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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 as well as the association between early stressful life events and atopic eczema (AE). Within the LISA plus (Life style - Immune system - Allergy) study, blood samples from children of 6 years of age were analyzed for concentration of the neuropeptides vasoactive intestinal peptide (VIP), somatostatin (SOM), substance P (SP) and the Th1/Th2 cytokines IFN-γ and 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. Furthermore, lifetime prevalence of AE and incidence after the assessment period of life events were compared. Our data suggest that separation/ divorce of parents increase childrens risk of developing AE later in life. 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-γ concentrations in childrens blood but not with neuropeptide levels. Thus, 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.
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The biology of the T cell cytokines Interleukin (IL-)17 and IL-22 has been a main focus in the field of clinical immunology in the last decade. This intensive interest in both cytokines has resulted in almost 5,000 scientific publications (www.pubmed.com) dealing with the molecular structure, extra- and intracellular signaling pathways, specific transcription factors and the function of IL-17 and IL-22. This review article highlights the main findings concerning IL-17 and IL-22 in the last years.
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The increasing prevalence of asthma, hay fever, and allergic sensitization in Western Germany after east-west division in 1949 and their rapid increase in East German children after re-unification in 1990 are strong indications for the role of life-style and/or environmental factors in the development of atopic diseases. Obviously, the perinatal period is crucial for priming the immune system. Therefore, explorations of determinants of atopic diseases need pregnancy or birth cohorts as the most appropriate epidemiological study designs. This review presents the design and selected results of the two German birth cohorts GINIplus and LISAplus. GINIplus and LISAplus recruited 5.991 and 3.097 healthy, term newborns, respectively, from Munich, Wesel, Leipzig, and Bad Honnef. Approximately 55% could be followed for the first 10 years. We analyzed the natural course of atopic diseases and the role of life-style, environmental, and genetic factors for disease onset, intermediate phenotypes, and genes involved in detoxification and oxidative stress. The results of these two large birth cohorts contributed substantially to the understanding of atopic diseases and their determinants.
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BACKGROUND: Availability of a safe smallpox vaccine may be necessary under certain circumstances. Use of the old life virus vaccine was associated with serious adverse events, particularly in the setting of atopic eczema (AE) and immunodeficiency. Modified virus Ankara (MVA)-BN, a highly attenuated strain of vaccinia virus, was developed for vaccination with improved safety profile. METHODS: A phase 1 study was conducted in 60 subjects without history of smallpox vaccination to gain experience with smallpox vaccination using this strain in healthy and atopic subjects. Healthy subjects, subjects with a history of AE, subjects with mild active AE and subjects with mild allergic rhinitis without AE were equally allocated into four groups. MVA-BN was injected s.c. in a dose of 108 TCID50 twice in a 4-week interval. RESULTS: No serious or unexpected adverse reactions were reported. All subjects experienced mild to moderate pain and redness at the injection site. Dermatologic examinations did not reveal any unfavourable reactions to the study medication, particularly no sign or exacerbation of eczema for as long as 196 days. All subjects seroconverted after two vaccinations and no significant difference in antibody titres between the four different groups was observed. CONCLUSIONS: A good safety profile of the MVA-BN vaccine was shown. The absence of adverse events in subjects with atopic disorders appears promising for the development of a safe smallpox vaccine for patients with AE or other atopic diseases.
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Eczema/tratamento farmacológico , Rinite Alérgica/tratamento farmacológico , Vacina Antivariólica , Adulto , Feminino , Humanos , Masculino , Projetos Piloto , Adulto JovemRESUMO
BACKGROUND: Besides allergens, pollen release bioactive, low molecular weight compounds that modulate and stimulate allergic reactions. Clinical relevance of these substances has not been investigated to date. OBJECTIVE: To elucidate the effect of a non-allergenic, low molecular weight factors from aqueous birch pollen extracts (Bet-APE < 3 kDa) on the human allergic immune response in vivo. METHODS: Birch and grass pollen allergic individuals underwent skin prick testing with allergen alone, allergen plus Bet-APE < 3 kDa, or allergen plus pre-identified candidate substances from low molecular pollen fraction. Nasal allergen challenges were performed in non-atopic and pollen allergic individuals using a 3 day repeated threshold challenge battery. Subjects were either exposed to allergen alone or to allergen plus Bet-APE< 3 kDa. Local cytokine levels, nasal secretion weights, nasal congestion and symptom scores were determined. RESULTS: Skin prick test reactions to pollen elicited larger weals when allergens were tested together with the low molecular weight compounds from pollen. Similar results were obtained with candidate pollen-associated lipid mediators. In nasal lining fluids of allergic patients challenged with allergen plus Bet-APE < 3 kDa, IL-8 and IgE was significantly increased as compared to allergen-only challenged patients. These patients also produced increased amounts of total nasal secretion and reported more severe rhinorrhea than the allergen-only challenged group. CONCLUSIONS: Low molecular compounds from pollen enhance the allergen specific immune response in the skin and nose. They are therefore of potential clinical relevance in allergic patients.
