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BackgroundBody composition measures, specifically low weight or reduced muscle mass, are associated with mortality in COPD, but the effect of longitudinal body composition changes is undefined.Research questionIs the longitudinal loss of fat-free mass (FFM) associated with increased mortality, including in those with initially normal or elevated body composition metrics?Study design and methodsParticipants with complete data for at least one visit in the COPDGene study (n= 9,268) and the ECLIPSE study (n= 1,760) were included and monitored for 12 and 8 years, respectively. Pectoralis muscle area (PMA) was derived from thoracic CT scans and used as a proxy for FFM. A longitudinal mixed submodel for PMA and a Cox proportional hazards submodel for survival were fitted on a joint distribution, using a shared random intercept parameter and Markov chain Monte Carlo parameter estimation.ResultsBoth cohorts demonstrated a left-shifted distribution of baseline FFM, not reflected in BMI, and an increase in all-cause mortality risk associated with longitudinal loss of PMA. For each 1-cm2 PMA loss, mortality increased 3.1%(95%CI, 2.4%-3.7%; P< .001) in COPDGene, and 2.4%(95%CI, 0.9%-4.0%; P< .001) in ECLIPSE. Increased mortality risk was independent of enrollment values for BMI and disease severity [BODE (body mass, airflow obstruction, dyspnea, and exercise capacity) index quartiles] and was significant even in participants with initially greater than average PMA.InterpretationLongitudinal loss of PMA is associated with increased all-cause mortality, regardless of BMI or initial muscle mass. Consideration of novel screening tests and further research into mechanisms contributing to muscle decline may improve risk stratification and identify novel therapeutic targets in ever smokers.

Contains fulltext : 220761.pdf (Publisher’s version ) (Open Access) Rationale: The decades-long progression of chronic obstructive pulmonary disease (COPD) renders identifying different trajectories of disease progression challenging.Objectives: To identify subtypes of patients with COPD with distinct longitudinal progression patterns using a novel machine-learning tool called "Subtype and Stage Inference" (SuStaIn) and to evaluate the utility of SuStaIn for patient stratification in COPD.Methods: We applied SuStaIn to cross-sectional computed tomography imaging markers in 3,698 Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1-4 patients and 3,479 controls from the COPDGene (COPD Genetic Epidemiology) study to identify subtypes of patients with COPD. We confirmed the identified subtypes and progression patterns using ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) data. We assessed the utility of SuStaIn for patient stratification by comparing SuStaIn subtypes and stages at baseline with longitudinal follow-up data.Measurements and Main Results: We identified two trajectories of disease progression in COPD: a "Tissue-->Airway" subtype (n = 2,354, 70.4%), in which small airway dysfunction and emphysema precede large airway wall abnormalities, and an "Airway-->Tissue" subtype (n = 988, 29.6%), in which large airway wall abnormalities precede emphysema and small airway dysfunction. Subtypes were reproducible in ECLIPSE. Baseline stage in both subtypes correlated with future FEV1/FVC decline (r = -0.16 [P < 0.001] in the Tissue-->Airway group; r = -0.14 [P = 0.011] in the Airway-->Tissue group). SuStaIn placed 30% of smokers with normal lung function at elevated stages, suggesting imaging changes consistent with early COPD. Individuals with early changes were 2.5 times more likely to meet COPD diagnostic criteria at follow-up.Conclusions: We demonstrate two distinct patterns of disease progression in COPD using SuStaIn, likely representing different endotypes. One third of healthy smokers have detectable imaging changes, suggesting a new biomarker of "early COPD."

