Association of Ground Glass Opacities with Systemic Inflammation and Progression of Emphysema.

RATIONAL: Ground glass opacities (GGO) in the absence of interstitial lung disease are understudied. OBJECTIVE: To assess the association of GGO with white blood cells (WBCs) and progression of quantified chest CT emphysema. METHODS: We analyzed data of participants in the Subpopulations and Intermediate Outcome Measures In COPD Study (SPIROMICS). Chest radiologists and pulmonologists labeled regions of the lung as GGO and adaptive multiple feature method (AMFM) trained the computer to assign those labels to image voxels and quantify the volume of the lung with GGO (%GGOAMFM). We used multivariable linear regression, zero-inflated negative binomial, and proportional hazards regression models to assess the association of %GGOAMFM with WBC, changes in %emphysema, and clinical outcomes. MEASUREMENTS AND MAIN RESULTS: Among 2,714 participants, 1,680 had COPD and 1,034 had normal spirometry. Among COPD participants, based on the multivariable analysis, current smoking and chronic productive cough was associated with higher %GGOAMFM. Higher %GGOAMFM was cross-sectionally associated with higher WBCs and neutrophils levels. Higher %GGOAMFM per interquartile range at visit 1 (baseline) was associated with an increase in emphysema at one-year follow visit by 11.7% (Relative increase; 95%CI 7.5-16.1%;P<0.001). We found no association between %GGOAMFM and one-year FEV1 decline but %GGOAMFM was associated with exacerbations and all-cause mortality during a median follow-up time of 1,544 days (Interquartile Interval=1,118-2,059). Among normal spirometry participants, we found similar results except that %GGOAMFM was associated with progression to COPD at one-year follow-up. CONCLUSIONS: Our findings suggest that GGOAMFM is associated with increased systemic inflammation and emphysema progression.

Response to high dose ipilimumab plus temozolomide after progression on standard or low dose ipilimumab in advanced melanoma: a retrospective analysis.

Background: Despite advancements in checkpoint inhibitor-based immunotherapy, patients with advanced melanoma who have progressed on standard dose ipilimumab (Ipi) + nivolumab continue to have poor prognosis. Several studies support a dose-response activity of Ipi, and one promising combination is Ipi 10mg/kg (Ipi10) + temozolomide (TMZ). Methods: We performed a retrospective cohort analysis of patients with advanced melanoma treated with Ipi10+TMZ in the immunotherapy refractory/resistant setting (n = 6), using similar patients treated with Ipi3+TMZ (n = 6) as comparison. Molecular profiling by whole exome sequencing (WES) and RNA-seq of tumors harvested through one responder's treatment was performed. Results: With a median follow up of 119 days, patients treated with Ipi10+TMZ had statistically significant longer median progression free survival of 144.5 days (range 27-219) vs 44 (26-75) in Ipi3+TMZ, p=0.04, and a trend for longer median overall survival of 154.5 days (27-537) vs 89.5 (26-548). All patients in the Ipi10 cohort had progressed on prior Ipi+Nivo. WES revealed only 12 shared somatic mutations including BRAF V600E. RNA-seq showed enrichment of inflammatory signatures, including interferon responses in metastatic lesions after standard dose Ipi + nivo and Ipi10 + TMZ compared to the primary tumor, and downregulated negative immune regulators including Wnt and TGFb signaling. Conclusion: Ipi10+TMZ demonstrated efficacy including dramatic responses in patients with advanced melanoma refractory to prior Ipi + anti-PD1, even with CNS metastases. Molecular data suggest a potential threshold of Ipi dose for activation of sufficient anti-tumor immune response, and higher dose Ipi is required for some patients.

Predicting severe chronic obstructive pulmonary disease exacerbations using quantitative CT: a retrospective model development and external validation study.

