Is the association between pet ownership and indoor endotoxin levels confounded or modified by outdoor residential greenspace?

BACKGROUND: Pet ownership is consistently associated with higher indoor endotoxin concentrations, but may also be related to the amount of greenspace around the home. This study examined whether the association between pet ownership and higher indoor endotoxin concentrations is confounded or modified by residential greenspace. METHODS: Information on pet ownership was collected at the time of recruitment of the German LISA birth cohort. Endotoxin levels were measured in settled house dust sampled from mothers' mattresses (N=1197) and living room floors (N=390). Greenspace around the home was assessed as the mean Normalized Difference Vegetation Index in 100m, 500m and 1000m buffers around the home, and as the distance to the nearest urban and natural green space. Linear regression models assessed cross-sectional associations between pet ownership and log-transformed endotoxin levels, adjusted for known predictors of endotoxin levels. Confounding by greenspace was assessed by additionally adjusting the models for each greenspace variable. Effect modification was assessed by including interaction terms between pet ownership and each greenspace variable, and by model stratification. RESULTS: Dog and cat ownership were associated with higher endotoxin levels in mothers' mattresses, whereas only dog ownership was associated with endotoxin levels in the floor samples. All associations were highly robust to further adjustment for greenspace, and there was little evidence to suggest any effect modification (interaction terms had p-values >0.05). CONCLUSIONS: Residential greenspace did not confound or modify the association between pet ownership and indoor endotoxin levels. Studies should continue investigating whether pets influence the indoor environment only by their presence, or also by acting as transmission vectors of the outdoors.

Specific risk factors for contracting Q fever: lessons from the outbreak Jena.

A Q fever outbreak with 331 reported cases in seven weeks occurred in a densely populated residential district in Jena (Germany) in 2005. Prompt identification of a stable infection source follow by an intense information policy, well defined and stable meteorological conditions and a large number of reported cases within one small community all allowed us to study promoting and protecting factors of Q fever. We conducted a cross-sectional study and investigated a part of the affected area for 100% sampling (in-home interviews). Out of 608 residents at home 460 (75.7%) participated in the study and 101 fulfilled our definition of an acute Q fever case. Our data revealed a critical zone for residency within 500 m of herds of gestating ewes in a typical urban dwelling area. We found an association between shift work and contracting Q fever. An association between outdoor activity and Q fever was only found after prolonged outdoor stays, on average more than 4h/day. Only open windows facing the putative source were associated with increased risk of Q fever. Therefore fully open windows of more than 6h/day is a significant parameter.

Airborne allergens, endotoxins, and particulate matter in elementary schools, results from Germany (LUPE 2).

Allergic disorders are the most common childhood-related chronic diseases in developed countries. It is essential to assess the exposure, especially in schools, where children spend a large portion of their time. We aimed to investigate allergen and endotoxin levels in the air of schools and to observe seasonal variations of these factors. We evaluated airborne concentrations of house dust mites allergens (Der p 1, Der f 1), cat allergen (Fel d 1), and endotoxin in PM10 in 14 classrooms during the school days in the region of Munich, each over 20 consecutive days and in 1 classroom over the course of a year (at 83 days); we also tested outdoor air close to the schools. Endotoxin levels were quantified using two different analytical methods. In addition, indoor air climate parameters were measured. The median daily indoor CO2 and PM10 concentrations in the classrooms ranged from 423 to 3,135 ppm (median: 1,211 ppm) and 9 to 390 µg/m(3) (median: 127 µg/m(3)), respectively. Fel d 1 in the PM10 samples was the most frequently detected allergen, with levels from 0.02 to 1.15 ng/m(3) in a total of 301 samples (median: 0.19 ng/m(3), 95th percentile: 0.57 ng/m(3)). Der p 1 and Der f 1 were detected in only 51% and 19% of the samples, with 95th percentiles at 0.5 and 0.3 ng/m(3). Endotoxin levels in the PM10 and inhalable dust samples ranged from 0.5 to 84.1 EU/m(3) (median: 15.3 EU/m(3); 95th percentile: 58.2 EU/m(3)) and from 0.03 to 115 EU/m(3) (median: 8.4 EU/m(3); 95th percentile: 27.9 EU/m(3)). Fel d 1 and endotoxin were found in higher levels in the winter months. The results of the two different indoor sampling techniques for endotoxin were statistically significantly correlated. The results of airborne allergens indicate a generally low exposure level in classrooms. With regard to endotoxin, our study showed higher levels in schools compared with residences.

