Chronic mucus hypersecretion and airway wall structure: Genes and environment

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    Abstract

    Chronic mucus hypersecretion (CMH) and airway wall thickening (AWT) are both features of chronic airway diseases and are strongly associated with lung function decline and worse quality of life.
    The underlying cause of CMH and AWT is chronic inflammation of the airway epithelial layer by exposure to irritating substances like cigarette smoke and occupational exposures. As not every person exposed develops CMH and/or AWT genetic factors likely play a role.
    We investigated risk factors for CMH and AWT in different populations, taking into account demographic characteristics and exposure to environmental and genetic factors.

    Risk factors for CMH
    Smoking appeared to be the strongest predictor of CMH. In subjects with chronic obstructive pulmonary disease (COPD) there was no association between CMH and occupational exposures. However, in subjects without COPD, exposure to gases & fumes increased the risk for CMH significantly.
    Investigation of genetic differences between heavy smokers with and without CMH showed a DNA-variant in the SATB1 gene to be strongly associated with CMH.

    Risk factors for AWT
    We developed a method to determine AWT by using low-dose CT-scans and software. We measured AWT in 500 male heavy smokers. A higher AWT was significantly associated with the presence of airway obstruction, independently from smoking habits.
    We investigated the genetics of AWT in 2,800 heavy smokers and repeated our findings in a comparable German population. DNA-variants in and close to genes were significantly associated with AWT. Interestingly, some of these genes were already known to be associated with features of COPD.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Awarding Institution
    • University of Groningen
    Supervisors/Advisors
    • Postma, Dirkje, Supervisor
    • Groen, Harry, Supervisor
    • Boezen, Marike, Supervisor
    • Vonk, Judith, Co-supervisor
    • Brusselle, GG, Assessment committee, External person
    • Vestbo, J., Assessment committee, External person
    • Kerstjens, Huib, Assessment committee
    Award date17-Jun-2014
    Place of Publication[S.l.]
    Publisher
    Print ISBNs978-90-6464-782-6
    Publication statusPublished - 2014

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