Publications by authors named "Sten Dreborg"

36 Publications

The pharmacokinetics of epinephrine/adrenaline autoinjectors.

Allergy Asthma Clin Immunol 2021 Mar 8;17(1):25. Epub 2021 Mar 8.

Department of Medicine, Western University, London, Canada.

Background: For a century, epinephrine has been the drug of choice for acute treatment of systemic allergic reactions/anaphylaxis. For 40 years, autoinjectors have been used for the treatment of anaphylaxis. Over the last 20 years, intramuscular epinephrine injected into the thigh has been recommended for optimal effect.

Objective: To review the literature on pharmacokinetics of epinephrine autoinjectors.

Results: Six studies assessing epinephrine autoinjector pharmacokinetics were identified. The studies, all on healthy volunteers, were completed by Simons, Edwards, Duvauchelle, Worm and Turner over the span of 2 decades. Simons et al. published two small studies that suggested that intramuscular injection was superior to subcutaneous injection. These findings were partially supported by Duvauchelle. Duvauchelle showed a proportional increase in C and AUC when increasing the dose from 0.3 to 0.5 mg epinephrine intramuscularly. Turner confirmed these findings. Simons, Edwards and Duvauchelle documented the impact of epinephrine on heart rate and blood pressure. Turner confirmed a dose-dependent increase in heart rate, cardiac output and stroke volume. Based on limited data, confirmed intramuscular injections appeared to lead to faster C. Two discernable C were identified in most of the studies. We identified similarities and discrepancies in a number of variables in the aforementioned studies.

Conclusions: Intramuscular injection with higher doses of epinephrine appears to lead to a higher C. There is a dose dependent increase in plasma concentration and AUC. Most investigators found two C with T 5-10 min and 30-50 min, respectively. There is a need for conclusive trials to evaluate the differences between intramuscular and subcutaneous injections with the epinephrine delivery site confirmed with ultrasound.
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http://dx.doi.org/10.1186/s13223-021-00511-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938517PMC
March 2021

Epinephrine auto-injector needle length: The impact of winter clothing.

Allergy Asthma Clin Immunol 2020 15;16:24. Epub 2020 Apr 15.

2Department of Medicine, Western University, London, Canada.

Background: Epinephrine auto-injectors are expected to deliver the drug intramuscularly.

Objective: To study whether injection through clothing influences the frequency of subcutaneous and intraosseous/periosteal deposition of epinephrine.

Methods: Skin to muscle and skin to bone distances were measured for 303 children and adolescents and 99 adults. Distance was determined by ultrasound, with high or low pressure on the ultrasound probe. The risk/percentage of subcutaneous and intraosseous/periosteal injections was calculated using the lower and upper limits for the authority-approved length of EAI needles as provided by two high pressure EAI manufacturers and one low pressure EAI manufacturer. The addition winter clothing on the delivery of epinephrine was illustrated by comparing drug delivery fissue depth with no clothes. Furthermore, the riof non-intramuscular delivery for the shortest and longest approved needle length was calculated.

Results: When using EpipenJr in children < 15 kg the risk of intraosseous/periostal injection was reduced from 1% and 59% for the shortest and longest approved needle length to 0 and 15% with winter clothes. The Auvi-Q 0.1 mg had no risk of intraosseous/periosteal injection. However, the subcutaneous deposition risk increased from 94% and 28% to 100% and 99% with winter clothes. The risk of subcutaneous injection using EpipenJr in the youngest children increased from 13% and 0% to 81% and 1% with winter clothes, and with Epipen in adults from 45% and 17% to 60% and 38%. Emerade, had a risk of subcutaneous injection in adults increasing from 14% and 10% to 28% and 21% adding winter clothes.

Conclusion: The risk of intraosseous/periosteal injections decreases and the risk of subcutaneous injection increases when injecting through winter clothes for all EAIs.
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http://dx.doi.org/10.1186/s13223-020-00422-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7160976PMC
April 2020

In-vivo diagnostic test allergens in Europe: A call to action and proposal for recovery plan-An EAACI position paper.

Allergy 2020 09;75(9):2161-2169

Allergy Section, Department of Internal Medicine, Hospital Valld'Hebron, Barcelona, Spain.

