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Lung injury associated with smoking tobacco or other substances results in a variety of clinical presentations and imaging patterns, depending on mechanism of injury and substance inhaled. Patients may present in the acute setting, as in the case of acute eosinophilic pneumonia, e-cigarette or vaping product use-associated lung injury, crack lung, or heroin inhalation. They may present with subacute shortness of breath and demonstrate findings of pulmonary Langerhans cell histiocytosis, respiratory bronchiolitis, or desquamative interstitial pneumonia. Alternatively, they may present with chronic dyspnea and demonstrate findings of emphysema or smoking-related interstitial lung fibrosis.

BACKGROUND: Smokers manifest varied phenotypes of pulmonary impairment. RESEARCH QUESTION: Which pulmonary phenotypes are associated with coronary artery disease (CAD) in smokers? STUDY DESIGN AND METHODS: We analyzed data from the University of Pittsburgh COPD Specialized Center for Clinically Oriented Research (SCCOR) cohort (n = 481) and the Genetic Epidemiology of COPD (COPDGene) cohort (n = 2,580). Participants were current and former smokers with > 10 pack-years of tobacco exposure. Data from the two cohorts were analyzed separately because of methodologic differences. Lung hyperinflation was assessed by plethysmography in the SCCOR cohort and by inspiratory and expiratory CT scan lung volumes in the COPDGene cohort. Subclinical CAD was assessed as the coronary artery calcium score, whereas clinical CAD was defined as a self-reported history of CAD or myocardial infarction (MI). Analyses were performed in all smokers and then repeated in those with airflow obstruction (FEV(1) to FVC ratio, < 0.70). RESULTS: Pulmonary phenotypes, including airflow limitation, emphysema, lung hyperinflation, diffusion capacity, and radiographic measures of airway remodeling, showed weak to moderate correlations (r < 0.7) with each other. In multivariate models adjusted for pulmonary phenotypes and CAD risk factors, lung hyperinflation was the only phenotype associated with calcium score, history of clinical CAD, or history of MI (per 0.2 higher expiratory and inspiratory CT scan lung volume; coronary calcium: OR, 1.2; 95% CI, 1.1-1.5; P = .02; clinical CAD: OR, 1.6; 95% CI, 1.1-2.3; P = .01; and MI in COPDGene: OR, 1.7; 95% CI, 1.0-2.8; P = .05). FEV(1) and emphysema were associated with increased risk of CAD (P < .05) in models adjusted for CAD risk factors; however, these associations were attenuated on adjusting for lung hyperinflation. Results were the same in those with airflow obstruction and were present in both cohorts. INTERPRETATION: Lung hyperinflation is associated strongly with clinical and subclinical CAD in smokers, including those with airflow obstruction. After lung hyperinflation was accounted for, FEV(1) and emphysema no longer were associated with CAD. Subsequent studies should consider measuring lung hyperinflation and examining its mechanistic role in CAD in current and former smokers.

RATIONALE: Multiple studies have demonstrated an increased risk of chronic obstructive pulmonary disease (COPD) in heterozygous carriers of the AAT (alpha-1 antitrypsin) Z allele. However, it is not known if MZ subjects with COPD are phenotypically different from noncarriers (MM genotype) with COPD. OBJECTIVES: To assess if MZ subjects with COPD have different clinical features compared with MM subjects with COPD. METHODS: Genotypes of SERPINA1 were ascertained by using whole-genome sequencing data in three independent studies. We compared outcomes between MM subjects with COPD and MZ subjects with COPD in each study and combined the results in a meta-analysis. We performed longitudinal and survival analyses to compare outcomes in MM and MZ subjects with COPD over time. MEASUREMENTS AND MAIN RESULTS: We included 290 MZ subjects with COPD and 6,184 MM subjects with COPD across the three studies. MZ subjects had a lower FEV(1)% predicted and greater quantitative emphysema on chest computed tomography scans compared with MM subjects. In a meta-analysis, the FEV(1) was 3.9% lower (95% confidence interval [CI], −6.55% to −1.26%) and emphysema (the percentage of lung attenuation areas

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.

Rationale: Increasing awareness of the prevalence and significance of Preserved Ratio Impaired Spirometry (PRISm), alternatively known as restrictive or Global Initiative for Chronic Obstructive Lu...

