Human biomonitoring follow-up study on PFOA contamination and investigation of possible influencing factors on PFOA exposure in a German population originally exposed to emissions from a fluoropolymer production plant.

BACKGROUND: In the past, perfluorooctanoic acid (PFOA) was produced and applied as an emulsifier in a fluoropolymer production plant in the Altötting district, southern Bavaria (Germany). This chemical was released directly into the environment, resulting in the contamination of the local drinking water. During a human biomonitoring (HBM) survey in 2018, increased median PFOA blood serum levels, compared to a normally exposed control group with no known source of PFOA exposure from Munich, Germany, were detected in the resident population (23.18 µg/l in the general population, 20.71 µg/l in the children's group). The follow-up study aimed to investigate whether purification of the drinking water as the main PFOA exposure source has been successful in reducing internal PFOA exposure and to estimate the association of internal PFOA exposure with possible influencing factors. METHODS: Only individuals who had already participated in the HBM study in 2018 were included. For the determination of the PFOA serum concentration, 5 ml of blood was drawn from each participating person. Blood samples were collected in the period from June to August 2022. Furthermore, information on sociodemographic characteristics, health status, dietary behaviour and other lifestyle factors were collected by means of a self-administered questionnaire. To examine the association of PFOA blood serum levels with possible influencing factors, such as age, gender and consumption of fish and game meat, a logistic regression model with a PFOA value > 10 µg/l as outcome was used. RESULTS: A total of 764 individuals participated in the follow-up study in 2022. Analyses were performed separately for the general population (n = 559), women of reproductive age (15-49 years old) (n = 120), and children under 12 years old (n = 30). Median PFOA blood levels have decreased by 56.9% in the general population, by 59.8% in the group of women of reproductive age and by 73.4% in the group of children under 12 years old. In the general population, a higher probability of a PFOA value > 10 µg/l was found for those aged 40-59 years (Odds ratio (OR) = 2.33 (95%CI: 1.23 to 4.43, p = 0.01) and those aged 60 years and older (OR = 5.32, 95%CI: 2.78 to 10.19, p < 0.001). CONCLUSIONS: In all study groups, the median PFOA serum levels decreased as expected after a half-life of four years, which confirms that contamination via drinking water has ceased. Furthermore, our study identified age as a significant predictor of internal PFOA exposure, while no influence was found for the consumption of fish and game meat. Further investigations are needed to quantify in a more detailed way the influence of dietary habits on PFOA exposure.

Polychlorinated dioxins and dibenzofurans (PCDD/F), polybrominated dioxins and dibenzofurans (PBDD/F), polychlorinated biphenyls (PCB), polybrominated diphenyl ethers (PBDE), and per- and polyfluoroalkyl substances (PFAS) in German breast milk samples (LUPE 8).

Most organic pollutants (POP) are persistent in the environment, accumulate in fatty tissues, and so a transfer through the food chain is probably, thereby causing various health effects. We quantified PCDD/F, PBDD/F, PCB, PBDE, perfluorinated substances, and ADONA in breast milk samples collected in two German federal states and breast milk and blood samples from subjects additionally exposed to PFOA. The median (95th percentile) concentrations were 2.43 (6.58) pgWHO2005TEQ/g l.w. for PCDD/F, 2.45 (4.82) pgWHO2005TEQ/g l.w. for dioxin-like PCB (dl-PCB), and 0.62 (2.69) pgWHO2005TEQ/g l.w. for PBDD/F. The relative contributions of the median values of PCDD/F, dl-PCB, and PBDD/F to the total-TEQ were approximately 41%, 42%, and 11%, respectively. Nondioxin-like PCB (ndl-PCB) concentrations were clearly dominated by the higher chlorinated PCB congeners, with medians of 23.2 ng/g l.w. for PCB 153, 13.9 ng/g l.w. for PCB 138, and 13.0 ng/g l.w. for PCB 180. The sum of the 3 congeners (PCB 138, 153, and 180) were multiplied with 1.64 (total PCB) and showed a median of 82.16 ng/g l.w. and a 95th percentile of 173.3 ng/g l.w. Only PFOA and PFOS could be quantified in 29% and 17% of in total 180 samples with 95th percentiles of 53 ng/l and 33 ng/l, respectively. Milk samples (n = 13) from subjects living on PFOA contaminated sites showed higher levels between 33 and 854 ng/l PFOA (mean: 199 ng/l), whilst PFOS could be quantified only in three samples. The sum of 17 PBDE congeners showed medians (95th percentile) of 1737 pg/g l.w. (22,806 pg/g l.w.), with the highest medians of 422 pg/g l.w. for BDE 209 and 378 pg/g l.w. for BDE 153. Overall, our study confirms the declining contamination level in breast milk during the last decade, but points out the need to further reduce the environmental contamination with persistent substances and subsequently the exposure in childhood.