Diagnosis of acute Q fever with emphasis on enzyme-linked immunosorbent assay and nested polymerase chain reaction regarding the time of serum collection.

A commercially available enzyme-linked immunosorbent assay (ELISA) (Virion/Serion [Wuerzburg, Germany]), an indirect fluorescent antibody test (IFAT) (BIOS/Focus [Cypress, CA]), and a nested polymerase chain reaction (PCR) were explored for diagnosis of acute Q fever in reference to time of serum collection. Serum samples of 22 patients with acute Q fever collected around the fifth day of illness were included. A sensitivity of 30% by ELISA and 80% by IFAT (P = 0.1) was found for the first 5 days of illness and 92% by ELISA and 83% by IFAT during the sixth and eleventh day. PCR revealed a positive result in 8 cases (36%) with 6 cases deriving from the first 5 days of illness. We conclude that ELISA aids especially in the diagnosis of Q fever after 5 days of illness. The benefit of PCR as an additional tool to ELISA was especially evident in the early days of serum sampling.

Longitudinal study on cat allergen exposure and the development of allergy in young children.

BACKGROUND: The influence of cat allergen exposure in early childhood on the development of sensitization and allergic diseases is complex. Little is known about the natural course of the sensitization development within individuals. OBJECTIVE: We investigated the association between cat allergen exposure in infancy and cat ownership and cat contact during childhood and the development of cat sensitization and allergic diseases up to age 6 years using a longitudinal analysis approach. METHODS: Overall, 2166 children from an ongoing birth cohort study were included in the analysis. House dust samples were collected 3 months after birth. Cat allergen levels were extracted. Blood samples were collected when the children were 2 and 6 years old. Information on the allergic symptoms of children and doctor-diagnosed allergic disease were collected at each follow-up using questionnaires. RESULTS: Cat allergen exposure in infancy was positively associated with sensitization at age 2 years but not at age 6 years. No associations existed between cat allergen exposure in infancy and allergic symptoms and diseases up to age 6 years. Cumulative allergen exposure from cat ownership and regular cat contact increased the risk of cat sensitization up to age 6 years. CONCLUSION: Cat allergen exposure in infancy increases the risk of sensitization development in early childhood but not in school-age children. Cumulative allergen exposure from cat ownership and regular cat contact during childhood contribute to sensitization development up to school age. CLINICAL IMPLICATIONS: Cat allergen avoidance at home alone might be not effective to prevent the development of allergic sensitization in young children.

Measurements of endotoxin on ambient loaded PM filters after long-term storage.

At present there exist unsolved questions, whether endotoxin measurements on PM filters show valid measurements after long-term storage of loaded PM filters. As part of the TRAPCA study we collected particles with a 50% aerodynamic cut-off diameter of 2.5 microm (PM(2.5)) at 40 outdoor sites and particles less than 10 microm in size (PM(10)) at a subset of these sites (N=12) in Munich. The PM filters were cut in halves and endotoxin was measured in the extract of one filter half 2-3 years after PM collection. Here we present the results of repeated endotoxin measurements, where the association between previously measured endotoxin concentrations, measurements from stored eluates, and measurements in extracts of the second filter halves were determined. No statistically significant changes were seen between our old measurements and those from the stored eluates. Additionally, no change was observed between previously measured endotoxin concentrations and those from the stored set of filter halves. We found an average increase of 5% between our old measurements and those from the stored eluates and of 19% between the old measurements and those from the stored set of filter halves. The correlations between the previously measured endotoxin concentrations and the repeated measurements from the stored eluates were high (r=0.789) for EU/m(3) PM(2.5). Since endotoxin was evaluated from the same set of filter halves, it is obvious that storage over three years did not substantially effect the correlation of the endotoxin content. Regarding the outliers from previous measurements unsymmetric endotoxin spots on one out of 48 filter halves could be determined. Apart from this we conclude that the endotoxin is homogenously distributed on the filter halves and that endotoxin levels, which were repeatedly measured from filters stored over three years, could be determined validly.