RationaleThe demographic, physiological, and computed tomography (CT) features associated with pneumothorax in smokers with and without chronic obstructive pulmonary disease (COPD) are not clearly defined.ObjectivesWe evaluated the hypothesis that pneumothorax in smokers is associated with male sex, tall and thin stature, airflow obstruction, and increased total and subpleural emphysema.MethodsThe study included smokers with and without COPD from the COPDGene Study, with quantitative chest CT analysis. Pleural-based emphysema was assessed on the basis of local histogram measures of emphysema. Pneumothorax history was defined by subject self-report.Measurements and main resultsPneumothorax was reported in 286 (3.2%) of 9,062 participants. In all participants, risk of prior pneumothorax was significantly higher in men (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.08-2.22) and non-Hispanic white subjects (OR, 1.90; 95% CI, 1.34-2.69). Risk of prior pneumothorax was associated with increased percent CT emphysema in all participants and participants with COPD (OR, 1.04 for each 1% increase in emphysema; 95% CI, 1.03-1.06). Increased pleural-based emphysema was independently associated with risk of past pneumothorax in all participants (OR, 1.05 for each 1% increase; 95% CI, 1.01-1.10). In smokers with normal spirometry, risk of past pneumothorax was associated with non-Hispanic white race and lifetime smoking intensity (OR, 1.20 for every 10 pack-years; 95% CI, 1.09-1.33).ConclusionsAmong smokers, pneumothorax is associated with male sex, non-Hispanic white race, and increased percentage of total and subpleural CT emphysema. Pneumothorax was not independently associated with height or lung function, even in participants with COPD. Clinical trial registered with www.clinicaltrials.gov (NCT00608764).

BACKGROUND The risk factors for acute episodes of respiratory disease in current and former smokers who do not have COPD are unknown. METHODS Eight thousand two hundred forty-six non-Hispanic white and black current and former smokers in the Genetic Epidemiology of COPD (COPDGene) cohort had longitudinal follow-up (LFU) every 6 months to determine acute respiratory episodes requiring antibiotics or systemic corticosteroids, an ED visit, or hospitalization. Negative binomial regression was used to determine the factors associated with acute respiratory episodes. A Cox proportional hazards model was used to determine adjusted hazard ratios (HRs) for time to first episode and an acute episode of respiratory disease risk score. RESULTS At enrollment, 4,442 subjects did not have COPD, 658 had mild COPD, and 3,146 had moderate or worse COPD. Nine thousand three hundred three acute episodes of respiratory disease and 2,707 hospitalizations were reported in LFU (3,044 acute episodes of respiratory disease and 827 hospitalizations in those without COPD). Major predictors included acute episodes of respiratory disease in year prior to enrollment (HR, 1.20; 95% CI, 1.15-1.24 per exacerbation), airflow obstruction (HR, 0.94; 95% CI, 0.91-0.96 per 10% change in % predicted FEV 1 ), and poor health-related quality of life (HR, 1.07; 95% CI, 1.06-1.08 for each 4-unit increase in St. George's Respiratory Questionnaire score). Risks were similar for those with and without COPD. CONCLUSIONS Although acute episode of respiratory disease rates are higher in subjects with COPD, risk factors are similar, and at a population level, there are more episodes in smokers without COPD.

Background COPD is associated with cardiovascular disease (CVD), and coronary artery calcification (CAC) provides incremental prognostic information. CAC is measured using Agatston scores on electrocardiographically gated CT scans. With increasing use of non-gated CT scans in clinical practice, we hypothesized that a simple visual Weston score would perform as well in predicting prevalent coronary artery disease (CAD) and incident CVD in COPD. Methods Current and former smokers (45-80 years) enrolled in the COPDGene study and followed for 5 years. At baseline, significant CAC was defined as Agatston >400 and Weston >7; incident CVD recorded as one/more of incident acute coronary event, stroke, peripheral arterial disease and coronary intervention. Results 1913 subjects were included; 813 with and 1100 without airflow obstruction. CAD was reported by 140(7.3%) subjects at baseline. 439(22.9%) and 748(39.1%) had significant CAC by Weston and Agatston respectively; the two methods correlated significantly (r=0.51;p 7 identified more patients with undiagnosed CAD who developed incident CVD (6.3% vs. 10.2%;p=0.01) than Agatston >400 (6.9% vs. 7.2%;p = 0.77). Conclusions A simple visual score for CAC performs well in predicting prevalent CAD and incident CVD in smokers with and without COPD.