Time trend of exposure to dechloranes: Plasma samples of German young adults from the environmental specimen bank collected from 1995 to 2017.

Dechloranes, like Dechlorane Plus® are commonly used flame retardants identified by the EU as substances of very high concern (SVHC) because of their persistence and bioaccumulation potential. To characterize the dechlorane exposure of Germans in the last two decades, 180 archived blood plasma samples of the German Environmental Specimen Bank (students aged 20-29 years) collected at six time points between 1995 and 2017 were analyzed for four dechloranes; namely Dechlorane Plus® (syn- and anti-DDC-CO), dechlorane 602 (DDC-DBF), and dechlorane 603 (DDC-Ant). These were quantified using a GC-MS/MS method. Overall, anti- and syn-DDC-CO were detected in 88% and 98% of the samples, whereas DDC-DBF and DDC-Ant were found in 40% and 37% of the samples, respectively. The median (95th percentile) values were 1.0 ng/g lipid weight (l.w.) (3.0 ng/g l.w.). for anti-DDC-CO, 0.6 ng/g l.w (1.9 ng/g l.w.). for syn-DDC-CO, 0.1 ng/g l.w (0.6 ng/g l.w.). for DDC-DBF, and 0.1 ng/g l.w (0.2 ng/g l.w.). for DDC-Ant. The 95th percentile concentrations of the sum of syn- and anti-DDC-CO decreased from 4.2 ng/g l.w. in 1995, to 2.9 ng/g l.w. in 1999, and subsequently increased to 3.7 ng/g l.w. in 2008, and up to 5.9 ng/g l.w. in 2017. A statistically significant decrease with time was observed for DDC-DBF and DDC-Ant, but not for DDC-CO. Our medians found in blood samples in 2017 are similar to those observed in Germany in 2013/14, but higher compared to values reported in other European countries. Overall, more toxicological and monitoring data is needed to better characterize the potential impact on health.

Siloxane in baking moulds, emission to indoor air and migration to food during baking with an electric oven.

Linear and cyclic volatile methylsiloxanes (l-VMS and c-VMS) are man-made chemicals with no natural source. They have been widely used in cosmetics, personal care products, coatings and many other products. As a consequence of their wide use, VMS can be found in different environmental media, as well as in humans. We bought 14 new silicone baking moulds and 3 metallic moulds from the market and used them in different baking experiments. Four of the silicone baking moulds were produced in Germany, two in Italy, four in China, and for the other moulds were no information available. The metal forms were all produced in Germany. VMS were measured in the indoor air throughout the baking process and at the edge and in the center of the finished cakes using a GC/MS system. Additionally, the particle number concentration (PNC) and particle size distribution were measured in the indoor air. The highest median concentrations of VMS were observed immediately following baking: 301 µg/m3 of D7, 212 µg/m3 of D6, and 130 µg/m3 of D8. The silicone moulds containing the highest concentrations of c-VMS corresponded with distinctly higher concentrations of the compounds in indoor air. Using a mould for more than one baking cycle reduced the indoor air concentrations substantially. Samples collected from the edge of the cake had higher concentrations relative to samples from the center, with a mean initial concentration of 6.6 mg/kg of D15, 3.9 mg/kg of D9, 3.7 mg/kg of D12, and 4.8 mg/kg of D18. D3 to D5 were measured only at very low concentrations. Before starting the experiment, an average PNC of 7300 particles/cm3 was observed in the room's air, while a PNC of 140,000 particles/cm3 was observed around the electric stove while it was baking, but this PNC slowly decreased after the oven was switched off. Baking with 4 of the moulds exceeded the German indoor precaution guide value for c-VMS, but the health hazard guide value was not reached during every experiment. Compared to other exposure routes, c-VMS contamination of cake from silicone moulds seems to be low, as demonstrated by the low concentrations of D4 and D6 measured. For less volatile c-VMS > D6 the results of the study indicate that food might play a more important role for daily intake. As a general rule, silicone moulds should be used only after precleaning and while strictly following the temperature suggestions of the producers.

