The LINA Study: Higher Sensitivity of Infant Compared to Maternal Eosinophil/Basophil Progenitors to Indoor Chemical Exposures.

PURPOSE: Enhanced eosinophil/basophil (Eo/B) progenitor cell levels are known to be associated with allergic inflammation and atopy risk. The aim of the present study was to investigate the influence of different indoor exposures on the recruitment and differentiation of Eo/B progenitors in mother-child pairs. METHODS: In 68 mother-child pairs of the LINA study peripheral blood mononuclear cells were used to assess Eo/B colony forming units (CFUs). Information about disease outcomes and indoor exposures was obtained from questionnaires. Indoor concentrations of volatile organic compounds (VOCs) were measured by passive sampling. RESULTS: Infant's Eo/B CFUs were positively associated with exposure to tobacco smoke, disinfectants, or VOCs. In contrast, for maternal Eo/B CFUs, only a few associations were seen. Higher numbers of infant Eo/B CFUs were observed in children with wheezing symptoms within the second year of life. CONCLUSIONS: We demonstrate that infant's hematopoietic cells seem to respond with more sensitivity to environmental exposure compared to maternal cells. At least in infants, an activation of these hematopoietic cells by environmental exposure could contribute to an enhanced risk for the development of respiratory outcomes.

Prenatal VOC exposure and redecoration are related to wheezing in early infancy.

UNLABELLED: Redecoration of dwellings is a common behavior of expecting parents. Former studies gave evidence that early childhood exposure to volatile organic compounds (VOC) resulting from renovation activities may increase the risk for wheeze in infants. OBJECTIVES: The aim of the present study was to evaluate the impact of prenatal exposure on early wheeze and to identify sensitive time windows. Within the LINA birth cohort study data on renovation activities and respiratory outcomes were assessed via questionnaires during pregnancy and at children's age of one. At both timepoints, also indoor VOC concentrations were measured. The associations were studied by logistic regression analysis. Floor covering during pregnancy contributed to an increased risk for physician treated wheeze (adjusted odds ratio OR=5.20, 95% confidence interval 1.8-15.2) during the first 12 months after birth in particular in children with an atopic predisposition. Thereby, wall-to-wall-carpets, PVC material, and laminate were the flooring materials which showed the strongest adverse associations. Floor covering was associated with enhanced concentrations of VOCs in the apartments. For the VOCs styrene, ethylbenzene, octane, 1-butanol, tridecane, and o-xylene, a significant association was found to the occurrence of wheezing symptoms. In contrast to pregnancy, exposure during the first 12 months after birth showed less detrimental associations. Only the association between wheezing and styrene as well as between wheezing and PVC flooring remained significant for exposure after birth. Redecoration during pregnancy, especially changing floor materials, increases the risk for respiratory diseases in early childhood and should therefore be avoided at least in families with a history of atopic diseases.

Renovation activities during pregnancy induce a Th2 shift in fetal but not in maternal immune system.

The aim of the present study was to investigate to which extent environmental influences like indoor renovation activities affect the immune system of mother and child during the gestation period. Within the LINA (Lifestyle and Environmental Factors and their Influence on Newborn Allergy risk) birth cohort study blood samples of mothers during pregnancy and cord blood samples were analyzed for concentrations of the Th1/Th2 cytokines IL-4, IL-5, IL-13, IFN-γ and IgE. Data on indoor renovation activities (painting, flooring and new furniture) were assessed with questionnaires. Data on cytokine blood concentrations and exposure variables were available for 422 mother/child pairs. Neonates, who were strongly affected by renovation activities (especially floor covering and new furniture) during pregnancy, had significantly higher concentrations of IL-4 and IL-5 in cord blood. Among the single activities, new furniture, particularly flake board, were associated with increased IL-4 levels. Elevated IL-4 levels were also observed in the cord blood of children whose mothers reported wall-to-wall carpeting. Among flooring, polyvinylchloride (PVC) showed the strongest effect with increased IL-5 concentrations. The Th1/Th2 imbalance towards Th2 at birth was related to allergic sensitization in children at the age of one. There were only few and negative associations between renovation activities and Th1/Th2 cytokine concentration in maternal blood. Our study shows that under similar exposure situations the fetal immune system is more susceptible to the influence of environmental factors, in particular renovation products (flake board, wall-to-wall carpets and PVC) compared to the maternal.