BACKGROUND: Quantitative CT is becoming increasingly common for the characterisation of lung disease; however, its added potential as a clinical tool for predicting severe exacerbations remains understudied. We aimed to develop and validate quantitative CT-based models for predicting severe chronic obstructive pulmonary disease (COPD) exacerbations. METHODS: We analysed the Subpopulations and Intermediate Outcome Measures In COPD Study (SPIROMICS) cohort, a multicentre study done at 12 clinical sites across the USA, of individuals aged 40-80 years from four strata: individuals who never smoked, individuals who smoked but had normal spirometry, individuals who smoked and had mild to moderate COPD, and individuals who smoked and had severe COPD. We used 3-year follow-up data to develop logistic regression classifiers for predicting severe exacerbations. Predictors included age, sex, race, BMI, pulmonary function, exacerbation history, smoking status, respiratory quality of life, and CT-based measures of density gradient texture and airway structure. We externally validated our models in a subset from the Genetic Epidemiology of COPD (COPDGene) cohort. Discriminative model performance was assessed using the area under the receiver operating characteristic curve (AUC), which was also compared with other predictors, including exacerbation history and the BMI, airflow obstruction, dyspnoea, and exercise capacity (BODE) index. We evaluated model calibration using calibration plots and Brier scores. FINDINGS: Participants in SPIROMICS were enrolled between Nov 12, 2010, and July 31, 2015. Participants in COPDGene were enrolled between Jan 10, 2008, and April 15, 2011. We included 1956 participants from the SPIROMICS cohort who had complete 3-year follow-up data: the mean age of the cohort was 63·1 years (SD 9·2) and 1017 (52%) were men and 939 (48%) were women. Among the 1956 participants, 434 (22%) had a history of at least one severe exacerbation. For the CT-based models, the AUC was 0·854 (95% CI 0·852-0·855) for at least one severe exacerbation within 3 years and 0·931 (0·930-0·933) for consistent exacerbations (defined as ≥1 acute episode in each of the 3 years). Models were well calibrated with low Brier scores (0·121 for at least one severe exacerbation; 0·039 for consistent exacerbations). For the prediction of at least one severe event during 3-year follow-up, AUCs were significantly higher with CT biomarkers (0·854 [0·852-0·855]) than exacerbation history (0·823 [0·822-0·825]) and BODE index 0·812 [0·811-0·814]). 6965 participants were included in the external validation cohort, with a mean age of 60·5 years (SD 8·9). In this cohort, AUC for at least one severe exacerbation was 0·768 (0·767-0·769; Brier score 0·088). INTERPRETATION: CT-based prediction models can be used for identification of patients with COPD who are at high risk of severe exacerbations. The newly identified CT biomarkers could potentially enable investigation into underlying disease mechanisms responsible for exacerbations. FUNDING: National Institutes of Health and the National Heart, Lung, and Blood Institute.

PLOSL: Population learning followed by one shot learning pulmonary image registration using tissue volume preserving and vesselness constraints.

This paper presents the Population Learning followed by One Shot Learning (PLOSL) pulmonary image registration method. PLOSL is a fast unsupervised learning-based framework for 3D-CT pulmonary image registration algorithm based on combining population learning (PL) and one-shot learning (OSL). The PLOSL image registration has the advantages of the PL and OSL approaches while reducing their respective drawbacks. The advantages of PLOSL include improved performance over PL, substantially reducing OSL training time and reducing the likelihood of OSL getting stuck in local minima. PLOSL pulmonary image registration uses tissue volume preserving and vesselness constraints for registration of inspiration-to-expiration and expiration-to-inspiration pulmonary CT images. A coarse-to-fine convolution encoder-decoder CNN architecture is used to register large and small shape features. During training, the sum of squared tissue volume difference (SSTVD) compensates for intensity differences between inspiration and expiration computed tomography (CT) images and the sum of squared vesselness measure difference (SSVMD) helps match the lung vessel tree. Results show that the PLOSL (SSTVD+SSVMD) algorithm achieved subvoxel landmark error while preserving pulmonary topology on the SPIROMICS data set, the public DIR-LAB COPDGene and 4DCT data sets.

Forced Expiratory Flow at 25%-75% Links COPD Physiology to Emphysema and Disease Severity in the SPIROMICS Cohort.

