Detection of COPD, lung function decline and emphysema progression in heavy smokers

Abstract

The work presented in this thesis has improved our insights in important determinants of lung function decline and emphysema progression in heavy smokers. Secondly, it improved our insight on the question which threshold of FEV1/FVC is most appropriate in diagnosing COPD. We showed in chapter 2 that the decline in lung function was the steepest in participants with higher lung function values. Regarding emphysema progression we found that it was least in the group with high lung function values and strongest in participants with lower lung function values. In chapter 3 we reported that a higher extent of CT-quantified emphysema was associated with a stronger decline in lung function and with an increased risk of the development of COPD during a 3-year follow-up. In addition we showed in chapter 4 that the distribution pattern also was associated with lung function decline. Participants with upper lobe predominant emphysema had a lower FEV1/FVC after follow-up than those with lower lobe predominant emphysema. In chapter 5 we examined the effects of duration of smoking cessation on lung function decline and progression of emphysema in heavy smokers. Smoking cessation for >4 years stabilized lung function decline and emphysema progression in both obstructed as non-obstructed participants. Our results show that smoking cessation is beneficial even in participants with a high smoking exposure. In chapter 6 we showed that the diffusion capacity of the lungs for carbon monoxide (Kco) was associated with lung function decline and progression of CT-quantified emphysema. In chapter 7 we showed that variants in the 15q24/25 locus are associated with lung function decline in active smokers. Current smokers homozygous for the rs1051730 A-allele or rs8034191 G-allele had significantly greater FEV1/FVC decline than homozygous carriers of wild-type alleles. These findings were replicated in an independent cohort of healthy smokers and subjects with varying COPD severity (GOLDI –IV). The same risk alleles conferred, respectively, a five- and four-fold increased risk to be referred for lung transplantation because of end-stage COPD. In chapter 8 we described the performance of a literature search of studies comparing diagnostic criteria of spirometric COPD: FEV1/FVC below the lower limit of normal (LLN) or below 70%. Prevalence rates according to the fixed criterion were higher than those according to the LLN. The major flaw of the founf cross sectional studies is that they compared the fixed criterion with the LLN, by taking the LLN as gold standard. In an attempt to investigate which threshold is to prefer we performed a diagnostic study (chapter 9). A panel diagnosis of COPD was used as reference standard and the FEV1/FVC <LLN and