Diagnostic allergens are defined as medicinal products in the EU. Marketing authorization by national authorities is necessary; however, diagnostic allergens are not homogeneously regulated in different EU member states. Allergen manufacturers argue with increasing costs forcing them to continuously reduce the diagnostic allergen portfolios offered to allergists. In contrast, EAACI and national European Allergy Societies see the need for the availability of a wide range of high-quality diagnostic allergens for in vivo diagnosis of IgE-mediated allergies not only covering predominant but also less frequent allergen sources. In a recent EAACI task force survey, the current practice of allergy diagnosis was shown to rely on skin tests as first option in almost 2/3 of all types of allergic diseases and in 90% regarding respiratory allergies. With the need to ensure the availability of high-quality diagnostic allergens in the EU, an action plan has been set up by EAACI to analyse the current regulatory demands in EU member states and to define possible solutions stated in this document: (a) simplification of authorization for diagnostic allergens; (b) specific regulation of special types of diagnostic allergens; (c) new models beyond the current model of homologous groups; (d) simplification of pharmacovigilance reporting; (e) reduction of regulation fees for diagnostic allergens; (f) reimbursement for diagnostic allergens. Joining forces of allergists, manufacturers and authorities are of high importance to ensure remaining relevant allergens in the EU markets to facilitate a sustainable and comprehensive service for the diagnosis and treatment of allergic diseases.
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http://dx.doi.org/10.1111/all.14329DOI Listing
September 2020

Epinephrine autoinjectors: The needle length matters.

Ann Allergy Asthma Immunol 2020 05 20;124(5):449-450. Epub 2019 Dec 20.

Department of Medicine, Western University, Canada; Department of Medicine, McMaster University, Canada.

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http://dx.doi.org/10.1016/j.anai.2019.12.014DOI Listing
May 2020

Standardization of Allergen Extracts.

Methods Mol Biol 2019 ;2020:63-76

Department of Women's and Children's Health, Uppsala University and Academic Hospital, Uppsala, Sweden.

Allergens are molecules with the capacity to elicit IgE responses in humans. When stimulated with allergens, most allergic patients respond with production of IgE specific for several proteins/allergens in the source material. The standardization of allergen extracts is essential in order to control variability and to achieve consistency and reproducibility in a clinical setting.Because the IgE binding capacity of an allergen extract is related to the content of one or a few major allergens, it is important that the standardization procedure ensures consistency, not only in the overall IgE binding potency, but also in the content and ratio of individual major allergens. Owing to the complexity of allergen extracts, a key element in standardization of allergen extracts is the use of standards.This chapter describes the principles for standardization of allergen extracts to be used by research laboratories. Other chapters in this volume describe in vitro methods in detail.
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http://dx.doi.org/10.1007/978-1-4939-9591-2_5DOI Listing
March 2020

Implications of variation of epinephrine auto-injector needle length.

Ann Allergy Asthma Immunol 2019 07 7;123(1):89-94. Epub 2019 May 7.

Department of Medicine, Western University, London, Canada; Department of Medicine, McMaster University, Hamilton, Canada.

Background: The variation of needle lengths of epinephrine auto-injectors (EAIs) has not been investigated.

Objective: To investigate the impact of the variation of the needle length of EAIs.

Methods: Skin-to-muscle (STMD) and skin-to-bone distances (STBD) were measured for 303 children and adolescents and 99 adults. Distance was determined by ultrasound, applying high or low pressure on the probe. The risk of subcutaneous and periosteal/intraosseous injection was calculated using the lower and upper acceptance limits for length of EAI needles as provided for 3 high-pressure EAIs (HPEAI) and 1 low-pressure EAI (LPEAI).

Results: The variation in needle length of the HPEAIs are for Epipen Jr/Epipen 5 mm, for Jext 2 mm, for Auvi-Q 2.5 mm, and for the LPEAI, Emerade, 1.5 mm. When using the longest acceptable needles for Epipen Jr, the risk of intraosseous/periosteal penetration was highest in children weighing less than 15 kg at 60% and for Jext at 43%. The risk was low for Auvi-Q and Emerade. The risk of subcutaneous injection was greatest with the shortest needles of the Auvi-Q 0.1 mg at 94% in children weighing less than 15 kg. In adults, the risk of subcutaneous injection using the shortest needles was for Epi-Pen at 41%, Jext at 36%, Auvi-Q at 38%, and Emerade at 12%.

Conclusion: The variation in needle length of EAIs influences the risk of subcutaneous and intraosseous/periosteal injections. Compared with Epipen Jr, the Auvi-Q 0.1 mg for children weighing less than 15 kg had a low risk of intraosseous/periosteal injection but a very high risk of subcutaneous injection. For adults, there is a significant risk of subcutaneous injection.
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http://dx.doi.org/10.1016/j.anai.2019.04.027DOI Listing
July 2019

Tissue compression and epinephrine deposition.

