Publications

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    ABSTRACT: The purpose of this study was to develop and validate a computer-aided diagnosis (CAD) tool for automatic classification of pulmonary nodules seen on low-dose computed tomography into solid, part-solid, and non-solid. Study lesions were randomly selected from 2 sites participating in the Dutch-Belgian NELSON lung cancer screening trial. On the basis of the annotations made by the screening radiologists, 50 part-solid and 50 non-solid pulmonary nodules with a diameter between 5 and 30 mm were randomly selected from the 2 sites. For each unique nodule, 1 low-dose chest computed tomographic scan was randomly selected, in which the nodule was visible. In addition, 50 solid nodules in the same size range were randomly selected. A completely automatic 3-dimensional segmentation-based classification system was developed, which analyzes the pulmonary nodule, extracting intensity-, texture-, and segmentation-based features to perform a statistical classification. In addition to the nodule classification by the screening radiologists, an independent rating of all nodules by 3 experienced thoracic radiologists was performed. Performance of CAD was evaluated by comparing the agreement between CAD and human experts and among human experts using the Cohen κ statistics. Pairwise agreement for the differentiation between solid, part-solid, and non-solid nodules between CAD and each of the human experts had a κ range between 0.54 and 0.72. The interobserver agreement among the human experts was in the same range (κ range, 0.56-0.81). A novel automated classification tool for pulmonary nodules achieved good agreement with the human experts, yielding κ values in the same range as the interobserver agreement. Computer-aided diagnosis may aid radiologists in selecting the appropriate workup for pulmonary nodules.
    Investigative radiology. 12/2014;
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    ABSTRACT: Pulmonary subsolid nodules (SSNs) have a high likelihood of malignancy, but are often indolent. A conservative treatment approach may therefore be suitable. The aim of the current study was to evaluate whether close follow-up of SSNs with computed tomography may be a safe approach. The study population consisted of participants of the Dutch-Belgian lung cancer screening trial (Nederlands Leuvens Longkanker Screenings Onderzoek; NELSON). All SSNs detected during the trial were included in this analysis. Retrospectively, all persistent SSNs and SSNs that were resected after first detection were segmented using dedicated software, and maximum diameter, volume and mass were measured. Mass doubling time (MDT) was calculated. In total 7135 volunteers were included in the current analysis. 264 (3.3%) SSNs in 234 participants were detected during the trial. 147 (63%) of these SSNs in 126 participants disappeared at follow-up, leaving 117 persistent or directly resected SSNs in 108 (1.5%) participants available for analysis. The median follow-up time was 95 months (range 20-110). 33 (28%) SSNs were resected and 28 of those were (pre-) invasive. None of the non-resected SSNs progressed into a clinically relevant malignancy. Persistent SSNs rarely developed into clinically manifest malignancies unexpectedly. Close follow-up with computed tomography may be a safe option to monitor changes. ©ERS.
    The European respiratory journal. 11/2014;
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    ABSTRACT: We aimed to test the interscan variation of semi-automatic volumetry of subsolid nodules (SSNs), as growth evaluation is important for SSN management. From a lung cancer screening trial all SSNs that were stable over at least 3 months were included (N = 44). SSNs were quantified on the baseline CT by two observers using semi-automatic volumetry software for effective diameter, volume, and mass. One observer also measured the SSNs on the second CT 3 months later. Interscan variation was evaluated using Bland-Altman plots. Observer agreement was calculated as intraclass correlation coefficient (ICC). Data are presented as mean (± standard deviation) or median and interquartile range (IQR). A Mann-Whitney U test was used for the analysis of the influence of adjustments on the measurements. Semi-automatic measurements were feasible in all 44 SSNs. The interscan limits of agreement ranged from -12.0 % to 9.7 % for diameter, -35.4 % to 28.6 % for volume and -27.6 % to 30.8 % for mass. Agreement between observers was good with intraclass correlation coefficients of 0.978, 0.957, and 0.968 for diameter, volume, and mass, respectively. Our data suggest that when using our software an increase in mass of 30 % can be regarded as significant growth. • Recently, recommendations regarding subsolid nodules have stressed the importance of growth quantification. • Volumetric measurement of subsolid nodules is feasible with good interscan agreement. • Increase of mass of 30 % can be regarded as significant growth.
