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Background: Gas trapping quantified on chest CT scans has been proposed as a surrogate for small airway disease in COPD. We sought to determine if measurements using paired inspiratory and expiratory CT scans may be better able to separate gas trapping due to emphysema from gas trapping due to small airway disease., Methods: Smokers with and without COPD from the COPDGene Study underwent inspiratory and expiratory chest CT scans. Emphysema was quantified by the percent of lung with attenuation < -950HU on inspiratory CT. Four gas trapping measures were defined: (1) Exp(-856), the percent of lung < -856HU on expiratory imaging; (2) E/I MLA, the ratio of expiratory to inspiratory mean lung attenuation; (3) RVC(856-950), the difference between expiratory and inspiratory lung volumes with attenuation between -856 and -950 HU; and (4) Residuals from the regression of Exp(-856) on percent emphysema., Results: In 8517 subjects with complete data, Exp(-856) was highly correlated with emphysema. The measures based on paired inspiratory and expiratory CT scans were less strongly correlated with emphysema. Exp(-856), E/I MLA and RVC(856-950) were predictive of spirometry, exercise capacity and quality of life in all subjects and in subjects without emphysema. In subjects with severe emphysema, E/I MLA and RVC(856-950) showed the highest correlations with clinical variables., Conclusions: Quantitative measures based on paired inspiratory and expiratory chest CT scans can be used as markers of small airway disease in smokers with and without COPD, but this will require that future studies acquire both inspiratory and expiratory CT scans.

Introduction: Targeting the proper left ventricular lead site is important in cardiac resynchronization therapy (CRT) procedures, as suboptimal lead locations may result in a lack of clinical response. Left ventricular lead locations are typically confirmed using fluoroscopy (fluoro) with AP, RAO, and LAO orientations. However, standard fluoro may inadequately delineate true left ventricular lead locations, due to insufficient angulation or extreme cardiac rotation. Posteroanterior and lateral chest radiograph (CXRPAL), performed routinely to verify lead stability and freedom from complication, may better confirm left ventricular lead location due to utilization of a straight lateral view., Hypothesis: Compared to fluoro, lead localization using CXRPAL will be more predictive of true left ventricular lead location in CRT patients., Methods: Of 252 medically optimized CHF patients who underwent CRT implantation by multiple operators from October 2001 to August 2011, 46 (mean age, 58.9 ± 13.2 years; 10 female; 19 ICM; 19 LBBB; mean ejection fraction, 26.6 ± 8.9 %; mean QRS width, 144.4 ms) had CT scanning performed as part of routine medical care and comprise this study. Operative reports of left ventricular lead location by fluoro were reviewed. Left ventricular lead location was identified on CXRPAL by three independent observers blinded to operative results. Left ventricular lead locations according to fluoro and CXRPAL were correlated with CT scan at a mean follow-up of 57.6 ± 28.8 months (Tables 1 and 2)., Results: Compared to standard fluoro, CXRPAL agreed better with CT scan (κ = 0.413 fluoro vs. κ = 0.864 CXRPAL on the vertical axis, and κ = 0.086 fluoro vs. κ = 0.864 CXRPAL on the horizontal axis) for identification of left ventricular lead location., Conclusions: In this small study of 46 CRT patients, interpretation of left ventricular lead location using CXRPAL correlated better with true lead location identified on CT scan, compared to standard fluoroscopy. Use of a steep lateral view during CRT implantation may be necessary to accurately identify left ventricular lead locations.