Respiratory effects of indoor particles in young children are size dependent.

BACKGROUND: Extensive epidemiological studies have provided evidence of an association between elevated outdoor particulate air pollution and adverse health effects. However, while people typically spend majority of time indoors, there is limited knowledge on airborne indoor particles and on the correlation between the concentrations of indoor particles and health effects. Even insights into the influence of differently sized indoor particles on human health are still rare. OBJECTIVE: The association between differentially sized indoor air particles and the development of respiratory diseases was studied for three year aged children. METHODS: Short-term measurements of particle mass and number concentrations were carried out in children's rooms. Information on possible particle sources (smoking habits, type of heating, and traffic) and respiratory outcomes were obtained from questionnaires. Measured indoor particle concentrations were correlated with possible sources of indoor particles and with respiratory health impacts. RESULTS: Daily smoking, smoking more than 5 cigarettes per day at home and traffic density in front of the window of children's room were found to be related to indoor exposure by particles of different diameters. High indoor particle exposures were associated with an increased risk for the development of obstructive bronchitis and in some extent of non-obstructive bronchitis. The strongest impact was observed for the mass concentration of particles <1 µm and the number concentration of particles >0.5 µm. The risk increases still remain significant if tested for stability changing the number of adjustment variables or omitting randomly selected cases, respectively. CONCLUSION: Our results show significant associations between indoor particle concentrations and the risks for respiratory diseases in young children. The applied short-term measurements can help to assess the health risks of indoor particles with different sizes within epidemiological studies.

Reduced IFN-gamma- and enhanced IL-4-producing CD4+ cord blood T cells are associated with a higher risk for atopic dermatitis during the first 2 yr of life.

The aim of this study was to analyse whether altered cytokine production by cord blood (CB) T cells is of relevance regarding the development of allergic diseases during the first 2 yr of life independent from known or suspected risk factors for allergy. Within an ongoing birth cohort study (Life style - Immune System - Allergy; LISA) the cytokine production of PMA/ionomycin-stimulated CB cells was measured by intracellular cytokine staining. Data of 98 children from Leipzig and Munich with complete information on cytokine production at birth and allergic outcomes during the first 2 yr were analysed. Statistical analysis was performed using a regression model adjusted for gender, month of birth, parental history of atopy, parental education, exposure to environmental tobacco smoke, maternal smoking during pregnancy, renovation activities during pregnancy, pet ownership and study centre. During the first 2 yr of life, 17.3% of the children developed a physician-diagnosed atopic dermatitis. Children with reduced frequencies of interferon-gamma (IFN-gamma)-producing CD4(+) T cells in the CB (1st quartile) had a higher risk to develop atopic dermatitis (adjusted OR 5.16, 95% CI: 1.04-25.6). Furthermore, a high percentage of interleukin (IL)-4-producing T cells in CB in children from the Leipzig cohort were associated with an increased risk for atopic dermatitis (adjusted OR 8.92, 95% CI: 1.40-56.93 for the 90th percentile). CD8(+) cytokine-producing CB T cells had no relation to increased risk for atopic dermatitis. Low amounts of IFN-gamma and high amounts of IL-4-producing T cells at birth may enhance the risk of subsequent development of atopic dermatitis.

Increase of inflammatory markers after indoor renovation activities: the LISA birth cohort study.

