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| 2. |
- Rieker-Schwienbacher, Juliane, et al.
(författare)
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Open-label parallel dose tolerability study of three subcutaneous immunotherapy regimens in house dust mite allergic patients
- 2013
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Ingår i: Clinical and Translational Allergy. - : Wiley. - 2045-7022. ; 3:16
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Tidskriftsartikel (refereegranskat)abstract
- Background The current maintenance dose (10,000 AUeq/monthly) of a subcutaneous allergoid for house dust mite (HDM) immunotherapy has previously shown significant clinical efficacy in patients with HDM induced allergic rhinitis or rhinoconjunctivitis. In order to comply with the 2009 EMA guidelines on immunotherapy products, a study was conducted to evaluate the safety, tolerability and short-term treatment effects of up-dosing regimens with high doses (up to 40,000 AUeq) of allergoid HDM immunotherapy. Methods In total 48 patients with HDM-allergic rhinitis or rhinoconjunctivitis (29 M/19 F; 18–53 years) were included and enrolled into one of three up-dosing regimens (1:4:4): 1) a regular regimen with up-dosing to 40,000 AUeq followed by two maintenance doses (total duration 17 weeks), 2) an intermediate regimen (14 weeks) or 3) a fast regimen (11 weeks). Safety and tolerability were evaluated by monitoring of early and late local reactions and systemic reactions. In addition, short-term effects were assessed by conjunctival provocation test (CPT) and levels of serum allergen-specific IgE, IgG and IgG4. Results Thirty-nine patients completed the study according to protocol. No early local reactions occurred. Late local reactions (LLR) were observed in 12% of the injections. In total, 31 systemic reactions, all grade 1, were reported of which two needed oral antihistamine treatment. No grade 2 or higher systemic reactions were observed. Six patients (15%) did not reach the highest dose due to LLR and/or systemic reactions needing antihistamines (20% in the regular regimen, 16% in the intermediate regimen and 13% in the fast regimen). At the end of the study, an improvement in the CPT was observed in 82.1% of patients, indirectly indicating an early treatment effect at the current dose and higher doses. In addition, IgG4 immunoglobulin levels were significantly increased in all groups following treatment. Conclusions In this open-label study, allergoid HDM immunotherapy in doses up to 40,000 AUeq was generally well tolerated and no clinically relevant safety issues were identified. In the safety aspects of the three up-dosing regimens no clinically relevant differences were encountered. Therefore, these dose ranges and up-dosing regimens can be safely included in future dose-finding efficacy studies.
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| 3. |
- Bossios, Apostolos, 1969, et al.
(författare)
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Effect of simulated gastro-duodenal digestion on the allergenic reactivity of beta-lactoglobulin
- 2011
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Ingår i: Clinical and Translational Allergy. - : Wiley. - 2045-7022. ; 1:6
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Background Cow's milk (CM) allergy affects about 2% of infants. The allergenicity of dietary proteins, including those from CM, has been related to their digestibility although the generality of the link and its causality remains to be demonstrated. In this study we use an in vitro digestion system, to investigate the digestibility of β-lactoglobulin (blg) during gastrointestinal transit and to assess the impact of this process on blg allergenic reactivity in CM allergic children. Methods Blg digesta were prepared using an in vitro digestion protocol simulating either gastric digestion alone or followed by duodenal digestion with or without phosphatidylcholine (PC). Biochemical analysis of blg digesta was performed by SDS-PAGE and their concentration was measured by a sandwich ELISA. Assessment of their allergenic reactivity was done in vitro by EAST inhibition, specific basophil activation (basotest) and lymphocyte proliferation (PCNA-flow cytometry) assays using sera and cells from patients allergic to blg and in vivo by skin prick testing (SPT) of these patients. Results Blg was only broken down to smaller peptides after gastro-duodenal digestion although a sizeable amount of intact protein still remained. Digestion did not modify the IgE binding capacity of blg except for gastro-duodenal digestion performed in the absence of PC. These results are consistent with the quantity of intact blg remaining in the digesta. Overall both gastric and gastroduodenal digestion enhanced activation of sensitized basophils and proliferation of sensitized lymphocytes by blg. However, there was a tendency towards reduction in mean diameter of SPT following digestion, the PC alone during phase 1 digestion causing a significant increase in mean diameter. Conclusions Digestion did not reduce the allergenic reactivity of blg to a clinically insignificant extent, PC inhibiting digestion and thereby protecting blg allergenic reactivity. SPT reactivity was reduced compared to blg immunoreactivity in in vitro tests.