Background: Tobacco smoking is a principal cause of COPD-emphysema (COPD-E). Whether discontinuing smoking for at least 4 years halts airway inflammation and progression of COPD-E in prior smokers is unknown. In this study we investigated whether discontinuing smoking for approximately 4 years in ex-smokers with GOLD (Global Initiative for Chronic Lung Disease) stage IIb (moderately severe) COPD-E stopped airway inflammation (ie, sputum biomarkers) and halted the progression of COPD-E on chest CT scan., Methods: Ten ex-smokers with COPD-E who had quit smoking underwent chest CT scans to document the extent of COPD-E, assessment of lung function (FEV(1) and diffusing capacity of lung for carbon monoxide), sputum induction for biomarkers of inflammation (measured by enzyme-linked immunosorbent assay), and blood cotinine levels at baseline and approximately 4 years later. Normal healthy subjects (n = 7) and normal current smokers with no CT scan evidence of COPD-E (n = 8) served as sputum biomarker comparison groups., Results: After approximately 4 years of not smoking (documented by cotinine levels), ex-smokers with COPD-E had persistent increased levels of mediators of inflammation in sputum (myeloperoxidase, leukotriene B4, IL-8, monocyte chemoattractant protein-1, matrix metalloprotease-9), which was associated with significant progression of COPD-E on chest CT scan., Conclusions: Cessation of tobacco smoking in heavy smokers with moderately severe COPD-E is associated with evidence of persistent airway inflammation and progression of COPD-E on CT scan 4 years later. Discontinuing smoking may slow the rate of progression of moderate severity COPD-E, but it does not prevent persistent airway inflammation and significant progression of COPD-E on CT scan.

We hypothesized that some of the heterogeneity of pulmonary blood flow present in the normal human lung in normoxia is due to hypoxic pulmonary vasoconstriction (HPV). If so, mild hyperoxia would decrease the heterogeneity of pulmonary perfusion, whereas it would be increased by mild hypoxia. To test this, six healthy nonsmoking subjects underwent magnetic resonance imaging (MRI) during 20 min of breathing different oxygen concentrations through a face mask [normoxia, inspired O(2) fraction (Fi(O(2))) = 0.21; hypoxia, Fi(O(2)) = 0.125; hyperoxia, Fi(O(2)) = 0.30] in balanced order. Data were acquired on a 1.5-T MRI scanner during a breath hold at functional residual capacity from both coronal and sagittal slices in the right lung. Arterial spin labeling was used to quantify the spatial distribution of pulmonary blood flow in milliliters per minute per cubic centimeter and fast low-angle shot to quantify the regional proton density, allowing perfusion to be expressed as density-normalized perfusion in milliliters per minute per gram. Neither mean proton density [hypoxia, 0.46(0.18) g water/cm(3); normoxia, 0.47(0.18) g water/cm(3); hyperoxia, 0.48(0.17) g water/cm(3); P = 0.28] nor mean density-normalized perfusion [hypoxia, 4.89(2.13) ml x min(-1) x g(-1); normoxia, 4.94(1.88) ml x min(-1) x g(-1); hyperoxia, 5.32(1.83) ml x min(-1) x g(-1); P = 0.72] were significantly different between conditions in either imaging plane. Similarly, perfusion heterogeneity as measured by relative dispersion [hypoxia, 0.74(0.16); normoxia, 0.74(0.10); hyperoxia, 0.76(0.18); P = 0.97], fractal dimension [hypoxia, 1.21(0.04); normoxia, 1.19(0.03); hyperoxia, 1.20(0.04); P = 0.07], log normal shape parameter [hypoxia, 0.62(0.11); normoxia, 0.72(0.11); hyperoxia, 0.70(0.13); P = 0.07], and geometric standard deviation [hypoxia, 1.88(0.20); normoxia, 2.07(0.24); hyperoxia, 2.02(0.28); P = 0.11] was also not different. We conclude that HPV does not affect pulmonary perfusion heterogeneity in normoxia in the normal supine human lung.