BACKGROUND: Forced expiratory volume in 1 second (FEV1) is central to the diagnosis of chronic obstructive pulmonary disease (COPD) but is imprecise in classifying disease burden. We examined the potential of the maximal mid-expiratory flow rate (forced expiratory flow rate between 25% and 75% [FEF25%-75%]) as an additional tool for characterizing pathophysiology in COPD. OBJECTIVE: To determine whether FEF25%-75% helps predict clinical and radiographic abnormalities in COPD. STUDY DESIGN AND METHODS: The SubPopulations and InteRediate Outcome Measures In COPD Study (SPIROMICS) enrolled a prospective cohort of 2978 nonsmokers and ever-smokers, with and without COPD, to identify phenotypes and intermediate markers of disease progression. We used baseline data from 2771 ever-smokers from the SPIROMICS cohort to identify associations between percent predicted FEF25%-75% (%predFEF25%-75%) and both clinical markers and computed tomography (CT) findings of smoking-related lung disease. RESULTS: Lower %predFEF25-75% was associated with more severe disease, manifested radiographically by increased functional small airways disease, emphysema (most notably with homogeneous distribution), CT-measured residual volume, total lung capacity (TLC), and airway wall thickness, and clinically by increased symptoms, decreased 6-minute walk distance, and increased bronchodilator responsiveness (BDR). A lower %predFEF25-75% remained significantly associated with increased emphysema, functional small airways disease, TLC, and BDR after adjustment for FEV1 or forced vital capacity (FVC). INTERPRETATION: The %predFEF25-75% provides additional information about disease manifestation beyond FEV1. These associations may reflect loss of elastic recoil and air trapping from emphysema and intrinsic small airways disease. Thus, %predFEF25-75% helps link the anatomic pathology and deranged physiology of COPD.

Mucus Plugs and Emphysema in the Pathophysiology of Airflow Obstruction and Hypoxemia in Smokers.

Rationale: The relative roles of mucus plugs and emphysema in mechanisms of airflow limitation and hypoxemia in smokers with chronic obstructive pulmonary disease (COPD) are uncertain.Objectives: To relate image-based measures of mucus plugs and emphysema to measures of airflow obstruction and oxygenation in patients with COPD.Methods: We analyzed computed tomographic (CT) lung images and lung function in participants in the Subpopulations and Intermediate Outcome Measures in COPD Study. Radiologists scored mucus plugs on CT lung images, and imaging software automatically quantified emphysema percentage. Unadjusted and adjusted relationships between mucus plug score, emphysema percentage, and lung function were determined using regression.Measurements and Main Results: Among 400 smokers, 229 (57%) had mucus plugs and 207 (52%) had emphysema, and subgroups could be identified with mucus-dominant and emphysema-dominant disease. Only 33% of smokers with high mucus plug scores had mucus symptoms. Mucus plug score and emphysema percentage were independently associated with lower values for FEV1 and peripheral oxygen saturation (P < 0.001). The relationships between mucus plug score and lung function outcomes were strongest in smokers with limited emphysema (P < 0.001). Compared with smokers with low mucus plug scores, those with high scores had worse COPD Assessment Test scores (17.4 ± 7.7 vs. 14.4 ± 13.3), more frequent annual exacerbations (0.75 ± 1.1 vs. 0.43 ± 0.85), and shorter 6-minute-walk distance (329 ± 115 vs. 392 ± 117 m) (P < 0.001).Conclusions: Symptomatically silent mucus plugs are highly prevalent in smokers and independently associate with lung function outcomes. These data provide rationale for targeting patients with mucus-high/emphysema-low COPD in clinical trials of mucoactive treatments.Clinical trial registered with www.clinicaltrials.gov (NCT01969344).

Idiopathic Pulmonary Fibrosis: Data-driven Textural Analysis of Extent of Fibrosis at Baseline and 15-Month Follow-up.