There is concern about indoor air quality as a possible cause for health impairment. Exposure to indoor renovation activities has been shown to be associated with airway symptoms and allergic manifestations in children. The aim of this study is to analyse immune markers responsible for disease development in relation to renovation activities. Within the LISAplus (Life style Immune System Allergy) birth cohort study, blood samples of 6-yr-old children were analysed for concentration of the inflammatory markers interleukin (IL)-8, IL-6, tumour necrosis factor-alpha, MCP-1 and IL-10. Data on indoor renovation activities (painting, flooring, new furniture) were assessed with a questionnaire filled in by the parents. Data on cytokine blood concentrations and exposure variables were available for 250 children. Increased levels of IL-8 and MCP-1 in children's blood were related to renovation activities. In particular, new floor covering was associated with increased inflammatory markers. Among floor covering materials only wall-to-wall carpets were associated with elevated IL-8 and Monocyte Chemoattractant Protein-1 (MCP-1) levels. No association between the single renovation activities painting and furnishing and blood concentration of inflammatory markers has been found. Our data shows that IL-8 and MCP-1 may be suitable markers for monitoring inflammatory reactions in relation with renovation activities. Among renovation activities floor covering seems to induce the strongest inflammatory reactions.

Relation between stressful life events, neuropeptides and cytokines: results from the LISA birth cohort study.

Stressful life events evidently have an impact on development of allergic diseases, but the mechanism linking stress to pathological changes of immune system function is still not fully understood. The aim of our study was to investigate the relationship between stressful life events, neuropeptide and cytokine concentrations in children. Within the LISAplus (Life style-Immune system-Allergy) study, blood samples from children of 6 yr of age were analysed for concentration of the neuropeptides vasoactive intestinal peptide (VIP), somatostatin (SOM), substance P (SP) and the Th1/Th2 cytokines interferon-gamma (IFN-gamma) and interleukin (IL)-4. Life events such as severe disease or death of a family member, unemployment or divorce of the parents were assessed with a questionnaire filled in by the parents. For 234 children, blood analysis and questionnaire data regarding life events were available. Children with separated/divorced parents showed high VIP levels and high concentrations of the Th2 cytokine IL-4 in their blood. Severe diseases and death of a family member were neither associated with neuropeptide levels nor with cytokine concentrations. Unemployment of the parents was associated with decreased IFN-gamma concentrations in children's blood but not with neuropeptide levels, whereas children experiencing concomitant severe disease and death of a family member had reduced SP blood levels. The neuropeptide VIP might be a mediator between stressful life events and immune regulation contributing to the Th2 shifted immune response in children with separated/divorced parents. Unemployment of the parents was associated with immune regulation in children on the basis of a still unknown mechanism whereas reduced SP levels seem to have no effect on immune regulation.

Timing of solid food introduction in relation to eczema, asthma, allergic rhinitis, and food and inhalant sensitization at the age of 6 years: results from the prospective birth cohort study LISA.

OBJECTIVE: Current prophylactic feeding guidelines recommend a delayed introduction of solids for the prevention of atopic diseases. This study investigates whether a delayed introduction of solids (past 4 or 6 months) is protective against the development of eczema, asthma, allergic rhinitis, and food or inhalant sensitization at the age of 6 years. METHODS: Data from 2073 children in the ongoing LISA birth cohort study were analyzed at 6 years of age. Multivariate logistic regression analyses were performed for all children and for children without skin or allergic symptoms within the first 6 months of life to take into account reverse causality. RESULTS: A delayed introduction of solids (past 4 or 6 months) was not associated with decreased odds for asthma, allergic rhinitis, or sensitization against food or inhalant allergens at 6 years of age. On the contrary, food sensitization was more frequent in children who were introduced to solids later. The relationship between the timing of solid food introduction and eczema was not clear. There was no protective effect of a late introduction of solids or a less diverse diet within the first 4 months of life. However, in children without early skin or allergic symptoms were considered, eczema was significantly more frequent in children who received a more diverse diet within the first 4 months. CONCLUSIONS: This study found no evidence supporting a delayed introduction of solids beyond 4 or 6 months for the prevention of asthma, allergic rhinitis, and food or inhalant sensitization at the age of 6 years. For eczema, the results were conflicting, and a protective effect of a delayed introduction of solids cannot be excluded. Positive associations between late introduction of solids and food sensitization have to be interpreted with caution. A true protective effect of a delayed introduction of solids on food sensitization seems unlikely.

