David A Lynch

National Jewish Health, Denver, Colorado, United States

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Publications (270)1213.35 Total impact

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    ABSTRACT: Purpose: The purposes of this study were to evaluate the effect of smoking status on quantitative computed tomography CT measures of low-attenuation areas (LAAs) on inspiratory and expiratory CT and to provide a method of adjusting for this effect. Materials and methods: A total of 6762 current and former smokers underwent spirometry and volumetric inspiratory and expiratory CT. Quantitative CT analysis was completed using open-source 3D Slicer software. LAAs were defined as lung voxels with attenuation values ≤-950 Hounsfield units (HU) on inspiratory CT and ≤-856 HU on expiratory CT and were expressed as percentage of CT lung volume (%LAAI-950 and %LAAE-856). Multiple linear regression was used to determine the effect of smoking status on %LAAI-950 and %LAAE-856 while controlling for demographic variables, spirometric lung function, and smoking history, as well as total lung capacity (%LAAI-950) or functional residual capacity (%LAAE-856). Quantile normalization was used to align the %LAAI-950 distributions for current and former smokers. Results: Mean %LAAI-950 was 4.2±7.1 in current smokers and 7.7±9.7 in former smokers (P<0.001). After adjusting for confounders, %LAAI-950 was 3.5 percentage points lower and %LAAE-856 was 6.0 percentage points lower in current smokers than in former smokers (P<0.001). After quantile normalization, smoking status was an insignificant variable in the inspiratory regression model, with %LAAI-950 being 0.27 percentage points higher in current smokers (P=0.13). Conclusions: After adjusting for patient demographics and lung function, current smokers display significantly lower %LAAI-950 and %LAAE-856 than do former smokers. Potential methods for adjusting for this effect would include adding a fixed value (eg, 3.5%) to the calculated percentage of emphysema in current smokers, or quantile normalization.
    Journal of thoracic imaging 10/2015; DOI:10.1097/RTI.0000000000000181 · 1.74 Impact Factor
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    ABSTRACT: Pulmonary x-ray computed tomographic (CT) and magnetic resonance imaging (MRI) research and development has been motivated, in part, by the quest to subphenotype common chronic lung diseases such as chronic obstructive pulmonary disease (COPD). For thoracic CT and MRI, the main COPD research tools, disease biomarkers are being validated that go beyond anatomy and structure to include pulmonary functional measurements such as regional ventilation, perfusion, and inflammation. In addition, there has also been a drive to improve spatial and contrast resolution while at the same time reducing or eliminating radiation exposure. Therefore, this review focuses on our evolving understanding of patient-relevant and clinically important COPD endpoints and how current and emerging MRI and CT tools and measurements may be exploited for their identification, quantification, and utilization. Since reviews of the imaging physics of pulmonary CT and MRI and reviews of other COPD imaging methods were previously published and well-summarized, we focus on the current clinical challenges in COPD and the potential of newly emerging MR and CT imaging measurements to address them. Here we summarize MRI and CT imaging methods and their clinical translation for generating reproducible and sensitive measurements of COPD related to pulmonary ventilation and perfusion as well as parenchyma morphology. The key clinical problems in COPD provide an important framework in which pulmonary imaging needs to rapidly move in order to address the staggering burden, costs, as well as the mortality and morbidity associated with COPD. J. Magn. Reson. Imaging 2015. © 2015 Wiley Periodicals, Inc.
    Journal of Magnetic Resonance Imaging 07/2015; DOI:10.1002/jmri.25010 · 3.21 Impact Factor
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    ABSTRACT: Many patients with an idiopathic interstitial pneumonia (IIP) have clinical features that suggest an underlying autoimmune process but do not meet established criteria for a connective tissue disease (CTD). Researchers have proposed differing criteria and terms to describe these patients, and lack of consensus over nomenclature and classification limits the ability to conduct prospective studies of a uniform cohort.The "European Respiratory Society/American Thoracic Society Task Force on Undifferentiated Forms of Connective Tissue Disease-associated Interstitial Lung Disease" was formed to create consensus regarding the nomenclature and classification criteria for patients with IIP and features of autoimmunity.The task force proposes the term "interstitial pneumonia with autoimmune features" (IPAF) and offers classification criteria organised around the presence of a combination of features from three domains: a clinical domain consisting of specific extra-thoracic features, a serologic domain consisting of specific autoantibodies, and a morphologic domain consisting of specific chest imaging, histopathologic or pulmonary physiologic features.A designation of IPAF should be used to identify individuals with IIP and features suggestive of, but not definitive for, a CTD. With IPAF, a sound platform has been provided from which to launch the requisite future research investigations of a more uniform cohort. Copyright ©ERS 2015.