Background Attenuation of transforming growth factor β by blocking angiotensin II has been shown to reduce emphysema in a murine model. General population studies have demonstrated that the use of angiotensin converting enzyme inhibitors (ACEis) and angiotensin-receptor blockers (ARBs) is associated with reduction of emphysema progression in former smokers and that the use of ACEis is associated with reduction of FEV1 progression in current smokers. Research Question Is use of ACEi and ARB associated with less progression of emphysema and FEV1 decline among individuals with COPD or baseline emphysema? Methods Former and current smokers from the Genetic Epidemiology of COPD Study who attended baseline and 5-year follow-up visits, did not change smoking status, and underwent chest CT imaging were included. Adjusted linear mixed models were used to evaluate progression of adjusted lung density (ALD), percent emphysema (%total lung volume Results Over 5 years of follow-up, compared with nonusers, ACEi and ARB users with COPD showed slower ALD progression (adjusted mean difference [aMD], 1.6; 95% CI, 0.34-2.9). Slowed lung function decline was not observed based on phase 1 medication (aMD of FEV1 % predicted, 0.83; 95% CI, –0.62 to 2.3), but was when analysis was limited to consistent ACEi and ARB users (aMD of FEV1 % predicted, 1.9; 95% CI, 0.14-3.6). No effect modification by smoking status was found for radiographic outcomes, and the lung function effect was more pronounced in former smokers. Results were similar among participants with baseline emphysema. Interpretation Among participants with spirometry-confirmed COPD or baseline emphysema, ACEi and ARB use was associated with slower progression of emphysema and lung function decline. Trial Registry ClinicalTrials.gov ; No.: NCT00608764; URL: www.clinicaltrials.gov

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."

Contains fulltext : 194255.pdf (Publisher’s version ) (Open Access) BACKGROUND: Emphysema has considerable variability in its regional distribution. Craniocaudal emphysema distribution is an important predictor of the response to lung volume reduction. However, there is little consensus regarding how to define upper lobe-predominant and lower lobe-predominant emphysema subtypes. Consequently, the clinical and genetic associations with these subtypes are poorly characterized. METHODS: We sought to identify subgroups characterized by upper-lobe or lower-lobe emphysema predominance and comparable amounts of total emphysema by analyzing data from 9,210 smokers without alpha-1-antitrypsin deficiency in the Genetic Epidemiology of COPD (COPDGene) cohort. CT densitometric emphysema was measured in each lung lobe. Random forest clustering was applied to lobar emphysema variables after regressing out the effects of total emphysema. Clusters were tested for association with clinical and imaging outcomes at baseline and at 5-year follow-up. Their associations with genetic variants were also compared. RESULTS: Three clusters were identified: minimal emphysema (n = 1,312), upper lobe-predominant emphysema (n = 905), and lower lobe-predominant emphysema (n = 796). Despite a similar amount of total emphysema, the lower-lobe group had more severe airflow obstruction at baseline and higher rates of metabolic syndrome compared with subjects with upper-lobe predominance. The group with upper-lobe predominance had greater 5-year progression of emphysema, gas trapping, and dyspnea. Differential associations with known COPD genetic risk variants were noted. CONCLUSIONS: Subgroups of smokers defined by upper-lobe or lower-lobe emphysema predominance exhibit different functional and radiological disease progression rates, and the upper-lobe predominant subtype shows evidence of association with known COPD genetic risk variants. These subgroups may be useful in the development of personalized treatments for COPD.

Sarcoidosis is a multisystem granulomatous process that most commonly involves the lungs. Radiographic findings consistent with sarcoidosis are important to the diagnosis of this disease, as no specific diagnostic test for sarcoidosis exists. The classic imaging manifestations of sarcoidosis are related to granulomatous involvement along the lymphatic pathways within the lungs, granulomatous involvement of lymph nodes, and fibrosis at the sites of previous inflammation. These findings sometimes take atypical forms. Additional manifestations of sarcoidosis are caused by involvement of the bronchi and bronchioles, the pulmonary arteries, and the heart. Fungal colonization may also occur. A range of thoracic imaging manifestations of sarcoidosis is illustrated to facilitate the diagnosis of this common, multifaceted disease.