Passive exposure to pollutants from conventional cigarettes and new electronic smoking devices (IQOS, e-cigarette) in passenger cars.

Smoking in car interiors is of particular concern because concentrations of potentially harmful substances can be expected to be high in such small spaces. To assess the potential exposure for occupants, especially children, we performed a comprehensive evaluation of the pollution in 7 passenger cars while tobacco cigarettes and new electronic smoking products (IQOS, e-cigarette) were being smoked. We collected data on the indoor climate and indoor air pollution with fine and ultrafine particles and volatile organic compounds while the cars were being driven. Smoking of an IQOS had almost no effect on the mean number concentration (NC) of fine particles (>300 nm) or on the PM2.5 concentration in the interior. In contrast, the NC of particles with a diameter of 25-300 nm markedly increased in all vehicles (1.6-12.3 × 104/cm3). When an e-cigarette was vaped in the interior, 5 of the 7 tested cars showed a strong increase in the PM2.5 concentration to 75-490 µg/m3. The highest PM2.5 levels (64-1988 µg/m3) were measured while tobacco cigarettes were being smoked. With the e-cigarette, the concentration of propylene glycol increased in 5 car interiors to 50-762 µg/m3, whereby the German indoor health precaution guide value for propylene glycol was exceeded in 3 vehicles and the health hazard guide value in one. In 4 vehicles, the nicotine concentration also increased to 4-10 µg/m3 while the e-cigarette was being used. The nicotine concentrations associated with the IQOS and e-cigarette were comparable, whereas the highest nicotine levels (8-140 µg/m3) were reached with tobacco cigarettes. Cigarette use also led to pollution of the room air with formaldehyde (18.5-56.5 µg/m3), acetaldehyde (26.5-141.5 µg/m3), and acetone (27.8-75.8 µg/m3). Tobacco cigarettes, e-cigarettes, and the IQOS are all avoidable sources of indoor pollutants. To protect the health of other non-smoking passengers, especially that of sensitive individuals such as children and pregnant women, these products should not be used in cars.

Electronic cigarettes: a task force report from the European Respiratory Society.

There is a marked increase in the development and use of electronic nicotine delivery systems or electronic cigarettes (ECIGs). This statement covers electronic cigarettes (ECIGs), defined as "electrical devices that generate an aerosol from a liquid" and thus excludes devices that contain tobacco. Database searches identified published articles that were used to summarise the current knowledge on the epidemiology of ECIG use; their ingredients and accompanied health effects; second-hand exposure; use of ECIGs for smoking cessation; behavioural aspects of ECIGs and social impact; in vitro and animal studies; and user perspectives.ECIG aerosol contains potentially toxic chemicals. As compared to conventional cigarettes, these are fewer and generally in lower concentrations. Second-hand exposures to ECIG chemicals may represent a potential risk, especially to vulnerable populations. There is not enough scientific evidence to support ECIGs as an aid to smoking cessation due to a lack of controlled trials, including those that compare ECIGs with licenced stop-smoking treatments. So far, there are conflicting data that use of ECIGs results in a renormalisation of smoking behaviour or for the gateway hypothesis. Experiments in cell cultures and animal studies show that ECIGs can have multiple negative effects. The long-term effects of ECIG use are unknown, and there is therefore no evidence that ECIGs are safer than tobacco in the long term. Based on current knowledge, negative health effects cannot be ruled out.