Purpose To evaluate associations between pulmonary function and both quantitative analysis and visual assessment of thin-section computed tomography (CT) images at baseline and at 15-month follow-up in subjects with idiopathic pulmonary fibrosis (IPF). Materials and Methods This retrospective analysis of preexisting anonymized data, collected prospectively between 2007 and 2013 in a HIPAA-compliant study, was exempt from additional institutional review board approval. The extent of lung fibrosis at baseline inspiratory chest CT in 280 subjects enrolled in the IPF Network was evaluated. Visual analysis was performed by using a semiquantitative scoring system. Computer-based quantitative analysis included CT histogram-based measurements and a data-driven textural analysis (DTA). Follow-up CT images in 72 of these subjects were also analyzed. Univariate comparisons were performed by using Spearman rank correlation. Multivariate and longitudinal analyses were performed by using a linear mixed model approach, in which models were compared by using asymptotic χ2 tests. Results At baseline, all CT-derived measures showed moderate significant correlation (P < .001) with pulmonary function. At follow-up CT, changes in DTA scores showed significant correlation with changes in both forced vital capacity percentage predicted (ρ = -0.41, P < .001) and diffusing capacity for carbon monoxide percentage predicted (ρ = -0.40, P < .001). Asymptotic χ2 tests showed that inclusion of DTA score significantly improved fit of both baseline and longitudinal linear mixed models in the prediction of pulmonary function (P < .001 for both). Conclusion When compared with semiquantitative visual assessment and CT histogram-based measurements, DTA score provides additional information that can be used to predict diminished function. Automatic quantification of lung fibrosis at CT yields an index of severity that correlates with visual assessment and functional change in subjects with IPF. © RSNA, 2017.

Texture-based Quantification of Centrilobular Emphysema and Centrilobular Nodularity in Longitudinal CT Scans of Current and Former Smokers.

RATIONALE AND OBJECTIVES: The effect of smoking cessation on centrilobular emphysema (CLE) and centrilobular nodularity (CN), two manifestations of smoking-related lung injury on computed tomography (CT) images, has not been clarified. The objective of this study is to leverage texture analysis to investigate differences in extent of CLE and CN between current and former smokers. MATERIALS AND METHODS: Chest CT scans from 350 current smokers, 401 former smokers, and 25 control subjects were obtained from the multicenter COPDGene Study, a Health Insurance Portability and Accountability Act-compliant study approved by the institutional review board of each participating clinical study center. Additionally, for 215 of these subjects, a follow-up CT scan was obtained approximately 5 years later. For each CT scan, 5000 circular regions of interest (ROIs) of 35-pixel diameter were randomly selected throughout the lungs. The patterns present in each ROI were summarized by 50 computer-extracted texture features. A logistic regression classifier was leveraged to classify each ROI as normal lung, CLE, or CN, and differences in the percentages of normal lung, CLE, and CN by study group were assessed. RESULTS: Former smokers had significantly more CLE (P <0.01) but less CN (P <0.001) than did current smokers, even after adjustment for important covariates such as patient age, GOLD stage, smoking history, forced expiratory volume in 1 second, gas trapping, and scanner model. Among patients with longitudinal CT scans, continued smoking led to a slight increase in CLE (P = 0.13), whereas sustained abstinence from smoking led to further reduction in CN (P <0.05). CONCLUSIONS: The proposed texture-based approach quantifies the extent of CN and CLE with high precision. Differences in smoking-related lung disease between longitudinal scans of current smokers and longitudinal scans of former smokers suggest that CN may be reversible on smoking cessation.

Cystatin C: a potential biomarker for pulmonary arterial hypertension.

BACKGROUND AND OBJECTIVE: Cystatin C (CysC), a novel marker of renal function, predicts left heart failure and cardiovascular mortality. The hypothesis that serum CysC levels correlate with right ventricular (RV) morphology, function and pressure in pulmonary arterial hypertension (PAH) was tested. METHODS: As part of a prospective study, 14 PAH subjects and 10 matched controls underwent same-day echocardiography, cardiac magnetic resonance imaging (CMR), and phlebotomy for CysC, brain natriuretic peptide (BNP), and N-terminal BNP (NT-ProBNP). RV ejection fraction (RVEF), end-diastolic volume, end-systolic volume and mass were calculated using CMR. RV systolic pressure (RVSP), strain and diastolic function (including tricuspid valve (TV) E velocity, A velocity, e' velocity, E/A ratio and E/e' ratio) were assessed using echocardiography. RESULTS: RVSP was significantly elevated in PAH subjects versus controls (57 ± 17 vs. 28 ± 8 mm Hg, P < 0.0001). CysC was abnormally elevated in the PAH cohort when compared with controls (1.00 ± 0.23 vs 0.78 ± 0.05 mg/L, P = 0.001). CysC positively correlated with RVSP (rho 0.61, P = 0.002), RV end-diastolic volume (rho 0.50, P = 0.01), RV end-systolic volume (rho 0.58, P = 0.003), mass index (rho 0.66, P = 0.0004), strain (rho 0.51, P = 0.01) and strain rate (rho 0.51, P = 0.01) and negatively correlated with RVEF (rho -0.58, P = 0.003) and TV e' (rho -0.75, P < 0.0001). The same correlations with BNP and NT-ProBNP were comparable with CysC. CONCLUSIONS: In a small cohort, CysC accurately correlates with RV pressure, function and morphology. CysC may represent a novel PAH biomarker.