J Allergy Clin Immunol Pract 2019 Jul - Aug;7(6):2096-2097. Epub 2019 May 2.

Division of Clinical Immunology and Allergy, Western University, London, Ontario, Canada; McMaster University, Hamilton, Ontario, Canada.

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http://dx.doi.org/10.1016/j.jaip.2019.03.038DOI Listing
May 2020

Mind the gaps: Clinical trial concepts to address unanswered questions in aeroallergen immunotherapy-An NIAID/AHRQ Workshop.

J Allergy Clin Immunol 2019 05 5;143(5):1711-1726. Epub 2019 Feb 5.

Division of Allergy, Immunology, and Transplantation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Md.

The Agency for Healthcare Research and Quality and the National Institute of Allergy and Infectious Diseases organized a workshop to develop trial concepts that could improve the use and effectiveness of aeroallergen immunotherapy (AAIT). Expert groups were formed to accomplish the following tasks: (1) propose a study design to compare the effectiveness and safety of subcutaneous versus sublingual AAIT; (2) propose a study design to compare the effectiveness and safety of AAIT by using 1 or a few allergens versus all or most allergens to which a patient is sensitized; (3) propose a study design to determine whether AAIT can alter the progression of childhood allergic airways disease; and (4) propose a study design to determine the optimal dose and duration of AAIT to achieve maximal effectiveness with acceptable safety. Study designs were presented by the workgroups, extensively discussed at the workshop, and revised for this report. The proposed trials would be of long duration and require large highly characterized patient populations. Scientific caveats and feasibility matters are discussed. These concepts are intended to help the development of clinical trials that can address some of the major questions related to the practice of AAIT for the management and prevention of allergic airways disease.
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http://dx.doi.org/10.1016/j.jaci.2019.01.032DOI Listing
May 2019

Authors' response.

Ann Allergy Asthma Immunol 2018 11;121(5):644-645

Department of Medicine, Western University, London, Ontario, Canada; Department of Medicine, McMaster University, Hamilton, Ontario, Canada.

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http://dx.doi.org/10.1016/j.anai.2018.09.456DOI Listing
November 2018

Methodological cutoff of basophil activation test and basophil activation test diagnostic value.

Authors:
Sten Dreborg

J Allergy Clin Immunol Pract 2018 May - Jun;6(3):1089-1090

Women's and Children's Health, Department of Child and Adolescent Allergology, Uppsala University, Uppsala, Sweden. Electronic address:

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http://dx.doi.org/10.1016/j.jaip.2017.10.038DOI Listing
September 2019

Epinephrine auto-injector needle lengths: Can both subcutaneous and periosteal/intraosseous injection be avoided?

Ann Allergy Asthma Immunol 2018 06 27;120(6):648-653.e1. Epub 2018 Feb 27.

Department of Medicine, Western University, London, Ontario, Canada; Department of Medicine, McMaster University, Hamilton, Ontario, Canada.

Background: Epinephrine should be administered intramuscularly in the anterolateral aspect of the thigh. The length of the epinephrine auto-injector (EAI) needle should ensure intramuscular injection.

Objective: To discuss suitable EAI needle lengths based on ultrasound measurements related to weight.

Methods: The skin-to-muscle distance (STMD) and skin-to-bone distance (STBD) were measured by ultrasound in the mid-third of the anterolateral area of the right thigh when applying high pressure (8 lb; high-pressure EAI [HPEAI]) or low pressure (low-pressure EAI [LPEAI]) on the ultrasound probe. The study included 302 children and adolescents and 99 adults. The maximum and minimum STMD and the maximum and minimum STBD were estimated.

Results: Using HPEAIs, the risk of periosteal or intraosseous penetration was 32% in children weighing less than 15 kg. The risk of subcutaneous injection was 12% in adolescents and 33% in adults. With LPEAIs, there was no risk of periosteal or intraosseous injection and the risk of subcutaneous injections in adolescents and adults was lower at 2% and 10%, respectively. A new EAI for injection in small children would have no risk of periosteal or intraosseous injection but would have 71% chance of subcutaneous deposit of epinephrine.