Nicotine delivery efficiency of first- and second-generation e-cigarettes and its impact on relief of craving during the acute phase of use.

Knowledge about the change in blood nicotine concentrations during the first five minutes (acute phase) of e-cigarette vaping is important to determine whether the used product has a dependence potential or may be an efficient nicotine replacement product. To address this issue, we monitored blood nicotine levels during the acute phase in volunteers using disposable cigalikes (CLs) and a tank model (TM) and compared them with blood nicotine levels in subjects using a tobacco cigarette (TC). In parallel, heart rate changes were continually measured and withdrawal symptoms and craving were assessed with the Questionnaire on Smoking Urges before and immediately after the vaping/smoking sessions. Additionally, at the end of each session negative health effects were rated on a visual analog scale. After five minutes of e-cigarette or TC use, the mean nicotine plasma concentrations were as follows: CLs, 5.5ng/ml; TM, 9.3ng/ml; TC, 17.1ng/ml. Nicotine levels increased significantly faster in the first 4min of consuming a TC than with the CLs and the TM. The highest rate of increase in nicotine concentration was found with the TC (6.8ng/ml) and TM (2.3ng/ml) between the 1st and 2nd minute, whereas the CLs showed comparatively small changes in the amount delivered over the five minutes. Withdrawal and craving for smoking decreased with the TM by the same amount as with the TC, even though less nicotine was delivered to the blood and considerably fewer side effects occurred. The heart rate of TM users was also markedly lower than that of the TC users. Unlike CLs, TM e-cigarettes represent an effective source of nicotine and might be used as an alternative nicotine replacement product to aid smoking cessation. However, nicotine plasma levels observed in TM users after short-time vaping have also the potential to produce and sustain nicotine addiction.

[Electronic Shiazo waterpipes: a new source of indoor air pollutants]. / Elektrische Shiazo-Wasserpfeifen: eine neue Quelle für Innenraumluftschadstoffe.

BACKGROUND: For some time, a new form of waterpipe smoking has been advertised, where steam stones moistened with aroma fluids (Shiazo) are heated electronically. Since there is no combustion of tobacco, it is often assumed that the produced vapor is not harmful to health. To clarify this issue, we performed a comprehensive inner and outer exposure assessment during the use of an electronic Shiazo waterpipe. METHODS: Three volunteers smoked an electronic waterpipe operated with nicotine-free Shiazo stones in a thoroughly ventilated room for 2 h. In three smoking sessions, three fluids with different flavorings were vaporized. In parallel, emissions of particles, volatile organic compounds, polycyclic aromatic hydrocarbons (PAH), and metals were measured in indoor air. Within a biomonitoring study, urinary metabolite profiles of air pollutants were checked. For comparison, the components of the Shiazo fluids were also analyzed. RESULTS: During the smoking sessions, concentrations of formaldehyde, acetaldehyde, glycerine, and propylene glycol rose significantly in the indoor environment. The content of putative carcinogenic PAH in indoor air increased by 42% to 174 ng/m3. Particle number concentrations ranged from 39,968 to 65,610 particles/cm3 (median), with peaks at diameters from 25 to 31 nm. 3­HPMA, the mercapturic acid metabolite of the pyrolysis product acrolein, was strongly elevated in urine samples of the smokers. All fluids contained high amounts of contact allergens. CONCLUSIONS: Electronic Shiazo waterpipes release various harmful substances that considerably impact indoor air quality. Compared to conventional waterpipes, the release of pollutants is lower. Nevertheless, smoking with Shiazo waterpipes is a source of health risks for both users and bystanders.

[The waterpipe (shisha) - indoor air quality, human biomonitoring, and health effects]. / Die Wasserpfeife (Shisha) ­ Innenraumluftqualität, Human-Biomonitoring und Gesundheitseffekte.