Objective: The vibration response imaging device that we studied (VRIxp) records the intensity and location of lung sounds during a cycle of breathing. The goals of this study were to describe the characteristic features and quantitative lung data recorded by the VRIxp device from healthy asymptomatic subjects., Subjects and Methods: Breath sounds (frequency range, 150-250 Hz) recorded from the backs of 151 healthy asymptomatic subjects (96 nonsmokers and 55 smokers) by the VRIxp device were mapped to create a sequence of 2D images. Three raters interpreted and scored the images for predefined static and dynamic features. In addition, quantitative lung data were analyzed for characteristic regional distributions., Results: The readers of the images had good inter- and intrarater agreement. Image development in 93% of the evaluations showed an inspiratory and expiratory phase with a progressive and regressive stage that developed bilaterally in a vertical and synchronized manner. Characteristic image features of the maximum energy frame included a smooth, rounded, uninterrupted contour and a planar distribution, area size, and intensity that had right-left symmetry. Quantitative lung data expressed as percentages of the total (100%) vibration energy were normally distributed with mean values (+/- SD) of 55% +/- 6% for the left lung and 45% +/- 6% for the right lung. Most of the subjects with images, quantitative lung data, or both lacking these typical features were cigarette smokers or had a history of smoking (p < 0.05)., Conclusion: Breath sounds in healthy asymptomatic subjects can be recorded and displayed in a dynamic series of images that have predictable and characteristic features recognizable and complemented by quantitative lung data. Identification and description of these characteristic image features in this study will facilitate future studies of vibration imaging in specific pulmonary diseases.

Definitions of types of emphysema within the framework of chronic obstructive pulmonary disease are given. The classic findings on the chest radiograph are described, and the advances in sensitivity and specificity achieved with computed tomography (CT) scanning are noted. The "density mask" and the "percentile point" measurements rely on the densitometric property of X-rays, but the scan also shows the severity and distribution of low-attenuation regions that usually represent pathologic emphysema. The alteration of absolute density with changes in lung inflation, CT slice thickness, collimation, and reconstruction algorithm make comparison between CT scans and across studies more difficult. Nevertheless, quantitative CT has superseded subjective scoring of scan appearance by readers as a sensitive way to measure emphysema.

The objective of this study was to describe the computed tomographic (CT) features of myofibroblastic inflammatory tumor of the lung with histopathologic correlation. The medical records and imaging studies of eight patients with pathologically proven myofibroblastic inflammatory tumor of the lung were reviewed. On radiographs and CT images, a poorly circumscribed mass or nodule was evident in five patients (six lesions), and a well-circumscribed lesion was evident in three patients (three lesions). Seven lesions were peripheral and two were centrally located. At CT, five lesions were of heterogeneous attenuation and four homogeneous. Increased perilesional parenchymal abnormalities, which were caused by peribronchial inflammatory infiltrates, were observed in three cases. The predominant histopathologic feature was organizing pneumonia type in three cases, lymphoplasmacytic type in three cases, and both organizing pneumonia and lymphoplasmacytic type in two cases. Variable degree of fibrous histiocytoma type was observed in all cases. The imaging characteristics of myofibroblastic inflammatory tumor of the lung are variable and nonspecific. The authors conclude that most cases appear as solitary, peripheral lesions with a predilection for the lower lobes. Associated findings may include perilesional inflammatory changes. Because myofibroblastic inflammatory tumor cannot be reliably differentiated from other pulmonary lesions based solely on the imaging appearance diagnostic biopsy is mandatory. Interpretation of the imaging findings combined with the histopathologic features of disease may help make correct diagnosis.