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Alérgenos/imunologia , Imunidade , Imunomodulação , Extratos Vegetais/imunologia , Pólen/imunologia , Rinite Alérgica Sazonal/imunologia , Basófilos/imunologia , Basófilos/metabolismo , Betula/imunologia , Degranulação Celular/imunologia , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Mediadores da Inflamação/metabolismo , Interleucina-8/metabolismo , Peso Molecular , Mucosa Nasal/imunologia , Mucosa Nasal/metabolismo , Testes de Provocação Nasal , Extratos Vegetais/química , Pólen/química , Rinite Alérgica Sazonal/diagnóstico , Rinite Alérgica Sazonal/metabolismo , Testes Cutâneos , Avaliação de Sintomas , Células Th2/imunologia , Células Th2/metabolismoRESUMO
BACKGROUND: The ImmunoCAP ISAC 112 platform is the only commercially available molecular allergy IgE multiplex test. Data on the comparison of this rather novel test with the molecular singleplex ImmunoCAP IgE platform are lacking. OBJECTIVE: To compare the multiplex ISAC 112 platform and the singleplex ImmunoCAP platform in regard to IgE to grass pollen allergens in untreated grass pollen-allergic patients in Germany. METHODS: Serum samples from 101 adults with grass pollen allergy were analyzed for specific IgE (sIgE) to 8 allergenic molecules from timothy grass pollen and to the 112 allergenic molecules included in the ISAC panel. The results for the multiplex and singleplex tests were subsequently analyzed statistically. RESULTS: Comparison of sIgE to grass pollen allergens detected by ISAC 112 and the singleplex ImmunoCAP assay revealed the following correlation coefficients: 0.88 (rPhl p 1), 0.96 (rPhl p 2), 0.70 (nPhl p 4), 0.94 (rPhl p 5b), 0.92 (rPhl p 6), 0.85 (rPhl p 11), and 0.78 (rPhl p 12). CONCLUSION: Molecular testing with ISAC 112 correlates well with the ImmunoCAP platform for respective molecular timothy grass pollen allergens.
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Imunoglobulina E/sangue , Testes Imunológicos , Técnicas de Diagnóstico Molecular , Poaceae/imunologia , Pólen/imunologia , Rinite Alérgica Sazonal/diagnóstico , Adolescente , Adulto , Antígenos de Plantas , Biomarcadores/sangue , Reações Cruzadas , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas de Plantas , Valor Preditivo dos Testes , Rinite Alérgica Sazonal/sangue , Rinite Alérgica Sazonal/imunologia , Adulto JovemRESUMO
BACKGROUND: B cells play a central role in IgE-mediated allergies. In damaged airway epithelium, they are exposed directly to aeroallergens. We aimed to assess whether direct exposure of B cells to pollen constituents affects allergic sensitization. METHODS: B cells from murine splenocytes and from blood samples of healthy donors were incubated for 8 days under Th2-like conditions with aqueous ragweed pollen extracts (Amb-APE) or its constituents. Secreted total IgM, IgG, and IgE was quantified by ELISA. Additionally, birch, grass, or pine-pollen extracts were tested. The number of viable cells was evaluated by ATP measurements. B-cell proliferation was measured by CFSE staining. IgE class switch was analyzed by quantitation of class switch transcripts. In an OVA/Alum i.p.-sensitization mouse model, Amb-APE was intranasally instilled for 11 consecutive days. RESULTS: Upon Th2 priming of murine B cells, ragweed pollen extract caused a dose-dependent increase in IgE production, while IgG and IgM were not affected. The low-molecular-weight fraction and phytoprostane E1 (PPE1) increased IgE production, while Amb a 1 did not. PPE1 enhanced IgE also in human memory B cells. Under Th1 conditions, Amb-APE did not influence immunoglobulin secretion. The IgE elevation was not ragweed specific. It correlated with proliferation of viable B cells, but not with IgE class switch. In vivo, Amb-APE increased total IgE and showed adjuvant activity in allergic airway inflammation. CONCLUSIONS: Aqueous pollen extracts, the protein-free fraction of Amb-APE, and the pollen-contained substance PPE1 specifically enhance IgE production in Th2-primed B cells. Thus, pollen-derived nonallergenic substances might be responsible for B-cell-dependent aggravation of IgE-mediated allergies.