Waterpipe (WP) smoking, also known as shisha or hookah smoking, is growing in western countries as an alternative to cigarette smoking, especially in younger age groups. A majority of smokers mistakenly believe that shisha smoking is a social entertainment practice that leads to more social behavior and relaxation and that this type of smoking is safe or less harmful and less addictive than cigarette smoking.In reality, WP smokers are exposed to hundreds of toxic substances that include well-known carcinogens. High exposures to carbon monoxide and nicotine are major health threats. There is growing evidence that WP smoke causes adverse effects on the pulmonary and cardiovascular systems and there are indications that WP smoke is associated with cancer. Persons exposed to secondhand WP smoke are also at risk.More research on the health effects of WP is urgently needed and more preventive measures for public health protection. Moreover, public WP facilities should be implemented under specific nonsmoker protection laws and consequently controlled.This review summarizes recent data on exposure to WP smoking in indoor environments, the results of biomonitoring data, and the known health effects based on currently available toxicological or epidemiological studies.

Use of electronic cigarettes (e-cigarettes) impairs indoor air quality and increases FeNO levels of e-cigarette consumers.

Despite the recent popularity of e-cigarettes, to date only limited data is available on their safety for both users and secondhand smokers. The present study reports a comprehensive inner and outer exposure assessment of e-cigarette emissions in terms of particulate matter (PM), particle number concentrations (PNC), volatile organic compounds (VOC), polycyclic aromatic hydrocarbons (PAH), carbonyls, and metals. In six vaping sessions nine volunteers consumed e-cigarettes with and without nicotine in a thoroughly ventilated room for two hours. We analyzed the levels of e-cigarette pollutants in indoor air and monitored effects on FeNO release and urinary metabolite profile of the subjects. For comparison, the components of the e-cigarette solutions (liquids) were additionally analyzed. During the vaping sessions substantial amounts of 1,2-propanediol, glycerine and nicotine were found in the gas-phase, as well as high concentrations of PM2.5 (mean 197 µg/m(3)). The concentration of putative carcinogenic PAH in indoor air increased by 20% to 147 ng/m(3), and aluminum showed a 2.4-fold increase. PNC ranged from 48,620 to 88,386 particles/cm(3) (median), with peaks at diameters 24-36 nm. FeNO increased in 7 of 9 individuals. The nicotine content of the liquids varied and was 1.2-fold higher than claimed by the manufacturer. Our data confirm that e-cigarettes are not emission-free and their pollutants could be of health concern for users and secondhand smokers. In particular, ultrafine particles formed from supersaturated 1,2-propanediol vapor can be deposited in the lung, and aerosolized nicotine seems capable of increasing the release of the inflammatory signaling molecule NO upon inhalation. In view of consumer safety, e-cigarettes and nicotine liquids should be officially regulated and labeled with appropriate warnings of potential health effects, particularly of toxicity risk in children.

Airborne indoor particles from schools are more toxic than outdoor particles.

High concentrations of particulate matter (PM(10)) were measured in classrooms. This study addresses the hazard of indoor particles in comparison to the better-studied outdoor particles. Samples were taken from six schools during teaching hours. Genome-wide gene expression in human BEAS-2B lung epithelial cells was analyzed and verified by quantitative PCR. Polycyclic aromatic hydrocarbons, endotoxin, and cat allergen (Fel d 1) were analyzed by standard methods. Enhancement of allergic reactivity by PM(10) was confirmed in human primary basophils. Acceleration of human blood coagulation was determined with supernatants of PM(10)-exposed human peripheral blood monocytes. Indoor PM(10) induced serine protease inhibitor B2 (involved in blood coagulation) and inflammatory genes (such as CXCL6, CXCL1, IL6, IL8; all P < 0.001). Outdoor PM(10) induced xenobiotic metabolizing enzymes (cytochrome P450 [CYP] 1A1, CYP1B1, TIPARP; all P < 0.001). The induction of inflammatory genes by indoor PM(10) was explained by endotoxin (indoor 128.5 ± 42.2 EU/mg versus outdoor 13.4 ± 21.5 EU/mg; P < 0.001), the induction of CYP by outdoor polycyclic aromatic hydrocarbons (indoor 8.3 ± 4.9 ng/mg versus outdoor 16.7 ± 15.2 ng/mg; P < 0.01). The induction of serine protease inhibitor B2 was confirmed by a more rapid human blood coagulation (P < 0.05). Indoor PM(10) only affected allergic reactivity from human primary basophils from cat-allergic individuals. This was explained by varying Fel d 1 concentrations in indoor PM(10) (P < 0.001). Indoor PM(10), compared with outdoor PM(10), was six times higher and, on an equal weight basis, induced more inflammatory and allergenic reactions, and accelerated blood coagulation. Outdoor PM(10) had significantly lower effects, but induced detoxifying enzymes. Therefore, preliminary interventions for the reduction of classroom PM(10) seem reasonable, perhaps through intensified ventilation.

