Functional and clinical translation of asthma and allergy associated genetic variants in IL33 and IL1RL1

In this thesis we aimed to unravel novel mechanisms underlying asthma and allergy, and to translate this to clinical application. The focus is on 2 genes: Interleukin 33 (IL33) and Interleukin-1-Receptor-Like-1 (IL1RL1). These encode the protein IL-33, an alarm substance in inflammation and the target protein it binds to: IL-1RL1. We describe the distinct genetic signals in IL33 and IL1RL1 that specifically associate with an eosinophilic subtype of asthma and with severe asthma characterized by low lung function. Eosinophilic asthma is asthma with high levels of eosinophilic immune cells. Also these genetic signals in IL33 and IL1RL1 linked to function of lung cells and immune cells, for example these associated with the levels of IL-33 and IL-1RL1, with less viability and increased immune response of these cells. We show that genotype and levels of this pathway could contribute to the prediction of specific asthma and allergy phenotypes. Therefore, this thesis concludes that genetic variation and levels could have potential as biomarker in the prediction of disease, as well as targeted drugs directed at the IL-33/IL-1RL1 pathway may be useful drugs in specific patient groups of asthma and allergy

Functional and clinical translation of asthma and allergy associated genetic variants in IL33 and IL1RL1

In this thesis we aimed to unravel novel mechanisms underlying asthma and allergy, and to translate this to clinical application. The focus is on 2 genes: Interleukin 33 (IL33) and Interleukin-1-Receptor-Like-1 (IL1RL1). These encode the protein IL-33, an alarm substance in inflammation and the target protein it binds to: IL-1RL1. We describe the distinct genetic signals in IL33 and IL1RL1 that specifically associate with an eosinophilic subtype of asthma and with severe asthma characterized by low lung function. Eosinophilic asthma is asthma with high levels of eosinophilic immune cells. Also these genetic signals in IL33 and IL1RL1 linked to function of lung cells and immune cells, for example these associated with the levels of IL-33 and IL-1RL1, with less viability and increased immune response of these cells. We show that genotype and levels of this pathway could contribute to the prediction of specific asthma and allergy phenotypes. Therefore, this thesis concludes that genetic variation and levels could have potential as biomarker in the prediction of disease, as well as targeted drugs directed at the IL-33/IL-1RL1 pathway may be useful drugs in specific patient groups of asthma and allergy

Evaluatie door casemanagers dementie: een explorerende praktijkstudie naar vormen en inhoud

Achtergrond Deze praktijkgerichte explorerende studie beoogt inzicht te geven in dewijzewaarop casemanagers dementie vorm en inhoud geven aan de evaluatie van hun begeleiding van het informele zorgnetwerk. Methode Er is gebruik gemaakt van een combinatie van kwantitatieve en kwalitatieve onderzoeksmethoden, uitgevoerd onder 57 casemanagers dementie, verbonden aan drie verschillende dementienetwerken. Resultaten De kwantitatieve en kwalitatieve data zijn ondergebracht in vier thema’s: (1) houding ten aanzien van evaluatie, (2) vormen van evaluatie, (3) uitvoering van evaluatie en (4) inhoud van evaluatie. Er bestaat diversiteit in vorm en inhoud van het evalueren door casemanagers met cliënten enmantelzorgers. Casemanagers erkennen het belang van een tussentijdse- en eindevaluatie, maar het ismoeilijk daarmethodisch vorm aan te geven. Belemmeringen die casemanagers ervaren, hebben te maken met cliënt- en professionalfactoren en laten hierin diverse aspecten zien. Conclusie Casemanagers evalueren vooral informeel en doorlopend om hun begeleiding op de behoeften van cliënt en mantelzorger af te stemmen. In mindere mate gebruiken casemanagers evaluatie om de kwaliteit van hun handelen systematisch te toetsen. Een vervolgdiscussie over vorm en inhoud van evalueren dientmet casemanagers en cliënten op individueel, professioneel en maatschappelijk niveau gevoerd te worden

Airway wall splice quantitative trait locus analysis reveals novel downstream mechanisms for known asthma single-nucleotide polymorphisms

Studying the effects of asthma SNPs on alternative splicing can lead to new insights into asthma pathophysiology. More specifically, a 17q12 SNP is associated to alternative splicing of GSDMB. https://bit.ly/3W49oTs