Daily time spent indoors in German homes--baseline data for the assessment of indoor exposure of German occupants.

Comprehensive time-activity studies, for use as a basis for estimates of personal exposure, are not readily available in Germany. This analysis of time spent indoors at home is based on data from "Dampness and mould in homes" (2000/ 2001)--a study of about 12,000 persons living in 5530 randomly selected apartments and houses in Germany. The results show the mean times per day people in Germany spend in their homes, classified by gender, age group, building location, city size, region, building type, owner-occupier status, number of people at home, smoking and ventilation habits, moisture emission and ill health factors such as asthma, allergy and number of acute respiratory infections per year. The overall mean time spent at home, 15.7 h per, is in accordance with results from US-American (15.6 h/day) and Canadian (15.8 h/day) human activity surveys carried out in the nineties, as well as being consistent with the German Environmental Survey (1990/92) and a small German study in 1987.

Relationship between indoor and outdoor levels of fine particle mass, particle number concentrations and black smoke under different ventilation conditions.

Fine particle mass (PM(2.5)), black smoke (BS) and particle number concentration (NC) were measured simultaneously indoors and outdoors at an urban location in Erfurt, Germany. Measurements were conducted during 2-month periods in summer and winter. Different ventilation modes were applied during each measurement period: windows closed; windows opened widely for 15 min twice per day; windows and door across the room opened widely for 5 min twice per day and windows tilted open all day long. The lowest indoor/outdoor (I/O) ratios for all pollutants were found for closed windows, whereas the ratios for ventilated environments were higher. For closed windows, the I/O ratios for PM(2.5) are larger than the corresponding values for BS and NC (0.63 vs. 0.44 or 0.33, respectively) probably due to lower penetration factors for particles sizes <500 nm and higher deposition rates for ultrafine particles (<100 nm). The largest differences for the I/O ratios between closed and tilted windows were found for NC (0.33 vs. 0.78). The indoor and outdoor levels of PM(2.5) and BS were strongly correlated for all ventilation modes. The linear regression models showed that more than 75% of the daily indoor variation could be explained by the daily outdoor variation for those pollutants. However, the correlation between indoor and outdoor NC for ventilation twice a day was weak. It indicates that rapid changes of the air exchange rates during the day may affect the correlation and regression analysis of NC indoor and outdoor concentrations. This effect was not observed for PM(2.5) or BS. This study shows the importance of the indoor air aerosol measurements for health effects studies and the need for more research on I/O transport mechanisms for NC.

TLR4 gene variants modify endotoxin effects on asthma.

BACKGROUND: Environmental exposure to endotoxin might have a crucial role in immune maturation and development of asthma. OBJECTIVE: The aim of this study was to investigate whether the effect of endotoxin concentration in settled house dust on asthma is modified by the presence of variation in the TLR4 gene. METHODS: We performed a cross-sectional study within the German follow-up of the European Community Respiratory Health Survey. Multivariate logistic regression analysis and nonparametric effect estimates (S-Plus) were applied to examine the association between endotoxin exposure and diagnosed asthma, related clinical symptoms, and bronchial hyperreactivity (BHR) stratified for noncarriers and carriers of G299/I399 polymorphism in the TLR4 gene. RESULTS: In the noncarrier group (n = 279), the prevalence of asthma was significantly increased with elevated endotoxin levels in house dust with adjusted odds ratio 6.24 (95% CI, 1.33-29.17) in the second tertile, and 4.54 (95% CI, 0.94-21.96) in the third tertile compared with the lowest endotoxin tertile. The carriers of the polymorphisms (n = 55) showed a nonsignificant trend to have a lower risk of asthma (crude odds ratio, 0.67; 95% CI, 0.06-8.06 for the second tertile and 1.33; 95% CI, 0.17-10.58 for the third tertile). We found a similar association for wheeze and endotoxin exposure that was also attenuated in subjects with G299/I399 polymorphisms. CONCLUSIONS: The G299/I399 polymorphisms were associated with a modified response to endotoxin, but the functional relationship still needs clarification.