Background: Bronchodilator responses are a hallmark of asthma and a subset of chronic obstructive pulmonary disease (COPD). We evaluated subjects with COPD and computed tomographic (CT) scan evidence of emphysema to determine the biomarker profile associated with a bronchodilator response., Objective: We investigated whether subjects with COPD and a bronchodilator response had increased levels of bronchoalveolar lavage (BAL) fluid eosinophil biomarkers, T(H)2 cytokines, CC chemokines, and serum allergen-specific IgE., Methods: All patients with COPD and control subjects (n = 31) had chest CT scans to detect emphysema and subsequent pulmonary function studies, BAL for biomarkers, and serum IgE measurements., Results: CT scan score, FEV(1), carbon monoxide single-breath diffusion capacity, and BAL fluid neutrophil biomarker levels were similar in subjects with COPD who had or did not have a bronchodilator response of greater than 12%. In contrast, levels of BAL fluid eosinophil biomarkers (eosinophil cationic protein [ECP] and eotaxin-1) were greater in patients with COPD with a bronchodilator response, whereas T(H)2 cytokines were not detectable in any patients with COPD. BAL fluid ECP and eotaxin-1 levels correlated with CT scan extent of emphysema. Immunostaining of COPD lung sections from a separate cohort of subjects with COPD and healthy subjects demonstrated epithelial expression of eotaxin-1 but no lung expression of IL-4 or IL-5., Conclusion: Subjects with COPD diagnosed on the basis of the presence of emphysema on CT scan who have a bronchodilator response have increased levels of BAL ECP and eotaxin-1 but not T(H)2 cytokines., Clinical Implications: Eosinophil biomarkers (ECP-1 and eotaxin-1) might identify a subset of subjects with COPD with emphysema on CT scans who have a bronchodilator response and an increased extent of emphysema on CT scanning.

Background: Retinoids promote alveolar septation in the developing lung and stimulate alveolar repair in some animal models of emphysema., Methods: One hundred forty-eight subjects with moderate-to-severe COPD and a primary component of emphysema, defined by diffusing capacity of the lung for carbon monoxide (Dlco) [37.1 +/- 12.0% of predicted] and CT density mask (38.5 +/- 12.8% of voxels <- 910 Hounsfield units) [mean +/- SD] were enrolled into a randomized, double-blind, feasibility study at five university hospitals. Participants received all-trans retinoic acid (ATRA) at either a low dose (LD) [1 mg/kg/d] or high dose (HD) [2 mg/kg/d], 13-cis retinoic acid (13-cRA) [1 mg/kg/d], or placebo for 6 months followed by a 3-month crossover period., Results: No treatment was associated with an overall improvement in pulmonary function, CT density mask score, or health-related quality of life (QOL) at the end of 6 months. However, time-dependent changes in Dlco (initial decrease with delayed recovery) and St. George Respiratory Questionnaire (delayed improvement) were observed in the HD-ATRA cohort and correlated with plasma drug levels. In addition, 5 of 25 participants in the HD-ATRA group had delayed improvements in their CT scores that also related to ATRA levels. Retinoid-related side effects were common but generally mild., Conclusions: No definitive clinical benefits related to the administration of retinoids were observed in this feasibility study. However, time- and dose-dependent changes in Dlco, CT density mask score, and health-related QOL were observed in subjects treated with ATRA, suggesting the possibility of exposure-related biological activity that warrants further investigation.

Nonneoplastic diseases of the central airways are uncommon but can be categorized as either focal or diffuse, although there is some overlap. Focal diseases include postintubation stenosis, postinfectious stenosis, posttransplantation stenosis, and various systemic diseases that may involve the airways and lead to focal stenosis (eg, Crohn disease, sarcoidosis, Behçet syndrome). Diffuse diseases of the central airways include Wegener granulomatosis, relapsing polychondritis, tracheobronchopathia osteochondroplastica, amyloidosis, papillomatosis, and rhinoscleroma. Conventional radiography is often the first step in the evaluation of suspected central airway disease and may be adequate in itself to identify the abnormality. However, computed tomography (CT) improves both the detection and characterization of central airway disease. Bronchoscopy remains the primary procedure for the diagnostic work-up of these disease entities. Nevertheless, a thorough radiologic evaluation with radiography and CT may demonstrate specific imaging findings (eg, calcification) that can help narrow the differential diagnosis and aid in the planning of bronchoscopy or therapeutic intervention.

Conflicts of interest have an erosive effect on trust in science, damaging first the attitude of the public toward scientists and their research, but also weakening the trusting interdependence of scientists. Disclosure is recognized as the key tool for management of conflicts, but rules with sanctions must be improved, new techniques for avoidance of financial conflicts by alternative funding of evaluative research must be sought, and there must be new thinking about institutional conflicts of interest. Our profession is education, and both the public and research professionals of all ages would benefit from greater understanding of how science should and does work.