Rationale: The American Thoracic Society (ATS)/European Respiratory Society defines a positive bronchodilator response (BDR) by a composite of BDR in either forced expiratory volume in 1 second (FEV(1)) and/or forced vital capacity (FVC) greater than or equal to 12% and 200 ml (ATS-BDR). We hypothesized that ATS-BDR components would be differentially associated with important chronic obstructive pulmonary disease (COPD) outcomes. Objectives: To examine whether ATS-BDR components are differentially associated with clinical, functional, and radiographic features in COPD. Methods: We included subjects with COPD enrolled in the COPDGene study. In the main analysis, we excluded subjects with self-reported asthma. We categorized BDR into the following: 1) No-BDR, no BDR in either FEV(1) or FVC; 2) FEV(1)-BDR, BDR in FEV(1) but no BDR in FVC; 3) FVC-BDR, BDR in FVC but no BDR in FEV(1); and 4) Combined-BDR, BDR in both FEV(1) and FVC. We constructed multivariable logistic, linear, zero-inflated negative binomial, and Cox hazards models to examine the association of BDR categories with symptoms, computed tomography findings, change in FEV(1) over time, respiratory exacerbations, and mortality. We also created models using the ATS BDR definition (ATS-BDR) as the main independent variable. Results: Of 3,340 COPD subjects included in the analysis, 1,083 (32.43%) had ATS-BDR, 182 (5.45%) had FEV(1)-BDR, 522 (15.63%) had FVC-BDR, and 379 (11.34%) had Combined-BDR. All BDR categories were associated with FEV(1) decline compared with No-BDR. Compared with No-BDR, both ATS-BDR and Combined-BDR were associated with higher functional residual capacity %predicted, greater internal perimeter of 10 mm, and greater 6-minute-walk distance. In contrast to ATS-BDR, Combined-BDR was independently associated with less emphysema (adjusted beta regression coefficient, −1.67; 95% confidence interval [CI], −2.68 to −0.65; P = 0.001), more frequent respiratory exacerbations (incidence rate ratio, 1.25; 95% CI, 1.03–1.50; P = 0.02) and severe exacerbations (incidence rate ratio, 1.34; 95% CI, 1.05–1.71; P = 0.02), and lower mortality (adjusted hazards ratio, 0.76; 95% CI, 0.58–0.99; P = 0.046). Sensitivity analysis that included subjects with self-reported history of asthma showed similar findings. Conclusions: BDR in both FEV(1) and FVC indicates a COPD phenotype with asthma-like characteristics, and provides clinically more meaningful information than current definitions of BDR.

Background Chronic bronchitis (CB) increases risk of COPD exacerbations. We have shown that the St. George's Respiratory Questionnaire (SGRQ) CB definition identifies patients with a similar clinical phenotype as classically defined CB. Whether the SGRQ CB definition is a predictor of future COPD exacerbations is unknown. Methods We analyzed 7,557 smokers with normal spirometry and Global Initiative for Chronic Obstructive Lung Disease stage 1-4 COPD in the Genetic Epidemiology of COPD study with longitudinal follow-up data on exacerbations. Subjects were divided into classic CB+ or classic CB–, using the classic definition. In addition, subjects were divided into SGRQ CB+ or SGRQ CB–. Exacerbation frequency and severe exacerbation frequency were determined in each group. Multivariable linear regressions were performed for exacerbation frequency with either classic CB or SGRQ CB and relevant covariates. Results There were 1,434 classic CB+ subjects and 2,290 SGRQ CB+ subjects. The classic CB+ group had a greater exacerbation frequency compared with the classic CB– group (0.69 ± 1.26 vs 0.36 ± 0.90 exacerbations per patient per year; P Conclusions The SGRQ CB definition identified more subjects at risk for future exacerbations than the classic CB definition. SGRQ CB was at least a similar if not better predictor of future exacerbations than classic CB.

Spirometric Volumes and Breathlessness Across Levels of Airflow Limitation : The COPDGene Study.

BACKGROUND:Eosinophilic airway inflammation in patients with chronic obstructive pulmonary disease (COPD) is associated with exacerbations and responsivity to steroids, suggesting potential shared mechanisms with eosinophilic asthma. However, there is no consistent blood eosinophil count that has been used to define the increased exacerbation risk. OBJECTIVE:We sought to investigate blood eosinophil counts associated with exacerbation risk in patients with COPD. METHODS:Blood eosinophil counts and exacerbation risk were analyzed in patients with moderate-to-severe COPD by using 2 independent studies of former and current smokers with longitudinal data. The Genetic Epidemiology of COPD (COPDGene) study was analyzed for discovery (n=1,553), and the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study was analyzed for validation (n=1,895). Asubset of the ECLIPSE study subjects were used to assess the stability of blood eosinophil counts over time. RESULTS:COPD exacerbation risk increased with higher eosinophil counts. An eosinophil count threshold of 300cells/μL or greater showed adjusted incidence rate ratios for exacerbations of 1.32 in the COPDGene study (95% CI, 1.10-1.63). The cutoff of 300cells/μL or greater was validated for prospective risk of exacerbation in the ECLIPSE study, with adjusted incidence rate ratios of 1.22 (95% CI, 1.06-1.41) using 3-year follow-up data. Stratified analysis confirmed that the increased exacerbation risk associated with an eosinophil count of 300cells/μL or greater was driven by subjects with a history of frequent exacerbations in both the COPDGene and ECLIPSE studies. CONCLUSIONS:Patients with moderate-to-severe COPD and blood eosinophil counts of 300cells/μL or greater had an increased risk exacerbations in the COPDGene study, which was prospectively validated in the ECLIPSE study.

