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Purpose To identify a prevalent computed tomography (CT) subtype in patients with chronic obstructive pulmonary disease (COPD) by separating emphysematous from nonemphysematous contributions to total gas trapping and to attempt to predict and grade the emphysematous gas trapping by using clinical and functional data. Materials and Methods Two-hundred and two consecutive eligible patients (159 men and 43 women; mean age, 70 years [age range, 41-85 years]) were prospectively studied. Pulmonary function and CT data were acquired by pulmonologists and radiologists. Noncontrast agent-enhanced thoracic CT scans were acquired at full inspiration and expiration, and were quantitatively analyzed by using two software programs. CT parameters were set as follows: 120 kVp; 200 mAs; rotation time, 0.5 second; pitch, 1.1; section thickness, 0.75 mm; and reconstruction kernels, b31f and b70f. Gas trapping obtained by difference of inspiratory and expiratory CT density thresholds (percentage area with CT attenuation values less than -950 HU at inspiration and percentage area with CT attenuation values less than -856 HU at expiration) was compared with that obtained by coregistration analysis. A logistic regression model on the basis of anthropometric and functional data was cross-validated and trained to classify patients with COPD according to the relative contribution of emphysema to total gas trapping, as assessed at CT. Results Gas trapping obtained by difference of inspiratory and expiratory CT density thresholds was highly correlated (r = 0.99) with that obtained by coregistration analysis. Four groups of patients were distinguished according to the prevalent CT subtype: prevalent emphysematous gas trapping, prevalent functional gas trapping, mixed severe, and mixed mild. The predictive model included predicted forced expiratory volume in 1 second/vital capacity, percentage of predicted forced expiratory volume in 1 second, percentage of diffusing capacity for carbon monoxide, and body mass index as emphysema regressors at CT, with 81% overall accuracy in classifying patients according to its extent. Conclusion The relative contribution of emphysematous and nonemphysematous gas trapping obtained by coregistration of inspiratory and expiratory CT scanning can be determined accurately by difference of CT inspiratory and expiratory density thresholds. CT extent of emphysema can be predicted with accuracy suitable for clinical purposes by pulmonary function data and body mass index. © RSNA, 2018 Online supplemental material is available for this article.

Rationale and Objectives The opened or closed status of the glottis might influence tracheal size changes in inspiratory and expiratory computed tomography (CT) scans. We investigated if the glottis status makes the tracheal collapse differently correlate with lung volume difference between inspiratory and expiratory CT scans. Materials and Methods Forty patients with chronic obstructive pulmonary disease whose glottis was included in the acquired scanned volume for lung CT were divided into two groups: 16 patients with the glottis closed in both inspiratory and expiratory CT, and 24 patients with the glottis open in at least one CT acquisition. Lung inspiratory (Vinsp) and expiratory (Vexp) volumes were automatically computed and lung ΔV was calculated using the following formula: (Vinsp − Vexp)/Vinsp × 100. Two radiologists manually measured the anteroposterior diameter and cross-sectional area of the trachea 1 cm above the aortic arch and 1 cm above the carina. Tracheal collapse was then calculated and correlated with lung ΔV. Results In the 40 patients, the correlations between tracheal Δanteroposterior diameter and Δcross-sectional area at each level and lung ΔV ranged between 0.68 and 0.74 (ρ) at Spearman rank correlation test. However, in the closed glottis group, the correlations were higher for all measures at the two levels (ρ range: 0.84–0.90), whereas in the open glottis group, correlations were low and not statistically significant (ρ range: 0.29–0.34) at the upper level, and moderate at the lower level (ρ range: 0.51–0.55). Conclusions A closed or open glottis influences the tracheal size change in inspiratory and expiratory CT scans. With closed glottis, the tracheal collapse shows a stronger correlation with the lung volume difference between inspiratory and expiratory CT scans.