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| 4. |
- Calderon, Moises A, et al.
(författare)
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EAACI: A European Declaration on Immunotherapy. Designing the future of allergen specific immunotherapy.
- 2012
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Ingår i: Clinical and translational allergy. - : Wiley. - 2045-7022. ; 2:1
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Tidskriftsartikel (refereegranskat)abstract
- Allergy today is a public health concern of pandemic proportions, affecting more than 150 million people in Europe alone. In view of epidemiological trends, the European Academy of Allergy and Clinical Immunology (EAACI) predicts that within the next few decades, more than half of the European population may at some point in their lives experience some type of allergy.Not only do allergic patients suffer from a debilitating disease, with the potential for major impact on their quality of life, career progression, personal development and lifestyle choices, but they also constitute a significant burden on health economics and macroeconomics due to the days of lost productivity and underperformance. Given that allergy triggers, including urbanization, industrialization, pollution and climate change, are not expected to change in the foreseeable future, it is imperative that steps are taken to develop, strengthen and optimize preventive and treatment strategies.Allergen specific immunotherapy is the only currently available medical intervention that has the potential to affect the natural course of the disease. Years of basic science research, clinical trials, and systematic reviews and meta-analyses have convincingly shown that allergen specific immunotherapy can achieve substantial results for patients, improving the allergic individuals' quality of life, reducing the long-term costs and burden of allergies, and changing the course of the disease. Allergen specific immunotherapy not only effectively alleviates allergy symptoms, but it has a long-term effect after conclusion of the treatment and can prevent the progression of allergic diseases.Unfortunately, allergen specific immunotherapy has not yet received adequate attention from European institutions, including research funding bodies, even though this could be a most rewarding field in terms of return on investments, translational value and European integration and, a field in which Europe is recognized as a worldwide leader. Evaluation and surveillance of the full cost of allergic diseases is still lacking and further progress is being stifled by the variety of health systems across Europe. This means that the general population remains unaware of the potential use of allergen specific immunotherapy and its potential benefits.We call upon Europe's policy-makers to coordinate actions and improve individual and public health in allergy by:Promoting awareness of the effectiveness of allergen specific immunotherapyUpdating national healthcare policies to support allergen specific immunotherapyPrioritising funding for allergen specific immunotherapy researchMonitoring the macroeconomic and health economic parameters of allergyReinforcing allergy teaching in medical disciplines and specialtiesThe effective implementation of the above policies has the potential for a major positive impact on European health and well-being in the next decade.
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| 5. |
- Cui, Zhi-Hua, 1958, et al.
(författare)
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Repeated allergen exposure reduce early phase airway response and leukotriene release despite upregulation of 5-lipoxygenase pathways.
- 2012
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Ingår i: Clinical and translational allergy. - : Wiley. - 2045-7022. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- Background Allergen induced early phase airway response and airway plasma exudation are predominantly mediated by inflammatory mast cell mediators including histamine, cysteinyl leukotrienes (cysLTs) and thromboxane A2 (TXA2). The aim of the present study was to evaluate whether repeated allergen exposure affects early phase airway response to allergen challenge. Methods A trimellitic anhydride (TMA) sensitized guinea pig model was used to investigate the effects of low dose repeated allergen exposure on cholinergic airway responsiveness, early phase airway response and plasma exudation, as well as local airway production of mast cell derived cysteinyl leukotrienes and thromboxane B2 (TXB2) after allergen challenge. Results Repeated low dose allergen exposure increased cholinergic airway responsiveness. In contrast, early phase airway response and plasma exudation in response to a high-dose allergen challenge were strongly attenuated after repeated low dose allergen exposure. Inhibition of the airway response was unspecific to exposed allergen and independent of histamine receptor blocking. Furthermore, a significant reduction of cysteinyl leukotrienes and TXB2 was found in the airways of animals repeatedly exposed to a low dose allergen. However, in vitro stimulation of airway tissue from animals repeatedly exposed to a low dose allergen with arachidonic acid and calcium ionophore (A23187) induced production of cysteinyl leukotrienes and TXB2, suggesting enhanced activity of 5-lipoxygenase and cyclooxygenase pathways. Conclusions The inhibition of the early phase airway response, cysteinyl leukotriene and TXB2 production after repeated allergen exposure may result from unresponsive effector cells.
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| 6. |
- Forsberg, Anna, et al.