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.

The heritability of chronic obstructive pulmonary disease (COPD) cannot be fully explained by recognized genetic risk factors identified as achieving genome-wide significance. In addition, the combined contribution of genetic variation to COPD risk has not been fully explored. We sought to determine: (1) whether studies of variants from previous studies of COPD or lung function in a larger sample could identify additional associated variants, particularly for severe COPD; and (2) the impact of genetic risk scores on COPD. We genotyped 3,346 single-nucleotide polymorphisms (SNPs) in 2,588 cases (1,803 severe COPD) and 1,782 control subjects from four cohorts, and performed association testing with COPD, combining these results with existing genotyping data from 6,633 cases (3,497 severe COPD) and 5,704 control subjects. In addition, we developed genetic risk scores from SNPs associated with lung function and COPD and tested their discriminatory power for COPD-related measures. We identified significant associations between SNPs near PPIC (P = 1.28 X 10(-8)) and PPP4R4/SERPINA1 (P = 1.01 X 10(-8)) and severe COPD; the latter association may be driven by recognized variants in SERPINA1. Genetic risk scores based on SNPs previously associated with COPD and lung function had a modest ability to discriminate COPD (area under the curve, similar to 0.6), and accounted for a mean 0.9-1.9% lower forced expiratory volume in 1 second percent predicted for each additional risk allele. In a large genetic association analysis, we identified associations with severe COPD near PPIC and SERPINA1. A risk score based on combining genetic variants had modest, but significant, effects on risk of COPD and lung function.

Iatrogenic complications of thoracic and cardiovascular surgery are relatively uncommon, but contribute to potentially significant patient morbidity and mortality. The incidence of iatrogenic disease reflects the complexity of surgical procedures, including lung resection, esophagectomy, coronary artery bypass grafting, thoracic aorta repair, and cardiac valve replacement. Some iatrogenic complications are minor and common to all procedures, whereas others can be potentially devastating and are associated with precise technical components of specific surgeries. Multimodality imaging plays an important role in the diagnosis and management of operative thoracic and cardiovascular iatrogenic disease.

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.

A biplane correlation (BCI) imaging system obtains images that can be viewed in stereo, thereby minimizing overlapping structures. This study investigated whether using stereoscopic visualization provides superior lung nodule detection compared to standard postero-anterior (PA) image display. Images were acquired at two oblique views of ±3° as well as at a standard PA position from 60 patients. Images were processed using optimal parameters and displayed on a stereoscopic display. The PA image was viewed in the standard format, while the oblique views were paired to provide a stereoscopic view of the subject. A preliminary observer study was performed with four radiologists who viewed and scored the PA image then viewed and scored the BCI stereoscopic image. The BCI stereoscopic viewing of lung nodules resulted in 71 % sensitivity and 0.31 positive predictive value (PPV) index compared to PA results of 86 % sensitivity and 0.26 PPV index. The sensitivity for lung nodule detection with the BCI stereoscopic system was reduced by 15 %; however, the total number of false positives reported was reduced by 35 % resulting in an improved PPV index of 20 %. The preliminary results indicate observer dependency in terms of relative advantage of either system in the detection of lung nodules, but overall equivalency of the two methods with promising potential for BCI as an adjunct diagnostic technique.

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

Thoracic imaging plays an essential role in understanding and diagnosing chest disease. It has traditionally relied on conventional anatomic and morphologic imaging, but as technology evolves, novel diagnostic strategies have the potential to improve accuracy. This includes incorporation of biomarkers, which are an objective measure of a biological or pathological process. Biomarkers can be used in multiple different scenarios, and may complement current imaging studies, particularly in establishing a diagnosis, determining prognosis or predicting response to therapy. However, it is important to develop and validate clinically relevant biomarkers. This is a complex, multidisciplinary subject that requires knowledge of the clinical problem, an understanding of the technology and pathology, and significant resources. Ultimately, integration of biomarkers into patient evaluation must be cost effective and improve outcomes. This article will describe the potential roles and limitations of biomarkers in thorac...