Background COPD is a heterogeneous disease, but there is little consensus on specific definitions for COPD subtypes. Unsupervised clustering offers the promise of 'unbiased' data-driven assessment of COPD heterogeneity. Multiple groups have identified COPD subtypes using cluster analysis, but there has been no systematic assessment of the reproducibility of these subtypes.Objective We performed clustering analyses across 10 cohorts in North America and Europe in order to assess the reproducibility of (1) correlation patterns of key COPD-related clinical characteristics and (2) clustering results.Methods We studied 17 146 individuals with COPD using identical methods and common COPD-related characteristics across cohorts (FEV1, FEV1/FVC, FVC, body mass index, Modified Medical Research Council score, asthma and cardiovascular comorbid disease). Correlation patterns between these clinical characteristics were assessed by principal components analysis (PCA). Cluster analysis was performed using k-medoids and hierarchical clustering, and concordance of clustering solutions was quantified with normalised mutual information (NMI), a metric that ranges from 0 to 1 with higher values indicating greater concordance.Results The reproducibility of COPD clustering subtypes across studies was modest (median NMI range 0.17-0.43). For methods that excluded individuals that did not clearly belong to any cluster, agreement was better but still suboptimal (median NMI range 0.32-0.60). Continuous representations of COPD clinical characteristics derived from PCA were much more consistent across studies.Conclusions Identical clustering analyses across multiple COPD cohorts showed modest reproducibility. COPD heterogeneity is better characterised by continuous disease traits coexisting in varying degrees within the same individual, rather than by mutually exclusive COPD subtypes.

Gianna Camiciottoli,1,2 Francesca Bigazzi,1 Chiara Magni,1 Viola Bonti,1 Stefano Diciotti,3 Maurizio Bartolucci,4 Mario Mascalchi,5 Massimo Pistolesi1 1Section of Respiratory Medicine, Department of Clinical and Experimental Medicine, 2Department of Clinical and Experimental Biomedical Sciences, University of Florence, Florence, 3Department of Electrical, Electronic, and Information Engineering “Guglielmo Marconi,” University of Bologna, Cesena, 4Department of Diagnostic Imaging, Careggi University Hospital, 5Radiodiagnostic Section, Department of Clinical and Experimental Biomedical Sciences, University of Florence, Florence, Italy Background: In addition to lung involvement, several other diseases and syndromes coexist in patients with chronic obstructive pulmonary disease (COPD). Our purpose was to investigate the prevalence of idiopathic arterial hypertension (IAH), ischemic heart disease, heart failure, peripheral vascular disease (PVD), diabetes, osteoporosis, and anxious depressive syndrome in a clinical setting of COPD outpatients whose phenotypes (predominant airway disease and predominant emphysema) and severity (mild and severe diseases) were determined by clinical and functional parameters. Methods: A total of 412 outpatients with COPD were assigned either a predominant airway disease or a predominant emphysema phenotype of mild or severe degree according to predictive models based on pulmonary functions (forced expiratory volume in 1 second/vital capacity; total lung capacity %; functional residual capacity %; and diffusing capacity of lung for carbon monoxide %) and sputum characteristics. Comorbidities were assessed by objective medical records. Results: Eighty-four percent of patients suffered from at least one comorbidity and 75% from at least one cardiovascular comorbidity, with IAH and PVD being the most prevalent ones (62% and 28%, respectively). IAH prevailed significantly in predominant airway disease, osteoporosis prevailed significantly in predominant emphysema, and ischemic heart disease and PVD prevailed in mild COPD. All cardiovascular comorbidities prevailed significantly in predominant airway phenotype of COPD and mild COPD severity. Conclusion: Specific comorbidities prevail in different phenotypes of COPD; this fact may be relevant to identify patients at risk for specific, phenotype-related comorbidities. The highest prevalence of comorbidities in patients with mild disease indicates that these patients should be investigated for coexisting diseases or syndromes even in the less severe, pauci-symptomatic stages of COPD. The simple method employed to phenotype and score COPD allows these results to be translated easily into daily clinical practice. Keywords: COPD phenotypes, COPD severity, comorbidities