Reproducibility of allergen, endotoxin and fungi measurements in the indoor environment.

Measurements of biocontaminants in settled house dust once a year are commonly used to assess long-term exposure. To examine stability over time and seasonal variation, we measured concentrations of mite and cat allergens, endotoxin and mold spores in living room floor dust in 745 German homes collected twice a year in two different seasons. The study population consisted of adults and children living in five different areas in Germany. All dust samples were collected in a standardized manner from the living room floor and taken during the years 1995 to 1998. The median interval between the two dust samplings was approximately 7 months. Mite and cat allergens were measured in settled house dust by monoclonal antibodies, endotoxin by the limulus amebocyte lysate method, and total spore counts by cultural methods. Crude Pearson's correlation coefficients between log-transformed concentrations in the first and second dust samples ranged between 0.65 and 0.75 for allergens, 0.59 for endotoxin and only 0.06 for total spore counts. The strongest and most consistent seasonal effects were observed for fungi with highest levels in July-September. Cat allergen concentrations were found consistently to be increased in January-March. Mite allergens did not show a strong and consistent seasonal pattern. We conclude that repeated measurements of mite and cat allergens and endotoxin in settled house dust improve the estimate for annual mean concentrations. However, even a single observation of these biocontaminants may be a good proxy for a 1-year exposure since repeated measures were highly correlated. However, repeated measurements of fungi levels were only weakly correlated and thus repeated observations for assessment of annual means of total spore counts are needed.

Seasonal variability of endotoxin in ambient fine particulate matter.

Endotoxin is a toxic, pro-inflammatory compound that has been detected in indoor air and dust in homes and occupational settings, and also in outdoor air. Data on the outdoor sampling of endotoxin are limited. Currently, little is known about the seasonal variation and influence of temperature on outdoor endotoxin levels. In the present study, we report endotoxin levels in fine fraction particulate matter with a 50% aerodynamic cutoff diameter of 2.5 microm (PM2.5) and describe the seasonal variation of endotoxin in Munich, Germany. In 1999-2000, PM2.5 was collected at forty outdoor monitoring sites across Munich. Approximately four samples were collected at each site for a total of 158 samples. Endotoxin concentrations in the PM2.5 samples were determined using the kinetic chromogenic Limulus Amebocyte Lysate (LAL) assay. The geometric mean endotoxin concentration was 1.07 EU mg PM2.5(-1) (95% C.I.: 0.915-1.251) or 0.015 EU m(-3) of sampled air (95% C.I.: 0.013-0.018). Munich endotoxin levels were significantly related to ambient temperature (p < 0.0001) and percent relative humidity (p < 0.0001). Sampling periods with higher average temperatures yielded higher levels of endotoxin in PM2.5 (r = 0.641), whereas decreases in percent relative humidity were associated with increased endotoxin levels in PM2.5 (r = -0.388). Endotoxin levels were significantly higher during the warmer seasons of spring [means ratio (MR): 2.5-2.7] and summer (MR: 2.1-3.0) than during winter. Although temperature and relative humidity do not explain all of the variability in endotoxin levels, their effects were significant in our data set. Temperature effects and seasonal variation of endotoxin should be considered in future studies of outdoor endotoxin.

Different effects of endotoxin versus mite and cat allergen exposure on T-cell differentiation in infants.