    European Respiratory Journal 07/2015; DOI:10.1183/13993003.00150-2015 · 7.64 Impact Factor
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    European Respiratory Journal 07/2015; DOI:10.1183/13993003.00570-2015 · 7.64 Impact Factor
  • David A. Lynch · Jonathan H. Chung
    Clinics in Chest Medicine 06/2015; 36(2). DOI:10.1016/S0272-5231(15)00039-8 · 2.07 Impact Factor
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    ABSTRACT: The NHLBI-sponsored IPF Clinical Research Network (IPFnet) studies enrolled subjects with idiopathic pulmonary fibrosis (IPF) to evaluate drug therapies in treatment trials. An Adjudication Committee (AC) provided a structured review of cases where there was uncertainty or disagreement regarding diagnosis or clinical event classification. This manuscript describes the diagnosis and adjudication processes. The diagnostic process was based on review of clinical data and HRCTs with central review of lung biopsies when available. The AC worked closely with the data coordinating center to obtain clinical, radiologic, and histologic data and to communicate with the clinical centers. AC utilized a multidisciplinary discussion model with four clinicians, one radiologist, and one pathologist to adjudicate diagnosis and outcome measures. The IPFnet trials screened 1015 subjects; of these, 23 cases required review by the AC to establish eligibility. The most common diagnosis for exclusion was suspected chronic hypersensitivity pneumonitis. AC reviewed 88 suspected acute exacerbations (AEx), 93 non-elective hospitalizations, and 16 cases of bleeding. Determination of AEx presented practical challenges to adjudicators as necessary clinical data was often not collected, particularly when subjects were evaluated outside of the primary study site. The IPFnet diagnostic process was generally efficient, but a multidisciplinary adjudication committee was critical to assure correct phenotype for study enrollment. The AC was key in adjudicating all adverse outcomes in two IPFnet studies terminated early due to safety issues. Future clinical trials in IPF should consider logistical and cost issues as they incorporate AEx and hospitalizations as outcome measures.
    Chest 06/2015; DOI:10.1378/chest.14-2889 · 7.48 Impact Factor
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    ABSTRACT: Airflow 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. To 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. Individuals 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. Physical function impairments, respiratory symptoms, CT abnormalities, use of respiratory medications, and reduced respiratory-specific quality of life. One 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 < .001) and a lower 6-minute walk distance, and 42.3% (127 of 300) of the GOLD 0 group had CT evidence of emphysema or airway thickening. The FEV1 percent predicted distribution and mean for the GOLD 0 group were lower but still within the normal range for the population. Current smoking was associated with more respiratory symptoms, but former smokers had greater emphysema and gas trapping. Advancing age was associated with smoking cessation and with more CT findings of disease. Individuals with respiratory impairments were more likely to use respiratory medications, and the use of these medications was associated with worse disease. Lung disease and impairments were common in smokers without spirometric COPD. Based on these results, we project that there are 35 million current and former smokers older than 55 years in the United States who may have unrecognized disease or impairment. The effect of chronic smoking on the lungs and the individual is substantially underestimated when using spirometry alone.
    JAMA Internal Medicine 06/2015; 175(9). DOI:10.1001/jamainternmed.2015.2735 · 13.12 Impact Factor
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    ABSTRACT: Chronic obstructive pulmonary disease (COPD) is defined by the presence of airflow limitation on spirometry, yet COPD subjects can have marked differences in CT imaging. These differences may be driven by genetic factors. We hypothesized that a genome-wide association study of quantitative imaging would identify loci not previously identified in analyses of COPD or spirometry. In addition, we sought to determine whether previously described genome-wide significant COPD and spirometric loci were associated with emphysema or airway phenotypes. To identify genetic determinants of quantitative imaging phenotypes. We performed a genome-wide association study on two quantitative emphysema and two quantitative airway imaging phenotypes in the COPDGene (non-Hispanic white and African-American), ECLIPSE, NETT, and GenKOLS studies; and on % gas trapping in COPDGene. We also examined specific loci reported as genome-wide significant for spirometric phenotypes related to airflow limitation or COPD. The total sample size across all cohorts was 12,031, of which 9,338 were from COPDGene. We identified five loci associated with emphysema-related phenotypes, one with airway-related phenotypes, and two with gas trapping. These loci included previously reported associations, including the HHIP, 15q25, and AGER loci, as well as novel associations near SERPINA10 and DLC1. All previously reported COPD and a significant number of spirometric GWAS loci were at least nominally (P < 0.05) associated with either emphysema or airway phenotypes. Genome-wide analysis may identify novel risk factors for quantitative imaging characteristics in COPD, and also identify imaging features associated with previously identified lung function loci. .