(författare)
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Pre- and postnatal administration of Lactobacillus reuteri decreases TLR2 responses in infants
- 2014
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Ingår i: Clinical and Translational Allergy. - : BioMed Central. - 2045-7022 .- 2045-7022. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Mice models indicate that intact Toll like receptor (TLR) signaling may be essential for the allergy protective effects of diverse bacterial exposure observed in clinical trials and epidemiological studies. Probiotic supplementation with Lactobacillus reuteri from pregnancy week 36 and to the infant through the first year of life decreased the prevalence of IgE-associated eczema at two years (ClinicalTrials. gov NCT01285830). The effect of this supplementation on innate immune responses to bacterial products and the expression of associated TLRs were explored.Methods: Blood mononuclear cells were collected at birth, 6, 12 and 24 months from 61 infants and cultured with TLR2, 4 and 9 ligands. Cytokine and chemokine secretion was determined as well as TLR2, 4 and 9 mRNA expression. Results: Probiotic supplementation was associated with decreased LTA (lipoteichoic acid) induced CCL4, CXCL8, IL-1 beta and IL-6 responses at 12 months and decreased CCL4 and IL-1 beta secretion at 24 months. TLR2 mRNA expression was not affected by probiotic treatment.Conclusions: Decreased responses to TLR2, the main receptor for LTA from Gram positive bacteria, in probiotic treated children seem to be dependent on factors downstream of TLR mRNA expression.
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| 7. |
- Gülen, Theo, et al.
(författare)
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The significance of diagnosing associated clonal mast cell diseases in patients with venom-induced anaphylaxis and the role of bone marrow investigation
- 2013
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Ingår i: Clinical and Translational Allergy. - : Wiley. - 2045-7022 .- 2045-7022. ; 3:1, s. 22-
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Tidskriftsartikel (refereegranskat)abstract
- Hymenoptera venom allergy (HVA) represents a particular risk for exceptionally severe anaphylactic sting reactions in patients with clonal mast cell disorders (CMD). Nevertheless, conventional investigations are not sufficient to do accurate risk assessments. Increased levels of baseline serum tryptase (sBT) (>11.4 μg/L) is highly associated with severe anaphylactic reactions and with a possible underlying CMD. The measurement of baseline serum tryptase, thus, has opened the possibility to screen for CMD. In the present study, we sought to investigate whether bone marrow evaluation provides more accurate diagnosis in patients with HVA.Three patients of the same sex and similar age with HVA were enrolled in this clinical study. The patients underwent comprehensive allergy work-up including skin prick testing, measurements of serum total IgE concentrations and baseline serum tryptase. Bone-marrow biopsies were also performed in all three patients to assess underlying CMD.We evaluated characteristics of the bone marrow mast cells by pathology, flow cytometry and detection of D816V mutation by using current WHO-criteria, which led to changes in the final diagnosis compared to the assessments done by classical allergy work-up and measurements of sBT. Three distinct diagnostic outcomes including systemic mastocytosis, monoclonal mast cell activation syndrome and non-clonal HVA were revealed.We conclude that a bone marrow investigation is required for the correct diagnosis of hymenoptera venom-induced anaphylactic reactions in patients with elevated baseline tryptase levels (>11.4 μg/L), and this has important implications for management strategies.
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| 8. |
- Hedman, Linnéa, et al.
(författare)
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Conventional epidemiology underestimates the incidence of asthma and wheeze-a longitudinal population-based study among teenagers
- 2012
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Ingår i: Clinical and Translational Allergy. - : Wiley. - 2045-7022. ; 2:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Because of shifts in the gender ratio and incidence and remission rates of asthma during the teen ages, the methodology of incidence studies among teenagers is important, i.e. if the time intervals between surveys are too long, the incident cases might not be properly identified. The aim was to study the impact of study design on the incidence rates of asthma and wheeze during the teen ages. Methods. In a study about asthma and allergic diseases within the OLIN studies (Obstructive Lung Disease in northern Sweden), a cohort of school children (n = 3,430) was followed annually by questionnaire from age 8 yrs. In the endpoint survey (age 18 yrs) 2,582 (75% of original responders) participated. Incident cases from age 12-18 yrs were identified by two methods: annual questionnaire reports (AR) and baseline-endpoint surveys only (BE). Results: The cumulative incidence of asthma and wheeze was significantly higher based on AR compared to BE. Compared to the incidence rates based on all the annual surveys, the calculated average annual rates based on BE were in general lower both among the boys and among the girls. There were no differences between boys and girls in incidence rates of asthma or wheeze during the early teen years. However, from the age of 15 years, the annual incidence rates were significantly or borderline significantly higher among girls than boys. At onset, the additional cases of current asthma identified by AR had significantly less severe asthma than those identified in BE (p < 0.02). Conclusion: the size of the incidence of asthma and wheeze during the teen ages was influenced by study design. By using the conventional prospective study design with longer follow-up time, the incidence was underestimated. © 2012 Hedman et al; licensee BioMed Central Ltd.
