Update on Silicosis.

Although silicosis has been an established disease with a recognized cause for more than 100 years, many workers continue to be exposed to silica and new outbreaks of disease continue to occur. This article describes some of the well-established and new exposures, including denim sandblasting, artificial stone cutting, and some forms of "coal worker's pneumoconiosis." The authors review the imaging and pathology of acute silicosis (silicoproteinosis), simple silicosis, and progressive massive fibrosis and summarize known and putative associations of silica exposure, including tuberculosis, lung cancer, connective tissue disease (especially systemic sclerosis), and vasculitis.

Lung imaging patterns in connective tissue disease-associated interstitial lung disease impact prognosis and immunosuppression response.

OBJECTIVES: Interstitial lung disease (ILD) in connective tissue diseases (CTD) have highly variable morphology. We aimed to identify imaging features and their impact on ILD progression, mortality and immunosuppression response. METHODS: Patients with CTD-ILD had high-resolution chest computed tomography (HRCT) reviewed by expert radiologists blinded to clinical data for overall imaging pattern (usual interstitial pneumonia [UIP]; non-specific interstitial pneumonia [NSIP]; organizing pneumonia [OP]; fibrotic hypersensitivity pneumonitis [fHP]; and other). Transplant-free survival and change in percent-predicted forced vital capacity (FVC) were compared using Cox and linear mixed effects models adjusted for age, sex, smoking, and baseline FVC. FVC decline after immunosuppression was compared with pre-treatment. RESULTS: Of 645 CTD-ILD patients, the frequent CTDs were systemic sclerosis (n = 215), rheumatoid arthritis (n = 127), and inflammatory myopathies (n = 100). NSIP was the most common pattern (54%), followed by UIP (20%), fHP (9%), and OP (5%). Compared with UIP, FVC decline was slower for NSIP (1.1%/year, 95%CI 0.2, 1.9) and OP (3.5%/year, 95%CI 2.0, 4.9), and mortality was lower for NSIP (HR 0.65, 95%CI 0.45, 0.93) and OP (HR 0.18, 95%CI 0.05, 0.57), but higher in fHP (HR 1.58, 95%CI 1.01, 2.40). The extent of fibrosis also predicted FVC decline and mortality. After immunosuppression, FVC decline was slower compared with pre-treatment in NSIP (by 2.1%/year, 95%CI 1.4, 2.8), with no change for UIP or fHP. CONCLUSION: Multiple radiologic patterns are possible in CTD-ILD, including a fHP pattern. NSIP and OP were associated with better outcomes and response to immunosuppression, while fHP had worse survival compared with UIP.

Integration and Application of Radiologic Patterns From Clinical Practice Guidelines on Idiopathic Pulmonary Fibrosis and Fibrotic Hypersensitivity Pneumonitis.

BACKGROUND: Clinical practice guidelines separately describe radiologic patterns of usual interstitial pneumonia (UIP) and fibrotic hypersensitivity pneumonitis (fHP), without direction on whether or how to apply these approaches concurrently within a single patient. RESEARCH QUESTION: How can we integrate guideline-defined radiologic patterns to diagnose interstitial lung disease (ILD) and what are the pitfalls associated with described patterns that require reassessment in future guidelines? STUDY DESIGN AND METHODS: Patients from the Canadian Registry for Pulmonary Fibrosis underwent detailed reevaluation in standardized multidisciplinary discussion. CT scan features were quantified by chest radiologists masked to clinical data, and guideline-defined patterns were assigned. Clinical data then were provided to the radiologist and an ILD clinician, who jointly determined the leading diagnosis. RESULTS: Clinical-radiologic diagnosis in 1,593 patients was idiopathic pulmonary fibrosis (IPF) in 26%, fHP in 12%, connective tissue disease-associated ILD (CTD-ILD) in 34%, idiopathic pneumonia with autoimmune features in 12%, and unclassifiable ILD in 10%. Typical and probable UIP patterns corresponded to a diagnosis of IPF in 66% and 57% of patients, respectively. Typical fHP pattern corresponded to an fHP clinical diagnosis in 65% of patients, whereas compatible fHP was nonspecific and associated with CTD-ILD or IPAF in 48% of patients. No pattern ruled out CTD-ILD. Gas trapping affecting > 5% of lung parenchyma on expiratory imaging was an important feature broadly separating compatible and typical fHP from other patterns (sensitivity, 0.77; specificity, 0.91). INTERPRETATION: An integrated approach to guideline-defined UIP and fHP patterns is feasible and supports > 5% gas trapping as an important branch point. Typical or probable UIP and typical fHP patterns have moderate predictive values for a corresponding diagnosis of IPF and fHP, although occasionally confounded by CTD-ILD; compatible fHP is nonspecific.