Patients with deflation cough (DC), the cough-like expulsive effort(s) evoked by maximal lung emptying during a slow vital capacity maneuver, also present symptoms of gastroesophageal reflux. DC can be inhibited by prior intake of antacids. We wished to assess DC prevalence and association between DC and chemical characteristics of refluxate in patients with gastroesophageal reflux symptoms.A total of 157 consecutive outpatients underwent DC assessment and 24-h multichannel intraluminal impedance pH (MII-pH) monitoring; 93/157 also had chronic cough. Patients performed two to four slow vital capacity maneuvers and DC was detected aurally. Subsequently, they underwent 24-h MII-pH monitoring, the outcomes of which were defined as abnormal when acid or non-acid reflux events were 73.DC occurred in 46/157 patients, 18 of whom had abnormal MII-pH outcomes; 28 of the remaining 111 patients without DC also had abnormal MII-pH findings. Thus, in the patients as a group, there was no association between DC and MII-pH outcomes. DC occurred in 40/93 of the chronic coughers; 15 of whom had acid reflux. All but 2 of the 53 patients without DC had normal MII-pH outcomes (P .001), and the negative predictive value of DC for excluding acid reflux was 96.2%. At follow-up, 65% of coughers showed significant improvement after treatment.The overall prevalence of DC was 29%, increasing to 43% in chronic coughers in whom the absence of DC virtually excludes acid reflux. Therefore, DC assessment may represent a useful screening test for excluding acid reflux in chronic coughers with reflux symptoms.

To determine whether the relationship between pulmonary function and computed tomographic (CT) lung attenuation in chronic obstructive pulmonary disease (COPD), which is traditionally described with single univariate and multivariate statistical models, could be more accurately described with a multiple model estimation approach.The study was approved by the local ethics committee. All participants provided written informed consent. The prediction of the percentage area with CT attenuation values less than -950 HU at inspiration (%LAA-950insp) and less than -910 HU at expiration (%LAA-910exp) obtained with single univariate and multivariate models was compared with that obtained with a multiple model estimation approach in 132 patients with COPD.At univariate analysis, %LAA-950insp and %LAA-910exp values higher than the mean value of this cohort (19.1% and 22.0%) showed better correlation with percentage of predicted diffusing capacity of lung for carbon monoxide (Dlco%) than with airflow obstruction (forced expiratory volume in 1 second [FEV1]/vital capacity [VC]). Conversely, %LAA-950insp and %LAA-910exp values lower than the mean value were correlated with FEV1/VC but not with Dlco%. Multiple model estimation performed with two multivariate regressions, each selecting the most appropriate functional variables (FEV1/VC for mild parenchymal destruction, Dlco% and functional residual capacity for severe parenchymal destruction), predicted better than single multivariate regression both %LAA-950insp (R(2) = 0.75 vs 0.46) and %LAA-910exp (R(2) = 0.83 vs 0.63).The relationship between pulmonary function data and CT densitometric changes in COPD varies with the level of lung attenuation impairment. The nonlinear profile of this relationship is accurately predicted with a multiple model estimation approach.

Airflow limitation in COPD results from different mechanisms, including emphysema and small airway disease. Unlike spirometry, computed tomography (CT) can quantify both emphysema extent as well as gas-trapping due to small airway disease. We aimed to predict by clinical and functional data the probability of having emphysema, as assessed on CT. We measured dynamic (FEV1, FVC, VC), static (TLC, FRC, RV) lung volumes, and diffusing capacity (DLco) in 180 COPD patients (GOLD 1-4). By post-processing image analysis of CT scans we measured the percent lung area with density The model included FEV1/VC, FEV1%, DLco%, and BMI as predictors of %LAA-950. The overall accuracy of the model was 81.1%, with a higher accuracy (88.0%) in those subjects with “milder” disease. We classified each subject according to the probability output values, from milder (group 1) to more severe (group 4) emphysema. The four outputs of the model had significantly different %LAA-950 (p The predictive model including FEV1/VC, FEV1%, DLco%, and BMI demonstrated a high accuracy in predicting the emphysema extent in COPD patients, as assessed on CT. The accuracy obtained by the model is suitable for daily clinical purposes as well as for clinical trials.

