Predicting the start, peak and end of the Betula pollen season in Bavaria, Germany.

Betula pollen is frequently found in the atmosphere of central and northern Europe. Betula pollen are health relevant as they cause severe allergic reactions in the population. We developed models of thermal requirements to predict start, peak and end dates of the Betula main pollen season for Bavaria (Germany). Betula pollen data of one season from 19 locations were used to train the models. Estimated dates were compared with observed dates, and the errors were spatially represented. External validation was carried out with time series datasets of 3 different locations (36years in total). RESULTS: The temperature requirements to detonate the main pollen season proved non-linear. For the start date model (error of 8,75days during external validation), daily mean temperatures above a threshold of 10°C from 28th of February onwards were the most relevant. The peak model (error of 3.58days) takes into account mean daily temperatures accumulated since the first date of the main pollen season in which the daily average temperature exceeded 11°C. The end model (error of 3.75days) takes into account all temperatures accumulated since the start of the main pollen season. CONCLUSION: These models perform predictions that enable the allergic population to better manage their disease. With the established relationship between temperatures and pollen season dates, changes in the phenological behaviour of Betula species due to climate change can be also estimated in future studies by taking into account the different climate scenarios proposed by previous climate change studies.

Conjunctivitis in atopic dermatitis patients with and without dupilumab therapy - international eczema council survey and opinion.

BACKGROUND: Conjunctivitis is common in patients with atopic dermatitis (AD) in general and a commonly reported adverse event in AD clinical trials with dupilumab. OBJECTIVE: To survey opinions and experience about conjunctivitis occurring in AD, including those during dupilumab treatment in a group of AD experts from the International Eczema Council (IEC). METHODS: Electronic survey and in-person discussion of management strategies. RESULTS: Forty-six (53.5%) IEC members from 19 countries responded to the survey. Consensus was reached for several statements regarding diagnostic workup, referral and treatment. IEC members suggest that patients with AD should (i) routinely be asked about ocular complaints or symptoms, (ii) obtain information about the potential for conjunctivitis before starting dupilumab therapy and (iii) if indicated, be treated with dupilumab despite previous or current conjunctivitis. In cases of new-onset conjunctivitis, there was consensus that dupilumab treatment should be continued when possible, with appropriate referral to an ophthalmologist. LIMITATIONS: The study relies on expert opinion from dermatologists. Responses from few dermatologists without dupilumab access were not excluded from the survey. CONCLUSION: The IEC recommends that dermatologists address conjunctivitis in patients with AD, especially during treatment with dupilumab.

Pollen derived low molecular compounds enhance the human allergen specific immune response in vivo.

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.

Pollen-derived nonallergenic substances enhance Th2-induced IgE production in B cells.

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.

Pollen-derived adenosine is a necessary cofactor for ragweed allergy.

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.

Pollen-derived low-molecular weight factors inhibit 6-sulfo LacNAc+ dendritic cells' capacity to induce T-helper type 1 responses.

BACKGROUND: Evidence is accumulating that the pollen exsudate contains an array of non-allergenic, pro-inflammatory and immunomodulatory substances acting on the innate and adaptive immune system. In this context, pollen-associated E(1)-phytoprostanes (PPE(1)) were shown to licence human monocyte-derived dendritic cells for T-helper type 2 (Th2) polarization of naïve T cells. OBJECTIVE: This study aims at analysing the impact of pollen-associated lipid mediators on cytokine secretion and maturation of 6-sulfo LacNAc(+) dendritic cells (slanDCs), the most abundant native dendritic cell (DC) in human peripheral blood, and further dissecting the biologically active substance(s) within aqueous pollen extracts. RESULTS: Aqueous birch pollen extracts dose-dependently inhibited the lipopolysaccharide (LPS)-induced IL-12 p70 production, while the levels of IL-6 remained unaffected. PPE(1) inhibited secretion of both IL-12 p70 and IL-6. Aqueous pollen extracts, but not PPE(1) or F(1)-phytoprostanes significantly reduced the LPS-induced surface expression of the maturation markers CD80, CD83, CD40 and CCR-7, an effect that was independent of proteins and that was still present in a 3 kDa cut-off fraction of the pollen extract. These effects were observed irrespective of the atopy status of the donors. Finally, slanDCs exposed to aqueous pollen extracts were impaired in eliciting an IFN-gamma response in naïve CD4(+) T cells. CONCLUSION: Our data show that slanDCs, a subset of human blood DCs with constitutively high potency to induce Th1 responses, are susceptible to the Th2 polarizing effect of low molecular weight, non-protein factors derived from pollen.

Impact of urbanization on the proteome of birch pollen and its chemotactic activity on human granulocytes.

BACKGROUND: Epidemiologic studies reveal a dramatic increase in allergies in the last decades. Air pollution is considered to be one of the factors responsible for this augmentation. The aim of this study was to analyze the impact of urbanization on birch pollen. The birch pollen proteome was investigated in order to identify differences in protein abundance between pollen from rural and urban areas. The allergenicity of birch pollen from both areas was evaluated by assessing its chemotactic potency as well as its protein and allergen contents. METHODS: Difference gel electrophoresis (DIGE) was used to analyze the pollen proteome. The chemotactic activity of aqueous pollen extracts was determined by migration assays of human neutrophils. RESULTS: DIGE revealed 26 differences in protein spot intensity between pollen from urban and rural areas. One of these proteins was identified by de novo sequencing as the 14-3-3 protein, which resembles a stress-induced factor in other plant species. Furthermore, extracts from pollen collected in urban areas had higher chemotactic activity on human neutrophils compared to pollen from rural sites. CONCLUSIONS: The present study points to an impact of air pollution on allergen carrier proteome and release of chemotactic substances. The increment in proinflammatory substances such as pollen-associated lipid mediators might contribute to the described urban-rural gradient of allergy prevalence. Furthermore, our study suggests that allergenicity is determined by more than the sole allergen content.