Conclusion: Common HPEAIs have a high risk of periosteal or intraosseous penetration in children and subcutaneous injections in overweight and obese adults. LPEAIs have some risk of subcutaneous injection in adults. HPEAIs with 0.1 mg of epinephrine and shorter needles have no risk of periosteal or intraosseous injection but have a high risk of subcutaneous deposit. For adult or overweight or obese patients, HPEAIs and LPEAIs should have longer needles. Future studies should focus on triggering pressures and variations in needle length.
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http://dx.doi.org/10.1016/j.anai.2018.02.028DOI Listing
June 2018

Erratum to: Do epinephrine auto-injectors have an unsuitable needle length in children and adolescents at risk for anaphylaxis from food allergy?

Allergy Asthma Clin Immunol 2017 7;13:33. Epub 2017 Jul 7.

Department of Medicine, Western University, London, Canada.

[This corrects the article DOI: 10.1186/s13223-016-0110-8.].
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http://dx.doi.org/10.1186/s13223-017-0205-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5501593PMC
July 2017

Current Evidence on Safety and Practical Considerations for Administration of Sublingual Allergen Immunotherapy (SLIT) in the United States.

J Allergy Clin Immunol Pract 2017 Jan - Feb;5(1):34-40.e2. Epub 2016 Nov 1.

Department of Pediatric Allergy, Women's and Children's Health, University of Uppsala, Uppsala, Sweden.

Liquid sublingual allergen immunotherapy (SLIT) has been used off-label for decades, and Food and Drug Administration (FDA)-approved grass and ragweed SLIT tablets have been available in the United States since 2014. Potentially life-threatening events from SLIT do occur, although they appear to be very rare, especially for FDA-approved products. Practice guidelines that incorporate safety precautions regarding the use of SLIT in the United States are needed. This clinical commentary attempts to address unresolved issues including controversy regarding the FDA mandate for the prescription of epinephrine autoinjectors for patients on SLIT; how to approach polysensitized patients; optimal timing and duration of SLIT administration; how to address gaps in therapy; whether antihistamines can prevent local reactions, if certain patient populations (such as persistent asthmatics) should not receive SLIT; and when to instruct patients to self-administer epinephrine. Key points are that physicians should focus on educating patients regarding: (1) when not to administer SLIT; (2) how to recognize a potentially serious allergic reaction to SLIT; and (3) when to administer epinephrine and seek emergency care.
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http://dx.doi.org/10.1016/j.jaip.2016.09.017DOI Listing
November 2017

Do epinephrine auto-injectors have an unsuitable needle length in children and adolescents at risk for anaphylaxis from food allergy?

Allergy Asthma Clin Immunol 2016 6;12:11. Epub 2016 Mar 6.

Department of Medicine, Western University, London, Canada ; Department of Medicine, McMaster University, Hamilton, ON Canada.

Background: Food allergy is the most common cause of anaphylaxis in children. Intramuscular delivery of epinephrine auto-injectors (EAI) is the standard of care for the treatment of anaphylaxis. We examined if children and adolescents at risk of anaphylaxis weighing 15-30 kg and >30 kg would receive epinephrine into the intramuscular space with the currently available EAI in North America and Europe.

Methods: The distance from skin to muscle (STMD) and skin to bone (STBD) on the mid third anterolateral area of the right thigh was measured by ultrasound applying either high pressure (max) or slight pressure (min) in 102 children weighing 15-30 kg (group 1) and 100 children and adolescents, weighing more than 30 kg (group 2).

Results: Using a high pressure EAI (HPEAI), Epipen Jr(®) and Auvi-Q(®)/Allerject(®) 0.15 mg, 11/102 (11 %) children in group 1 and 38/102 (38 %) using another HPEAI, Jext(®), had a STMDmax that showed a risk of intraosseous injection. There was a 1 % risk of subcutaneous injection with these devices. There was no risk of intraosseous injection using a low pressure EAI (LPEAI), Emerade(®). In group 2, the risk of intraosseous injection using a HPEAI was 3 % and no risk using a LPEAI. However, the risk of subcutaneous injection using HPEAI was 9 % and using LPEAI was 2 %.

Conclusion: There is a risk of intraosseous injection using HPEAI (Epipen(®)/Epipen Jr(®), Auvi-Q(®)/Allerject(®) and especially Jext(®)) in children at risk of anaphylaxis. There was also a risk of subcutaneous injection using the currently available HPEAI in children and adolescents.
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http://dx.doi.org/10.1186/s13223-016-0110-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4779571PMC
March 2016

Debates in allergy medicine: food intolerance does not exist.