Airway obstruction and parenchymal destruction underlie phenotype and severity in chronic obstructive pulmonary disease (COPD). We aimed to predict, by clinical and pulmonary function data, the predominant type and severity of pathological changes quantitatively assessed by computed tomography (CT). Airway wall thickness (AWT-Pi10) and percentage of lung area with X-ray attenuation values

The purposes of this study were: to describe chest CT findings in normal nonsmoking 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 interobserver variation, visual assessment of chest CT scans in cigarette smokers provides information regarding lung disease severity; visual scoring may be complementary to quantitative evaluation.

Diffuse "true" cystic lung disease is rare, and the specificity of high-resolution computed tomography (HRCT) has reduced the need for biopsy. We present 5 patients with similar clinical and HRCT features of cystic lung disease that were sufficiently atypical to warrant surgical lung biopsies that showed coexistent small airway diseases (SAD). There were 4 female patients and 1 male patient with a mean age of 43 years. All were never smokers. Four had symptoms such as dyspnea (1), cough (2), or both (1). HRCTs showed variably sized thin-walled cystic airspaces without zonal distribution, some with prominent vessels in their walls. One case was unilateral. Surgical lung biopsy showed cystic change comprising localized loss of alveolar density with coexistent SADs [chronic bronchiolitis (n=2), eosinophilic bronchiolitis, probable asthma (n=1), and diffuse idiopathic neuroendocrine cell hyperplasia (n=2)]. Two patients who were tested for Birt-Hogg-Dube-related gene mutations proved negative, and all lacked other features of Birt-Hogg-Dube. We hypothesize that chronic damage to small airways may lead to cystic degeneration in a minority of patients. Precedents in relation to Sjogren syndrome and hypersensitivity pneumonitis raise the possibility of a causal association between pathologies in these 2 anatomic compartments, although HRCT data in relation to common SADs indicate that this would be a rare phenomenon. The driving factor remains unknown.

Exacerbations are recommended (GOLD2011) as a new dimension to stage COPD and guide its therapeutic approach. We investigated: 1) the relationship of exacerbations with clinical examination, pulmonary function and lung CT changes; 2) the stability of exacerbation frequency in 133 COPD outpatients over two years of follow-up. Exacerbation frequency occurring in the year prior and the year following a chest CT scan was collected by a standardized questionnaire. Patients with ≥2 episodes/year were considered “frequent exacerbators” . By principal component analysis of CT values of parenchymal destruction (%LAA-950) and airway wall thickness (AWT-Pi10) we assessed quantitatively the CT predominant phenotype (airway disease or emphysema) and the overall severity of COPD (Camiciottoli et al ERJ 2013). Patients with more severely impaired lung function, higher BODE score and more severe CT changes had more frequent exacerbations in the year prior the examination. Exacerbation frequency was not significantly different in patients with airways disease or emphysema CT predominant phenotype. Fifty% of the 42 “frequent exacerbators” in the first year became “infrequent exacerbators” in the second year, while only 5% of the 91 “infrequent exacerbators” became “frequent exacerbators”. Exacerbations frequency does not reflect the predominant mechanism of airflow limitation as determined by quantitative CT. Although exacerbations frequency could be a reliable index of COPD severity, the so called “frequent exacerbator phenotype” is not a stable disease characteristic and its prevalence may be influenced by medical treatment or other sociological interactions. Larger population longitudinal studies are needed to clarify this point.

