COPD is characterized by persistent and often progressive airflow obstruction caused by an abnormal inflammatory response to noxious particles and gases. Smoking is regarded to be the most important risk factor for COPD, yet an estimated proportion of 25 to 45% of all COPD patients have never smoked, suggesting that other (environmental) risk factors exist. Moreover, genetic susceptibility to the detrimental effects of exposure to noxious particles and gases likely plays an important role. In this thesis we investigated subjects from the general population and provide evidence that environmental exposures, such as environmental tobacco smoke exposure and occupational exposure to dusts, gases, fumes and pesticides, independently from personal smoking are associated with a lower level of lung function, an accelerated decline in lung function and an increased prevalence of airway obstruction. Additionally we identified several factors that affect individual susceptibility to the detrimental effects of the environmental exposures, such as personal tobacco smoking and genetic variants in several novel identified genes, i.e. PCDH9, GALNT13, PDE4D, TMEM176A and NOS1. Further research should determine whether the identified (novel) genes are true susceptibility loci for lung function impairment due to environmental exposure, and via which biological mechanisms these genetic variants essentially lead to the development COPD. This knowledge may contribute to the development of therapeutic targets for COPD treatment. Finally interventions to reduce exposure to environmental tobacco smoke or noxious particles and gases at the workplace may benefit lung health in general and may essentially contribute to lowering the global burden of COPD.
|Translated title of the contribution||Genen, omgeving en gezondheid van de longen|
|Qualification||Doctor of Philosophy|
- Boezen, Hendrika, Supervisor
- Postma, Dirkje, Supervisor
- Vonk, Judith, Co-supervisor
|Place of Publication||[S.l.]|
|Publication status||Published - 2014|