Integration and Application of Clinical Practice Guidelines for the Diagnosis of Idiopathic Pulmonary Fibrosis and Fibrotic Hypersensitivity Pneumonitis.

Recent clinical practice guidelines have addressed the diagnosis of idiopathic pulmonary fibrosis (IPF) and fibrotic hypersensitivity pneumonitis (fHP). These disease-specific guidelines were developed independently, without clear direction on how to apply their respective recommendations concurrently within a single patient, where discrimination between these two fibrotic interstitial lung diseases represents a frequent diagnostic challenge. The objective of this review, created by an international group of experts, was to suggest a pragmatic approach on how to apply existing guidelines to distinguish IPF and fHP. Key clinical, radiologic, and pathologic features described in previous guidelines are integrated in a set of diagnostic algorithms, which then are placed in the broader context of multidisciplinary discussion to guide the generation of a consensus diagnosis. Although these algorithms necessarily reflect some uncertainty wherever strong evidence is lacking, they provide insight into the current approach favored by experts in the field based on currently available knowledge. The authors further identify priorities for future research to clarify ongoing uncertainties in the diagnosis of fibrotic interstitial lung diseases.

Algorithmic Approach to the Diagnosis of Organizing Pneumonia: A Correlation of Clinical, Radiologic, and Pathologic Features.

Organizing pneumonia (OP), characterized histopathologically by patchy filling of alveoli and bronchioles by loose plugs of connective tissue, may be seen in a variety of conditions. These include but are not limited to after an infection, drug reactions, radiation therapy, and collagen vascular diseases. When a specific cause is responsible for this entity, it is referred to as "secondary OP." When an extensive search fails to reveal a cause, it is referred to as "cryptogenic OP" (previously called "bronchiolitis obliterans with OP"), which is a clinical, radiologic, and pathologic entity classified as an interstitial lung disease. The clinical presentation of OP often mimics that of other disorders, such as infection and cancer, which can result in a delay in diagnosis and inappropriate management of the underlying disease. The radiographic presentation of OP is polymorphous but often has subpleural consolidations with air bronchograms or solitary or multiple nodules, which can wax and wane. Diagnosis of OP sometimes requires histopathologic confirmation and exclusion of other possible causes. Treatment usually requires a prolonged steroid course, and disease relapse is common. The aim of this article is to summarize the clinical, radiographic, and histologic presentations of this disease and to provide a practical diagnostic algorithmic approach incorporating clinical history and characteristic imaging patterns.

Diagnosis of Hypersensitivity Pneumonitis: Review and Summary of American College of Chest Physicians Statement.

Assessment of lung biopsies for the diagnosis of hypersensitivity pneumonitis (HP) is one of the most difficult diagnostic problems for surgical pathologists. It is a form of interstitial lung disease resulting from an immune reaction provoked by an inhaled antigen in susceptible individuals. Although this definition sounds simple, in practice, the diagnosis of HP can be challenging. To address these issues, the American College of Chest Physicians (CHEST) has recently published a guideline for the diagnosis of HP. In this review, we will explore the multidisciplinary diagnostic evaluation of HP with a focus on the pathologic features as outlined in the CHEST guidelines. The histologic criteria are divided into 4 diagnostic categories: (1) Typical nonfibrotic HP or fibrotic HP; (2) Compatible with nonfibrotic HP or fibrotic HP; (3) Indeterminate for nonfibrotic or fibrotic HP; and (4) Alternative Diagnosis. It is important to emphasize that patterns 1 to 3 do not represent discrete histologic entities or pathologic diagnoses. Rather, these categories are meant to serve as a practical guide for organizing a complex set of overlapping histologic patterns into an integrated diagnostic framework for facilitating multidisciplinary discussion. High-resolution computed tomography features are also summarized, emphasizing how the correlation of lung biopsies with computed tomography findings can help to favor the diagnosis, particularly in cases where biopsies are not typical for HP. This review highlights details of the histologic spectrum of HP as well as the utility of different types of biopsies and bronchoalveolar lavage. We also emphasize the importance of multidisciplinary discussion and the complex differential diagnosis.

Chronic Lung Allograft Dysfunction: Review of CT and Pathologic Findings.