A 64-year-old man was diagnosed with acute myeloid leukemia (AML) 5 years following single lung transplantation performed for severe pulmonary hypertension from scleroderma. Chemotherapy for treatment of AML with fludarabine, cytosine arabinoside, G-CSF (FLAG) regimen was initiated. Despite intensive antibiotic treatment for a presumptive diagnosis of bacterial pneumonia, the patient developed acute respiratory failure and died before a complete cycle of chemotherapy could be administered. At autopsy, both native and allograft lungs showed widespread alveolar proteinosis that was determined as the main cause of acute respiratory failure. Alveolar proteinosis, a potentially treatable disease, should be considered in the radiologic differential diagnosis of diffuse lung disease in this clinical setting.

We investigated the distribution of pulmonary arteriopathy in chronic pulmonary hypertension (PH) in a quantitative histopathologic study, using computer-assisted image analysis. We also examined the histologic manifestations and cellular phenotypes of various obstructive intimal lesions in PH with an immunohistochemical method. A total of 53 lungs removed at autopsy or explantation were obtained for the study from 51 documented cases of moderate to severe PH (15 cases of primary pulmonary hypertension [PPH], eight cases of Eisenmenger's syndrome [EISEN], 22 cases of chronic major-vessel thromboembolic disease [CTED], and three cases of PH associated with other known causes), and two unused donor lungs served as normal controls. Intimal thickening in PPH was most prominent in small pulmonary arteries and arterioles less than 200 micrometer in diameter. Plexiform lesions in PPH were associated with significantly smaller arteries than in EISEN. Arteries larger than 400 micrometer showed a significant intimal thickening only in CTED. Obstructive intimal lesions in PH comprised a morphologic spectrum with frequent intermediate forms between plexiform and thrombotic lesions. Most cells within various intimal lesions showed an immunoprofile of myofibroblasts that were positive for vimentin and alpha-smooth muscle actin, but negative for desmin and endothelial markers including Factor VIII, clonal designator (CD)31, and CD34. Endothelial markers were positive only in the single layer of cells lining slitlike lumens, when the latter were present. In conclusion, major types of PH had characteristic distribution patterns of obstructive intimal lesions, showing mainly a myofibroblastic phenotype and variable endothelial/vascular differentiation.

Objectives: To compare isokinetic peak torque in the symptomatic and asymptomatic limbs of women with lateral epicondyle or forearm pain due to cumulative trauma disorders (CTDs), and to compare peak torque in women with CTDs to peak torque in healthy women., Design: Case control comparison., Setting: Private occupational rehabilitation clinic and a sports science tertiary education center., Subjects: Women with CTDs involving one arm (n=17) and a convenience sample of healthy women (n=7), Intervention: Subjects performed isokinetic strength testing for wrist extension and flexion, wrist supination and pronation, and knee extension and flexion., Main Outcome Measures: Peak torque at 120 degrees/sec on a Biodex isokinetic dynamometer., Results: Control subjects had significantly higher peak torque in wrist extension, flexion, supination, and pronation than CTD subjects on the symptomatic side. Control subjects also had significantly higher peak torque of wrist flexion, pronation, and supination than CTD subjects on the asymptomatic side; wrist extension was greater, but this did not reach significance. In addition, control subjects had significantly higher peak torque in knee extension and flexion than CTD subjects. CTD subjects had significantly greater left-right asymmetry in wrist extension torque than did control subjects., Conclusions: Isokinetic peak torque is diffusely reduced in women with unilateral CTDs compared with healthy control subjects, these differences occurring in symptomatic and asymptomatic limbs.