The protean clinical presentation of pulmonary embolism (PE) is the consequence of a complex series of haemodynamic and respiratory changes caused by the impact of thrombi within the pulmonary vasculature. Haemodynamic changes result from obstruction of the pulmonary arterial bed leading to increased pulmonary vascular resistances and they are manifested clinically as dyspnoea, engorgement of neck veins, and systemic arterial hypotension. Respiratory changes are characterised by lung volume reduction, hypocapnia and hypoxaemia. Reduced lung volume is mainly due to pulmonary consolidation, atelectasis and decreased distension of the thoracic cage due to chest pain. These pathophysiological changes affect both perfusion and ventilation and could explain the low sensitivity of the ventilation/perfusion (V/Q) mismatch scintigraphic approach in diagnosing PE. Acute PE causes redistribution of pulmonary blood flow from non-perfused areas and, to a lesser extent, of ventilation; this is a further factor arguing against the use of V/Q mismatch for the scintigraphic diagnosis of the disease. Hypoxaemia is primarily the consequence of V/Q abnormalities, namely the development of areas with a low V/Q ratio. On a Q scan this can easily be appreciated from hyperperfused lung areas that, by themselves, are a marker for the scintigraphic diagnosis of PE. In conclusion, a Q scan without a V scan, when properly interpreted according to the prospective investigative study of acute pulmonary embolism diagnosis methodology (presence or absence of wedge-shaped perfusion defects) and combined with the formulation of a pre-test clinical probability, can be used in most patients with clinical suspicion of PE, reducing costs and radiation load, increasing the practicality of the examination, and providing diagnostic accuracy comparable to that of CT angiography.

COPD is a heterogeneous disorder whose assessment is going to be increasingly multidimensional. Grading systems such as BODE (Body-Mass Index, Obstruction, Dyspnea, Exercise), mBODE (BODE modified in grading of walked distance), ADO (Age, Dyspnea, Obstruction) are proposed to assess COPD severity and outcome. Computed tomography (CT) is deemed to reflect COPD lung pathologic changes. We studied the relationship of multidimensional grading systems (MGS) with clinically determined COPD phenotypes and CT lung density. Seventy-two patients underwent clinical and chest x-ray evaluation, pulmonary function tests (PFT), 6-minute walking test (6MWT) to derive: predominant COPD clinical phenotype, BODE, mBODE, ADO. Inspiratory and expiratory CT was performed to calculate mean lung attenuation (MLA), relative area with density below-950 HU at inspiration (RAI(-950)), and below -910 HU at expiration (RAE(-910)). MGS, PFT, and CT data were compared between bronchial versus emphysematous COPD phenotype. MGS were correlated with CT data. The prediction of CT density by means of MGS was investigated by direct and stepwise multivariate regression. MGS did not differ in clinically determined COPD phenotypes. BODE was more closely related and better predicted CT findings than mBODE and ADO; the better predictive model was obtained for CT expiratory data; stepwise regression models of CT data did not include 6MWT distance; the dyspnea score MRC was included only to predict RA-950 and RA-910 which quantify emphysema extent. BODE reflect COPD severity better than other MGS, but not its clinical heterogeneity. 6MWT does not significantly increase BODE predictivity of CT lung density changes.

Gianna Camiciottoli,1 Stefano Diciotti,2 Francesca Bigazzi,1 Simone Lombardo,3 Maurizio Bartolucci,4 Matteo Paoletti,1 Mario Mascalchi,3 Massimo Pistolesi1 1Section of Respiratory Medicine, Department of Clinical and Experimental Medicine, University of Florence, Florence, Italy; 2Department of Electrical, Electronic, and Information Engineering “Guglielmo Marconi,” University of Bologna, Cesena, Italy; 3Radiodiagnostic Section, Department of Clinical and Experimental Biomedical Sciences, University of Florence, Florence, Italy; 4Department of Diagnostic Imaging, Careggi University Hospital, Florence,Italy Abstract: A substantial proportion of patients with chronic obstructive pulmonary disease (COPD) develops various degree of intrathoracic tracheal collapsibility. We studied whether the magnitude of intrathoracic tracheal collapsibility could be different across clinical phenotypes and sex in COPD. Intrathoracic tracheal collapsibility measured at paired inspiratory–expiratory low dose computed tomography (CT) and its correlation with clinical, functional, and CT-densitometric data were investigated in 69 patients with COPD according to their predominant conductive airway or emphysema phenotypes and according to sex. Intrathoracic tracheal collapsibility was higher in patients with predominant conductive airway disease (n=28) and in females (n=27). Women with a predominant conductive airway phenotype (n=10) showed a significantly greater degree of collapsibility than women with predominant emphysema (28.9%±4% versus 11.6%±2%; P