Chronic lung allograft dysfunction (CLAD) is the most common cause of mortality in lung transplant recipients after the 1st year of transplantation. CLAD has traditionally been classified into two distinct obstructive and restrictive forms: bronchiolitis obliterans syndrome and restrictive allograft syndrome. However, CLAD may manifest with a spectrum of imaging and pathologic findings and a combination of obstructive and restrictive physiologic abnormalities. Although the initial CT manifestations of CLAD may be nonspecific, the progression of findings at follow-up should signal the possibility of CLAD and may be present on imaging studies prior to the development of functional abnormalities of the lung allograft. This review encompasses the evolution of CT findings in CLAD, with emphasis on the underlying pathogenesis and pathologic condition, to enhance understanding of imaging findings. The purpose of this article is to familiarize the radiologist with the initial and follow-up CT findings of the obstructive, restrictive, and mixed forms of CLAD, for which early diagnosis and treatment may result in improved survival. Supplemental material is available for this article. © RSNA, 2021.

Radiological Society of North America (RSNA) Expert Consensus Statement Related to Chest CT Findings in COVID-19 Versus CO-RADS: Comparison of Reporting System Performance Among Chest Radiologists and End-User Preference.

PURPOSE: The RSNA expert consensus statement and CO-RADS reporting system assist radiologists in describing lung imaging findings in a standardized manner in patients under investigation for COVID-19 pneumonia and provide clarity in communication with other healthcare providers. We aim to compare diagnostic performance and inter-/intra-observer among chest radiologists in the interpretation of RSNA and CO-RADS reporting systems and assess clinician preference. METHODS: Chest CT scans of 279 patients with suspected COVID-19 who underwent RT-PCR testing were retrospectively and independently examined by 3 chest radiologists who assigned interpretation according to the RSNA and CO-RADS reporting systems. Inter-/intra-observer analysis was performed. Diagnostic accuracy of both reporting systems was calculated. 60 clinicians participated in a survey to assess end-user preference of the reporting systems. RESULTS: Both systems demonstrated almost perfect inter-observer agreement (Fleiss kappa 0.871, P < 0.0001 for RSNA; 0.876, P < 0.0001 for CO-RADS impressions). Intra-observer agreement between the 2 scoring systems using the equivalent categories was almost perfect (Fleiss kappa 0.90-0.92, P < 0.001). Positive predictive values were high, 0.798-0.818 for RSNA and 0.891-0.903 CO-RADS. Negative predictive value were similar, 0.573-0.585 for RSNA and 0.573-0.58 for CO-RADS. Specificity differed between the 2 systems, 68-73% for CO-RADS and 52-58% for RSNA with superior specificity of CO-RADS. Of 60 survey participants, the majority preferred the RSNA reporting system rather than CO-RADS for all options provided (66.7-76.7%; P < 0.05). CONCLUSIONS: RSNA and CO-RADS reporting systems are consistent and reproducible with near perfect inter-/intra-observer agreement and excellent positive predictive value. End-users preferred the reporting language in the RSNA system.

RSNA Expert Consensus Statement on Reporting Chest CT Findings Related to COVID-19: Interobserver Agreement Between Chest Radiologists.

PURPOSE: To assess the interobserver variability between chest radiologists in the interpretation of the Radiological Society of North America (RSNA) expert consensus statement reporting guidelines in patients with suspected coronavirus disease 2019 (COVID-19) pneumonia in a setting with limited reverse transcription polymerase chain reaction testing availability. METHODS: Chest computed tomography (CT) studies in 303 consecutive patients with suspected COVID-19 were reviewed by 3 fellowship-trained chest radiologists. Cases were assigned an impression of typical, indeterminate, atypical, or negative for COVID-19 pneumonia according to the RSNA expert consensus statement reporting guidelines, and interobserver analysis was performed. Objective CT features associated with COVID-19 pneumonia and distribution of findings were recorded. RESULTS: The Fleiss kappa for all observers was almost perfect for typical (0.815), atypical (0.806), and negative (0.962) COVID-19 appearances (P < .0001) and substantial (0.636) for indeterminate COVID-19 appearance (P < .0001). Using Cramer V analysis, there were very strong correlations between all radiologists' interpretations, statistically significant for all (typical, indeterminate, atypical, and negative) COVID-19 appearances (P < .001). Objective CT imaging findings were recorded in similar percentages of typical cases by all observers. CONCLUSION: The RSNA expert consensus statement on reporting chest CT findings related to COVID-19 demonstrates substantial to almost perfect interobserver agreement among chest radiologists in a relatively large cohort of patients with clinically suspected COVID-19. It therefore serves as a reliable reference framework for radiologists to accurately communicate their level of suspicion based on the presence of evidence-based objective findings.