Overlapping anatomical structures may confound the detection of abnormal pathology, including lung nodules, in conventional single-projection chest radiography. To minimize this fundamental limiting factor, a dedicated digital multi-projection system for chest imaging was recently developed at the Radiology Department of Duke University. We are reporting the design of the multi-projection imaging system and its initial performance in an ongoing clinical trial. The system is capable of acquiring multiple full-field projections of the same patient along both the horizontal and vertical axes at variable speeds and acquisition frame rates. These images acquired in rapid succession from slightly different angles about the posterior-anterior (PA) orientation can be correlated to minimize the influence of overlying anatomy. The developed system has been tested for repeatability and motion blur artifacts to investigate its robustness for clinical trials. Excellent geometrical consistency was found in the tube motion, with positional errors for clinical settings within 1%. The effect of tube-motion on the image quality measured in terms of impact on the Modulation Transfer Function (MTF) was found to be minimal. The system was deemed clinic-ready and a clinical trial was subsequently launched. The flexibility of image acquisition built into the system provides a unique opportunity to easily modify it for different clinical applications, including tomosynthesis, correlation imaging (CI), and stereoscopic imaging.

ImportanceAirflow obstruction on spirometry is universally used to define chronic obstructive pulmonary disease (COPD), and current or former smokers without airflow obstruction may assume that they are disease free.ObjectiveTo identify clinical and radiologic evidence of smoking-related disease in a cohort of current and former smokers who did not meet spirometric criteria for COPD, for whom we adopted the discarded label of Global Initiative for Obstructive Lung Disease (GOLD) 0.Design, setting, and participantsIndividuals from the Genetic Epidemiology of COPD (COPDGene) cross-sectional observational study completed spirometry, chest computed tomography (CT) scans, a 6-minute walk, and questionnaires. Participants were recruited from local communities at 21 sites across the United States. The GOLD 0 group (n = 4388) (ratio of forced expiratory volume in the first second of expiration [FEV1] to forced vital capacity >0.7 and FEV1 ≥80% predicted) from the COPDGene study was compared with a GOLD 1 group (n = 794), COPD groups (n = 3690), and a group of never smokers (n = 108). Recruitment began in January 2008 and ended in July 2011.Main outcomes and measuresPhysical function impairments, respiratory symptoms, CT abnormalities, use of respiratory medications, and reduced respiratory-specific quality of life.ResultsOne or more respiratory-related impairments were found in 54.1% (2375 of 4388) of the GOLD 0 group. The GOLD 0 group had worse quality of life (mean [SD] St George's Respiratory Questionnaire total score, 17.0 [18.0] vs 3.8 [6.8] for the never smokers; P

The objective of our study was to evaluate repeatability and reproducibility of lung nodule volume measurements using volumetric nodule-sizing software.Fifty nodules, less than 20 mm in diameter, in 29 patients were scanned with 1.25-mm collimation using MDCT (time 1 = T1). During the same session, two additional scans, using identical technique, were obtained through each nodule (T2, T3). Three observers working independently then obtained volumetric measurements using a semiautomated volumetric nodule-sizing software package. Qualitative nodule characterization was also performed. The Bland-Altman method for assessing measurement agreement was used to calculate the 95% limits for agreement for nodule volumes at T1, T2, and T3.Automated nodule segmentation was successful in 438 (97%) of 450 measurements. Forty-three nodules were available for final evaluation. Twenty-six nodules had well-defined edges, and 17 had irregular or spiculated margins. Seventeen were freestanding, 16 were juxtapleural, and 10 were juxtavascular in location. Average nodule volume was 345.5 mm(3) (range, 49.3-1,434 mm(3)). The mean interobserver variability (repeatability) was 0.018% (SD = 0.73%), and the SD of the mean for the three contemporaneous scans (reproducibility) was 13.1% (confidence limits, +/- 25.6%). SD and confidence limits narrowed as volumes increased.Volumetric measurements show minimal interobserver variability (0.018%) but an interscan SEM of 13.1% (confidence limits, +/- 25.6%). Repeatability and reproducibility of volumetric measurements are better than those of linear measurements reported in the literature.

Background: Chest computed tomographic (CT) scanning is used frequently to evaluate symptomatic patients for pulmonary embolus (PE). The incidence of PE diagnosed by helical CT scanning in asymptomatic patients is unknown. Methods: Asymptomatic trauma patients with an Injury Severity Score ≥ 9 were studied with contrast-enhanced helical CT images of the chest, pelvis, and lower extremities. Clot burden was assessed using an anatomic scoring system. Patients not receiving anticoagulation were followed. Results: Twenty-two of 90 patients had a PE. Four had major clot burden, including one patient with a saddle embolus. Risk factors for asymptomatic PE include age (odds ratio [OR], 1.04), head injury (OR, 6.78), chest injury (OR, 4.51), lower extremity injury (OR, 5.03), and transfusion (OR, 3.42). Thirty percent of patients receiving pharmacologic prophylaxis had a PE. Conclusion: Asymptomatic PE occur in 24% of moderately to severely injured patients. Age, head, chest, and lower extremity injury are associated with an increased risk. Standard thromboembolic prophylaxis is not reliably protective.

