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.
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.
Toll-like receptors (TLR) play a pivotal role in the induction of first-line defense mechanisms of the innate immune system and trigger adaptive immune responses to microbial pathogens. Genetic ...variations in innate immunity genes have been reported to be associated with a range of inflammatory disorders. Deficiencies on the level of immunity receptors such as pathogen-recognition receptors are suspected to affect the maturation of our immune system and to avail thereby the high prevalence of atopic diseases and susceptibility of atopic patients to microbial infections. We evaluated TLR9 as susceptibility gene for atopic eczema (AE). Analyses of four tag single-nucleotide polymorphisms in two panels of families containing a total of 483 parent-affected offspring trios as well as a cohort of 274 unrelated adult AE cases and 252 hypernormal population-based controls have been performed. In both family cohorts, polymorphism C-1237T, which is located within the promoter region of the TLR9 gene, was significantly associated with AE, in particular the intrinsic subtype of AE. No associations were seen in the case-control cohort. Luciferase reporter gene assays revealed significantly higher promoter activity of the TT allelic variant at this single nucleotide polymorphism site. These observations suggest that the TLR9 promoter polymorphism C-1237T might affect AE susceptibility in particular in patients with the intrinsic variant of AE.
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.
Quantifying P losses to surface waters at different scales and partitioning of the loads into P losses from point sources and diffuse sources are significant future challenges for river basin ...managers. The agricultural share of P losses to surface waters is, in many river basins, increasing and therefore becoming more important to quantify and analyse. The importance of phosphorus losses from agricultural land was analysed using monitoring data and two different models for 35 micro-catchments (<30 km²) in the Nordic-Baltic region of Europe, 17 European macro-catchments (250-11 000 km²) and 10 large European river basins (>50 000 km²). Average annual phosphorus loss from agricultural land in the micro-catchments varied from 0.1 to 4.7 kg P ha⁻¹ and showed no relationship with the short-term P surplus on agricultural land. The average annual total P loss from agricultural land showed equally large variation in the 17 macro-catchments (0.1-6.0 kg P ha⁻¹), but the range was less for the 10 larger river basins (0.09-2.0 kg P ha⁻¹). The annual P loss from the 35 micro-catchments was greatest in the micro-catchments characterized by soil erosion and a high proportion of surface run-off as in the Norwegian catchments. The same pattern was true for the 17 macro-catchments where the model-simulated total P loss from agricultural land was greatest in the catchments in northern and southern parts of Europe. The main diffuse pathways for total P loads in the 17 macro-catchments were simulated with the MONERIS model. On average, soil erosion and surface run-off was estimated to have contributed 53% (4.1-81%), groundwater 14% (0.2-41.7%) and tile drainage water 3% (0-14.0%).
In this paper we show the quantitative and relative importance of phosphorus (P) losses from agricultural areas within European river basins and demonstrate the importance of P pathways, linking ...agricultural source areas to surface water at different scales. Agricultural P losses are increasingly important for the P concentration in most European rivers, lakes, and estuaries, even though the quantity of P lost from agricultural areas in European catchments varies at least one order of magnitude (<0.2 kg P ha(-1) to >2.1 kg P ha(-1)). We focus on the importance of P for the implementation of the EU Water Framework Directive and discuss the benefits, uncertainties, and side effects of the different targeted mitigation measures that can be adopted to combat P losses from agricultural areas in river basins. Experimental evidence of the effects of some of the main targeted mitigation measures hitherto implemented is demonstrated, including: (i) soil tillage changes, (ii) treatment of soils near ditches and streams with iron to reduce P transport from source areas to surface waters, (iii) establishment of buffer zones for retaining P from surface runoff, (iv) restoration of river-floodplain systems to allow natural inundation of riparian areas and deposition of P, and (v) inundation of riparian areas with tile drainage water for P retention. Furthermore, we show how river basin managers can map and analyze the extent and importance of P risk areas, exemplified by four catchments differing in size in Norway, Denmark, and the Netherlands. Finally, we discuss the factors and mechanisms that may delay and/or counteract the responses of mitigation measures for combating P losses from agricultural areas when monitored at the catchment scale.
Summary
Background
At the time of the German reunification in 1990, manifestations of most allergic diseases were less prevalent in East than in West Germany. It was hypothesized that these East–West ...differences would diminish with lifestyle and pollution changes in East Germany.
Objective
To investigate whether changes in the prevalence of asthma, hayfever, eczema or allergic sensitization in East Germany approached the levels seen in West Germany and to identify possible lifestyle or environmental factors that may influence this.