Timing of solid food introduction in relation to atopic dermatitis and atopic sensitization: results from a prospective birth cohort study.

OBJECTIVE: Prophylactic feeding guidelines recommend a delayed introduction of solid foods for the prevention of atopic diseases. Scientific evidence for this is scarce. This study investigates whether a delayed introduction of solids (past 4 months or 6 months) is protective against the development of atopic dermatitis (AD) and atopic sensitization when considering reverse causality. METHODS: Data from 2612 infants in an ongoing birth cohort study were analyzed at 2 years of age. Information on diet and on symptoms and diagnoses of AD was collected semiannually, and information on specific immunoglobulin E levels was collected at 2 years of age. RESULTS: Solid food introduction past the first 4 months of life decreased the odds of symptomatic AD but not for doctor-diagnosed AD, combined doctor-diagnosed and symptomatic AD, or atopic sensitization. Postponing the introduction beyond the sixth month of life was not protective in relation to either definition of AD or atopic sensitization. There was also no evidence for a protective effect of a delayed introduction of solids on AD and atopic sensitization in children of atopic parents. There was clear evidence for reverse causality between early skin or allergic symptoms and the introduction of solids. CONCLUSIONS: This study does not find evidence supporting a delayed introduction of solids beyond the sixth month of life for the prevention of AD and atopic sensitization. We cannot rule out that delaying the introduction of solids for the first 4 months of life might offer some protection. Measures to avoid reverse causality have to be considered in the conduction, analysis, and interpretation of cohort studies on the topic.

Well water--one source of Helicobacter pylori colonization.

Helicobacter pylori (H. pylori) is one of the world's most widespread microorganisms. Its acquisition in humans remains poorly understood, however, epidemiological studies have identified drinking water as reservoir for the bacterium. The aim of this study was to investigate the prevalence of H. pylori infection among individuals using or drinking previously H. pylori tested well water. Applying household cluster sampling, a total of 91 subjects, all using or drinking well water (13 of either H. pylori positive or negative wells), were screened for their H. pylori status. The group was comprised of 73 adults and 19 children under the age of 18. H. pylori infection was determined using the [13C]urea breath test. A self-administered or parent-completed questionnaire provided information on living conditions and lifestyle habits including the use or drinking of well water. Logistic regression analyses associated the drinking of H. pylori positive well water with a positive colonization status [Odds Ratio (OR) 8.3; 95% confidence interval (95% CI) 2.4-29]. In summary, the use or drinking of H. pylori contaminated well water appears associated with the acquisition of a H. pylori infection. This study is based on a relatively small and inhomogeneous population sample and should be repeated to confirm the results.

Redecoration of apartments promotes obstructive bronchitis in atopy risk infants--results of the LARS Study.