Relationships between airflow obstruction and quantitative CT measurements of emphysema, air trapping, and airways in subjects with and without chronic obstructive pulmonary disease.

OBJECTIVE: This study evaluates the relationships between quantitative CT (QCT) and spirometric measurements of disease severity in cigarette smokers with and without chronic obstructive pulmonary disease (COPD). MATERIALS AND METHODS: Inspiratory and expiratory CT scans of 4062 subjects in the Genetic Epidemiology of COPD (COPDGene) Study were evaluated. Measures examined included emphysema, defined as the percentage of low-attenuation areas≤-950 HU on inspiratory CT, which we refer to as "LAA-950I"; air trapping, defined as the percentage of low-attenuation areas≤-856 HU on expiratory CT, which we refer to as "LAA-856E"; and the inner diameter, inner and outer areas, wall area, airway wall thickness, and square root of the wall area of a hypothetical airway of 10-mm internal perimeter of segmental and subsegmental airways. Correlations were determined between spirometry and several QCT measures using statistics software (SAS, version 9.2). RESULTS: QCT measurements of low-attenuation areas correlate strongly and significantly (p<0.0001) with spirometry. The correlation between LAA-856E and forced expiratory volume in 1 second (FEV1) and the ratio of FEV1 to forced vital capacity (FVC) (r=-0.77 and -0.84, respectively) is stronger than the correlation between LAA-950I and FEV1 and FEV1/FVC (r=-0.67 and r=-0.76). Inspiratory and expiratory volume changes decreased with increasing disease severity, as measured by the Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) staging system (p<0.0001). When airway variables were included with low-attenuation area measures in a multiple regression model, the model accounted for a statistically greater proportion of variation in FEV1 and FEV1/FVC (R2=0.72 and 0.77, respectively). Airway measurements alone are less correlated with spirometric measures of FEV1 (r=0.15 to -0.44) and FEV1/FVC (r=0.19 to -0.34). CONCLUSION: QCT measurements are strongly associated with spirometric results showing impairment in smokers. LAA-856E strongly correlates with physiologic measurements of airway obstruction. Airway measurements can be used concurrently with QCT measures of low-attenuation areas to accurately predict lung function.

Computed tomographic measures of pulmonary vascular morphology in smokers and their clinical implications.

RATIONALE: Angiographic investigation suggests that pulmonary vascular remodeling in smokers is characterized by distal pruning of the blood vessels. OBJECTIVES: Using volumetric computed tomography scans of the chest we sought to quantitatively evaluate this process and assess its clinical associations. METHODS: Pulmonary vessels were automatically identified, segmented, and measured. Total blood vessel volume (TBV) and the aggregate vessel volume for vessels less than 5 mm(2) (BV5) were calculated for all lobes. The lobe-specific BV5 measures were normalized to the TBV of that lobe and the nonvascular tissue volume (BV5/T(issue)V) to calculate lobe-specific BV5/TBV and BV5/T(issue)V ratios. Densitometric measures of emphysema were obtained using a Hounsfield unit threshold of -950 (%LAA-950). Measures of chronic obstructive pulmonary disease severity included single breath measures of diffusing capacity of carbon monoxide, oxygen saturation, the 6-minute-walk distance, St George's Respiratory Questionnaire total score (SGRQ), and the body mass index, airflow obstruction, dyspnea, and exercise capacity (BODE) index. MEASUREMENTS AND MAIN RESULTS: The %LAA-950 was inversely related to all calculated vascular ratios. In multivariate models including age, sex, and %LAA-950, lobe-specific measurements of BV5/TBV were directly related to resting oxygen saturation and inversely associated with both the SGRQ and BODE scores. In similar multivariate adjustment lobe-specific BV5/T(issue)V ratios were inversely related to resting oxygen saturation, diffusing capacity of carbon monoxide, 6-minute-walk distance, and directly related to the SGRQ and BODE. CONCLUSIONS: Smoking-related chronic obstructive pulmonary disease is characterized by distal pruning of the small blood vessels (<5 mm(2)) and loss of tissue in excess of the vasculature. The magnitude of these changes predicts the clinical severity of disease.