Chest CT target sign in a couple with COVID-19 pneumonia.

We describe a target sign on chest CT characterized by a combination of peripheral ring-like opacity and a central nodular ground-glass opacity surrounding a vessel in a couple with COVID-19 pneumonia confirmed by real-time reverse transcriptase fluorescence polymerase chain reaction sputum analysis.

Descrevemos o sinal do alvo na TC de tórax representando combinação de opacidade com aspecto de anel periférico e componente central nodular em vidro fosco circundando estrutura vascular em um casal com COVID-19 confirmada por reação em cadeia da polimerase com transcrição reversa.

The Role of Emergency Radiology in COVID-19: From Preparedness to Diagnosis [Formula: see text].

Emergency trauma radiology, although a relatively new subspecialty of radiology, plays a critical role in both the diagnosis/triage of acutely ill patients, but even more important in providing leadership and taking the lead in the preparedness of imaging departments in dealing with novel highly infectious communicable diseases and mass casualties. This has become even more apparent in dealing with COVID-19, the disease caused by the novel coronavirus SARS-CoV-2, first emerged in late 2019. We review the symptoms, epidemiology, and testing for this disease. We discuss characteristic imaging findings of COVID-19 in relation to other modern coronavirus diseases including SARS and MERS. We discuss roles that community radiology clinics, outpatient radiology departments, and emergency radiology departments can play in the diagnosis of this disease. We review practical methods to reduce spread of infections within radiology departments.

Role of a Regional Multidisciplinary Conference in the Diagnosis of Interstitial Lung Disease.

RATIONALE: The interstitial lung disease (ILD) specialists in Vancouver participate in a multidisciplinary discussion (MDD) that is primarily used internally for patients seen by these specialists. The MDD is also used remotely (externally) by general pulmonologists to increase access to this service. OBJECTIVES: To describe the impact of an MDD on the diagnosis and management of ILD in these two patient cohorts, and to report the satisfaction of referring pulmonologists with this service. METHODS: This retrospective cross-sectional study included patients who underwent MDD review between March 2014 and June 2017. Data were extracted from standardized MDD records and comparisons were made between the internal and external ILD cohorts. Pulmonologists who used the external review service completed an anonymous survey addressing their satisfaction with components of the MDD. RESULTS: The 209 internal patients and 91 external patients had similar clinical characteristics. MDD review led to a change in diagnosis in 40% of patients, including 36% of internal patients and 48% of external patients (P = 0.04). For patients without a working diagnosis, 44% were provided a confident ILD diagnosis following MDD, including 78% of patients with a surgical lung biopsy and 37% of patients without a surgical lung biopsy (P < 0.001). After MDD review, treatment was started in 45% of patients on no ILD therapy, and treatment was changed in 45% of patients on ILD therapy. Overall, 93% of the 14 respondents (out of 16 surveyed) were very or somewhat satisfied with the MDD external review service. CONCLUSIONS: Similar to previous publications, our study suggests an important role of MDD in the diagnosis and management of ILD, and further demonstrates that MDD of external patients is a viable service that allows greater and more rapid access to ILD expertise.

Screening of miners and millers at decreasing levels of asbestos exposure: comparison of chest radiography and thin-section computed tomography.

BACKGROUND: Chest radiography (CXR) is inferior to Thin-section computed tomography in the detection of asbestos related interstitial and pleural abnormalities. It remains unclear, however, whether these limitations are large enough to impair CXR´s ability in detecting the expected reduction in the frequency of these asbestos-related abnormalities (ARA) as exposure decreases. METHODS: Clinical evaluation, CXR, Thin-section CT and spirometry were obtained in 1418 miners and millers who were exposed to progressively lower airborne concentrations of asbestos. They were separated into four groups according to the type, period and measurements of exposure and/or procedures for controlling exposure: Group I (1940-1966/tremolite and chrysotile, without measurements of exposure and procedures for controlling exposure); Group II (1967-1976/chrysotile only, without measurements of exposure and procedures for controlling exposure); Group III (1977-1980/chrysotile only, initiated measurements of exposure and procedures for controlling exposure) and Group IV (after 1981/chrysotile only, implemented measurements of exposure and a comprehensive procedures for controlling exposure). RESULTS: In all groups, CXR suggested more frequently interstitial abnormalities and less frequently pleural plaques than observed on Thin-section CT (p<0.050). The odds for asbestosis in groups of decreasing exposure diminished to greater extent at Thin-section CT than on CXR. Lung function was reduced in subjects who had pleural plaques evident only on Thin-section CT (p<0.050). In a longitudinal evaluation of 301 subjects without interstitial and pleural abnormalities on CXR and Thin-section CT in a previous evaluation, only Thin-section CT indicated that these ARA reduced as exposure decreased. CONCLUSIONS: CXR compared to Thin-section CT was associated with false-positives for interstitial abnormalities and false-negatives for pleural plaques, regardless of the intensity of asbestos exposure. Also, CXR led to a substantial misinformation of the effects of the progressively lower asbestos concentrations in the occurrence of asbestos-related diseases in miners and millers.

