AWMF mold guideline "Medical clinical diagnostics for indoor mold exposure" - Update 2023 AWMF Register No. 161/001.

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Inter-Day Variability of Metabolites of DEHP and DnBP in Human Urine-Comparability of the Results of Longitudinal Studies with a Cross-Sectional Study.

In the current paper, we compare the inter-day variability of the metabolite concentration of di(2-ethylhexyl) phthalate (DEHP) and di-n-butyl phthalate (DnBP) in 247 morning urine samples obtained from 19 probands of different age and sex with the metabolite concentration in morning urine obtained from 215 probands of the "Tübingen Survey" cross-sectional study. In the first longitudinal study the morning urine of seven volunteers was collected four times a year for seven consecutive days (course of the year study). In a second study the morning urine of 12 students of a boarding school was collected on five consecutive days (course of a week study). For participants of the two different longitudinal studies we obtained mean concentrations in first void morning urine for mono(2-ethyl-5-hydroxyhexyl) phthalate (5OH-MEHP) in the range from 21.3 to 110 µg/L, 10.5 to 35.6 µg/L for mono(2-ethyl-5-oxohexyl) phthalate (5oxo-MEHP), and 45.5 to 143 µg/L for mono(2-ethyl-5-carboxypentyl) phthalate (5cx-MEPP). The corresponding relative standard deviations (rel. Std.D in %) for these DEHP-metabolites vary between 45.2% and 262%. The 50th percentiles vary for 5OH-MEHP between 17.5 and 65.6 µg/L, for 5oxo-MEHP between 9.0 and 20.3 µg/L and for 5cx-MEPP between 42.5 and 82.0 µg/L. For participants of the "Tübingen Survey" cross-sectional study the means vary for 5OH-MEHP between 58.2 and 85.0 µg/L, between 33.6 and 38.7 µg/L for 5oxo-MEHP and between 110 and 158 µg/L for 5cx-MEPP with rel. standard deviations in a range between 86.5 to 175%. The corresponding 50th percentiles vary for 5OH-MEHP between 26.5 and 42.3 µg/L, for 5oxo-MEHP between 18.0 and 26.3 µg/L, and for 5cx-MEPP between 57.2 and 77.6 µg/L. In order to compare the data from the longitudinal studies with the data from the cross-sectional study, the frequency distribution of the results of both types of studies was compared first. In a second step, the results of a t-test (p-values) was used to check whether the results of the long-term studies differ statistically significantly from the results of the cross-sectional study (p < 0.05). The present data show that the frequency distributions of DEHP-metabolites are comparable. For most of the participants respectively subject groups t-test results prove that no statistical significant difference between results obtained from longitudinal studies compared to the results of the cross-sectional study are apparent. The available data on the exposure of individual subjects mirror the data obtained from cross-sectional studies of the general population and give hints to the risk of individual increased DEHP exposure. Results also highlight the importance of living conditions on the risk of increased DEHP exposure.

Abridged version of the AWMF guideline for the medical clinical diagnostics of indoor mould exposure: S2K Guideline of the German Society of Hygiene, Environmental Medicine and Preventive Medicine (GHUP) in collaboration with the German Association of Allergists (AeDA), the German Society of Dermatology (DDG), the German Society for Allergology and Clinical Immunology (DGAKI), the German Society for Occupational and Environmental Medicine (DGAUM), the German Society for Hospital Hygiene (DGKH), the German Society for Pneumology and Respiratory Medicine (DGP), the German Mycological Society (DMykG), the Society for Pediatric Allergology and Environmental Medicine (GPA), the German Federal Association of Pediatric Pneumology (BAPP), and the Austrian Society for Medical Mycology (ÖGMM).