To test the ability of positive end-expiratory pressure to offset the reduction of resting lung volume caused by intra abdominal hypertension, unilateral pleural effusion, and their combination.: Controlled application of intrapleural fluid, raised abdominal pressure and their combination before and after positive end-expiratory pressure in an anesthetized porcine model of controlled ventilation.Large animal laboratory of a university-affiliated hospital.Fourteen deeply anesthetized swine (weight 30-35 kg).Unilateral pleural effusion instillation (13 mL/kg), intra-abdominal hypertension (15 mm Hg), and simultaneous pleural effusion/intra abdominal hypertension.Tidal compliance, end-expiratory lung aeration by gas dilution functional residual capacity, and quantitative analyses of computerized tomograms of the lungs at the extremes of the tidal cycle.Positive end-expiratory pressure of 10 cm H2O (positive end-expiratory pressure 10) increased mean functional residual capacity by 368 mL when pleural effusion was present and by 184 mL when intra-abdominal hypertension was present. When pleural effusion and intra-abdominal hypertension were simultaneously applied, positive end-expiratory pressure 10 failed to improve tidal compliance and increased functional residual capacity by only 77 mL, whereastidal recruitment during ventilation remained substantial.The presence of intra-abdominal hypertension negates most of the positive end-expiratory pressure 10 benefit in reversing pleural effusion-induced de-recruitment. Relief of intra-abdominal hypertension may be instrumental to the treatment of pleural effusion-associated lung restriction and cyclical tidal collapse and reopening.

The value of quantitative CT (QCT) to identify chronic obstructive pulmonary disease (COPD) phenotypes is increasingly appreciated. The authors hypothesised that QCT-defined emphysema and airway abnormalities relate to St George's Respiratory Questionnaire (SGRQ) and Body-Mass Index, Airflow Obstruction, Dyspnea and Exercise Capacity Index (BODE).1200 COPDGene subjects meeting Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria for COPD with QCT analysis were included. Total lung emphysema was measured using the density mask technique with a -950 Hounsfield unit threshold. An automated programme measured mean wall thickness (WT), wall area percentage (WA%) and 10 mm lumenal perimeter (pi10) in six segmental bronchi. Separate multivariate analyses examined the relative influence of airway measures and emphysema on SGRQ and BODE.In separate models predicting SGRQ score, a 1 unit SD increase in each airway measure predicted higher SGRQ scores (for WT, 1.90 points higher, p=0.002; for WA%, 1.52 points higher, p=0.02; for pi10, 2.83 points higher p0.001). The comparable increase in SGRQ for a 1 unit SD increase in emphysema percentage in these models was relatively weaker, significant only in the pi10 model (for emphysema percentage, 1.45 points higher, p=0.01). In separate models predicting BODE, a 1 unit SD increase in each airway measure predicted higher BODE scores (for WT, 1.07-fold increase, p0.001; for WA%, 1.20-fold increase, p0.001; for pi10, 1.16-fold increase, p0.001). In these models, emphysema more strongly influenced BODE (range 1.24-1.26-fold increase, p0.001).Emphysema and airway disease both relate to clinically important parameters. The relative influence of airway disease is greater for SGRQ; the relative influence of emphysema is greater for BODE.

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.