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Alérgenos/imunologia , Formação de Anticorpos/imunologia , Linfócitos B/imunologia , Imunoglobulina E/imunologia , Pólen/imunologia , Células Th2/imunologia , Ambrosia/imunologia , Animais , Antígenos de Plantas/imunologia , Linfócitos B/metabolismo , Feminino , Humanos , Imunização , Memória Imunológica , Ativação Linfocitária/imunologia , Camundongos , Ovalbumina/imunologia , Extratos Vegetais/imunologia , Pneumonia/imunologia , Pneumonia/metabolismo , Pneumonia/patologia , Células Th2/metabolismoRESUMO
BACKGROUND: Ragweed (Ambrosia artemisiifolia) is a strong elicitor of allergic airway inflammation with worldwide increasing prevalence. Various components of ragweed pollen are thought to play a role in the development of allergic responses. The aim of this study was to identify critical factors for allergenicity of ragweed pollen in a physiological model of allergic airway inflammation. METHODS: Aqueous ragweed pollen extract, the low molecular weight fraction or the major allergen Amb a 1 was instilled intranasally on 1-11 consecutive days, and allergic airway inflammation was evaluated by bronchoalveolar lavage, lung histology, serology, gene expression in lung tissue, and measurement of lung function. Pollen-derived adenosine was removed from the extract enzymatically to analyze its role in ragweed-induced allergy. Migration of human neutrophils and eosinophils toward supernatants of ragweed-stimulated bronchial epithelial cells was analyzed. RESULTS: Instillation of ragweed pollen extract, but not of the major allergen or the low molecular weight fraction, induced specific IgG1 , pulmonary infiltration with inflammatory cells, a Th2-associated cytokine signature in pulmonary tissue, and impaired lung function. Adenosine aggravated ragweed-induced allergic lung inflammation. In vitro, human neutrophils and eosinophils migrated toward supernatants of bronchial epithelial cells stimulated with ragweed extract only if adenosine was present. CONCLUSIONS: Pollen-derived adenosine is a critical factor in ragweed-pollen-induced allergic airway inflammation. Future studies aim at therapeutic strategies to control these allergen-independent pathways.
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Adenosina/metabolismo , Antígenos de Plantas/imunologia , Imunização/métodos , Extratos Vegetais/imunologia , Hipersensibilidade Respiratória/fisiopatologia , Administração Intranasal , Animais , Asma/imunologia , Asma/fisiopatologia , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Modelos Animais de Doenças , Células Epiteliais/imunologia , Células Epiteliais/metabolismo , Feminino , Humanos , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , Distribuição Aleatória , Medição de Risco , Sensibilidade e Especificidade , Células Th2/imunologia , Células Th2/metabolismoRESUMO
The increase of allergies in East Germany--reaching West German prevalence shortly after the reunification--is considered a model for the allergy epidemic in the western world. Whether such a pattern was observed in all comparison studies and for all allergic manifestations is not known because a complete overview is missing. Hints about possible causal factors for the allergy epidemic could be gained by identifying known risk factors, which explain the observed pattern of allergy development in Germany. Again, an overview about these efforts is missing. We identified 14 cross-sectional studies conducted after 1989 and calculated prevalence ratios (West/East) for asthma, hayfever, eczema and allergic sensitization. Additionally, a tabular overview about the explanatory power of risk factors hypothesized in the nineties and covering outdoor exposure, indoor factors, early childhood influences, nutrition as well as awareness is given. At the time of the German reunification, the prevalence ratio West/East was largest for hayfever and sensitization to birch pollen, less pronounced for the other phenotypes and even less than one for atopic eczema. Hayfever and sensitization to birch pollen also showed the steepest increase in East Germany afterwards. Single-room heating with fossil fuels and living as only child in a family were identified as explaining up to 23.5% of the excess trend in East compared to the trend in West. Hayfever as most typical atopic disease showed the difference in allergy pattern between East and West Germany clearest. Risk factors identified for these phenotypes are completely different (single child) or even act in the opposite direction (single-room heating) from classical risk factors for airway diseases. This might be the most important lesson from the West/East German experience. It already stimulated many other studies focussing on protective factors such as microbial stimulation.