This article is an abridged version of the AWMF mould guideline "Medical clinical diagnostics of indoor mould exposure" presented in April 2016 by the German Society of Hygiene, Environmental Medicine and Preventive Medicine (Gesellschaft für Hygiene, Umweltmedizin und Präventivmedizin, GHUP), in collaboration with the above-mentioned scientific medical societies, German and Austrian societies, medical associations and experts. Indoor mould growth is a potential health risk, even if a quantitative and/or causal relationship between the occurrence of individual mould species and health problems has yet to be established. Apart from allergic bronchopulmonary aspergillosis (ABPA) and mould-caused mycoses, only sufficient evidence for an association between moisture/mould damage and the following health effects has been established: allergic respiratory disease, asthma (manifestation, progression and exacerbation), allergic rhinitis, hypersensitivity pneumonitis (extrinsic allergic alveolitis), and increased likelihood of respiratory infections/bronchitis. In this context the sensitizing potential of moulds is obviously low compared to other environmental allergens. Recent studies show a comparatively low sensitizing prevalence of 3-10% in the general population across Europe. Limited or suspected evidence for an association exist with respect to mucous membrane irritation and atopic eczema (manifestation, progression and exacerbation). Inadequate or insufficient evidence for an association exist for chronic obstructive pulmonary disease, acute idiopathic pulmonary hemorrhage in children, rheumatism/arthritis, sarcoidosis and cancer. The risk of infection posed by moulds regularly occurring indoors is low for healthy persons; most species are in risk group 1 and a few in risk group 2 (Aspergillus fumigatus, A. flavus) of the German Biological Agents Act (Biostoffverordnung). Only moulds that are potentially able to form toxins can be triggers of toxic reactions. Whether or not toxin formation occurs in individual cases is determined by environmental and growth conditions, above all the substrate. In the case of indoor moisture/mould damage, everyone can be affected by odour effects and/or mood disorders. However, this is not a health hazard. Predisposing factors for odour effects can include genetic and hormonal influences, imprinting, context and adaptation effects. Predisposing factors for mood disorders may include environmental concerns, anxiety, condition, and attribution, as well as various diseases. Risk groups to be protected particularly with regard to an infection risk are persons on immunosuppression according to the classification of the German Commission for Hospital Hygiene and Infection Prevention (Kommission für Krankenhaushygiene und Infektionsprävention, KRINKO) at the Robert Koch- Institute (RKI) and persons with cystic fibrosis (mucoviscidosis); with regard to an allergic risk, persons with cystic fibrosis (mucoviscidosis) and patients with bronchial asthma should be protected. The rational diagnostics include the medical history, physical examination, and conventional allergy diagnostics including provocation tests if necessary; sometimes cellular test systems are indicated. In the case of mould infections the reader is referred to the AWMF guideline "Diagnosis and Therapy of Invasive Aspergillus Infections". With regard to mycotoxins, there are currently no useful and validated test procedures for clinical diagnostics. From a preventive medicine standpoint it is important that indoor mould infestation in relevant dimension cannot be tolerated for precautionary reasons. With regard to evaluating the extent of damage and selecting a remedial procedure, the reader is referred to the revised version of the mould guideline issued by the German Federal Environment Agency (Umweltbundesamt, UBA).

Medical diagnostics for indoor mold exposure.

In April 2016, the German Society of Hygiene, Environmental Medicine and Preventative Medicine (Gesellschaft für Hygiene, Umweltmedizin und Präventivmedizin (GHUP)) together with other scientific medical societies, German and Austrian medical societies, physician unions and experts has provided an AWMF (Association of the Scientific Medical Societies) guideline 'Medical diagnostics for indoor mold exposure'. This guideline shall help physicians to advise and treat patients exposed indoors to mold. Indoor mold growth is a potential health risk, even without a quantitative and/or causal association between the occurrence of individual mold species and health effects. Apart from the allergic bronchopulmonary aspergillosis (ABPA) and the mycoses caused by mold, there is only sufficient evidence for the following associations between moisture/mold damages and different health effects: Allergic respiratory diseases, asthma (manifestation, progression, exacerbation), allergic rhinitis, exogenous allergic alveolitis and respiratory tract infections/bronchitis. In comparison to other environmental allergens, the sensitizing potential of molds is estimated to be low. Recent studies show a prevalence of sensitization of 3-10% in the total population of Europe. The evidence for associations to mucous membrane irritation and atopic eczema (manifestation, progression, exacerbation) is classified as limited or suspected. Inadequate or insufficient evidence for an association is given for COPD, acute idiopathic pulmonary hemorrhage in children, rheumatism/arthritis, sarcoidosis, and cancer. The risk of infections from indoor molds is low for healthy individuals. Only molds that are capable to form toxins can cause intoxications. The environmental and growth conditions and especially the substrate determine whether toxin formation occurs, but indoor air concentrations are always very low. In the case of indoor moisture/mold damages, everyone can be affected by odor effects and/or impairment of well-being. Predisposing factors for odor effects can be given by genetic and hormonal influences, imprinting, context and adaptation effects. Predisposing factors for impairment of well-being are environmental concerns, anxieties, conditioning and attributions as well as a variety of diseases. Risk groups that must be protected are patients with immunosuppression and with mucoviscidosis (cystic fibrosis) with regard to infections and individuals with mucoviscidosis and asthma with regard to allergies. If an association between mold exposure and health effects is suspected, the medical diagnosis includes medical history, physical examination, conventional allergy diagnosis, and if indicated, provocation tests. For the treatment of mold infections, it is referred to the AWMF guidelines for diagnosis and treatment of invasive Aspergillus infections. Regarding mycotoxins, there are currently no validated test methods that could be used in clinical diagnostics. From the perspective of preventive medicine, it is important that mold damages cannot be tolerated in indoor environments.