Authors:
Sten Dreborg

World Allergy Organ J 2015 14;8:37. Epub 2015 Dec 14.

Women's and Children's Health, University of Uppsala, Uppsala, Sweden.

Background: The term "intolerance" is not mentioned in the World Allergy Organization (WAO) document on allergy nomenclature. "Intolerance" has been used to describe some non-immunological diseases. However, pediatric gastroenterologists mix allergy and intolerance, e.g. by using the term "cow's milk protein allergy/intolerance (CMPA/I)", lumping together all types of mechanisms for not tolerating cow's milk. The basis for this mix is the fact that double-blind oral food challenges are time-consuming and expensive. Therefore, cow's milk exclusion and reintroduction is proposed to be used in primary care for the diagnosis of CMPA in children with common gastrointestinal (GI) problems such as colic and constipation. This may lead to a widespread use of hypoallergenic formulas in children without proven CMPA. In lay language, intolerance describes "not tolerating".

Objective: To discuss the reasons why the term "intolerance" should not be used in the area of allergy.

Results: Presently, intolerance is not part of the allergy nomenclature. It is used by lay persons to describe "not tolerating". Pediatricians use intolerance to describe non-immunological hypersensitivity such as lactose intolerance which is acceptable. However, using the mixed term CMPA/I describing a variety of gastrointestinal symptoms in children, should be avoided. The WAO Nomenclature does not clearly distinguish between non-IgE-mediated allergy and non-allergic hypersensitivity.

Conclusion: The term "intolerance" should not be used within the area of allergy. Intolerance should be better defined and the term restricted to some non-immunological/non-allergic diseases and not mixed with allergy, e.g. by using the term CMPA/I. A revision of the WAO nomenclature is proposed.
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http://dx.doi.org/10.1186/s40413-015-0088-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4677433PMC
December 2015

Cow's milk protein allergy and common gastrointestinal symptoms in infants.

Authors:
Sten Dreborg

Acta Paediatr 2016 Mar;105(3):253-4

Pediatric Allergology, Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.

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http://dx.doi.org/10.1111/apa.13311DOI Listing
March 2016

Allergen skin prick test should be adjusted by the histamine reactivity.

Authors:
Sten Dreborg

Int Arch Allergy Immunol 2015 3;166(1):77-80. Epub 2015 Mar 3.

Department of Women's and Children's Health, Department of Pediatric Allergology, Uppsala University Hospital, Uppsala, Sweden.

Background: Skin prick test results are mostly reported as mean wheal diameter obtained with one concentration of allergen. Differences in technique between personnel causes variation in wheal size. The research question was whether the influence of differences in skin prick test technique among assistants and centers can be reduced by relating the allergen wheal response to that of histamine.

Methods: Two methods for estimating skin reactivity, the method of Nordic Guidelines using histamine as a reference and the method of Brighton et al. [Clin Allergy 1979;9:591-596] not using histamine as a reference, were applied to data from two biological standardization trials, using the same batch of freeze-dried timothy pollen preparation.

Results: The concentration defining the Nordic biological unit, defined as a concentration of allergen eliciting a wheal of the same size as that of histamine dihydrochloride 10 mg/ml, did not differ between the centers. When not using histamine as a reference, applying the method of Brighton et al., there was a 15-fold difference in the estimate of the biological activity between the trials that was eliminated by adjusting the allergen response to that of the histamine reference.

Conclusions: To reduce the influence of differences in test technique among assistants and centers responses to allergen-induced skin prick tests should be compared to that of histamine.
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http://dx.doi.org/10.1159/000371848DOI Listing
May 2015

Evaluation of methods for the estimation of threshold concentrations by the skin prick test.

Int Arch Allergy Immunol 2015 3;166(1):71-6. Epub 2015 Mar 3.

Department of Women's and Children's Health, Department of Pediatric Allergology, Uppsala University Hospital, Uppsala, Sweden.

Background: The allergen dose-response curve is flat; thus, small changes in wheal size reflect large differences in skin sensitivity. The sensitivity as measured by provocation tests is given by the threshold concentration that causes symptoms and/or objective signs. The threshold concentrations differ by several magnitudes between the most and the least sensitive individuals clinically allergic to the same allergen. Variation in technique can be minimized by relating allergen responses to that to histamine. The aim here is to present and validate simple methods for estimation of the skin sensitivity given as the concentration inducing a wheal of the same size as that with the positive reference, 10 mg/ml of histamine HCl, in the same patient.