Introduction of helical CT started a new era in the diagnosis of PE. It is noninvasive and readily available. Developments in helical CT technology (particularly introduction of multidetector scanners) improved image quality by decreasing the scanning time and slice thickness. With the addition of indirect CT venography to CT pulmonary angiography, CT also took the role of venous ultrasound, thus creating a single examination for diagnosis of VTD. On the other hand, CT is not perfect at all circumstances, especially in the evaluation of subsegmental arteries. Careful selection of patients for imaging studies will save time, cost, and radiation.

CTPA has dramatically changed the diagnostic approach to PE in the last decade. The addition of CTV has created a single diagnostic test that can evaluate for both important components of venous thromboembolic disease. Newer, multislice scanners will provide thinner images and more complete anatomic coverage. Shorter scan times will minimize motion artifacts. These improvements may continue to improve the diagnostic yield of CTPA. The availability of an accurate noninvasive diagnostic tool to evaluate for PE and DVT should lead to a better understanding of the wide range of presentations of thromboembolic disease. The next decade may produce improvements in understanding of the epidemiology of PE and perhaps to a more tailored approach to treatment for thromboembolic disease.

Summary The differential diagnosis of diffuse acute lung disease in the immunocompetent patient includes hydrostatic and permeability edema (with or without DAD), infectious pneumonia, acute eosinophilic pneumonia, hypersensitivity pneumonitis, pulmonary hemorrhage, and acute interstitial pneumonitis. Although there is much overlap among the radiologic appearance of these diseases, the combination of several CT or radiographic findings can suggest the correct diagnosis. CT findings of diffuse opacity with a gravitational gradient are most consistent with ARDS from an extrapulmonary source. Acute hydrostatic pulmonary edema may have a similar appearance on CT but typically also shows evidence of septal and bronchovascular thickening. Acute interstitial pneumonitis may also have a similar appearance to ARDS but may be differentiated by evidence of fibrosis as manifest by traction bronchiectasis and architectural distortion. Infections are a common cause of ARDS. The CT scans of patients with ARDS caused by pulmonary infection may show nondependent dense opacities rather than a gravitational gradient. Less severe infections may be suggested by the presence of segmental opacities or patchy centrilobular nodules and centrilobular branching structures (impacted bronchioles). Diffuse, ill-defined centrilobular nodules, especially when combined with ground-glass opacities or air trapping, favor hypersensitivity pneumonitis. The presence of lobular opacities is nonspecific and may be caused by infections and several other disease states. Recognition of concurrent radiologic or clinical findings may suggest the correct diagnosis. The combination of lobular opacities and septal thickening can be seen in hydrostatic edema, eosinophilic pneumonia, and pulmonary hemorrhage. Pleural effusions, however, or extensive septal thickening are much more common in the first 2 diseases. Evolution of lung opacities from alveolar to interstitial over time would instead suggest the diagnosis of pulmonary hemorrhage. Diffuse acute lung disease in immunocompetent hosts is most often caused .by pulmonary edema (cardiogenic or noncardiogenic) and or infection. Despite the imaging findings described in this article, our ability as radiologists to differentiate between these conditions is imperfect. The radiologist's input is most important in those cases in which the diagnosis of pulmonary edema or infection is clouded by conflicting clinical findings. Less common diseases, such as AIP, acute eosinophilic pneumonia, and hypersensittivity pneumonitis may not be initially considered by clinicians. It will continue to be our role to raise the possibility of these diagnoses when characteristic radiologic findings are detected.

Extracardiac nonsurgical vascular shunts in the thorax are a group of well-recognized heterogeneous conditions, frequently symptomatic, in which there is diversion of blood flow from one vessel to another or from a vessel to a cardiac chamber. The authors describe and classify many of these nonsurgical extracardiac shunts or fistulas according to their source and endpoint (eg, systemic-to-systemic, systemic-to-pulmonic, pulmonic-to-systemic, and pulmonic-to-pulmonic) and to whether the oxygenated blood mixes with deoxygenated systemic venous flow (left-to-right shunts), deoxygenated blood bypasses the pulmonary capillary bed (right-to-left shunts), or oxygenated blood recirculates (left-to-left shunts). Clinical manifestations and imaging appearances of these conditions are highlighted.