Biomonitoring of the di(2-ethylhexyl) phthalate metabolites mono(2-ethyl-5-hydroxyhexyl) phthalate and mono(2-ethyl-5-oxohexyl) phthalate in children and adults during the course of time and seasons.

Di(2-ethylhexyl) phthalate (DEHP) is a commonly used plasticizer with ubiquitous spread. Its metabolites are suspected to impair endocrine functions and fertility in man. This study is aimed to assess the DEHP exposure in children and adults, to evaluate the intraindividual variability, the influence of seasons and to identify potential routes of intake. Urine samples were collected from 6 people (age 4-58) over 7 consecutive days 4-times during a year to test for seasonal factors. 5-OH-MEHP and 5-oxo-MEHP were quantified by GC-MS. Urine concentrations of both metabolites were highly correlated with each other. Both female subjects showed remarkably low and stable 5-OH-MEHP concentrations throughout the year (median

Concentrations of particulate matter in schools in southwest Germany.

During the winter season 2005/2006, measurements of small particulate matter were taken in 22 schools in southwest Germany. PM2.5 was measured gravimetrically. Laser particle counter (LPC) and condensation particle counter (CPC) were used to determine different particle fractions. The investigation included measurements inside (in classrooms) and outside of school buildings. During the whole investigation period continuous reference measurements were taken near the State Health Office in the city of Stuttgart. Information on building-specific data and traffic near the schools was collected via questionnaire. Although distances between the different schools and the location of the State Health Office building in Stuttgart in some cases exceeded 100 km, the concentration levels of particles > 0.3 microm measured by LPC near the different schools were similar to those measured in Stuttgart. The differences between the measurements in Stuttgart and at the other locations were smaller than the variation in time. In the winter season, the impaction of particulate matter was strongly influenced by specific weather conditions. Time resolution of measurements in classrooms showed variation in particle concentration depending on the type of building and indoor activities like cleaning or moving during breaks. Concentrations of very small particles in buildings and in ambient air measured by CPC were influenced by traffic emissions. The observed data give reason to assume that the influence of high traffic emissions to indoor particle concentration may have been overestimated. Furthermore, there is an urgent need for standardization of measurement protocols, sampling, and determination of indoor particulate matter. The classical gravimetric methods are less appropriate since they do not allow for a time resolution of measurements.

Baden-Wuerttemberg Environmental Health Survey (BW-EHS) from 1996 to 2003: toxic metals in blood and urine of children.

The environmental health surveillance system in the Federal State of Baden-Wuerttemberg (South Germany), among others, was implemented to monitor pollutant exposures and their temporal and regional trends in children at the age of about 10 years. The investigations were performed in two larger cities, one small city and one rural area. Between 1996 and 2003, in total 5470 children were investigated in consideration of environmental health parameters in four cross-sectional studies. The data presented here cover the results of the determination of the internal load with toxic metals. The median values observed in the investigation in 2002/03 were: 4.6 microg/l urine for arsenic, less than 0.2 microg/l urine for mercury, 20.7 microg/l blood for lead, and 0.25 microg/l blood for cadmium. From 1996 to 2003, mercury concentrations showed a substantial decrease (-0.027 microg/l/year) and lead levels also decreased (-0.25 microg/l/year), whereas arsenic and cadmium levels did not change significantly over time. There was no consistent difference in the mean internal load of the metals between the four investigation areas. Important factors influencing the measured concentrations were consumption of fish in the last 48 h, which had an impact on arsenic (factor 2), and amalgam fillings, which accounted for an increase in mercury (factor 4.6). In the 2002/03 study period, levels above the limit of health concern for children (German HBM values) were found in about 0.5% of the lead measurements (maximum value 180 microg/l blood) and in about 0.2% of the mercury measurements (maximum value 8.2 microg/l urine). In conclusion, this environmental health survey generates objective data on secular trends and regional differences and provides insight into probable sources of toxic metal exposure in children.