Findings by other authors indicate that exposure to chemical emissions from indoor paint is related to asthma symptoms in adults. In their first years of life children are receptive to obstructive airway diseases. The aim of this study was to investigate the influence of redecoration of the apartment on airway symptoms in infants during the first two years of life. The Leipzig Allergy Risk Children Study (LARS) is a birth cohort study with the following inclusion criteria: double positive family atopy anamnesis, cord blood IgE > 0.9 kU/l, or low birth weight between 1500-2500 g. Within the context of LARS, 186 parents of risk children completed a questionnaire on the respiratory symptoms of their children and the redecoration of their apartment at the end of the first and second year of life. A total 22% of the children suffered from obstructive bronchitis once or more during their first year, and 11% experienced this condition during their second year of life. Redecoration of the apartment had a significant influence on the appearance of obstructive bronchitis in the first (OR 4.1 95% CI 1.4-11.9) and in the second year of life (OR 4.2 95% CI 1.4-12.9). (The OR are adjusted for cord blood-IgE > 0.9 kU/l, birth weight < or = 2500 g, male sex and double positive parental atopy anamnesis, dampness, smoking or pet in the apartment). Simultaneous contamination from redecoration activities and additional exposures such as smoking, a pet or dampness in the apartment increased the risk for obstructive bronchitis in the first year (OR 9.1; 95% CI 2.3-34.8) as well as in the second year (OR 5.1; 95% CI 1.6-15.6). Our data suggest that redecoration of the apartment is associated with the development of acute inflammations, but not with a chronic influence on the airways in atopy risk infants. At an exposure to more than one environmental factor, pronounced effects were seen.

Natural history of serum immunoglobulin concentrations in low birth weight infants and association with respiratory tract infections.

UNLABELLED: Infections are a significant cause of morbidity and mortality among low birth weight (LBW) infants. THE AIMS OF OUR STUDY WERE: (1) to investigate whether serum antibody concentrations in 62 LBW infants (1,500-2,500 g) were normalized by 1 year of life, and (2) to determine the clinical relevance of humoral immaturity in these children during the 1st year compared to 20 appropriate-for-gestational-age (AGA) term infants. At 1 year of life, immunoglobulin serum concentrations in LBW infants were comparable to those of the control group. The incidence of respiratory tract infections during the 1st year of life was not significantly different between LBW and AGA term infants. Interestingly, we demonstrated that LBW infants with a higher frequency of reported febrile upper respiratory tract infections had more elevated serum total IgG, IgG(1), IgG(3), total IgA, and IgA(1) concentrations. Thus, infants with a birth weight of 1,500-2,500 g do not appear to have an increased risk of respiratory tract infections compared to AGA term children during the 1st year of life. Furthermore, our data suggest that especially febrile infections induce higher serum immunoglobulin concentrations in LBW infants.

Increased incidence of allergic sensitisation and respiratory diseases due to mould exposure: results of the Leipzig Allergy Risk children Study (LARS).

To investigate mould effects on health, the concentration of mould spores in air and dust was determined during a prospective cohort study. Clinical outcome was estimated by questionnaires and determination of specific IgE antibodies and intracellular cytokine production of T cells. A significant association was observed between the incidence of respiratory tract infections and exposure to Penicillium spores. Moreover, Aspergillus exposure was found to be associated with allergic rhinitis or related symptoms. In addition, T cells of children exposed to Aspergillus showed a significantly lower content of TH1 cytokines (IFN-gamma, TNF-alpha, IL-2) producing cells. Our data suggest that mould exposure is associated with several effects on health, depending on the species involved.

Passive smoking, excretion of metabolites, and health effects: results of the Leipzig's Allergy Risk Study (LARS).

Over a 5-yr period, the Leipzig's Allergy Risk Study (LARS) investigated the influence of typical indoor-contaminant burdens on the development of allergies and upper respiratory tract infections in allergy-prone children. Typical indoor volatile organic compounds (VOCs) and excretion of certain VOC metabolites in urine were measured in children 3 yr of age. Data analyses were based on parent-completed questionnaires, exposure measurements, and medical examinations. Evaluation of passive smoking was of special interest. Generally, residences with a high burden of passive smoking had higher benzene concentrations than residences inhabited by nonsmokers. Obstructive bronchitis was observed more frequently in children exposed to increased concentrations of benzene, as well as toluene, styrene, and m,p-xylene. In addition, atopic symptoms were associated with excretion of certain VOC metabolites. For example, the authors found an association between eczema and exposure to toluene and between eczema and increased excretion of the toluene metabolite S-benzylmercapturic acid. The results suggest that if an association with certain health effects is to be demonstrated, evaluation of external exposures should be supplemented with evaluations of internal exposure.