    European radiology. 11/2014;
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    ABSTRACT: We present a novel descriptor for the characterization of pulmonary nodules in computed tomography (CT) images. The descriptor encodes information on nodule morphology and has scale-invariant and rotation-invariant properties. Information on nodule morphology is captured by sampling intensity profiles along circular patterns on spherical surfaces centered on the nodule, in a multi-scale fashion. Each intensity profile is interpreted as a periodic signal, where the Fourier transform is applied, obtaining a spectrum. A library of spectra is created and labeled via unsupervised clustering, obtaining a Bag-of- Frequencies, which is used to assign each spectra a label. The descriptor is obtained as the histogram of labels along all the spheres. Additional contributions are a technique to estimate the nodule size, based on the sampling strategy, as well as a technique to choose the most informative plane to cut a 2-D view of the nodule in the 3-D image. We evaluate the descriptor on several nodule morphology classification problems, namely discrimination of nodules versus vascular structures and characterization of spiculation. We validate the descriptor on data from European screening trials NELSON and DLCST and we compare it with state-of-the-art approaches for 3-D shape description in medical imaging and computer vision, namely SPHARM and 3-D SIFT, outperforming them in all the considered experiments.
    IEEE transactions on medical imaging. 11/2014;
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    ABSTRACT: CT angiography is a widely used technique for the noninvasive evaluation of neurovascular pathology. Because CTA is a snapshot of arterial contrast enhancement, information on flow dynamics is limited. Dynamic CTA techniques, also referred to as 4D-CTA, have become available for clinical practice in recent years. This article provides a description of 4D-CTA techniques and a review of the available literature on the application of 4D-CTA for the evaluation of intracranial vascular malformations and hemorrhagic and ischemic stroke. Most of the research performed to date consists of observational cohort studies or descriptive case series. These studies show that intracranial vascular malformations can be adequately depicted and classified by 4D-CTA, with DSA as the reference standard. In ischemic stroke, 4D-CTA better estimates thrombus burden and the presence of collateral vessels than conventional CTA. In intracranial hemorrhage, 4D-CTA improves the detection of the "spot" sign, which represents active ongoing bleeding.
    AJNR. American journal of neuroradiology. 10/2014;
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    ABSTRACT: To determine whether semiautomatic volumetric software can differentiate part-solid from nonsolid pulmonary nodules and aid quantification of the solid component.
    European radiology. 10/2014;
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    ABSTRACT: Purpose To determine the intervendor variability of Agatston scoring determined with state-of-the-art computed tomographic (CT) systems from the four major vendors in an ex vivo setup and to simulate the subsequent effects on cardiovascular risk reclassification in a large population-based cohort. Materials and Methods Research ethics board approval was not necessary because cadaveric hearts from individuals who donated their bodies to science were used. Agatston scores obtained with CT scanners from four different vendors were compared. Fifteen ex vivo human hearts were placed in a phantom resembling an average human adult. Hearts were scanned at equal radiation dose settings for the systems of all four vendors. Agatston scores were quantified semiautomatically with software used clinically. The ex vivo Agatston scores were used to simulate the effects of different CT scanners on reclassification of 432 individuals aged 55 years or older from a population-based study who were at intermediate cardiovascular risk based on Framingham risk scores. The Friedman test was used to evaluate overall differences, and post hoc analyses were performed by using the Wilcoxon signed-rank test with Bonferroni correction. Results Agatston scores differed substantially when CT scanners from different vendors were used, with median Agatston scores ranging from 332 (interquartile range, 114-1135) to 469 (interquartile range, 183-1381; P < .05). Simulation showed that these differences resulted in a change in cardiovascular risk classification in 0.5%-6.5% of individuals at intermediate risk when a CT scanner from a different vendor was used. Conclusion Among individuals at intermediate cardiovascular risk, state-of the-art CT scanners made by different vendors produced substantially different Agatston scores, which can result in reclassification of patients to the high- or low-risk categories in up to 6.5% of cases. © RSNA, 2014.