Methods: Data from previously reported trials on the biological equilibration of allergen extracts were used to document a method to calculate the concentration of allergen required to induce a wheal of the same size as that with 10 mg/ml of histamine dihydrochloride in the same patient, and to validate the methods using the parallel line bioassay as the gold standard.

Results: The validated methods correlated well with the results obtained using the gold standard method and provide results of skin prick testing based on threshold concentrations of allergen.

Conclusions: The validated methods reduce the error of differences in testing techniques and make it possible to report skin sensitivity at threshold concentrations. A simple method to be used in clinical practice and a method suitable to describe changes in skin reactivity over time or during treatment are proposed.
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http://dx.doi.org/10.1159/000366203DOI Listing
May 2015

Evaluation of allergen immunotherapy.

Authors:
Sten Dreborg

J Allergy Clin Immunol Pract 2015 Mar-Apr;3(2):267-8

Department of Women's and Children's Health, University of Uppsala, Uppsala, Sweden. Electronic address:

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http://dx.doi.org/10.1016/j.jaip.2014.12.003DOI Listing
December 2015

[Reported research fraud just the tip of the iceberg?].

Authors:
Sten Dreborg

Lakartidningen 2013 Sep 11-17;110(37):1584-5

Kvinnors och barns halsa, Uppsala universitet; Barn- och ungdomsallergologi, Uppsala.

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December 2013

When should adrenaline be given and by whom?

Authors:
Sten Dreborg

Pediatr Allergy Immunol 2013 Feb;24(1):97-8

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http://dx.doi.org/10.1111/pai.12033DOI Listing
February 2013

The history of pediatric allergy in Europe - from a working group to ESPACI and SP-EAACI.

Pediatr Allergy Immunol 2013 Feb;24(1):88-96

Department of Pediatric Allergy, Women's and Children's Health, University of Uppsala, Uppsala, Sweden.

A Working Group on Pediatric Allergology was formed in 1984, which rapidly developed to become the European Society on Pediatric Allergology and Clinical Immunology (ESPACI) in 1988 with its own journal, Pediatric Allergology and Immunology. ESPACI worked together with the European Academy of Allergology and Clinical Immunology (EAACI) to form a Section of Pediatrics within EAACI (SP-EAACI) in 1996. The ESPACI and the SP-EAACI formally merged in 2001. Within the EAACI organization, the Pediatric Section has continued to grow. The Pediatric Section is working to develop pediatric allergology across Europe, focusing on postgraduate education, facilitating the research agenda and advocating for children and adolescents with allergies.
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http://dx.doi.org/10.1111/pai.12029DOI Listing
February 2013

Clinical Use of Probiotics in Pediatric Allergy (CUPPA): A World Allergy Organization Position Paper.

World Allergy Organ J 2012 Nov;5(11):148-67

1Department of Pediatrics - Division of Allergy - Pediatric Hospital Bambino Gesù - Rome, Vatican City 2Department of Pediatrics, University of North Carolina, Chapel Hill, NC, USA 3Department of Pediatrics and Medicine, Section of Allergy and Immunology, Louisiana State University Health Sciences Center, Shreveport, LA 4Department of Medicine, University of Medicine and Dentistry of New Jersey Medical School, Newark, NJ 5Department of Paediatrics, Imperial College London, London, United Kingdom 6Division of Allergy, Clinical Immunology and Rheumatology, Department of Pediatrics, Federal University of São Paulo, São Paulo, Brazil 7Department of Pediatric Allergology, Women's and Children's Health, University of Uppsala, Uppsala, Sweden 8Department of Food Science & Technology University of Nebraska, Lincoln, NE, USA 9Skin and Allergy Hospital, University of Helsinki, Helsinki, Finland 10Department of Allergy and Immunology, Royal Children's Hospital, University of Melbourne, Murdoch Childrens Research Institute, Melbourne, Australia 11King's College London, Asthma-UK Centre in Allergic Mechanisms of Asthma, Department of Paediatric Allergy, St Thomas' Hospital, London, United Kingdom 12Sydney Medical School, University of Sydney, New South Wales, Australia 13Jaffe Food Allergy Institute, Mount Sinai School of Medicine, New York, NY 14Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand 15Department of Paediatrics, National University of Singapore, Singapore.