Objectives: Although pleural effusion reduces respiratory system compliance by restricting the lungs, the effusion volume is partially accommodated by chest wall expansion. The implications for these opposing volume changes on airway pressure monitoring in ventilated patients with pleural effusion are unreported. We investigated the interactions among pleural effusion, positive end-expiratory pressure, and indices of respiratory mechanics in a swine model. Design: Interventional animal model. Setting: Hospital animal research facility. Subjects: Nine deeply anesthetized swine. Interventions: The preparation included tracheostomy, arterial/ venous catheter placement, and chest tube insertion. Animals were ventilated throughout the study at 9 mL/kg, and frequency was adjusted to maintain normocapnia (inspiratory:expiratory = 1:2, FIO 2 = 0.5) and positive end-expiratory pressure of 1 cm H 2 O and 10 cm H 2 O. Fluid was instilled into the right pleural space to simulate effusions of 13 mL/kg (pleural effusion 1) and 26 mL/kg (pleural effusion 2). Measurements and Main Results: Quantitative computerized tomography studies (in five animals) and functional residual capacity volumes (wash-in/wash-out technique) were obtained for each pleural effusion/positive end-expiratory pressure combination. Mean functional residual capacity compared to baseline at positive end-expiratory pressure of 1 cm H 2 0 was decreased by pleural effusion 1 and pleural effusion 2 (―42%, ―64%) and restored by positive end-expiratory pressure of 10 cm H 2 O (moderate) to +23% of baseline for pleural effusion 1 and +1% for pleural effusion 2. Plateau pressure increased and compliance decreased in response to pleural effusion 1 and pleural effusion 2. Moderate positive end-expiratory pressure applied during both pleural effusion quantities restored plateau pressure and tidal compliance to prepleural effusion values. Computed tomography studies revealed lung compression and tidal derecruitment cycles occurring with pleural effusion at positive end-expiratory pressure of 1 cm H 2 O, whereas a moderate positive end-expiratory pressure restored prepleural effusion functional residual capacity and prevented lung and intratidal derecruitment. Conclusions: When pleural effusion is present, respiratory mechanics must be interpreted cautiously and sufficient positive end-expiratory pressure should be applied to prevent extensive collapse and intratidal cycles of recruitment/derecruitment.

Background Cigarette smoking is a major risk factor for chronic obstructive pulmonary disease (COPD) and COPD severity. Previous genome-wide association studies (GWAS) have identified numerous single nucleotide polymorphisms (SNPs) associated with the number of cigarettes smoked per day (CPD) and a dopamine beta-hydroxylase (DBH) locus associated with smoking cessation in multiple populations. Objective To identify SNPs associated with lifetime average and current CPD, age at smoking initiation, and smoking cessation in patients with COPD. Methods GWAS were conducted in four independent cohorts encompassing 3441 ever-smoking patients with COPD (Global Initiative for Obstructive Lung Disease stage II or higher). Untyped SNPs were imputed using the HapMap (phase II) panel. Results from all cohorts were meta-analysed. Results Several SNPs near the HLA region on chromosome 6p21 and in an intergenic region on chromosome 2q21 showed associations with age at smoking initiation, both with the lowest p=2x10(-7). No SNPs were associated with lifetime average CPD, current CPD or smoking cessation with p

Summary Background: Airway secretions are a source of complications for patients with acute and chronic lung diseases, yet lack of techniques to quantitatively track secretions hampers research into clinical measures to reduce their pathologic consequences. Methods: In a preserved swine lung model, we tracked a contrasted mucus simulant (CMS) using sequential computed tomography (CT). Known drivers of secretion movement – gravity and ventilation – were tested. Ten millilitres of CMS were unilaterally introduced (1 ml min−1) into the airways of 12 lung sets. After instillation, six lung sets were maintained prone and six were rotated 180°. Subsequently, all were mechanically ventilated for 10 min. CTs were obtained before infusion, after infusion and after ventilation ± rotation. For CT analysis, the lungs were partitioned into eight sub-cuboids using anatomic landmarks. The volumes of two CT number ranges representing CMS and poor aeration/collapse were computed in every sub-cuboid for each CT acquisition. Volume differences between study time points were used to quantify changes. Results: CMS and poor aeration/collapse volume change distributed gravitationally after infusion. After ventilation without rotation, the CMS and poor aeration/collapse volumes remained within the originally injected sub-cuboid, although the poor aeration/collapse volume expanded (27·3 ± 6·150·5 ± 7·4 ml, P

RadiologyInfo is a public information Web site created and maintained as an unprecedented joint collaborative effort of the Radiological Society of North America and the American College of Radiology. Conceived in 1997 and operating since 2000, the site has grown to become a leading medical information site, currently with more than 100 radiologic examinations and treatments described. Each month, well over half a million visitors connect to RadiologyInfo (660,000 visits in March 2007). The information is now also available in Spanish and French. New procedures, current topics, and additional images are added on an ongoing basis. © American College of Radiology, 2008