Methods
Between 1991 and 2000, 6‐year‐old children from four areas in East Germany participated in an annual survey. Every 3rd year, a parallel survey was performed in four areas of West Germany. In total, 31 903 children were included. Parents completed a questionnaire regarding lifestyle factors and diagnoses and symptoms of asthma, hayfever and eczema. In sub‐areas, eczema was clinically assessed by a dermatologist. Specific IgE sensitization was determined for 6121 children. Logistic regression was used to analyse differences in time trends and the influence of lifestyle and pollution changes.
Results
Lifestyle and pollution changed significantly differently between East and West Germany. The trends in hayfever and in strong (specific IgE >3.5) sensitization against pollen, and particularly birch pollen, were steeper in East than in West Germany. The trend towards marked pollen sensitization was four times stronger (95% confidence interval 1.2–13.9) in East than in West Germany. Increasing numbers of only children, less single‐room heating with fossil fuels and increasing importance of traffic‐related pollution in East Germany partly explained these differences in time trends.
Conclusions
Hayfever and sensitization against pollen were the most sensitive allergic manifestations to changes experienced specifically in East Germany. Influences of lifestyle (single‐room heating, living as a single child) were important in explaining different trend developments.
Cite this as: U. Krämer, H. Oppermann, U. Ranft, T. Schäfer, J. Ring and H. Behrendt, Clinical & Experimental Allergy, 2010 (40) 289– 298.
Summary
Background
Food allergy is common, especially in childhood, where 6–8% of children are affected. Identification of early and efficient markers for later development of food allergy is very ...important.
Objective
We examined the ability of repeated measurements of food sensitization in early childhood to predict doctor‐diagnosed food allergy (DDFA) at the age of 6 years.
Methods
The analysis was based on data from a prospective birth cohort study. Information was collected by parental questionnaires, and blood samples were obtained at 2 and 6 years of age. Children with repeated determination of sensitization to food allergens at 2 and 6 years of age were categorized into the sensitization phenotypes: no, early onset, late onset and persistent sensitization. The association between sensitization phenotypes and DDFA was prospectively investigated using multiple logistic regression analyses.
Results
Of 3097 children recruited at birth, a complete follow‐up of IgE measurements and questionnaires at 1.5, 2 and 6 years were available for 1082 children. Early food allergen sensitization (fx5) was a strong risk for DDFA at 6 years odds ratio (OR)=4.7; 95% confidence intervals (95% CI) 2.0–11.2 and for a new onset of DDFA at 6 years (OR=4.1; 95% CI 1.5–11.3). Additionally, persistent food allergen sensitization increased the risk of DDFA at 6 years (OR=6.1; 95% CI 2.7–13.7). Early sensitized children with a history of parental atopy showed the highest risk for DDFA at 6 years.
Conclusion
Food‐sensitized children during the first 2 years of life, especially with a family history of atopy, might be considered as a susceptible subgroup that requires specific attention concerning the development of food allergy‐related symptoms.
>Cite this as: E. Schnabel, S. Sausenthaler, B. Schaaf, T. Schäfer, I. Lehmann, H. Behrendt, O. Herbarth, M. Borte, U. Krämer, A. von Berg, H.‐E. Wichmann, J. Heinrich, and for the LISA Study Group, Clinical & Experimental Allergy, 2010 (40) 450–457.
The effect of dog ownership during childhood on the development of allergy has been investigated in few studies with conflicting results. The association between dog contact and indoor endotoxin ...exposure during infancy and the development of allergic sensitisation and atopic disease up to age 6 yrs was investigated. Two ongoing birth cohorts, the German Infant Nutrition Intervention Programme (GINI; n = 1,962) and the Influences of Lifestyle Related Factors on the Human Immune System and Development of Allergies in Children (LISA; n = 1,193), were analysed. In both studies, information on children's contact with dogs and their allergic symptoms and doctor-diagnosed allergic disease were collected during follow-up using questionnaires. Specific immunoglobulin E to common aeroallergens was measured at age 6 yrs. House dust samples were collected at age 3 months and the amount of endotoxin was determined. Dog ownership in early childhood was associated with a significantly lower rate of mixed pollen and inhalant sensitisation but not with dog sensitisation or allergic symptoms and diseases up to age 6 yrs. Regular contact with dogs, without ownership, during childhood was not associated with those health outcomes. No associations were found between house dust endotoxin exposure during infancy and sensitisation outcomes. In conclusion, dog ownership in early childhood protects against the development of inhalant sensitisation and this effect cannot be attributed to the simultaneous exposure to endotoxin.
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