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Hipersensibilidade/epidemiologia , Hipersensibilidade/etiologia , Hipersensibilidade/imunologia , Exposição Ambiental/efeitos adversos , Poluição Ambiental/efeitos adversos , Feminino , Alemanha/epidemiologia , História do Século XX , História do Século XXI , Humanos , Hipersensibilidade/história , Masculino , Prevalência , Fatores de RiscoRESUMO
BACKGROUND: Data on molecular allergy diagnostics in adults with grass pollen allergy with regard to conjunctival and nasal provocation test outcome and specific immunotherapy are lacking to date. OBJECTIVE: To assess whether molecular allergy diagnostics for grass pollen allergens could help with predicting provocation test outcomes and serve as a basis for future component-resolved specific immunotherapy. METHODS: Sera of 101 adults with grass pollen allergy was analysed for IgE against timothy grass pollen (Phleum pratense), rPhl p 1, rPhl p 2, nPhl p 4, rPhl p 5b, rPhl p 6, rPhl p 7, rPhl p 11 and rPhl p12 and correlated with the individuals' outcome in the nasal and conjunctival provocation tests and investigated in regard to a potential component-resolved specific immunotherapy. RESULTS: An increasing number of sensitizations to timothy grass allergens was correlated to a positive reaction in the conjunctival (4.9 vs. 3.6, P = 0.003) and nasal provocation tests (4.5 vs. 2.2, P = 0.0175). In molecular sensitization profiles, a substantial heterogeneity was detected, with none of the patients exactly matching the allergen composition of a previously published component-resolved specific immunotherapy containing Phl p 1, Phl p 2, Phl p 5a/b and Phl p 6. The results indicate that in 95% of the patients, a proportion of 50% of timothy-IgE would be targeted with such a specific immunotherapy, while in 50% and 10% of patients, 80% and 90% of timothy-IgE would be targeted, respectively. CONCLUSION AND CLINICAL RELEVANCE: Molecular allergy diagnostics is a prerequisite for future component-resolved specific immunotherapy due to the high heterogeneity of sensitization profiles. However, of current clinical relevance is the observed correlation between the number of sensitizations and provocation test outcome.
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Alérgenos/imunologia , Poaceae/efeitos adversos , Pólen/imunologia , Rinite Alérgica Sazonal/imunologia , Adulto , Dessensibilização Imunológica , Feminino , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Masculino , Phleum/imunologia , Proteínas de Plantas/imunologia , Análise Serial de Proteínas , Rinite Alérgica Sazonal/diagnóstico , Rinite Alérgica Sazonal/terapiaRESUMO
BACKGROUND AND OBJECTIVE: Allergic diseases of the respiratory tract are common atopic diseases in the population. Pollen of plants are one of their main causes. Pollen of trees, grasses, and weeds like mugwort are of particular importance in this context. The purpose of the present study was to determine the association between typical respiratory symptoms due to pollen allergens and the sensitization to pollen of ragweed and mugwort in adults. METHODS: 1039 participants (18 to 66 years) from Southwest Germany were included in this cross-sectional study. Complains typically for aeroallergens were recorded by questionnaire. In-vitro existing sensitizations were determined for grasses/early bloomer (gx1), trees (tx6), mugwort (w6 and Art-v1) and ragweed (w1 and Amb-a1) by testing for specific IgE-antibodies. RESULTS: In a screening test with a mixed allergen sample (sx1) 36.0 % of the participants showed an aeroallergen sensitization. Consecutive investigations of these 374 positive samples revealed a sensitization to grasses/early bloomer, trees, ragweed (w1), mugwort (w6) and the major allergens ragweed (Amb-a1) and mugwort (Art-v1) in 61.8 %, 54.5 %, 29.9 %, 24.3 %, 1.9 %, and 12.3 %, respectively. This corresponds to 22.2 %, 19.6 %, 10.8 %, 8.7 %, 0.7 % and 4.4 %, respectively, in the whole study population. The participants tested positively stated significantly more disorders. On average, 51.1 % had known hay fever, 65.2 % sneezing without cold and 41.5 % sneezing due to contact with grasses or flowers. In contrast, participants tested negatively stated disorders in only 4.4 %, 32.5 %, and 3.9 %, respectively. CONCLUSION: In Southwest Germany, sensitizations to plant pollen mainly are still caused by grasses, trees, and weeds like mugwort. A sensitization to pollen of ragweed alone is rare until now. However, in case of continuous allergic disorders of the respiratory tract in late summer, a sensitization to ragweed can be important for differential diagnostics.