Background: : Probiotic administration has been proposed for the prevention and treatment of specific allergic manifestations such as eczema, rhinitis, gastrointestinal allergy, food allergy, and asthma. However, published statements and scientific opinions disagree about the clinical usefulness.

Objective: : A World Allergy Organization Special Committee on Food Allergy and Nutrition review of the evidence regarding the use of probiotics for the prevention and treatment of allergy.

Methods: : A qualitative and narrative review of the literature on probiotic treatment of allergic disease was carried out to address the diversity and variable quality of relevant studies. This variability precluded systematization, and an expert panel group discussion method was used to evaluate the literature. In the absence of systematic reviews of treatment, meta-analyses of prevention studies were used to provide data in support of probiotic applications.

Results: : Despite the plethora of literature, probiotic research is still in its infancy. There is a need for basic microbiology research on the resident human microbiota. Mechanistic studies from biology, immunology, and genetics are needed before we can claim to harness the potential of immune modulatory effects of microbiota. Meanwhile, clinicians must take a step back and try to link disease state with alterations of the microbiota through well-controlled long-term studies to identify clinical indications.

Conclusions: : Probiotics do not have an established role in the prevention or treatment of allergy. No single probiotic supplement or class of supplements has been demonstrated to efficiently influence the course of any allergic manifestation or long-term disease or to be sufficient to do so. Further epidemiologic, immunologic, microbiologic, genetic, and clinical studies are necessary to determine whether probiotic supplements will be useful in preventing allergy. Until then, supplementation with probiotics remains empirical in allergy medicine. In the future, basic research should focus on homoeostatic studies, and clinical research should focus on preventive medicine applications, not only in allergy. Collaborations between allergo-immunologists and microbiologists in basic research and a multidisciplinary approach in clinical research are likely to be the most fruitful.
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http://dx.doi.org/10.1097/WOX.0b013e3182784ee0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3651185PMC
November 2012

The risk of allergic reactions to allergen extracts in personnel.

Authors:
Sten Dreborg

J Allergy Clin Immunol 2012 Mar 11;129(3):870-1; author reply 871. Epub 2012 Jan 11.

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http://dx.doi.org/10.1016/j.jaci.2011.11.048DOI Listing
March 2012

Standardization of allergen extracts.

Methods Mol Med 2008 ;138:133-45

ALK-Abello, Horsholm, Denmark.

Allergens are molecules with the capacity to elicit IgE responses in humans. When stimulated with allergens, most allergic patients respond with production of IgE specific for several proteins/allergens in the source material. The standardization of allergen extracts is essential in order to control variability and to achieve consistency and reproducibility in a clinical setting. Because the IgE binding capacity of an allergen extract is related to the content of one or a few major allergens, it is important that the standardization procedure ensures consistency, not only in the overall IgE binding potency, but also in the content and ratio of individual major allergens. Owing to the complexity of allergen extracts, a key element in standardization of allergen extracts is the use of standards. This chapter describes the principles for standardization of allergen extracts to be used by research laboratories. Other chapters in this volume describe methods in detail.
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http://dx.doi.org/10.1007/978-1-59745-366-0_12DOI Listing
August 2008

Dietary prevention of allergic diseases in infants and small children.

Pediatr Allergy Immunol 2008 Feb;19(1):1-4

Department of Pediatrics, Odense University Hospital, Odense, Denmark.

Because of scientific fraud four trials have been excluded from the original Cochrane meta-analysis on formulas containing hydrolyzed protein for prevention of allergy and food intolerance in infants. Unlike the conclusions of the revised Cochrane review the export group set up by the Section on Paediatrics, European Academy of Allergology and Clinical Immunology (SP-EAACI) do not find that the exclusion of the four trials demands a change of the previous recommendations regarding primary dietary prevention of allergic diseases. Ideally, recommendations on primary dietary prevention should be based only on the results of randomized and quasi-randomized trials (selection criteria in the Cochrane review). However, regarding breastfeeding randomization is unethical, Therefore, in the development of recommendations on dietary primary prevention, high-quality systematic reviews of high-quality cohort studies should be included in the evidence base. The study type combined with assessment of the methodological quality determines the level of evidence. In view of some methodological concerns in the Cochrane meta-analysis, particularly regarding definitions and diagnostic criteria for outcome measures and inclusion of non peer-reviewed studies/reports, a revision of the Cochrane analysis may seem warranted. Based on analysis of published peer-reviewed observational and interventional studies the results still indicate that breastfeeding is highly recommended for all infants irrespective of atopic heredity. A dietary regimen is effective in the prevention of allergic diseases in high-risk infants, particularly in early infancy regarding food allergy and eczema. The most effective dietary regimen is exclusively breastfeeding for at least 4-6 months or, in absence of breast milk, formulas with documented reduced allergenicity for at least the first 4 months, combined with avoidance of solid food and cow's milk for the first 4 months.
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http://dx.doi.org/10.1111/j.1399-3038.2007.00680.xDOI Listing
February 2008

[Do breast milk and cow's milk hydrolysate protect against cow milk allergy or allergic disease?].