Effect of acupuncture on allergen-induced basophil activation in patients with atopic eczema:a pilot trial.

OBJECTIVE AND METHODS: The crucial symptom of atopic eczema is itch. Acupuncture has been shown to exhibit a significant effect on experimental itch; however, studies focusing on clinical itch in atopic eczema and corresponding mechanisms are lacking. The study design was a unicenter, single-blinded (observer), prospective, randomized clinical pilot trial with an additional experimental part. In 10 patients with atopic eczema, we investigated the effect of acupuncture treatment (n = 5) compared to no treatment (n = 5) on itch intensity and in vitro basophil CD63 expression upon allergen stimulation (house dust mite and timothy grass pollen) in a pilot trial. RESULTS: Mean itch intensity in a visual analog scale was rated significantly lower in the acupuncture group (-25% ± 26% [day 15-day 0]; -24% ± 31% [day 33-day 0]) than in the control group (15% ± 6% [day 15-day 0]; 29% ± 9% [day 33-day 0]). From day 0 (before treatment) to day 15 (after 5 acupuncture treatments) as well as day 33 (after 10 acupuncture treatments), the acupuncture group showed less CD63 positive basophils than the control group regarding stimulation with house dust mite and grass pollen allergen at various concentrations (5 ng/mL, 1 ng/mL, 0.5 ng/mL, or 0.25 ng/mL). CONCLUSIONS: Our results show a reduction of itch intensity and of in vitro allergen-induced basophil activation in patients with atopic eczema after acupuncture treatment. Reducing basophil activation can be a further tool in investigating the mechanisms of action of acupuncture in immunoglobulin E-mediated allergy. Due to the limited number of patients included in our pilot trial, further studies are needed to strengthen the hypothesis.

Metabolic activation of phenanthrene by human and mouse cytochromes P450 and pharmacokinetics in CYP1A2 knockout mice.

In the present study V79 Chinese hamster cells were genetically engineered for stable expression of the cytochromes P450 1A1, 1A2, 1B1, and 2E1 from man and mouse to investigate species-specific differences in the regioselective metabolism and toxicity of phenanthrene (Phe), the simplest polycyclic aromatic hydrocarbon (PAH) forming a bay-region. Phe is present in various environmental samples and serves as a model substrate for PAH exposure in human biomonitoring studies. For this reason we explored metabolite profiles and metabolite-dependent cytotoxic activities in vitro. The total turnover of CYP-mediated transformation of Phe was as follows: human CYP1B1>CYP1A1>CYP1A2>>CYP2E1, and for mouse CYP1A2>>CYP2E1>CYP1A1. Striking species differences were seen as mouse CYP1B1 did not activate Phe at all, but human CYP1B1 exhibited a significant metabolic turnover comparable to CYP1A1 and CYP1A2. In vivo studies monitoring the whole blood Phe elimination in CYP1A2 knockout and wild-type mice after oral administration confirmed involvement of CYP1A2 in the bioactivation of Phe, but other processes must contribute also. Our data suggest that in humans not only CYP1A2 expressed solely in the liver plays a crucial role in Phe metabolism, but also constitutively expressed extrahepatic CYP1B1 in tissues such as lung, kidney or intestine. This finding will substantially improve the validity of human biomonitoring studies using individual Phe metabolites for the assessment of PAH exposure.