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Artemisia/imunologia , Hipersensibilidade Imediata/epidemiologia , Hipersensibilidade Imediata/imunologia , Hipersensibilidade Respiratória/epidemiologia , Hipersensibilidade Respiratória/imunologia , Rinite Alérgica Sazonal/epidemiologia , Rinite Alérgica Sazonal/imunologia , Adolescente , Adulto , Idoso , Ambrosia/imunologia , Comorbidade , Feminino , Alemanha/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Material Particulado/imunologia , Medição de Risco , Adulto JovemRESUMO
The immune system is regulated to protect the host from exaggerated stimulatory signals establishing a state of tolerance in healthy individuals. The disequilibrium in immune regulatory vs effector mechanisms results in allergic or autoimmune disorders in genetically predisposed subjects under certain environmental conditions. As demonstrated in allergen-specific immunotherapy and in the healthy immune response to high-dose allergen exposure models in humans, T regulatory cells are essential in the suppression of Th2-mediated inflammation, maintenance of immune tolerance, induction of the two suppressive cytokines interleukin-10 and transforming growth factor-ß, inhibition of allergen-specific IgE, and enhancement of IgG4 and IgA. Also, suppression of dendritic cells, mast cells, and eosinophils contributes to the construction of peripheral tolerance to allergens. This review focuses on mechanisms of peripheral tolerance to allergens with special emphasis on recent developments in the area of immune regulation.
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Alérgenos/imunologia , Formação de Anticorpos/imunologia , Tolerância Imunológica/imunologia , Tolerância Periférica/imunologia , Alérgenos/efeitos adversos , Linfócitos B Reguladores/citologia , Linfócitos B Reguladores/imunologia , Citocinas/imunologia , Citocinas/metabolismo , Células Dendríticas/citologia , Células Dendríticas/imunologia , Dessensibilização Imunológica/métodos , Humanos , Hipersensibilidade/imunologia , Hipersensibilidade/fisiopatologia , Hipersensibilidade/terapia , Tolerância Imunológica/fisiologia , Imunoglobulina G/imunologia , Interleucina-10/imunologia , Interleucina-10/metabolismo , Tolerância Periférica/fisiologia , Sensibilidade e Especificidade , Linfócitos T Reguladores/citologia , Linfócitos T Reguladores/imunologia , Células Th17/citologia , Células Th17/imunologiaRESUMO
The sensation of itch - defined as unpleasant sensation inducing the urge to scratch - is processed by a network of different brain regions contributing to the encoding of sensory, emotional, attention-dependent, cognitive-evaluative and motivational patterns. Patients with atopic eczema show different activation patterns and kinetics compared to healthy volunteers. This review summarizes current studies investigating itch in the brain.
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Encéfalo/diagnóstico por imagem , Prurido/diagnóstico por imagem , Encéfalo/anatomia & histologia , Encéfalo/metabolismo , Dermatite Atópica/diagnóstico por imagem , Dermatite Atópica/metabolismo , Histamina/metabolismo , Humanos , Imageamento por Ressonância Magnética , Neuroimagem , Tomografia por Emissão de Pósitrons , Prurido/metabolismo , TemperaturaRESUMO
Numerous chronic diseases in childhood and adulthood have their origins in perinatal life and are potentially influenced by trans-generational epigenetic processes. Therefore, prospective birth cohorts can substantially contribute to our knowledge about the etiology of diseases including modifiable risk factors. The two population-based German birth cohorts GINIplus and LISAplus aim to describe the natural course of chronic diseases and intermediate phenotypes in childhood and its determinants, and to identify potential genetic effect modifications. In the mid-1990s, 5,991 (GINIplus) and 3,097 (LISAplus) healthy, term newborns were recruited for long-term follow-up in four regions of Germany. The follow-up rate for the first 10 years was about 55%. We analyzed the growth and development of overweight, infections and allergic diseases, mental and oral health, metabolic and inflammatory parameters and the role of potential risk factors including genetics. The results of these two birth cohorts substantially contribute to the current knowledge about the natural course of these health parameters. These data were included in many international projects and consortia for purposes of international comparisons of prevalence and consistency of findings, and to increase the power of the analyses.