    Radiology 08/2014; · 6.34 Impact Factor
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    ABSTRACT: The VESSEL12 (VESsel SEgmentation in the Lung) challenge objectively compares the performance of different algorithms to identify vessels in thoracic computed tomography (CT) scans. Vessel segmentation is fundamental in computer aided processing of data generated by 3D imaging modalities. As manual vessel segmentation is prohibitively time consuming, any real world application requires some form of automation. Several approaches exist for automated vessel segmentation, but judging their relative merits is difficult due to a lack of standardized evaluation. We present an annotated reference dataset containing 20 CT scans and propose nine categories to perform a comprehensive evaluation of vessel segmentation algorithms from both academia and industry. Twenty algorithms participated in the VESSEL12 challenge, held at International Symposium on Biomedical Imaging (ISBI) 2012. All results have been published at the VESSEL12 website http://vessel12.grand-challenge.org. The challenge remains ongoing and open to new participants. Our three contributions are: (1) an annotated reference dataset available online for evaluation of new algorithms; (2) a quantitative scoring system for objective comparison of algorithms; and (3) performance analysis of the strengths and weaknesses of the various vessel segmentation methods in the presence of various lung diseases.
    Medical Image Analysis. 07/2014;
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    ABSTRACT: Optimizing CT brain perfusion protocols is a challenge because of the complex interaction between image acquisition, calculation of perfusion data, and patient hemodynamics. Several digital phantoms have been developed to avoid unnecessary patient exposure or suboptimum choice of parameters. The authors expand this idea by using realistic noise patterns and measured tissue attenuation curves representing patient-specific hemodynamics. The purpose of this work is to validate that this approach can realistically simulate mean perfusion values and noise on perfusion data for individual patients.
    Medical physics. 07/2014; 41(7):071907.
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    ABSTRACT: We evaluated the effects of hybrid and model-based iterative reconstruction (IR) algorithms from different vendors at multiple radiation dose levels on image quality of chest phantom scans.
    Journal of computer assisted tomography. 06/2014;
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    ABSTRACT: To analyse the effects of radiation dose reduction and iterative reconstruction (IR) algorithms on coronary calcium scoring (CCS).
    European radiology. 06/2014;
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    ABSTRACT: Lung cancer is the most frequent cause of tumor-associated death and only has a good prognosis if detected at a very early tumor stage. For the first time the American National Lung Screening Trial (NLST) could prove that low-dose computed tomography (CT) screening is able to reduce lung cancer mortality by 20 %. To date, however, three much smaller and therefore statistically underpowered European trials could not confirm the positive results of the NLST. The results of the largest European trial NELSON are expected within the next 2 years. In addition, there are a number of open or not yet satisfactorily answered questions, such as the definition of the appropriate screening population, the management of nodules detected by screening, the effects of over-diagnosis and the risk of cumulative radiation exposure. The success of the NLST prompted several predominantly American professional societies to issue a positive recommendation about the implementation of lung cancer screening in a population at risk. However, potentially conflicting results of European studies and a number of not yet optimized issues justify caution and call for a pooled analysis of European studies in order to provide statistically sound results and to ensure a high efficiency of screening with respect to the radiation applied, mental and physical patient burden and, last but not least, the financial efforts.
    Der Radiologe 05/2014; 54(5):462-9. · 0.47 Impact Factor
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    ABSTRACT: Silica dust-exposed individuals are at high risk of developing silicosis, a fatal and incurable lung disease. The presence of disseminated micronodules on thoracic CT is the radiological hallmark of silicosis but locating micronodules, to identify subjects at risk, is tedious for human observers. We present a computer-aided detection scheme to automatically find micronodules and quantify micronodule load. The system used lung segmentation, template matching, and a supervised classification scheme. The system achieved a promising sensitivity of 84% at an average of 8.4 false positive marks per scan. In an independent data set of 54 CT scans in which we defined four risk categories, the CAD system automatically classified 83% of subjects correctly, and obtained a weighted kappa of 0.76.