Authors:
Sten Dreborg

Lakartidningen 2006 May 17-30;103(20):1627-8

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June 2006

Bronchial hyper-responsiveness predicts the development of mild clinical asthma within 2 yr in school children with hay-fever.

Pediatr Allergy Immunol 2005 Sep;16(6):478-86

Department of Paediatrics, University Hospital of Linköping, Linköping, Sweden.

In children with mild asthma, symptoms are not always apparent. Therefore, results of tests play an important role for the diagnosis. First, to investigate whether children with bronchial hyper-responsiveness (BHR) but no symptoms of asthma in 1992 had developed clinical asthma at follow up in 1994. The second aim was to find out the diagnostic properties of tests for asthma/allergic inflammation, using either doctor diagnosed asthma (DDA), self-assessed symptoms of asthma or iso-capnic hyperventilation of cold air (IHCA), as the standard, to diagnose asthma in a group of children with hay fever. Twenty-eight children with pollinosis, 12 of them with a history of asthma for the first time during the season 1992, were studied during the birch pollen season and in the autumn of 1994. During both periods, the bronchial hyper-reactivity was estimated by methacholine bronchial provocation tests (MBPT), bronchial variability by peak expiratory flow rate variability, subjective symptoms of asthma by visual analogue scale (VAS) and bronchial inflammation by serum and urine levels of inflammatory mediators. In 1994 IHCA was added during both seasons. Eight of 16 children with BHR but without clinical asthma in 1992 had developed asthma in 1994, 14 of 16 reacted to IHCA and 13 to MBPT. All 12 children with DDA in 1992 had still asthma in 1994 and 14 children with BHR in 1992 had persistent BHR in 1994. Of 23 children with BHR in 1992, 17 had DDA in 1994 and all maintained their BHR. Furthermore, 20 of them reacted to IHCA in 1994. In 1994, 24 of 28 hay-fever children had a positive IHCA tests and 24 had positive MBPT. In relation to VAS, the sensitivity of IHCA and MBPT to predict present asthma was high, but the specificity low, whereas the specificity of most other tests was high, but based on few individuals. In relation to DDA both the IHCA test (65-80%) and the MBPT test (79-85%) had a high sensitivity and it was three to six times more likely to find a positive test among asthmatics than in non-asthmatics. Children with hay fever without clinical asthma have a high risk of developing asthma within 2 yr. In relation to DDA, inhalation of cold air and the MBPT showed a high sensitivity.
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http://dx.doi.org/10.1111/j.1399-3038.2005.00296.xDOI Listing
September 2005

Evaluation of allergen exposure.

Authors:
Sten Dreborg

J Allergy Clin Immunol 2005 Sep;116(3):620-2

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http://dx.doi.org/10.1016/j.jaci.2005.06.027DOI Listing
September 2005

Dietary prevention of allergic diseases in infants and small children. Part III: Critical review of published peer-reviewed observational and interventional studies and final recommendations.

Pediatr Allergy Immunol 2004 Aug;15(4):291-307

Department of Pediatrics, University of Padua, Padua, Italy.

The role of primary prevention of allergic diseases has been a matter of debate for the last 40 years. In order to shed some light on this issue, a group of experts of the Section of Pediatrics EAACI reviewed critically the existing literature on the subject. An analysis of published peer-reviewed observational and interventional studies was performed following the statements of evidence as defined by WHO. The results of the analysis indicate that breastfeeding is highly recommended for all infants irrespective of atopic heredity. A dietary regimen is unequivocally effective in the prevention of allergic diseases in high-risk children. In these patients breastfeeding combined with avoidance of solid food and cow's milk for at least 4-6 months is the most effective preventive regimen. In the absence of breast milk, formulas with documented reduced allergenicity for at least 4-6 months should be used.
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http://dx.doi.org/10.1111/j.1399-3038.2004.00127.xDOI Listing
August 2004