In a patient with acute respiratory illness (cough, sputum production, chest pain, and/or dyspnea), the need for chest imaging depends on the severity of illness, age of the patient, clinical history, physical and laboratory findings, and other risk factors. Chest radiographs seem warranted when one or more of the following are present: ageor = 40; dementia; a positive physical examination; hemoptysis; associated abnormalities (leukocytosis, hypoxemia); or other risk factors, including coronary artery disease, congestive heart failure, or drug-induced acute respiratory failure. Chest CT may be warranted in complicated cases of severe pneumonia and in febrile neutropenic patients with normal or nonspecific chest radiographic findings. Literature on the indications and usefulness of radiologic studies for acute respiratory illness in different clinical settings is reviewed.

The sternum and sternoclavicular joints--critical structures of the anterior chest wall--may be affected by various anatomic anomalies and pathologic processes, some of which require treatment. Pectus excavatum and pectus carinatum are common congenital anomalies that are usually benign but may warrant surgical treatment if they cause compression of vital internal structures. By contrast, developmental variants such as the sternal foramen are asymptomatic and do not require further evaluation or treatment. Arthritides of the sternoclavicular joint (osteoarthritis, septic arthritis, and seronegative arthropathies) are common and must be differentiated before an appropriate management method can be selected. The recognition of complications of sternotomy (eg, sternal dehiscence, secondary osteomyelitis) is critical to avoid life-threatening sequelae such as acute mediastinitis. Likewise, the detection of sternal fractures and sternoclavicular dislocations is important, especially where they impinge on vital structures. In addition, sternal malignancies (most commonly, metastases and chondrosarcoma) must be distinguished from benign neoplasms. To achieve accurate and timely diagnoses that facilitate appropriate treatment, radiologists must be familiar with the appearances of these normal anatomic variants and diseases of the sternum.

Pulmonary blastomycosis is an uncommon pathologic condition that is endemic to Canada and the upper Midwest of the United States. Blastomycosis has a variety of radiologic manifestations, including airspace consolidation, focal masses, intermediate-sized nodules, interstitial disease, miliary disease, and cavitary lesions. Affected patients may be asymptomatic or may present with clinical manifestations ranging from mild chronic cough to acute respiratory distress syndrome-like symptoms. Patients with acute symptoms are more likely to have airspace consolidation, whereas chronic manifestations may be associated with masslike lesions. Intermediate-sized nodules with accompanying airspace consolidation, particularly in the upper lobes, should raise suspicion for fungal disease. Lymphadenopathy and pleural effusions are quite uncommon, and calcification is not often seen. Blastomycosis may be aggressive and require treatment. Dissemination from the lung is not unusual and can involve any organ. Diagnosis is often delayed because blastomycosis can mimic many other disease processes, including bacterial pneumonia, malignancy, and tuberculosis. Radiologists can best contribute to the care of patients who live or travel in endemic areas by maintaining a high degree of suspicion for blastomycosis and being familiar with its myriad manifestations.

Pulmonary infection is a common reason for imaging of the lung and a common incidental finding in immunocompetent patients. Findings on chest radiography are nonspecific in defining acute infection; however, the radiologist should be aware of classically described patterns of infection, including air space, bronchopneumonia, and interstitial patterns. The radiologist must also be aware of potential limitations of the sensitivity of chest radiography. Imaging findings at computed tomography in acute infection have been poorly studied but may be more specific. Aspiration and septic emboli are additional potential radiographic patterns of infection that may be very characteristic in appearance. In the setting of nonresolving pneumonia, the differential diagnosis includes noninfectious causes as well as a variety of atypical infectious agents, specifically, mycobacterial and fungal agents, which have overlapping but distinctive clinical and radiographic presentations.

Background Little is known about the incidence of and associated management outcomes of occult hemothorax in blunt trauma patients. The increased use of computed thoracic tomography for the evaluation of the multiply injured blunt trauma patient has led to an increase in the identification of these hemothoraces and management dilemmas. Methods A retrospective review of blunt trauma patients with occult hemothoraces was performed. Patients were divided into 2 groups: chest tube versus no chest tube. Outcomes and complications for the 2 groups were defined. Data included demographics, Injury Severity Score, length of stay, need for mechanical ventilation and thoracic consult, pneumonia, and empyema. The size of the occult hemothorax was measured on the computed thoracic tomography. Results Eighty-eight patients (21.4%) had a total of 107 occult hemothoraces. Patients in the chest tube group were more likely to have a higher Injury Severity Score and an associated occult pneumothorax and to have smaller hemothoraces. Conclusions Occult pneumothoraces occur in a significant proportion of the multiply injured blunt trauma population. Small, isolated, occult hemothoraces can be managed safely in the stable patient.