Effect of emphysema on CT scan measures of airway dimensions in smokers.

BACKGROUND: In CT scans of smokers with COPD, the subsegmental airway wall area percent (WA%) is greater and more strongly correlated with FEV1 % predicted than WA% obtained in the segmental airways. Because emphysema is linked to loss of airway tethering and may limit airway expansion, increases in WA% may be related to emphysema and not solely to remodeling. We aimed to first determine whether the stronger association of subsegmental vs segmental WA% with FEV1 % predicted is mitigated by emphysema and, second, to assess the relationships among emphysema, WA%, and total bronchial area (TBA). METHODS: We analyzed CT scan segmental and subsegmental WA% (WA% = 100 × wall area/TBA) of six bronchial paths and corresponding lobar emphysema, lung function, and clinical data in 983 smokers with COPD. RESULTS: Compared with segmental WA%, the subsegmental WA% had a greater effect on FEV1% predicted (-0.8% to -1.7% vs -1.9% to -2.6% per 1-unit increase in WA%, respectively; P < .05 for most bronchial paths). After adjusting for emphysema, the association between subsegmental WA% and FEV1 % predicted was weakened in two bronchial paths. Increases in WA% between bronchial segments correlated directly with emphysema in all bronchial paths (P < .05). In multivariate regression models, emphysema was directly related to subsegmental WA% in most bronchial paths and inversely related to subsegmental TBA in all bronchial paths. CONCLUSION: The greater effect of subsegmental WA% on airflow obstruction is mitigated by emphysema. Part of the emphysema effect might be due to loss of airway tethering, leading to a reduction in TBA and an increase in WA%.

Chronic obstructive pulmonary disease: lobe-based visual assessment of volumetric CT by Using standard images--comparison with quantitative CT and pulmonary function test in the COPDGene study.

PURPOSE: To provide a new detailed visual assessment scheme of computed tomography (CT) for chronic obstructive pulmonary disease (COPD) by using standard reference images and to compare this visual assessment method with quantitative CT and several physiologic parameters. MATERIALS AND METHODS: This research was approved by the institutional review board of each institution. CT images of 200 participants in the COPDGene study were evaluated. Four thoracic radiologists performed independent, lobar analysis of volumetric CT images for type (centrilobular, panlobular, and mixed) and extent (on a six-point scale) of emphysema, the presence of bronchiectasis, airway wall thickening, and tracheal abnormalities. Standard images for each finding, generated by two radiologists, were used for reference. The extent of emphysema, airway wall thickening, and luminal area were quantified at the lobar level by using commercial software. Spearman rank test and simple and multiple regression analyses were performed to compare the results of visual assessment with physiologic and quantitative parameters. RESULTS: The type of emphysema, determined by four readers, showed good agreement (κ = 0.63). The extent of the emphysema in each lobe showed good agreement (mean weighted κ = 0.70) and correlated with findings at quantitative CT (r = 0.75), forced expiratory volume in 1 second (FEV(1)) (r = -0.68), FEV(1)/forced vital capacity (FVC) ratio (r = -0.74) (P < .001). Agreement for airway wall thickening was fair (mean κ = 0.41), and the number of lobes with thickened bronchial walls correlated with FEV(1) (r = -0.60) and FEV(1)/FVC ratio (r = -0.60) (P < .001). CONCLUSION: Visual assessment of emphysema and airways disease in individuals with COPD can provide reproducible, physiologically substantial information that may complement that provided by quantitative CT assessment.

Automated texture-based quantification of centrilobular nodularity and centrilobular emphysema in chest CT images.