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Estudos de Coortes , Doenças do Recém-Nascido/epidemiologia , Parto , Feminino , Alemanha/epidemiologia , Humanos , Recém-Nascido , Masculino , Prevalência , Fatores de RiscoRESUMO
BACKGROUND: Itch is the major symptom of atopic dermatitis (AD). Acupuncture has been shown to exhibit a significant effect on experimental itch in AD. Our study evaluated acupuncture and antihistamine itch therapy (cetirizine) on type I hypersensitivity itch and skin reaction in AD using a patient and examiner-blinded, randomized, placebo-controlled, crossover trial. METHODS: Allergen-induced itch was evaluated in 20 patients with AD after several interventions in separate sessions: preventive (preceding) and abortive (concurrent) verum acupuncture (VAp and VAa), cetirizine (10 mg, VC), corresponding placebo interventions (preventive, PAp, and abortive, PAa, placebo acupuncture; placebo cetirizine pill, PC) and a no-intervention control (NI). Itch was induced on the forearm and temperature modulated over 20 min, using our validated model. Outcome parameters included itch intensity, wheal and flare size and the D2 attention test. RESULTS: Mean itch intensity (SE: 0.31 each) was significantly lower following VAa (31.9) compared with all other groups (PAa: 36.5; VC: 36.8; VAp: 37.6; PC: 39.8; PAp: 39.9; NI: 45.7; P < 0.05). There was no significant difference between VAp and VC (P > 0.1), although both therapies were significantly superior to their respective placebo interventions (P < 0.05). Flare size following VAp was significantly smaller (P = 0.034) than that following PAp. D2 attention test score was significantly lower following VC compared with all other groups (P < 0.001). CONCLUSIONS: Both VA and cetirizine significantly reduced type I hypersensitivity itch in patients with AD, compared with both placebo and NI. Timing of acupuncture application was important, as VAa had the most significant effect on itch, potentially because of counter-irritation and/or distraction. Itch reduction following cetirizine coincided with reduced attention.
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Terapia por Acupuntura , Cetirizina/administração & dosagem , Dermatite Atópica/terapia , Antagonistas dos Receptores Histamínicos/administração & dosagem , Prurido/prevenção & controle , Administração Oral , Estudos Cross-Over , Dermatite Atópica/complicações , Método Duplo-Cego , Feminino , Humanos , Masculino , Prurido/etiologia , Adulto JovemRESUMO
UNLABELLED: Outdoor particulate matter (PM(10)) is associated with detrimental health effects. However, individual PM(10) exposure occurs mostly indoors. We therefore compared the toxic effects of classroom, outdoor, and residential PM(10). Indoor and outdoor PM(10) was collected from six schools in Munich during teaching hours and in six homes. Particles were analyzed by scanning electron microscopy and X-ray spectroscopy (EDX). Toxicity was evaluated in human primary keratinocytes, lung epithelial cells and after metabolic activation by several human cytochromes P450. We found that PM(10) concentrations during teaching hours were 5.6-times higher than outdoors (117 ± 48 µg/m(3) vs. 21 ± 15 µg/m(3), P < 0.001). Compared to outdoors, indoor PM contained more silicate (36% of particle number), organic (29%, probably originating from human skin), and Ca-carbonate particles (12%, probably originating from paper). Outdoor PM contained more Ca-sulfate particles (38%). Indoor PM at 6 µg/cm(2) (10 µg/ml) caused toxicity in keratinocytes and in cells expressing CYP2B6 and CYP3A4. Toxicity by CYP2B6 was abolished with the reactive oxygen species scavenger N-acetylcysteine. We concluded that outdoor PM(10) and indoor PM(10) from homes were devoid of toxicity. Indoor PM(10) was elevated, chemically different and toxicologically more active than outdoor PM(10). Whether the effects translate into a significant health risk needs to be determined. Until then, we suggest better ventilation as a sensible option. PRACTICAL IMPLICATIONS: Indoor air PM(10) on an equal weight base is toxicologically more active than outdoor PM(10). In addition, indoor PM(10) concentrations are about six times higher than outdoor air. Thus, ventilation of classrooms with outdoor air will improve air quality and is likely to provide a health benefit. It is also easier than cleaning PM(10) from indoor air, which has proven to be tedious.
