Allergic inflammation in children with pet allergy and asthma : mechanisms, markers and clinical consequences
Immunological background: Allergic inflammation is a multiple-step process with many actors, where eosinophils and the release of their granula proteins play an important role. The recruitment of eosinophils is a crucial event in the inflammatory process. What determines the direction of production and recruitment of eosinophils is still somewhat unclear but it is known that the process is driven by key molecules (cytokines/chemokines).
Clinical background: Asthma coexists with allergy, and the prevalence of asthma among schoolchildren in Sweden is 8%. Half of them have an associated pet allergy. Exposure to allergens triggers asthma in the sensitized child and is one of the reasons why children with asthma and pet allergy require continuous therapy with inhaled glucocorticosteroids (GC). This also makes asthma a "hidden" handicap for the pet-allergic child.
Objective: To investigate the usefeulness of markers of inflammation in predicting asthma deterioration caused by allergen exposure, in untreated children and children undergoing GC therapy.
Methods: The five papers included in this thesis, are primarily based on three clinical studies: study of allergen exposure at school, a double-blinded prospective study of inhaled budesonide and an allergen challenge study. As a complement two in vitro studies have been performed based on the same material.
Results: Exposure of asthmatic children to animal dander in school dust during one week causes recruitment of eosinophils to the airways and increased bronchial reactivity - both possible signs of mild inflammation.
Peripheral blood eosinophil count (PBE) and S-ECP levels can be used to estimate the risk for deterioration and the need for corticosteroid treatment in cases of mild to moderate asthma. Furthermore exhaled NO (ENO) in addition to PBE and S-ECP can serve as a marker for increased inflammation after withdrawal of inhaled GC.
Children treated with inhaled GC have decreased expression of the IL-5 receptor on the eosinophil, suggesting a steroid mechanism by which cell-surface receptors are downregulated.
Allergen challenge of allergic children in vivo promotes an increased eosinophil migration capacity in vitro (within 2 hours), which can be further enhanced by eotaxin. The results are compatible with the initial stage of allergic inflammation.
General conclusion: We have been able to show that allergic inflammation is a dynamic process involving eosinophils. Many markers and methods are available, but no single marker can provide the answers to all questions. Yet, as this thesis shows, by selecting suitable markers and by combining the information the markers provide, it is possible to draw conclusions about the process of allergic inflammation and the inflammatory state of an individual patient.
List of scientific papers
I. Lonnkvist K, Hallden G, Dahlen SE, Enander I, van Hage-Hamsten M, Kumlin M, Hedlin G (1999). Markers of inflammation and bronchial reactivity in children with asthma, exposed to animal dander in school dust. Pediatr Allergy Immunol. 10(1): 45-52.
https://pubmed.ncbi.nlm.nih.gov/10410917
II. Lonnkvist K, Hellman C, Lundahl J, Hallden G, Hedlin G (2001). Eosinophil markers in blood, serum, and urine for monitoring the clinical course in childhood asthma: impact of budesonide treatment and withdrawal. J Allergy Clin Immunol. 107(5): 812-7.
https://pubmed.ncbi.nlm.nih.gov/11344347
III. Hellman C, Lonnkvist K, Hedlin G, Hallden G, Lundahl J (2002). Down-regulated IL-5 receptor expression on peripheral blood eosinophils from budesonide-treated children with asthma. Allergy. 57: 1-7.
IV. Lonnkvist K, Anderson M, Hedlin G, Svartengren M (2002). Levels of exhaled nitric oxide (ENO), bronchial hyperresponsiveness, lung function and eosinophil activity in blood, nasal lavage (NAL) and sputum in children with allergic asthma after withdrawal of inhaled steroids: A randomized, double blind controlled trail. [Manuscript]
V. Lonnkvist K, Moshfegh A, Pedroletti C, Hedlin G, Hallden G, Lundahl J (2002). Increased eosinophil transmigration after nasal allergen challenge in children with allergic asthma and rhinitis. [Submitted]
History
Defence date
2002-05-31Department
- Department of Women's and Children's Health
Publication year
2002Thesis type
- Doctoral thesis
ISBN-10
91-7349-219-1Number of supporting papers
5Language
- eng