation were measured by Luminex technology™ and the BrdU incorporation assay, respectively. All 12 substances investigated affected the release of one or more cytokines, and each of the substances showed different cytokine release patterns. Within the limitations of the study design, the present study suggests that the effect of the substances on mitogen-induced cytokine release from PBMC cannot predict their immunotoxic potential, but may be useful in mechanistic studies.

Soluble CD14 at 2 yr of age: gender-related effects of tobacco smoke exposure, recurrent infections and atopic diseases.

The endotoxin receptor soluble CD14 (sCD14) has been implicated in the 'hygiene hypothesis' suggesting reduced allergic sensitization with bacterial stimulation. However, the relationship between early life sCD14 and allergic diseases is conflicting. We aimed to investigate whether possible risk factors for allergic diseases were associated with sCD14 levels at 2 yr of age. In the nested case-control study of the birth cohort studies 'Environment and Childhood Asthma study in Oslo' 411 children selected with recurrent bronchial obstruction (rBO) (n=241) and no bronchial obstruction (n=170) by 2 yr were investigated with skin prick test and structured parental interview at age 2 yr. Exposure to tobacco smoke, pets and infections was recorded semi-annually by questionnaires (0-2 yr). The sCD14 was analysed from frozen, stored serum by ELISA technique. Regression analyses were performed in all subjects with complete data (n=406, 180 girls), and in girls and in boys separately. Mean sCD14 (ng/ml) was significantly higher among girls 2035 (1973-2096) vs. 1947 (1890-2004) (boys). The sCD14 was significantly reduced among girls exposed to antenatal maternal smoking and with parental asthma, after adjusting for age, parental rhino-conjunctivitis, pet keeping and childhood infections. Recurrent otitis media (OM) increased and common colds significantly decreased sCD14 levels in girls. Boys with atopic dermatitis and rBO had reduced sCD14. Pet exposure was not significantly associated with sCD14. We report novel gender-related effects of sCD14 in early life and suggest that gender, tobacco smoke exposure, age and middle ear disease in particular should be accounted for when assessing the role of sCD14 in childhood allergic diseases.

Asthma in every fifth child in Oslo, Norway: a 10-year follow up of a birth cohort study.

BACKGROUND: The western world's increase in childhood asthma is suggested to level off. We aimed to investigate asthma prevalence in 10-year-old children within the prospective birth cohort Environment and Childhood Asthma (ECA) Study in Oslo established in 1992/1993. SUBJECTS AND METHODS: Six hundred and sixteen (77%) of 803 children (mean age 10.9 +/- 0.9 (SD) years) with lung function measurements at birth were reinvestigated at age 10 years. At birth they corresponded to the entire birth cohort (n = 3754) regarding gender, socio-demographic factors, parental allergic diseases, pet keeping and maternal smoking. Results from structured parental interview, spirometry, and skin prick test for inhalant and food allergens are presented. Asthma definition required minimum two positive criteria, (i) doctor's diagnosis of asthma, (ii) wheeze and/or chest tightness, (iii) use of anti-asthmatic treatment. Current asthma required asthma definition plus either (ii) and/or (iii) in the last 12 months, and/or > or = 10% fall in forced expired volume in 1 s after treadmill running. RESULTS: Lifetime prevalence of asthma was 20.2%; current asthma 11.1%, doctor diagnosis of asthma 16.1% and wheezes ever 30.3%. Allergic sensitization (29.3% overall) was more common among children with current (56.3%) compared to asymptomatic (last 12 months) (26.0%) or no asthma (27.6%) (P < 0.001). Boys more often than girls had current asthma (14.4 vs 7.1%, P = 0.004), wheeze ever (36.9 vs 22.5%, P = 0.002) and allergic sensitization (36.2 vs 22.1%, respectively, P < 0.001). CONCLUSION: Childhood asthma apparently continues to increase in Oslo, having affected every fifth 10-year-old child.

IgE Adjuvant Activity of Particles-What Physical Characteristics are Important?

Diesel exhaust particles (DEP) are reported to increase the allergic immune response to ovalbumin (OVA) and pollen. There are studies reporting that both the adsorbed chemical substances and the carbon core of DEP may contribute to the immunoglobulin E (IgE) adjuvant effect. The aim of this study was to investigate which physical properties of particles per se, that is, the particles by themselves, might be important for their IgE adjuvant effect, namely, dose weight, size, number, and surface area. Since DEP have a tendency to form aggregates of varying shapes and sizes, evaluation of the relative importance of these characteristics is difficult using DEP. We therefore decided to use well-characterized, spherical polystyrene particles (PSP). We performed four different types of experiments, in which the total dose weight (12.25 mg), size (0.1 µm in diameter), total number (8 x 10(10)), or total surface area (1300 cm(2)) of PSP, respectively, was kept constant. NIH/Ola mice were given 2 intraperitoneal injections with PSP plus OVA or OVA alone, over a 16-day period. The mice were exsanguinated at the end of each experiment, and the serum concentration of IgE anti-OVA was measured. The serum levels of IgE anti-OVA increased with both an increasing number and surface area of PSP. We found no clear association between PSP size and the levels of IgE anti-OVA, but because of the relatively small size range of PSP used, no definitive conclusions can be made on whether size is an important factor for the IgE adjuvant effect of PSP. There seemed to be no covariation between the dose weight and the levels of IgE anti-OVA. Our findings indicate that the total number and total surface area of PSP, rather than the dose weight, are important parameters for the IgE adjuvant activity from PSP, and possibly also for particles in general.

Leptin does not influence the IgE response to ovalbumin in mice.

Leptin is important for maintenance of the body's energy homeostasis and it also increases Th1 and suppresses Th2 cytokine production. We have investigated the effect of leptin on the allergic immune response to the model allergen ovalbumin (OA) by using the popliteal lymph node assay (PLNA) and serum antibody determination in mice. Mice were injected with either leptin i.v. plus OA in one hind footpad, or leptin or OA alone. A booster dose of leptin was given twice and of OA once and the animals were exsanguinated on experimental day 19 when the PLNs also were removed. End-point measurements were serum levels of IgE, IgG1, and IgG2a anti-OA and weight and cell number of the excised PLNs. Leptin given i.v. with the protocol employed altered neither the cellular PLN response nor the specific serum IgE, IgG1, or IgG2a anti-OA levels compared with the group given OA without leptin. Our data indicate that systemic administration of leptin neither suppresses nor enhances the Th2-dependent antibody responses in the present mouse model.