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| 9. |
- Lâm, Hoàng Thị, et al.
(författare)
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Allergic rhinitis in northern Vietnam : increased risk of urban living according to a large population survey
- 2011
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Ingår i: Clinical and Translational Allergy. - : BioMed Central. - 2045-7022 .- 2045-7022. ; 1:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Little is known about prevalence and risk factors of allergic rhinitis and chronic nasal symptoms among adults in Vietnam. We aimed to estimate the prevalence, risk factor patterns and co-morbidities of allergic rhinitis and chronic nasal symptoms in one urban and one rural area in northern Vietnam.Methods: A cross-sectional questionnaire survey was conducted from August 2007 to January 2008 in urban Hoankiem and rural Bavi in Hanoi among adults aged 21-70 years. Of 7008 randomly selected subjects, 91.7% participated in Bavi and 70.3% in Hoankiem.Results: Allergic rhinitis ever or chronic nasal symptoms were reported by 50.2%. The prevalence of allergic rhinitis ever was considerably higher in Hoankiem compared to Bavi, 29.6% vs 10.0% (p < 0.001). Allergic rhinitis ever and chronic nasal symptoms were both significantly associated with asthma and respiratory symptoms, respectively (p < 0.001). Exposure to gas, dust or fumes at work was significantly associated with allergic rhinitis ever, OR 1.57 (95% CI 1.34 - 1.84), nasal blocking, OR 1.90 (95% CI 1.68 - 2.15) and runny nose, OR 1.32 (95% CI 1.17 - 1.49), while somewhat surprisingly no association with smoking was found. Female sex was a significant risk factor for both nasal blocking and runny nose.Conclusions: Allergic rhinitis ever was considerably more common in the urban area. Nasal blocking and runny nose was each reported by about one third of the studied sample with no major urban-rural difference. Further, exposure to air pollution at work was significantly associated with allergic rhinitis ever, nasal blocking and runny nose.
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| 10. |
- Lâm, Hoàng Thị, et al.
(författare)
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Sensitization to airborne allergens among adults and its impact on allergic symptoms : a population survey in northern Vietnam
- 2014
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Ingår i: Clinical and Translational Allergy. - : BioMed Central. - 2045-7022 .- 2045-7022. ; 4:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The knowledge about allergic sensitization and its relationship with clinical symptoms and diseases among adults in South-East Asia is poor. The aim of this study was to investigate the prevalence and pattern of allergic sensitization and the association with asthma and allergic rhinitis in adults in urban and rural Vietnam. METHODS: Among 5,782 responders to a questionnaire survey in northern Vietnam, a random sample was invited to a clinical follow-up and 684 (46%) participated. The methods included a structured interview using a modified GA2LEN study questionnaire on symptoms and possible determinants for diseases. Skin prick test (SPT) with ten common airborne indoor and outdoor allergens, lung function test, and methacholine test was performed among subjects ≤60 years of age. RESULTS: In total, one third of subjects had a positive SPT reaction to at least one allergen, 36.9% of men and 31.0% of women (n.s.). The most common sensitizer was the storage mite B. tropicalis (men 27.7%; women 18.7%) followed by house dust mite D. pteronyssinus (men 16.5%; women 10.6%), and D. farinae (men 15.3%; women 6.3%), and cockroach (men 16.5%; women 10.2%). Sensitization to all major allergens were significantly more common among men and among subjects ≤45 years compared with women and subjects >45 years, respectively. The prevalence of sensitization to animals, pollen and molds were low. The majority of cockroach-sensitized subjects were also sensitized to mites. Sensitization to any allergen and all major allergens were significantly associated with rhinitis, but not with asthma. However, bronchial hyper-reactivity was significantly associated with increasing number of positive SPTs (p = 0.047). CONCLUSIONS: Among adults in northern Vietnam sensitization to mite and cockroach most common in both rural and urban areas. The dominant sensitizer was the storage mite B. tropicalis, which should be included in future studies and also in clinical practice, owing to its association with clinical symptoms. As in the Western world allergic sensitization was associated with rhinitis and bronchial hyper-reactivity. The lack of association with asthma in South-East Asia needs to be studied further.
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