Differential impact of diesel particle composition on pro-allergic dendritic cell function.

Diesel exhaust particles (DEP) were described as potent adjuvant in the induction and maintenance of allergic diseases, suggesting that they might play a role in the increase of allergic diseases in the industrialized countries. However, the cellular basis by which these particles enhance allergic immune responses is still a matter of debate. Thus, we exposed immature murine bone marrow-derived dendritic cells (BMDC) to different particles or particle-associated organic compounds in the absence or presence of the maturation stimuli lipopolysaccharide (LPS) and analyzed the cellular maturation, viability, and cytokine production. Furthermore, we monitored the functionality of particle-exposed BMDC to suppress B cell isotype switching to immunoglobulin (Ig) E. Only highly polluted DEP (standard reference material 1650a [SRM1650a]) but not particle-associated organic compounds or less polluted DEP from modern diesel engines were able to modulate the dendritic cell phenotype. SRM1650a particles significantly suppressed LPS-induced IL-12p70 production in murine BMDC, whereas cell-surface marker expression was not altered. Furthermore, SRM1650a-exposed immature BMDC lost the ability to suppress IgE isotype switch in B cells. This study revealed that highly polluted DEP not only interfere with dendritic cell maturation but also additionally with dendritic cell function, thus suggesting a role in T(h)2 immune deviation.

Polycyclic aromatic hydrocarbons from diesel emissions exert proallergic effects in birch pollen allergic individuals through enhanced mediator release from basophils.

BACKGROUND: Diesel exhaust particles (DEPs) act as adjuvants in the immune system and contribute to the increased prevalence and morbidity of asthma and allergic rhinitis. Polycyclic aromatic hydrocarbons (PAHs) are major components of DEPs, which may be involved in the induction and enhancement of proallergic processes. In this study we explored adjuvant effects of DEP-PAHs on activation parameters of human basophils, fostering allergic inflammation through the release of preformed or granule-derived mediators. METHODS: Heparinized blood samples from birch pollen allergic and control donors were stimulated with Bet v 1, the major allergen of birch pollen grains, alone or together with a mixture of 16 environmental prominent PAHs (EPA-PAH standard). Flow cytometric analysis was performed for quantitative determination of PAH-enhanced basophil activation. To assess direct PAH effects on basophils, enriched cultures from both donor groups were exposed to benzo[a]pyrene (B[a]P) or phenanthrene (Phe), two major DEP-PAHs, with and without allergen. Supernatants were assayed for IL-4 and IL-8 secretion and histamine release by means of ELISA. RESULTS: At environmental relevant exposure levels EPA-PAH standard synergized with antigen and significantly enhanced basophil activation of all birch pollen allergic individuals up to 95%. Single PAHs significantly drove IL-8 secretion from sensitized basophils of all patients tested, and there was no further enhancement by addition of rBet v 1. B[a]P and Phe also significantly induced IL-4 secretion, a key factor for Th2 development, from purified sensitized basophils in the absence of antigen suggesting an adjuvant role of DEP-PAHs in allergic sensitization. None of the basophil samples from healthy controls showed any PAH effect on mediator release. CONCLUSION: DEP-PAHs exert proallergic effects on sensitized basophils in an allergen independent fashion, suggesting a potential role of these pollutants for the allergic breakthrough in atopic individuals, who have not developed an allergic disease yet.

Human mast cells express androgen receptors but treatment with testosterone exerts no influence on IgE-independent mast cell degranulation elicited by neuromuscular blocking agents.

Women predominate in the anaphylactic reactions to neuromuscular blocking agents (NMBA). The expression of oestrogen receptors has been demonstrated in mast cells and oestrogen treatment can enhance mast cell degranulation, but the influence of androgens remains largely unclear. Our immunocytochemical study showed the expression of androgen receptor (AR) in mast cells isolated from human foreskin as well as in two human mast cell lines, HMC-1 and LAD2. The amount of AR was most abundant in human skin mast cells as determined by real-time polymerase chain reaction analysis. Treatment of the HMC-1 mast cells with testosterone or 17beta-oestradiol, alone or in combination with different NMBA, did not affect mast cell degranulation as measured by the release of beta-hexosaminidase. Our study shows for the first time the expression of AR in human skin mast cells. Further studies using primary human mast cell cultures are needed to understand whether and how sex hormones can influence mast cell activation.