Chronic pulmonary microaspiration: high-resolution computed tomographic findings in 13 patients.

PURPOSE: The aim of the study was to describe the high-resolution computed tomography (CT) manifestations of chronic pulmonary microaspiration, a condition characterized by recurrent subclinical aspiration of small droplets of gastric contents or foreign particles into the lungs. MATERIALS AND METHODS: We reviewed the CT findings in 13 consecutive patients with clinical (n=13) and histologic (n=1) diagnosis of chronic pulmonary microaspiration. Twelve patients presented with persistent cough, but none had a clinical history of acute aspiration. One patient was asymptomatic. All patients had volumetric CT of the chest reconstructed using thin sections (1 to 1.3 mm) at the time of diagnosis. The CT scans were interpreted by 3 chest radiologists who reached a final decision by consensus. RESULTS: All 13 patients had centrilobular nodules and ground-glass opacities that involved mainly the dependent lung regions in 11 patients and had a random distribution in 2. Other common findings included branching opacities (n=10), small foci of consolidation (n=7), septal lines (n=5), and bronchiectasis (n=7). The 13 patients had at least 1 risk factor for aspiration including gastroesophageal reflux (n=9), hiatus hernia (n=6), esophageal dysfunction (n=3), oropharyngeal dysphagia (n=1), esophageal carcinoma (n=1), and use of sedatives (n=2). CONCLUSIONS: The high-resolution CT manifestations of chronic pulmonary microaspiration consist mainly of centrilobular nodules and ground-glass opacities that tend to involve predominately the dependent regions. Branching opacities and small foci of consolidation are seen in the majority of cases.

Expression of matrix metalloproteinase-1 in alveolar macrophages, type II pneumocytes, and airways in smokers: relationship to lung function and emphysema.

BACKGROUND: An imbalance between proteolytic enzymes and their inhibitors is thought to be involved in the pathogenesis of chronic obstructive pulmonary disease. Matrix metalloproteinase-1, also known as interstitial collagenase, has been implicated as a potentially important proteinase in the genesis of chronic obstructive pulmonary disease and, more specifically, emphysema. METHODS: We performed quantitative immunohistochemical assessment of matrix metalloproteinase-1 expression in the resected lung of 20 smokers/ex-smokers who had varying severity of airflow obstruction and emphysema and compared this with the lungs of 5 nonsmokers. Emphysema was measured using a morphometric measure of the lungs' surface area/volume ratio and with qualitative and quantitative computed tomography (CT) measures of emphysema. RESULTS: There were significantly more matrix metalloproteinase-1-expressing alveolar macrophages and type II pneumocytes as well as a greater percentage of small airways that stained positively for matrix metalloproteinase-1 in the lungs of smokers than in those of nonsmokers (p < 0.0001, p < 0.0001, and p = 0.0003, respectively). The extent of staining of type II pneumocytes and airways for matrix metalloproteinase-1 was significantly related to the extent of smoking (p = 0.012 and p = 0.013, respectively). In addition, the extent of matrix metalloproteinase-1 staining of alveolar macrophages was related to the lung surface area/volume ratio and to qualitative estimates of emphysema on CT. CONCLUSION: These findings suggest that cigarette smoking increases expression of matrix metalloproteinase-1 in alveolar macrophages as well as in alveolar and small airway epithelial cells. Smokers who develop emphysema have increased alveolar macrophage expression of matrix metalloproteinase-1.

COPD phenotypes in biomass smoke- versus tobacco smoke-exposed Mexican women.