Sentinel health department project in Baden-Wuerttemberg (Germany)--a useful tool for monitoring children's health and environment.

In the Federal State of Baden-Wuerttemberg, Germany, an environmental health surveillance system has been established focusing on children aged 10 years. Four study regions (two larger cities, one small city, and one rural area) were designated in order to get information about the body burden of persistent chemicals (toxic metals and chlorinated compounds) in children and about lung function, frequency of respiratory diseases, and allergies. From 1992/1993 to 2002/2003, seven cross-sectional investigations were carried out, and more than 10,000 children took part in the study. DDE, HCB, PCB-138, PCB-153 and PCB-180 were measured in individual blood samples of about 400 children per year, whereas PCDD/PCDF and coplanar PCBs were determined in pooled blood samples. From 1993 to 2003, blood concentrations of these compounds decreased 2 to 4-fold. Concerning regional differences, slightly lower concentrations of DDE, PCBs and PCDD/PCDF could be seen in children from the municipal population of Mannheim compared to other regions. Breast feeding was associated with considerably higher concentrations of PCBs and most other chlorinated compounds. Static and dynamic lung function parameters showed no differences between the investigated areas. For prevalences of respiratory diseases and allergies, no time trend was observed except for pertussis, which showed a decrease in 2002/2003 probably due to an increase of vaccination rates. In addition, the prevalence of atopic sensitization against aero allergenes remained unchanged at about 35% during the observation period. In conclusion, this environmental health survey delivers objective data about spatial and temporal trends and provides information about possible sources of children's exposure to toxic compounds in the environment. Adaptations of the survey to new problems are discussed.

A new method to measure air-borne pyrogens based on human whole blood cytokine response.

Air-borne microorganisms, as well as their fragments and components, are increasingly recognized to be associated with pulmonary diseases, e.g. organic dust toxic syndrome, humidifier lung, building-related illness, "Monday sickness." We have previously described and validated a new method for the detection of pyrogenic (fever-inducing) microbial contaminations in injectable drugs, based on the inflammatory reaction of human blood to pyrogens. We have now adapted this test to evaluate the total inflammatory capacity of air samples. Air was drawn onto PTFE membrane filters, which were incubated with human whole blood from healthy volunteers inside the collection device. Cytokine release was measured by ELISA. The test detects endotoxins and non-endotoxins, such as fungal spores, Gram-positive bacteria and their lipoteichoic acid moiety and pyrogenic dust particles with high sensitivity, thus reflecting the total inflammatory capacity of a sample. When air from different surroundings such as working environments and animal housing was assayed, the method yielded reproducible data which correlated with other parameters of microbial burden tested. We further developed a standard material for quantification and showed that this assay can be performed with cryopreserved as well as fresh blood. The method offers a test to measure the integral inflammatory capacity of air-borne microbial contaminations relevant to humans. It could thus be employed to assess air quality in different living and work environments.

Biomonitoring of persistent organochlorine pesticides, PCDD/PCDFs and dioxin-like PCBs in blood of children from South West Germany (Baden-Wuerttemberg) from 1993 to 2003.

In the context of a monitoring program, persistent organic pollutants (POPs) were quantified in the blood of 10 year old children at four different demographic regions in Baden-Wuerttemberg, a highly industrialised federal state in South West Germany. DDE, HCB, PCB 138, PCB 153 and PCB 180 were measured in 1996/1997, 1998/1999, 2000/2001 and 2002/2003 in individual samples of about 400 children per year. PCDD/PCDFs and some relevant coplanar PCBs were determined in pooled samples from children in seven cycles from 1993 to 2003. Blood concentrations of the investigated compounds decreased in that time period by a factor of 2-4 with the exception of most PCDFs. The concentrations of POPs in the blood of the children were distinctly lower than the concentrations reported for adults. Breast feeding was associated with about 30% higher median concentrations of DDE, HCB, PCBs and a 30% increase for mean PCDD/PCDF concentrations. Concerning demographic differences, significant lower concentrations of HCB, PCBs and PCDD/PCDFs could be seen in children from Mannheim compared to the region of Aulendorf. About 10-20% higher concentrations were found in boys compared to girls for HCB, indicator PCBs and PCDD/PCDFs. The pattern of non-ortho and mono-ortho PCBs in the blood of children was similar to the pattern reported for mother's milk, and PCB 126 and PCB 156 contributed about 70% to the toxicity of dioxin-like PCBs and about one-third to total TEQ including PCDD/PCDFs.