BACKGROUND: Early exposure to bacterial endotoxin has been proposed to protect against allergy development in children. Whether endotoxin is able to direct T-cell differentiation into a predominance of type 1 immunity is still unresolved. OBJECTIVE: We sought to compare the effects of endotoxin and mite and cat allergens on T-cell differentiation in infants. METHODS: In a random population sample of 135 2-year-old children of an ongoing birth-cohort study, peripheral blood CD4+ and CD8+ T-cell subsets were defined by the expression of the chemokine receptors CCR5 and CCR3 as surrogate markers for type 1 and type 2 T cells, respectively. Endotoxin and mite and cat allergens were measured in house dust collected from the mother's mattress at the child's age of 3 months to assess early exposure. RESULTS: In the CD4+ T-cell subset, endotoxin levels were positively associated with high proportions of type 1 CCR5+ cells (odds ratio for fourth exposure quartile [OR(Q4)], 7.68; 95% CI, 1.35-43.75), whereas cat allergen levels were associated with increased proportions of type 2 CCR3+ cells (OR(Q4), 4.07; 95% CI, 1.05-15.85). In contrast to endotoxin, allergen levels were associated with CD8+ T cells, showing an inverse relationship between mite allergen concentrations and high proportions of CCR5+ or CCR3+ cells (CCR5+ cells: OR(Q4), 0.14; 95% CI, 0.03-0.74; CCR3+ cells: OR(Q4), 0.16; 95% CI, 0.03-0.89) and a positive association of cat allergen levels with increased proportions of CCR5+ cells (OR(Q4), 9.24, 95% CI, 1.61-53.10), as well as CCR3+ cells (OR(Q3), 6.64; 95% CI, 1.21-36.51). CONCLUSION: Our results indicate that endotoxin has the potential to promote the development of type 1 CD4+ T cells, whereas mite and cat allergens primarily modify the proportion of CD8+ cells of both types.

House dust endotoxin and allergic sensitization in children.

A higher exposure to endotoxin was hypothesized to contribute to lower prevalence of allergic sensitization and hay fever in children growing up on a farm. We studied the association between house dust endotoxin and allergic sensitization. We randomly selected 740 children, aged between 5 and 10 years, from a group of children who participated in two cross-sectional surveys performed in Saxony-Anhalt, Germany, from 1992 to 1993 and from 1995 to 1996, such that 50% of the children were atopic or had a diagnosis of asthma. From 1996 to 1998, we collected living-room floor dust in the homes of 454 of these children (61%). The content of endotoxin in house dust was quantified using a chromogenic kinetic limulus amoebocyte lysate test and was related with health outcomes measured in the preceding cross-sectional surveys. Multiple logistic regression analyses adjusted for place of residence, sex, age, parental education, parental atopy, and pet ownership showed a negative association between exposure to endotoxin and sensitization to one or more allergens (aOR [95% CI] 0.95 [0.83; 1.10]) and two or more allergens (aOR [95% CI] 0.80 [0.67; 0.97]) using 0.35 kU/L as the cutoff value for sensitization. The protective effect was strengthened with increasing degree of sensitization. In conclusion, exposure to higher levels of house dust endotoxin is associated with lower prevalence of allergic sensitization in children.

Indoor exposure to molds and allergic sensitization.

Evidence that indoor dampness and mold growth are associated with respiratory health has been accumulating, but few studies have been able to examine health risks in relation to measured levels of indoor mold exposure. In particular, little is known about the contribution of indoor molds to the development of allergic sensitization. As a part of an ongoing study examining the effects of ambient air pollutants on respiratory health and atopic diseases in German school children, we examined the relation between viable mold levels indoors and allergic sensitization in 272 children. We examined whether allergic sensitization in children is associated with higher fungal spore count in settled house dust sampled from living room floors. Adjusting for age, sex, parental education, region of residency, and parental history of atopy, we found that mold spore counts for Cladosporium and Aspergillus were associated with an increased risk of allergic sensitization. Sensitized children exposed to high levels of mold spores (> 90th percentile) were more likely to suffer from symptoms of rhinoconjunctivitis. We conclude that elevated indoor concentrations of molds in wintertime might play a role in increasing the risk of developing atopic symptoms and allergic sensitization not only to molds but also to other common, inhaled allergens. These effects were strongest in the group of children who had lived in the same home since birth.