    SPIE Medical Imaging; 03/2014
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    ABSTRACT: Das akut erkrankte Kind erfordert eine rasche radiologische Abklärung mit besonderer Berücksichtung der geänderten Untersuchungsparameter bei gleichzeitig hohem Anspruch an den Strahlenschutz. Hochauflösende Schallköpfe, Multislice-CT und schnelle MR-Sequenzen erlauben eine bessere Anpassung der Untersuchungsmethoden an die Bedürfnisse in der Kinderradiologie. Ziel dieses Artikels ist eine Übersicht über die verschiedenen radiologischen Untersuchungstechniken sowie deren Anpassung an kindliche Anforderungen und die Angabe von Untersuchungsalgorithmen der häufigsten pädiatrischen Notfälle. In der Projektionsradiographie erlaubt die Optimierung der Aufnahmetechnik (digitale Radiographie, unterschiedliche Klassen von Film-Folien-Systemen, Belichtungsparameter) eine deutliche Reduktion der Strahlendosis bei diagnostisch ausreichender Qualität. Spiral- oder Multislice-CT ermöglichen eine Verkürzung der Untersuchungsdauer und eine exaktere Anpassung der Expositionsparameter (Pitchfaktor, mAs-Produkt) mit deutlicher Senkung der Strahlenbelastung. Die MRT wird trotz schneller Sequenzen vorwiegend bei neurologischen und spinalen Notfällen eingesetzt. Die Aufgabe des Radiologen liegt darin, in Abhängigkeit von den erwarteten pädiatrischen Differenzialdiagnosen die korrekte Untersuchungsmodalität zu wählen und die Untersuchungstechnik individuell anzupassen. Paediatric emergencies demand a quick and efficient radiological investigation with special attention to specific adjustments related to patient age and radiation protection. Imaging modalities are improving rapidly and enable to diagnose childhood diseases and injuries more quickly, accurately and safely. This article provides an overview of imaging techniques adjusted to the age of the child and an overview of imaging strategies of common paediatric emergencies. Optimising the imaging parameters (digital radiography, different screen-film systems, exposure specifications) allows for substantial reduction of radiation dose. Spiral- and multislice-CT reduce scan time and enable a considerable reduction of radiation exposure if scanning parameters (pitch setting, tube current) are properly adjusted. MRI is still mainly used for neurological or spinal emergencies despite the advent of fast imaging sequences. The radiologist's task is to select an appropriate imaging strategy according to expected differential diagnosis and to adjust the imaging techniques to the individual patient.
    Der Radiologe 03/2014; 42(3):146-152. · 0.47 Impact Factor
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    ABSTRACT: Subsolid pulmonary nodules occur less often than solid pulmonary nodules, but show a much higher malignancy rate. Therefore, accurate detection of this type of pulmonary nodules is crucial. In this work, a computer-aided detection (CAD) system for subsolid nodules in computed tomography images is presented and evaluated on a large data set from a multi-center lung cancer screening trial. The paper describes the different components of the CAD system and presents experiments to optimize the performance of the proposed CAD system. A rich set of 128 features is defined for subsolid nodule candidates. In addition to previously used intensity, shape and texture features, a novel set of context features is introduced. Experiments show that these features significantly improve the classification performance. Optimization and training of the CAD system is performed on a large training set from one site of a lung cancer screening trial. Performance analysis on an independent test from another site of the trial shows that the proposed system reaches a sensitivity of 80% at an average of only 1.0 false positive detections per scan. A retrospective analysis of the output of the CAD system by an experienced thoracic radiologist shows that the CAD system is able to find subsolid nodules which were not contained in the screening database.