RATIONALE AND OBJECTIVES: Characterization of smoking-related lung disease typically consists of visual assessment of chest computed tomographic (CT) images for the presence and extent of emphysema and centrilobular nodularity (CN). Quantitative analysis of emphysema and CN may improve the accuracy, reproducibility, and efficiency of chest CT scoring. The purpose of this study was to develop a fully automated texture-based system for the detection and quantification of centrilobular emphysema (CLE) and CN in chest CT images. MATERIALS AND METHODS: A novel approach was used to prepare regions of interest (ROIs) within the lung parenchyma for representation by texture features associated with the gray-level run-length and gray-level gap-length methods. These texture features were used to train a multiple logistic regression classifier to discriminate between normal lung tissue, CN or "smoker's lung," and CLE. This classifier was trained and evaluated on 24 and 71 chest CT scans, respectively. RESULTS: During training, the classifier correctly classified 89% of ROIs depicting normal lung tissue, 74% of ROIs depicting CN, and 95% of ROIs manifesting CLE. When the performance of the classifier in quantifying extent of CN and CLE was evaluated on 71 chest CT scans, 65% of ROIs in smokers without CLE were classified as CN, compared to 31% in nonsmokers (P < .001) and 28% in smokers with CLE (P < .001). CONCLUSIONS: The texture-based framework described herein facilitates successful discrimination among normal lung tissue, CN, and CLE and can be used for the automated quantification of smoking-related lung disease.

A combined pulmonary-radiology workshop for visual evaluation of COPD: study design, chest CT findings and concordance with quantitative evaluation.

UNLABELLED: The purposes of this study were: to describe chest CT findings in normal non-smoking controls and cigarette smokers with and without COPD; to compare the prevalence of CT abnormalities with severity of COPD; and to evaluate concordance between visual and quantitative chest CT (QCT) scoring. METHODS: Volumetric inspiratory and expiratory CT scans of 294 subjects, including normal non-smokers, smokers without COPD, and smokers with GOLD Stage I-IV COPD, were scored at a multi-reader workshop using a standardized worksheet. There were 58 observers (33 pulmonologists, 25 radiologists); each scan was scored by 9-11 observers. Interobserver agreement was calculated using kappa statistic. Median score of visual observations was compared with QCT measurements. RESULTS: Interobserver agreement was moderate for the presence or absence of emphysema and for the presence of panlobular emphysema; fair for the presence of centrilobular, paraseptal, and bullous emphysema subtypes and for the presence of bronchial wall thickening; and poor for gas trapping, centrilobular nodularity, mosaic attenuation, and bronchial dilation. Agreement was similar for radiologists and pulmonologists. The prevalence on CT readings of most abnormalities (e.g. emphysema, bronchial wall thickening, mosaic attenuation, expiratory gas trapping) increased significantly with greater COPD severity, while the prevalence of centrilobular nodularity decreased. Concordances between visual scoring and quantitative scoring of emphysema, gas trapping and airway wall thickening were 75%, 87% and 65%, respectively. CONCLUSIONS: Despite substantial inter-observer variation, visual assessment of chest CT scans in cigarette smokers provides information regarding lung disease severity; visual scoring may be complementary to quantitative evaluation.

The clinical features of the overlap between COPD and asthma.

BACKGROUND: The coexistence of COPD and asthma is widely recognized but has not been well described. This study characterizes clinical features, spirometry, and chest CT scans of smoking subjects with both COPD and asthma. METHODS: We performed a cross-sectional study comparing subjects with COPD and asthma to subjects with COPD alone in the COPDGene Study. RESULTS: 119 (13%) of 915 subjects with COPD reported a history of physician-diagnosed asthma. These subjects were younger (61.3 vs 64.7 years old, p=0.0001) with lower lifetime smoking intensity (43.7 vs 55.1 pack years, p=0.0001). More African-Americans reported a history of asthma (33.6% vs 15.6%, p<0.0001). Subjects with COPD and asthma demonstrated worse disease-related quality of life, were more likely to have had a severe COPD exacerbation in the past year, and were more likely to experience frequent exacerbations (OR 3.55 [2.19, 5.75], p<0.0001). Subjects with COPD and asthma demonstrated greater gas-trapping on chest CT. There were no differences in spirometry or CT measurements of emphysema or airway wall thickness. CONCLUSION: Subjects with COPD and asthma represent a relevant clinical population, with worse health-related quality of life. They experience more frequent and severe respiratory exacerbations despite younger age and reduced lifetime smoking history. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00608764.