Indoor fungi levels in homes of children with and without allergy history.

A study was performed at the four sentinel health departments of Baden-Württemberg between November 1999 and March 2000 to investigate the indoor levels of fungi at the homes of school children (mean age 10 y) and to describe possible associations with allergy statuses. Three hundred and ninety-seven households of school children with (n = 199) and without (n = 198) allergic history were included in the study. The median of colony forming units (CFU/m3) of fungi, measured in the children's bedrooms' in indoor air, was 105 (range 5 to 15,000), in outdoor air 110 (range 10 to 1500). The median of viable mould spores (CFU/g dust) in floor dust was 28,500 (range 1500 to 1,235,000), in mattresses 16,250 (range 0 to 2,500,000). Neither climatological conditions, nor differences between urban and rural regions showed a systematic influence on fungi counts. There was no difference in concentrations and distribution of fungi species levels between children with and without allergic history. The sensitization rate against molds (IgE) was higher for children with allergic condition (9.2%) than in control children (4.4%), but there was no association with the fungi counts in the rooms. In conclusion, the study defined the mould levels in children's rooms, but did not find an association with allergic history of the children or their sensitization rate.

The Aral Sea disaster--human biomonitoring of Hg, As, HCB, DDE, and PCBs in children living in Aralsk-and Akchi, Kazakhstan.

Mercury and arsenic have been measured in urine samples and HCB, DDE and PCBs in blood samples of children from Aralsk and Akchi, Kazakhstan. Due to the special situation of Aralsk in the desert left by the drying out Aral Sea, environmental pollution with heavy metals and organic contaminants is believed to be higher than elsewhere in Kazakhstan. Aralsk was formerly located at the shore of the Aral Sea and is now far away from it. Akchi is a similar village and was included in this study as a Kazakh reference site. Urine concentrations of arsenic were higher in Akchi (9.4 microg/l) than in Aralsk (5.5 microg/l) and compared to children from Mannheim, Germany (4.25 microg/l; Median values). Regarding Hg, differences between children of Aralsk and Akchi were not significant and concentrations were lower than reference values from Germany. DDE contamination of children from Aralsk (2.48 microg/l) was significantly higher compared to Akchi (1.35 microg/l). DDE concentrations in blood samples from children in both cities were also significantly higher than the German reference value (0.7 microg/l). HCB and PCBs levels differed significantly between both Kazakh groups. However, concentrations of these compounds were lower than German reference values and there was no significant difference to samples from Mannheim children.

Pathways of trihalomethane uptake in swimming pools.

Chlorination of pool water leads to the formation of numerous disinfection by-products (DBPs), chloroform usually being most abundant. Bathers and pool guardians take up various amounts of DBPs by different pathways. Identification of different uptake paths is important in order to develop a technical strategy for swimming pool water treatment and to develop focussed technical solutions to minimize THM uptake. Basically, trihalomethanes (THMs) can be taken up by inhalation, by dermal absorption, or orally (swallowing of water). In our experimental study involving up to 17 participants we quantified the body burden resulting from exposure to three different concentrations of chloroform in water and air of an indoor swimming pool, during a 60 min exercising period. Chloroform concentration of the water was 20.7, 7.1, and 24.8 microg/l and was not influenced artificially. Corresponding air CHCl3 concentrations were measured at two different levels (20 cm and 150 cm) and ranged from to 85 to 235 microg/m3. To dissociate the dermal exposure route from that of inhalation, THM concentrations were measured in the blood of subjects practicing in an indoor pool with and without scuba tanks, as well as in the blood of subjects walking around the pool without swimming. Chloroform concentrations were measured in blood samples before and after each exercise period. Blood chloroform concentration of participants with scuba tanks was 0.32 +/- 0.26 microg/l, without scuba tanks 0.99 +/- 0.47 micro/l, and for persons walking around the pool 0.31 +/- 0.25 microg/l. Our results indicate that THMs are mainly taken up over the respiratory pathway. Only about one third of the total burden is taken up over the skin. We examined the relationship between blood concentration and environmental chloroform concentrations by using linear regression models. Blood concentrations are correlated to air chloroform concentrations; correlation to water concentrations is less obvious.