    Medical image analysis 12/2013; 18(2):374-384. · 3.09 Impact Factor
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    ABSTRACT: PURPOSE Recently published recommendations by the Fleischner Society differentiate between non-solid and part-solid nodules. For the latter follow up or invasive diagnostic procedures are recommended depending on the size of the solid core. For solid nodules, different recommendations apply. We evaluated inter- and intra-reader variability of nodule classification and the impact on patient management. METHOD AND MATERIALS 20 part-solid, 10 non-solid and 10 solid nodular lesions were randomly selected from the NELSON screening trial. Data had been acquired using a low dose (16x0.75mm, 120-140 kVp, 30 mAs) protocol. Complete CTs were shown with axial and coronal projections with 1mm section thickness. Readers could interactively scroll through the scans, use magnification, windowing and manual calibre measurements as warranted. Four readers of varying experience were asked to classify the lesions as solid (1), part-solid with a core > 5mm and < 5mm, respectively (2 and 3), or as non-solid (4). All readings were done twice in six sessions, in which all permutations of nodules and section thicknesses were presented in different random orders. Inter- and intra-reader agreement were calculated using Cohen’s kappa statistics. To evaluate possible consequences on patient management, the number of differences between assigned scores of 1 or 2 (invasive diagnosis) and scores of 3 or 4 (follow up) were calculated. All results stated are averaged over all reading sessions. RESULTS Inter-reader agreement was low with mean kappa of 0.33 (range 0.02-0.58). Intra-reader agreement was moderate with mean kappa 0.54 (range 0.31-0.72). Patient management would have differed in 27% caused by interreader disagreement, and would have changed in 8% caused by intrareader variability. 28% of all nodules were uniformly classified over all reading sessions. Of these, 18% were classified as solid and 73% as non-solid. CONCLUSION Inter- and intra-reader agreement are low and moderate for the classification of pulmonary nodules according to Fleischner criteria if pure visual analysis is used. This may affect patient management. CLINICAL RELEVANCE/APPLICATION Variability in nodule classification may have consequences on patient management; use of digital analysis tools appears to be necessary to improve classification.
    Radiological Society of North America 2013 Scientific Assembly and Annual Meeting; 12/2013
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    ABSTRACT: PURPOSE Recently published recommendations by the Fleischner Society differentiate between solid, part-solid, and non-solid nodules. A section thickness of 1mm is recommended for evaluation. It is, however, common practice to reconstruct thicker (3mm or 5mm) sections to reduce the number of sections to evaluate. Purpose of this study was to evaluate the impact of section thickness on nodule classification agreement. METHOD AND MATERIALS 20 part-solid, 10 non-solid and 10 solid nodular lesions were randomly selected from the NELSON screening trial. A reference standard was established using the consensus reading of two experienced chest radiologists. Data had been acquired using a low dose (16x0.75mm, 120-140 kVp, 30 mAs) protocol. Complete CTs were shown with axial and coronal projections with either 1mm, 3mm or 5mm section thickness, the latter two with 1mm overlap. Readers could interactively scroll through the scans, use magnification, windowing and manual calibre measurements as warranted. Four readers of varying experience were asked to classify the lesions as solid (1), part-solid (2), or non-solid (3). All readings were done twice in six sessions, in which all permutations of nodules and section thicknesses were presented in different random orders. We report percentage agreement between observers and the consensus reference. All results stated are averaged over all reading sessions. RESULTS Mean agreement rate with the reference standard decreased from 85% (range 78-95%) to 77% (range 68-84%) and 75% (range 68-84%), for 1mm, 3mm, and 5mm section thickness, respectively. Readers were affected differently by increasing section thickness. The most experienced reader was influenced the least (agreement = 84-82-80%). Two readers demonstrated a major decrease in performance already for 3mm (81-72-70% and 91-78-81%). One reader showed a stepwise performance decline (86-77-69%). CONCLUSION Nodule classification is affected by section thickness. The degree of loss of accuracy appears to be reader dependent. CLINICAL RELEVANCE/APPLICATION Nodule classification is impaired by increasing section thickness which may have consequences for patient management. Visual classification therefore requires acquisition and storage of 1mm sections.
