Barbro Dahlén group - Phenotyping of asthma and other mast cell mediated disorders
The overall aim of the research conducted in the group, is to provide scientific evidence in relation to three clinical problems, aspirin/NSAID-intolerant asthma, trigger-factor evoked bronchoconstriction and severe asthma.The main focus is on the role of mast cells and their mediators in asthma.
A human research programme to improve phenotyping of asthma and other mast cell mediated disorders. The goal is to develop diagnostic biomarkers and define new treatment strategies for different phenotypes of asthma and allied disorders.
The method used to achieve this goal is to define mechanisms in experimental studies of subjects with asthma. One main investigative tool is to cause controlled asthma attacks by the use of bronchial provocations. This permits assessment of changes in lung function and biomarkers, as well as alterations in mediators and cellular responses during the induced airway inflammation. The overall aim is to provide scientific evidence in relation to three clinical problems, aspirin/NSAID-intolerant asthma, trigger-factor evoked bronchoconstriction and severe asthma.
The main focus is on the role of mast cells and their mediators in asthma.
Asthma, human, mast cells, lipid mediators, hypersensitivity, bronchoprovocations
1. E-Type: A mechanistic study to evaluate the efficacy of the selective CysLT1 antagonist montelukast on airway function in asthma.
An investigator sponsored study, the purpose of which is to explore the possibility of an atypical CysLT receptor which is not blocked by current clinically available antagonists.
Main collaborations: IMM and MBB.
Funding: Heart Lung Foundation, ALF.
2. Biosynthesis of endogenous protective factors in exercise-induced asthma.
Refractoriness occurring after physical exercise, and similarly after repeated challenge with dry air, enables experimental studies of bronchoprotective mechanisms in humans. To this end urinary samples are collected in the challenge setting and analyzed using mass spectrometry for monitoring of all the main lipid mediator pathways.
Main collaborations: IMM, MBB and masspec platform at KI/SciLifeLab.
Funding: MRC, Heart Lung Foundation, ALF.
3. IggE: A controlled study evaluating a new anti-IgE treatment in asthma induced by allergen inhalation challenge.
Collaboration as member of the Canadian CIC (Clinical Investigators Collaborative) network of excellence, performing proof of concept studies of new potential treatments for asthma.
4. U-BIOPRED: Unbiased BIOmarkers for the Prediction of Respiratory Disease outcomes
European multi-centre study aiming at understanding severe asthma.
Funding: Innovative Medicines Initiative
5. MaCho: Ex vivo diagnosis of aspirin/NSAID-intolerant asthma using blood cells, stem cells and explanted airway tissues.
The goal is to find a diagnostic test for this type of life threatening non-allergic hypersensitivity. For the time being, diagnosis can only be made by time-consuming inhalation challenges using nebulized aspirin.
Collaboration with: IMM, MBB and the Dpt of Clinical Immunology at KI.
Funding: Heart Lung Foundation, ALF, The Asthma and Allergy Research Foundation.
6. Prostaglandin D2 metabolites as biomarkers of anaphylaxis and mast cell activating disorders.
Collaboration with: masspec platform at KI SciLifeLab.
Funding: MRC, Heart Lung Foundation, ALF and AZ-KI SciLifeLab grant.
Refractoriness to exercise challenge: a review of the mechanisms old and new.
Larsson J, Anderson S, Dahlén S, Dahlén B
Immunol Allergy Clin North Am 2013 Aug;33(3):329-45, viii
The significance of diagnosing associated clonal mast cell diseases in patients with venom-induced anaphylaxis and the role of bone marrow investigation.
Gülen T, Dahlén B, Sander B, Hägglund H, Nilsson G
Clin Transl Allergy 2013 Jul;3(1):22
Detection of exacerbations in asthma based on electronic diary data: results from the 1-year prospective BIOAIR study.
Kupczyk M, Haque S, Sterk P, Niżankowska-Mogilnicka E, Papi A, Bel E, et al
Thorax 2013 Jul;68(7):611-8
Adhesion molecules in subjects with COPD and healthy non-smokers: a cross sectional parallel group study.
Blidberg K, Palmberg L, James A, Billing B, Henriksson E, Lantz A, et al
Respir. Res. 2013 May;14():47
Corticosteroid treatment selectively decreases mast cells in the smooth muscle and epithelium of asthmatic bronchi.
James A, Gyllfors P, Henriksson E, Dahlén S, Adner M, Nilsson G, et al
Allergy 2012 Jul;67(7):958-61
Effects of celecoxib on major prostaglandins in asthma.
Daham K, Song W, Lawson J, Kupczyk M, Gülich A, Dahlén S, et al
Clin. Exp. Allergy 2011 Jan;41(1):36-45
The occurrence of refractoriness and mast cell mediator release following mannitol-induced bronchoconstriction.
Larsson J, Perry C, Anderson S, Brannan J, Dahlén S, Dahlén B
J. Appl. Physiol. 2011 Apr;110(4):1029-35
Increased levels of cysteinyl-leukotrienes in saliva, induced sputum, urine and blood from patients with aspirin-intolerant asthma.
Gaber F, Daham K, Higashi A, Higashi N, Gülich A, Delin I, et al
Thorax 2008 Dec;63(12):1076-82
EAACI/GA2LEN guideline: aspirin provocation tests for diagnosis of aspirin hypersensitivity.
Nizankowska-Mogilnicka E, Bochenek G, Mastalerz L, Swierczyńska M, Picado C, Scadding G, et al
Allergy 2007 Oct;62(10):1111-8
Bronchial responsiveness to leukotriene D4 is resistant to inhaled fluticasone propionate.
Gyllfors P, Dahlén S, Kumlin M, Larsson K, Dahlén B
J. Allergy Clin. Immunol. 2006 Jul;118(1):78-83
Relation between bronchial responsiveness to inhaled leukotriene D4 and markers of leukotriene biosynthesis.
Gyllfors P, Kumlin M, Dahlén S, Gaber F, Ehrs P, Dahlén B
Thorax 2005 Nov;60(11):902-8
Influence of zafirlukast and loratadine on exercise-induced bronchoconstriction.
Dahlén B, Roquet A, Inman M, Karlsson O, Naya I, Anstrén G, et al
J. Allergy Clin. Immunol. 2002 May;109(5):789-93
Celecoxib in patients with asthma and aspirin intolerance. The Celecoxib in Aspirin-Intolerant Asthma Study Group.
Dahlén B, Szczeklik A, Murray J,
N. Engl. J. Med. 2001 Jan;344(2):142