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Purpose: The change of emphysema distribution with increasing COPD severity is not yet assessed. Especially, involvement of the upper aspect of the lower lobe is unknown. The primary aim was to quantitatively determine regional distribution of emphysema in anatomically (lung lobes) and non-anatomically defined lung regions (upper/lower lung halves as well as core and rind regions) in a cohort covering equally all COPD severity stages using CT., Material and Methods: Basically 100 CT data sets were quantitatively evaluated for regional distribution of emphysema. Emphysema characteristics (emphysema index, mean lung density and 15th percentile of the attenuation values of lung voxels) were compared (t-test) in: upper lobes vs. upper halves, lower lobes vs. lower halves, core vs. rind region., Results: In patients with ≤ GOLD II, a significantly higher emphysema burden was found in the upper lobes as compared to upper halves. In subjects with GOLD III/IV the differences were not significant for all emphysema characteristics. A high difference between lobes and halves in subjects with ≤ GOLD II was found, in contrast to low difference in higher GOLD stages., Conclusions: Lobar segmentation provides improved characterization of cranio-caudal emphysema distribution compared to a non-anatomic approach in subjects up to GOLD stage II.

Background: Chronic mucus hypersecretion (CMH) is associated with an increased frequency of respiratory infections, excess lung function decline, and increased hospitalisation and mortality rates in the general population. It is associated with smoking, but it is unknown why only a minority of smokers develops CMH. A plausible explanation for this phenomenon is a predisposing genetic constitution. Therefore, we performed a genome wide association (GWA) study of CMH in Caucasian populations., Methods: GWA analysis was performed in the NELSON-study using the Illumina 610 array, followed by replication and meta-analysis in 11 additional cohorts. In total 2,704 subjects with, and 7,624 subjects without CMH were included, all current or former heavy smokers (≥20 pack-years). Additional studies were performed to test the functional relevance of the most significant single nucleotide polymorphism (SNP)., Results: A strong association with CMH, consistent across all cohorts, was observed with rs6577641 (p = 4.25×10(-6), OR = 1.17), located in intron 9 of the special AT-rich sequence-binding protein 1 locus (SATB1) on chromosome 3. The risk allele (G) was associated with higher mRNA expression of SATB1 (4.3×10(-9)) in lung tissue. Presence of CMH was associated with increased SATB1 mRNA expression in bronchial biopsies from COPD patients. SATB1 expression was induced during differentiation of primary human bronchial epithelial cells in culture., Conclusions: Our findings, that SNP rs6577641 is associated with CMH in multiple cohorts and is a cis-eQTL for SATB1, together with our additional observation that SATB1 expression increases during epithelial differentiation provide suggestive evidence that SATB1 is a gene that affects CMH.

Objective: To assess the interobserver agreement for a semi-quantitative evaluation of the interlobar fissures integrity in volumetric thin-section CT images, looking for more detailed information regarding fissural defects; and describe prevalence and severity of fissural defects between the different functional groups of subjects., Materials and Methods: Volumetric scans of 247 individuals exposed to tobacco with different functional status (normal to severe COPD), were retrospectively and independently evaluated by 2 chest radiologists, with a consensual reading additionally with a third reader in disagreement cases. Right oblique (RO), right horizontal (RH) and left oblique fissures (LO) integrity was estimated using a 5% scale. GOLD classification was available for all subjects., Results: Interobserver agreement (weighted Kappa-index) for fissural categorization was 0.76, 0.70 and 0.75, for RO, RH and LO, respectively. Final evaluation found 81%, 89% and 50% of RO, RH and LO to be incomplete, with respective mean integrity of 80%, 58% and 80%. Small fissure gaps (<10%) were present in 30% of patients. Prevalence and severity of fissural defects were not different between the GOLD categories., Conclusions: A substantial agreement between readers was found in the analysis of interlobar fissures integrity. The semi-quantitative method allowed a detailed description of the fissural defects, information that can be important, for example, in endoscopic lung volume reduction therapies for emphysema. Small fissure gaps, overlooked in previous studies, were found in almost a third of the patients. A higher than previously described prevalence of fissural defects was described, but without significant differences among the distinct functional groups., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)