The effectiveness of pleural sealing with a compressed collagen foam plug in preventing the development of pneumothorax was evaluated in a prospective, comparative study of 50 patients undergoing transthoracic needle biopsies. The 4-cm-long plug was deposited through the thin-walled guidance needle at the end of the procedure in a position where it would cross both the visceral and the parietal pleura. The prevalence of postbiopsy pneumothorax was 28% (seven of 25 patients) in the control group and 8% (two of 25 patients) in the plug group. In each study group, two patients with pneumothoraces required chest tubes. Although further experience is necessary, the authors conclude that transpleural collagen foam plug placement may be an effective supplement for transthoracic needle biopsies.

Previous studies comparing the sensitivity between different radiological exams have concluded that conventional axial computed tomography (CT; nonhelical) is unsuitable in the assessment of mandibular fractures. Axial CT was shown to have a reduced sensitivity compared with plain radiographs and panoramic tomography because it missed nondisplaced fractures in the posterior portion of the mandible. Because the resolution of CT has improved from the time of these previous studies, the authors were interested in assessing whether axial CT (nonhelical) could now provide additional clinically useful information and enhance our understanding of mandibular fractures, beyond that obtained from panoramic tomography alone. In their study, 5 staff surgeons initially evaluated the panoramic tomograms and then the CT scans of 39 patients with 66 fractures. A series of four questions assessed the relative contribution of these two radiological exams in formulating an optimal operative plan for each patient. The authors found that axial CT provided supplementary information regarding missed fractures, comminution, and the exact size and degree of displacement of fracture fragments. This additional data could have changed the operative plan in a substantial proportion of patients (17 of 39). Axial CT demonstrated two missed parasymphyseal fractures (2 of 39 patients) that were not seen on these patients' panoramic tomograms. Axial CT also revealed undiscovered comminution or demonstrated fracture displacement more precisely in 39% of patients (15 of 39) and 24% of fractures (16 of 66). This study demonstrates that axial CT was clinically useful as an additional investigation to panoramic tomography. Axial CT helped elucidate further the nature of suspected mandibular fractures.

The objective of the study was to describe the CT findings of pulmonary venoocclusive disease.Eight patients with CT scans of the thorax and a diagnosis of pulmonary venoocclusive disease were identified from three institutions. The six males and two females had a mean age of 32 years old (range, 5-58 years old). All scans were evaluated with consensus reading by two chest radiologists. Lung parenchyma were assessed for the type and distribution of disease. Bronchi, pleura, hila, mediastina, and chest walls were evaluated for abnormalities. Pathologic specimens from five patients were reviewed and specifically correlated with the radiologic findings.Seven of the eight patients had interlobular septal thickening. All eight patients had regions of ground-glass opacity. Four of the eight patients had a mosaic pattern of lung attenuation. No enlarged hilar or mediastinal nodes were revealed. Five patients had bilateral pleural effusions.The most common CT findings in these eight patients with pulmonary venoocclusive disease were smooth interlobular septal thickening, diffuse multifocal regions of ground-glass opacity, pleural effusions, enlarged central pulmonary arteries, and pulmonary veins of normal caliber. Four patients had a mosaic pattern of lung attenuation on the CT scans. These findings are highly suggestive of pulmonary venoocclusive disease and may be helpful in difficult cases. Definitive diagnosis requires lung biopsy.

Pulmonary emphysema results in hyperinflation of the lungs and concomitant changes in the configuration of the thoracic cavity. We describe a patient who underwent bilateral lung transplantation for emphysema due to alpha, antitrypsin deficiency. Dramatic changes in chest dimensions and configuration occurred following transplantation, demonstrating the dynamic and reversible nature of the thoracic cavity abnormalities of emphysema. (Chest 1989; 96:421–22)