We hypothesised that biomass smoke exposure is associated with an airway-predominant chronic obstructive pulmonary disease (COPD) phenotype, while tobacco-related COPD is associated with an emphysema-predominant phenotype. In this cross-sectional study, female never-smokers with COPD and biomass exposure (n=21) and female ex-cigarette smokers with COPD without biomass exposure (n=22) completed computed tomography (CT) at inspiration and expiration, pulmonary function, blood gas, exercise tolerance, and quality of life measures. Two radiologists scored the extent of emphysema and air trapping on CT. Quantitative emphysema severity and distribution and airway wall thickness were calculated using specialised software. Women in the tobacco group had significantly more emphysema than the biomass group (radiologist score 2.3 versus 0.7, p=0.001; emphysema on CT 27% versus 19%, p=0.046; and a larger size of emphysematous spaces, p=0.006). Women in the biomass group had significantly more air trapping than the tobacco group (radiologist score 2.6 and 1.5, respectively; p=0.02) and also scored lower on the symptom, activities and confidence domains of the quality of life assessment and had lower oxygen saturation at rest and during exercise (p<0.05). Biomass smoke exposure is associated with less emphysema but more air trapping than tobacco smoke exposure, suggesting an airway-predominant phenotype.

Interobserver variability in the CT assessment of honeycombing in the lungs.

PURPOSE: To quantify observer agreement and analyze causes of disagreement in identifying honeycombing at chest computed tomography (CT). MATERIALS AND METHODS: The institutional review board approved this multiinstitutional HIPAA-compliant retrospective study, and informed patient consent was not required. Five core study members scored 80 CT images with a five-point scale (5 = definitely yes to 1 = definitely no) to establish a reference standard for the identification of honeycombing. Forty-three observers from various subspecialties and geographic regions scored the CT images by using the same scoring system. Weighted κ values of honeycombing scores compared with the reference standard were analyzed to investigate intergroup differences. Images were divided into four groups to allow analysis of imaging features of cases in which there was disagreement: agreement on the presence of honeycombing, agreement on the absence of honeycombing, disagreement on the presence of honeycombing, and other (none of the preceding three groups applied). RESULTS: Agreement of scores of honeycombing presence by 43 observers with the reference standard was moderate (Cohen weighted κ values: 0.40-0.58). There were no significant differences in κ values among groups defined by either subspecialty or geographic region (Tukey-Kramer test, P = .38 to >.99). In 29% of cases, there was disagreement on identification of honeycombing. These cases included honeycombing mixed with traction bronchiectasis, large cysts, and superimposed pulmonary emphysema. CONCLUSION: Identification of honeycombing at CT is subjective, and disagreement is largely caused by conditions that mimic honeycombing.

The presence and progression of emphysema in COPD as determined by CT scanning and biomarker expression: a prospective analysis from the ECLIPSE study.

BACKGROUND: Emphysema is a key contributor to airflow limitation in chronic obstructive pulmonary disease (COPD) and can be quantified using CT scanning. We investigated the change in CT lung density in a longitudinal, international cohort of patients with COPD. We also explored the potential relation between emphysema and patient characteristics, and investigated if certain circulating biomarkers were associated with decline in CT lung density. METHODS: We used a random coefficient model to assess predictors of both CT lung density and its longitudinal change over 3 years in 1928 patients with COPD enrolled in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study. Lung density was measured for every voxel in the CT scan and after correcting for lung volume was expressed as the density at lowest 15th percentile point of the distribution. This study is registered with ClinicalTrials.gov, number NCT00292552. FINDINGS: Lung density at baseline was influenced by age, sex, body-mass index, current smoking status and smoking history, and severity of airflow limitation. The observed decline in lung density was variable (mean decline -1·13 g/L [SE 0·06] per year). The annual decline in lung density was more rapid in women (additional -0·41 [SE 0·14] g/L per year, p=0·003) than men and in current smokers (additional -0·29 [SE 0·14] g/L per year, p=0·047) than in former smokers. Circulating levels of the biomarkers surfactant protein D (SP-D) and soluble receptor for advanced glycation endproduct (sRAGE) were significantly associated with both baseline lung density and its decline over time. INTERPRETATION: This study shows that decline in lung density in COPD can be measured, that it is variable, and related to smoking and gender. We identified potential biochemical predictors of the presence and progression of emphysema. FUNDING: GlaxoSmithKline.

Thoracic computed tomographic manifestations of tuberous sclerosis in adults.

The purpose of this article is to illustrate the various manifestations that can be encountered on thoracic computed tomography of tuberous sclerosis in adults. The pulmonary findings include lymphangioleiomyomatosis and multifocal micronodular pneumocyte hyperplasia. The extrapulmonary manifestations are divided into cardiac, vascular, mediastinal, osseous, and upper abdominal findings.