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Although some of the associations between chronic obstructive pulmonary disease (COPD) and atherosclerosis are based on shared risk factors such as smoking, recent epidemiological evidence suggests that COPD is a risk factor for vascular disease due to systemic inflammation. The present study assessed the hypothesis that disease severity (as expressed by the GOLD stage) independently predicts the extent of vascular calcifications. A total of 160 smokers diagnosed with COPD (GOLD I-IV, 40 subjects of each GOLD stage) and 40 smokers at risk (GOLD 0; median age of 60 years old; Q1:56;Q3:65; 135 males and 65 females) underwent non-contrast, non-electrocardiography synchronized chest computerised tomography. The volume of thoracic aortic calcifications was quantified semi-automatically within a region from T1 through T12. Multiparametric associations with GOLD stage, smoking history, sex, age, body mass index and emphysema index were evaluated using generalized linear regression analysis. Thoracic aortic calcifications were highly prevalent in this cohort (187/200 subjects, 709 (Q1:109;Q3:2163) mm 3 ). Analysis of variance on ranks demonstrated a significant difference in calcium between different GOLD-stages as well as patients at risk of COPD (F=36.8, P<0.001). In the multivariable analysis, GOLD-stages were indicated to be predictive of thoracic aortic calcifications (P≤0.0033) besides age (P<0.0001), while age appeared to be the strongest predictor. Other variables were not statistically linked to thoracic aortic calcifications in the multivariable model. COPD severity, as expressed by the GOLD-stage, is a significant predictor of thoracic aortic calcifications, independent of covariates such as age or tobacco consumption.

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.

Rationale: Airway wall thickness (AWT) is affected by both environmental and genetic factors and is strongly associated with airflow limitation in smaller airways., Objectives: To investigate the genetic component of AWT., Methods: AWT was measured on low-dose computed tomography scans in male heavy smokers participating in a lung cancer screening study (n = 2,640). Genome-wide association studies on AWT were performed under an additive model using linear regression (adjusted for pack-years, lung volume), followed by metaanalysis. An independent cohort was used for validation of the most strongly associated single-nucleotide polymorphisms (SNPs). The functional relevance of significant SNPs was evaluated., Measurements and Main Results: Three significant loci on chromosomes 2q (rs734556; P =  6.2 × 10(-7)) and 10q (rs10794108, P = 8.6 × 10(-8); rs7078439, P = 2.3 × 10(-7)) were associated with AWT and confirmed in the metaanalysis in cohorts with comparable lung function: P values = 4.6 × 10(-8), 7.4 × 10(-8), and 7.5 × 10(-8), respectively. SNP rs734556 was associated with decreased lung tissue expression of SERPINE2, a susceptibility gene for emphysema. Two nominally significant SNPs showed effects with similar direction: rs10251504 in MAGI2 (P = 5.8 × 10(-7)) and rs4796712 in NT5C3B (P = 3.1 × 10(-6)). Higher MAGI2 expression in bronchial biopsies of patients with chronic obstructive pulmonary disease was significantly associated with fewer inflammatory cells. The presence of the NT5C3B risk allele was associated with higher lung tissue expression (P = 1.09 × 10(-41))., Conclusions: Genetic variants contribute to AWT. Among others, the identified genes are also involved in emphysema, airway obstruction, and bronchial inflammation.

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.)

Background: Finding new therapeutic agents is of great clinical interest in neuroblastoma research because prognosis of children with disseminated stages of disease is still poor. As xenograft mouse models are frequently used for studying anticancer drugs in vivo, small animal imaging is an important method of monitoring in anticancer research., Materials and Methods: SCID mice inoculated with human neuroblastoma SK-N-SH cells were examined with positron-emission tomography-computed tomography (PET-CT) using [18F]fluorodeoxyglucose (FDG) or [18F]fluoro-L-thymidine (FLT) and with magnetic resonance imaging (MRI)., Results: All neuroblastomas were detected by MRI. In PET-CT imaging, no tumour was visualized with [18F]FDG, but 13 out of 14 (93%) were found with [18F]FLT. Uptake of [18F]FLT was significantly associated with tumour weight. Necrotic areas could not be identified either by MR imaging or on PET-CT scans., Conclusion: Both MR and PET-CT imaging with [18F]FLT are highly qualified for the detection of neuroblastomas grown in SCID mice. However, [18F]FDG, which is the standard tracer in clinical PET-CT imaging, is not suited for PET-CT imaging in the neuroblastoma model.