The aim of this study was to compare symptoms, signs, grip strength, passive wrist flexion angle, and self-rated disability in work-related upper extremity disorders (WRUEDs) to determine predictors of work disability in 106 consecutive patients. Age, gender, and duration of symptoms were unrelated to current work status. The best predictors of current work hours were, in descending order, the Fibromyalgia Impact Questionnaire (FIQ), Modified Stanford Health Assessment Questionnaire (SHAQ), weeks of work absence, passive wrist flexion angle of the affected arm, neck pain or stiffness on movement, and grip in affected arm. FIQ and SHAQ scores were significantly correlated with objective measures of upper-extremity function. FIQ and SHAQ scores are valid measures of work disability in WRUEDs, which are more closely related to current work hours than to time off work, symptoms, or physical signs.

Despite the considerable amount of research that has been undertaken on poststroke depression, a review of the literature demonstrates that there are many inconclusive findings in the area. In particular, the causes and course of the disorder remain to be firmly established. While studies of prevalence differ with respect to the nature and timing of their assessment procedures, most conclude that poststroke depression has a negative impact on the rehabilitation of the stroke patient. Very little research is available on te relationship between poststroke depression and care-giver burden. However, recent studies have adopted more rigorous methodological procedures, allowing some insights into the complex mixture of factors which determine the occurrence of poststroke depression.

The author offers advice to faculty, students, and staff who become involved in issues of research misconduct, whether as the accuser or as the accused. After reviewing the different definitions of research misconduct used by various authorities and discussing other kinds and degrees of misconduct, he provides information to those who suspect research misconduct, to help them identify their responsibilities and the risks involved: he makes it clear that an accusation of research fraud or other misconduct has serious consequences for all parties. The author then discusses how to pursue concerns about improper research practices, emphasizing a nonconfrontational approach and the use of proper channels for reporting. He explains the process of a formal review, including characteristic institutional responses; the role of the Office of Research Integrity; and when to seek the advice of an attorney. He argues that education is clearly preferable to denunciation as a way to improve scientists' ethics and practices. The author then gives similarly detailed advice to the accused, including a caution not to take criticism of methods or results as an accusation of fraud. He discusses the significances of the two stages of review of an allegation of misconduct, with practical advice for cooperative participation in any review; use of legal counsel; the importance of avoiding retaliation; information about due process and material evidence; the impact of a formal investigation; peer standards for evaluating misconduct; and the unavoidable discomfort that the accused will experience during the lengthy process. He advises that practicing good science is the first step in avoiding this unpleasant experience.

Intravascular bronchioloalveolar tumor, the pulmonary counterpart of epithelioid hemangioendothelioma, typically presents as bilateral pulmonary nodules in young women. We report a case of intravascular bronchioloalveolar tumor that clinically mimicked acute pulmonary thromboembolic disease initially and was subsequently proven to have pulmonary hypertension with right ventricular dysfunction by angiography. The diagnosis of intravascular bronchioloalveolar tumor was confirmed by immunohistochemical and ultrastructural studies after it was suspected on routine histologic examination. In addition, the tumor cells expressed glycoprotein cell adhesion molecule CD44, which has been implicated in increased tumor invasiveness and metastasis in various carcinomas and several aggressive non-Hodgkin's lymphomas.

This study was designed to determine the impact of central sleep apnea with or without Cheyne-Stokes respiration (CSR) on morbidity and mortality. Central sleep apnea was found in 77 male general medical ward in-patients. Cheyne-Stokes respiration was found in 49 of the 77 men; in 15 men, CSR was severe, ie, > or = 25 percent of the night spent in CSR, in 34 men CSR was mild (1 to 25 percent CSR). Twenty-eight men had central sleep apnea but no CSR. An additional 31 patients had no sleep apnea and no CSR. The patients with severe CSR had more central apneas, more, but shorter desaturations, more awakenings and more wake time during the night, but spent more time in bed than those with no CSR or no apnea. Radiographic evidence was consistent with an association of CSR and heart failure. In addition, patients with severe CSR were at almost twice the risk of dying compared with those with no apnea and had a shorter survival time. Nevertheless, we could not confirm that CSR was an independent predictor of elevated mortality risk, implying that some other factors specific to severe CSR predispose these patients to shorter survival time.