    Radiological Society of North America 2013 Scientific Assembly and Annual Meeting; 12/2013
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    ABSTRACT: PURPOSE The recently completed LIDC/IDRI database provides by far the largest public resource to assess the performance of algorithms for the detection of pulmonary nodules in thoracic CT scans. We report the performance of two detection systems, and address the issue of completeness of the reference standard. METHOD AND MATERIALS The LIDC/IDRI database contains 890 thoracic CT scans with section thickness of 2.5mm or lower, one per patient, from 7 centers acquired with 17 different scanner models from 4 manufacturers. Cases have been annotated in an extensive reading process comprising a blinded and an unblinded review by four radiologists who indicated all nodules <3mm and >3mm effective diameter. We define nodules >3mm indicated by all four observers as positive findings. We applied two pulmonary nodule detection systems: Herakles, an industry research prototype (MeVis Medical Solutions, Bremen, Germany) and ISICAD (Image Sciences Institute, Utrecht, The Netherlands), a system trained with data from the Dutch-Belgian NELSON lung cancer screening trial. We report sensitivity at 1, 2, and 4 false positive (FP) detections per scan and analyze the FPs. RESULTS The 890 scans contained 775 positive findings. At 1, 2, and 4 FP/scan, Herakles had a sensitivity of 69%, 75%, and 79%, respectively. For ISICAD this was 51%, 63%, 72%. We analyzed the FPs of Herakles at an operating point of 2 FP/scan. Of these, 31% were annotated by at least one radiologist as a nodule >3mm. An additional 17% were indicated by at least one radiologist as a nodule <3mm. A human expert visually inspected the remaining FPs using multiple slices of all three orthogonal views. A substantial part of these marks (41%) were located on nodular lesions that had not been indicated by any of the four radiologists involved in the annotation of the LIDC/IDRI data set . CONCLUSION The LIDC/IDRI data set is an excellent benchmarking tool for nodule detection algorithms. Automated detection can identify pulmonary nodules that have not been annotated in an extensive reading process with blinded and unblinded review by four human observers. CLINICAL RELEVANCE/APPLICATION Algorithms for automatic detection of pulmonary nodules can be compared and improved through the availability of a common database for benchmarking.
    Radiological Society of North America 2013 Scientific Assembly and Annual Meeting; 12/2013
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    ABSTRACT: MR angiography is proposed as a safer and less expensive alternative to the reference standard, DSA, in the follow-up of intracranial aneurysms treated with endovascular coil occlusion. We performed a systematic review and meta-analysis to evaluate the accuracy of TOF-MRA and contrast-enhanced MRA in detecting residual flow in the follow-up of coiled intracranial aneurysms. Literature was reviewed through the PubMed, Cochrane, and EMBASE data bases. In comparison with DSA, the sensitivity of TOF-MRA was 86% (95% CI: 82-89%), with a specificity of 84% (95% CI: 81-88%), for the detection of any recurrent flow. For contrast-enhanced MRA, the sensitivity and specificity were 86% (95% CI: 82-89%) and 89% (95% CI: 85-92%), respectively. Both TOF-MRA and contrast-enhanced MRA are shown to be highly accurate for detection of any recanalization in intracranial aneurysms treated with endovascular coil occlusion.
    American Journal of Neuroradiology 09/2013; · 3.17 Impact Factor
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    ABSTRACT: Finding phenotypes within COPD patients may prove imperative for optimizing treatment and prognosis. We hypothesized that it would be possible to discriminate emphysematous, large airway wall thickening and small airways disease dominant phenotypes. Inspiratory and expiratory CTs were performed in 1140 male smokers without or with mild COPD to quantify emphysema, airway wall thickness and air trapping. Spirometry, residual volume to total lung capacity (RV/TLC) and diffusion capacity (Kco) were measured. Dominant phenotype (emphysema, airway wall thickening or air trapping dominant) was defined as one of the respective CT measure in the upper quartile, with the other measures not in the upper quartile. 573 subjects had any of the three CT measures in the upper quartile. Of these, 367 (64%) were in a single dominant group and 206 (36%) were in a mixed group. Airway wall thickening dominance was associated with younger age (p < 0.001), higher body mass index (p < 0.001), more wheezing (p < 0.05) and lower FEV1 %predicted (p < 0.001). Emphysema dominant subjects had lower FEV1/FVC (p < 0.05) and Kco %predicted (p < 0.05). There was no significant difference in respiratory related hospitalizations (p = 0.09). CT measures can discriminate three different CT dominant groups of disease in male smokers without or with mild COPD. ISRCTN63545820, registered at www.trialregister.nl.
    Respiratory medicine 08/2013; · 2.33 Impact Factor

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