The purpose of our study was to investigate clinician response and patient outcome associated with the radiologist's report of isolated subsegmental pulmonary emboli (ISSPE) or indeterminate or inconclusive results on MDCT for venous thromboembolism.All patients were examined using 8- or 16-MDCT. Reported findings on combined CT pulmonary angiography and CT venography of 1,435 consecutive patients were analyzed retrospectively. The charts of patients of interest with ISSPE or with indeterminate or inconclusive pulmonary embolism results were analyzed for clinician response and recurrent symptoms of venous thromboembolism in both treated and untreated patients during the following 3 months.We studied 207 patients of interest, and follow-up was available on 192 (92.8%) (67 ISSPEs, 125 inconclusive). Of the 192 patients, 25 (37%) of 67 patients with ISSPE and 108 (86%) of 125 patients with inconclusive results did not receive anticoagulation. Two patients with ISSPE and two patients with inconclusive results returned with new symptoms suggesting recurrent venous thromboembolism, but no venous thromboembolism was found. Thirteen (10%) of 133 untreated patients died without clinical evidence of recurrent venous thromboembolism. In 61 patients who received anticoagulation (42/67 [63%] ISSPE and 17/125 [14%] inconclusive), five patients returned with venous thromboembolism symptoms. None had recurrent emboli. Two (3%) of 61 patients who received anticoagulation died of other diseases.Patients with ISSPE more commonly received anticoagulation than not. In the patients who did not receive anticoagulation, no recurrent pulmonary embolism was identified on follow-up. In most patients with inconclusive findings on CT pulmonary angiography, clinicians chose to withhold anticoagulation without additional imaging workup. No adverse effects of this clinical decision were uncovered.

To prospectively compare the vascular attenuation achieved with the iso-osmolar dimeric contrast agent iodixanol with that achieved with the nonionic monomeric contrast agent iohexol for computed tomographic (CT) venography after CT pulmonary angiography.Institutional review board approval and informed consent were obtained, and 51 consecutive patients undergoing CT pulmonary angiography and CT venography were recruited. A 130-mL dose of iodixanol 320 was injected intravenously at a rate of 4 mL/sec and followed by injection of 50 mL of saline. CT venography was performed after 3.5 minutes. From prior studies, 51 patients of similar weight were picked as control subjects. They received a similar iodine load with iohexol 300 and were studied with a similar technique. Section thickness was 1.25 mm for pulmonary emboli and 5 mm for deep venous thrombosis. Test and control group characteristics (ie, sex, age, and weight) were not significantly different (P.05). Additionally, in test patients who had undergone CT pulmonary angiography and CT venography during the two preceding years, current and previously obtained CT scans were compared (ie, paired studies). Regions of interest were measured in four pulmonary artery and four lower extremity vein locations by two independent observers.Iodixanol increased average attenuation by 7 HU (P.05) in the lower extremities and decreased average attenuation by 42 HU (P.05) in the pulmonary arteries. In the 11 paired studies, similar results were obtained.Iodixanol caused a modest but statistically significant improvement in venous attenuation and a decrease in arterial attenuation. The diagnostic importance of this small increase in venous attenuation is not clear.

Pulmonary embolism (PE) and deep venous thrombosis (DVT) constitute the two clinical manifestations of venous thromboembolic disease (VTE). The recent innovation of computed tomography venography (CTV) in conjunction with CT pulmonary arteriography (CTPA) provides a single noninvasive diagnostic test that can evaluate both components of VTE. PE is often an underestimated, underdiagnosed, and, consequently, undertreated disease entity. Herein, we review the epidemiology of thromboembolic disease, the diagnostic algorithm used in evaluation of patients with suspected VTE, and protocols for performing CTPA and CTV. Interpretation of these examinations is discussed in detail, because CTPA may pose new challenges to the practicing radiologist.

Pulmonary embolism (PE) and deep venous thrombosis (DVT) represent two manifestations of the same syndrome, venous thromboembolism. Contrast-enhanced computed tomography (CT) angiography is a practical, efficient alternative to conventional imaging for PE. Following the pulmonary examination, the inferior vena cava (IVC) and the iliac, femoral, and popliteal veins can be studied with CT without additional intravenous contrast administration. Indirect CT venography (CTV) after CT pulmonary angiography (CTPA) simplifies and shortens venous thromboembolism work-up. Initial studies indicate that CTV is comparable to ultrasound in the evaluation of femoral/popliteal DVT. CTV has the advantage of evaluating the iliac veins and inferior vena cava, vessels poorly seen on sonography and venography. Combining CTV with CTPA increases confidence in withholding treatment when results for both the pulmonary arteries and leg veins are negative and increases the diagnosis of venous thromboembolism by 25% over CTPA alone. This pictorial essay will review the normal venous anatomy, CTV technique, and the findings of acute and chronic DVT. Interpretive pitfalls and alternative diagnoses are also reviewed.