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Poluição do Ar em Ambientes Fechados/efeitos adversos , Poluição do Ar em Ambientes Fechados/análise , Material Particulado/análise , Material Particulado/toxicidade , Hidrocarboneto de Aril Hidroxilases/metabolismo , Biotransformação , Carbonato de Cálcio/análise , Carbonato de Cálcio/toxicidade , Linhagem Celular , Células Cultivadas , Criança , Citocromo P-450 CYP2B6 , Citocromo P-450 CYP3A/metabolismo , Alemanha , Habitação , Humanos , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Microscopia Eletrônica de Varredura , Oxirredutases N-Desmetilantes/metabolismo , Tamanho da Partícula , Instituições Acadêmicas , Silício/análise , Silício/toxicidade , Enxofre/análise , Enxofre/toxicidadeRESUMO
BACKGROUND: There is minimal data available concerning the dose-response relationship between allergen exposure and clinical reactivity for outdoor aeroallergens, such as timothy grass pollen. Timothy pollen-specific IgE (sIgE) determinations might assist in predicting the clinical reactivity in patients with allergic rhinoconjunctivitis (ARC). METHODS: Allergen-sIgE antibody levels of timothy grass pollen were correlated with individual threshold doses eliciting allergic reactions in skin prick test (SPT), conjunctival (CPT) and nasal (NPT) provocation tests in patients suffering from pollen-induced rhinoconjunctivitis and healthy controls. RESULTS: One hundred and four patients with ARC (median age: 27 years; range: 18-64; females: 58%) and 36 controls (25 years (22-77); females: 70%) were included in the study. Ninety-six percent of the patients showed a positive reaction in the nasal and 57% showed a positive reaction in the conjunctival provocation. With regarding to titrated SPT, 98% of the patients showed a positive skin test reaction; correlating with the level of sIgE for timothy (P < 0.001). For both provocation protocols, there was no correlation between the provocation concentration at the reaction and the level of sIgE for timothy. The ratio of sIgE/total IgE correlated with the dilution level of SPT (P < 0.002) and CPT (P < 0.01), respectively. CONCLUSION AND CLINICAL RELEVANCE: A dose-response relationship between the levels of sIgE and clinical outcome of timothy allergen exposure could not be established. Although IgE-determination remains an important key element in allergy diagnosis, provocation tests are procedures of choice if the clinical relevance of an allergen has to be confirmed.
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Alérgenos/imunologia , Imunoglobulina E/análise , Testes Imunológicos/métodos , Phleum/imunologia , Pólen/imunologia , Rinite Alérgica Sazonal/diagnóstico , Rinite Alérgica Sazonal/imunologia , Adolescente , Adulto , Alérgenos/efeitos adversos , Reações Antígeno-Anticorpo , Feminino , Humanos , Imunoglobulina E/imunologia , Masculino , Pessoa de Meia-Idade , Testes de Provocação Nasal , Pólen/efeitos adversos , Estudos Prospectivos , Testes Cutâneos , Adulto JovemRESUMO
Within the framework of Integrated Water Resources Management (IWRM) the nutrient and heavy metal levels within the Kharaa river basin were investigated. By the application of the MONERIS model, which quantifies nutrient emissions into river basins, various point and diffuse pathways, as well as nutrient load in rivers, could be analysed. Despite seasonal variations and inputs of point sources (e.g. Wastewater Treatment Plant Darkhan) the nutrient concentrations in most of the subbasins are on a moderate level. This shows evidence for a nutrient limited ecosystem as well as dilution effects. However, in the middle and lower reaches heavy metal concentrations of arsenic and mercury, which are linked to mining activities in many cases, are a point of concern. Thus measures are necessary to protect the valuable chemical and ecological status of the Kharaa River and its tributaries. As a result of the growing economic pressure Mongolia will enhance the agricultural production by irrigation. Until 2015 about 60% of the agricultural land shall be irrigated. In addition the gold mining activities shall increase by 20% a year. Both sectors have a high demand for water quantity and quality. The model MONERIS allows the assessment of measures which are inevitable to protect the water quality under shrinking water availability.