Vertebral artery dissection presenting with ispilateral acute C5 and C6 sensorimotor radiculopathy: A case report.

Spinal manifestations of vertebral artery dissection (VAD) are rare events and are typically symptomatic with neck pain and ischemic brain injury. We report a patient presenting with unusual peripheral paresis of the right upper limb due to an intramural hematoma of the right vertebral artery with local compression of C5 and C6 as the cause of cervical radiculopathy. These symptoms completely resolved after anticoagulation and physical therapy.

Year-to-year variation in release of Bet v 1 allergen from birch pollen: evidence for geographical differences between West and South Germany.

BACKGROUND: The release of the aeroallergen Bet v 1 from pollen is a major determinant in the etiology of allergic airway disease due to birch pollen. OBJECTIVE: We determined the release of the major birch pollen allergen Bet v 1 from pollen of birch trees growing in 2 different geographic regions in Germany for 2 consecutive years. METHODS: Catkins were collected during pollination in 2002 and 2003 from 82 healthy trees in South (Munich) and West Germany (North Rhine-Westphalia). The release of Bet v 1 from pollen samples was determined by a Bet v 1-specific ELISA. RESULTS: Pollen from South Germany released about 3 times more Bet v 1 than those from West Germany in both 2002 and 2003 (p = 0.034 and p = 0.007, respectively). This was independent of the number of pollen during the pollen flight season. In 2003, the release of Bet v 1 from pollen was more than 5 times higher than in 2002 in both regions (South Germany 6.1 times, p < 0.001; West Germany 5.4 times, p = 0.003). CONCLUSIONS: Despite large individual differences, there seem to be regional and year-to-year variations in Bet v 1 release from birch pollen. Therefore, the combination of pollen count and release of Bet v 1 from this pollen must be assessed to estimate Bet v 1 exposure reliably.

Environmental polycyclic aromatic hydrocarbons (PAHs) enhance allergic inflammation by acting on human basophils.

Diesel exhaust particles (DEPs) have been implicated in the worldwide increased incidence of allergic airway diseases over the past century. There is growing evidence that DEP-associated polycyclic aromatic hydrocarbons (PAHs) participate in the development and maintenance of immunoglobulin (Ig) E-mediated allergic diseases. To address this issue we investigated the impact of U.S. Environmental Protection Agency (EPA) priority PAHs as well as of PAH-containing airborne extracts on antigen-induced CD63 upregulation and mediator release from human basophils. Whole blood samples from birch pollen allergic and control subjects were incubated in the presence of organic extracts of urban aerosol (AERex) or EPA-PAH standard with or without rBet v 1. Basophils were analyzed for CD63 expression as a measure of basophil activation by using multiparameter flow cytometry. In addition, purified basophils from birch pollen allergic donors were incubated for 2 h in the presence of 1 muM benzo[a]pyrene (BaP) or phenanthrene (Phe) and then stimulated with rBet v 1 for 45 min. Supernatants were assayed for histamine, interleukin (IL)-4, and IL-8 by means of enzyme-linked immunosorbent assay (ELISA). Basophils exposed in vitro simultaneously to AERex or EPA-PAH standard and rBet v 1 expressed CD63 significantly more than with antigen alone. PAHs synergized with rBet v 1 dose dependently, but did not activate basophils from nonallergic donors. BaP and Phe significantly enhanced cytokine secretion (IL-4, IL-8) and histamine release from purified basophils without antigen added, and secretion was not further enhanced by rBet v 1 stimulation. In conclusion, PAHs from roadside emissions can directly activate sensitized basophils to cytokine secretion and drive proallergic processes through enhanced Fcepsilon RI-coupled mediator release from human basophils.