    American Journal of Respiratory and Critical Care Medicine 06/2015; 192(5). DOI:10.1164/rccm.201501-0148OC · 13.00 Impact Factor
  • David A Lynch · Jonathan H Chung
    Clinics in chest medicine 05/2015; 36(2):xv-xvi. DOI:10.1016/j.ccm.2015.03.001 · 2.07 Impact Factor
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    ABSTRACT: To propose and evaluate a method to reduce variability in emphysema quantification among different computed tomography (CT) reconstructions by normalizing CT data reconstructed with varying kernels. We included 369 subjects from the COPDGene study. For each subject, spirometry and a chest CT reconstructed with two kernels were obtained using two different scanners. Normalization was performed by frequency band decomposition with hierarchical unsharp masking to standardize the energy in each band to a reference value. Emphysema scores (ES), the percentage of lung voxels below -950 HU, were computed before and after normalization. Bland-Altman analysis and correlation between ES and spirometry before and after normalization were compared. Two mixed cohorts, containing data from all scanners and kernels, were created to simulate heterogeneous acquisition parameters. The average difference in ES between kernels decreased for the scans obtained with both scanners after normalization (7.7 ± 2.7 to 0.3 ± 0.7; 7.2 ± 3.8 to -0.1 ± 0.5). Correlation coefficients between ES and FEV1, and FEV1/FVC increased significantly for the mixed cohorts. Normalization of chest CT data reduces variation in emphysema quantification due to reconstruction filters and improves correlation between ES and spirometry. • Emphysema quantification is sensitive to the reconstruction kernel used. • Normalization allows comparison of emphysema quantification from images reconstructed with varying kernels. • Normalization allows comparison of emphysema quantification obtained with scanners from different manufacturers. • Normalization improves correlation of emphysema quantification with spirometry. • Normalization can be used to compare data from different studies and centers.
    European Radiology 05/2015; DOI:10.1007/s00330-015-3824-y · 4.01 Impact Factor
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    ABSTRACT: Idiopathic pulmonary fibrosis is a progressive fibrotic lung disease that distorts pulmonary architecture, leading to hypoxia, respiratory failure, and death. Diagnosis is difficult because other interstitial lung diseases have similar radiological and histopathological characteristics. A usual interstitial pneumonia pattern is a hallmark of idiopathic pulmonary fibrosis and is essential for its diagnosis. We aimed to develop a molecular test that distinguishes usual interstitial pneumonia from other interstitial lung diseases in surgical lung biopsy samples. The eventual goal of this research is to develop a method to diagnose idiopathic pulmonary fibrosis without the patient having to undergo surgery.
    05/2015; 3(6). DOI:10.1016/S2213-2600(15)00140-X
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    ABSTRACT: The purpose of this statement is to describe and define the phenotypic abnormalities that can be identified on visual and quantitative evaluation of computed tomographic (CT) images in subjects with chronic obstructive pulmonary disease (COPD), with the goal of contributing to a personalized approach to the treatment of patients with COPD. Quantitative CT is useful for identifying and sequentially evaluating the extent of emphysematous lung destruction, changes in airway walls, and expiratory air trapping. However, visual assessment of CT scans remains important to describe patterns of altered lung structure in COPD. The classification system proposed and illustrated in this article provides a structured approach to visual and quantitative assessment of COPD. Emphysema is classified as centrilobular (subclassified as trace, mild, moderate, confluent, and advanced destructive emphysema), panlobular, and paraseptal (subclassified as mild or substantial). Additional important visual features include airway wall thickening, inflammatory small airways disease, tracheal abnormalities, interstitial lung abnormalities, pulmonary arterial enlargement, and bronchiectasis. (©) RSNA, 2015.
    Radiology 05/2015; DOI:10.1148/radiol.2015141579 · 6.87 Impact Factor
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    ABSTRACT: CT is increasingly being used to stage and quantify the extent of diffuse lung diseases both in clinical practice and in treatment trials. The role of CT in the assessment of patients entering treatment trials has greatly expanded as clinical researchers and pharmaceutical companies have focused their efforts on developing safe and effective drugs for interstitial lung diseases, particularly for idiopathic pulmonary fibrosis. These efforts have culminated in the simultaneous approval by the US Food and Drug Administration of two new drugs for the treatment of idiopathic pulmonary fibrosis. CT features are a key part of the inclusion criteria in many drug trials and CT is now being used to refine the type of patients enrolled. Interest in the potential use of serial CT as an effectiveness endpoint is increasing. For chronic progressive diseases, mortality may not be a feasible endpoint and many surrogate markers have been explored, ranging from pulmonary function decline to biomarkers. However, these surrogate markers are not entirely reliable and combinations of endpoints, including change in disease extent on CT, are being investigated. Methods to assess disease severity with CT range from simple visual estimates to sophisticated quantification by use of software. In this Position Paper, which cannot be regarded as a comprehensive set of guidelines in view of present knowledge, we examine the uses of serial CT in clinical practice and in drug trials and draw attention to uncertainties and challenges for future research. Copyright © 2015 Elsevier Ltd. All rights reserved.
    05/2015; 3(6). DOI:10.1016/S2213-2600(15)00096-X
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    ABSTRACT: Pulmonary involvement is a frequent manifestation of connective tissue disease (CTD)-related thoracic disease. It is important to characterize the underlying pattern when pulmonary involvement occurs in a patient with CTD, and to exclude other causes. A systematic approach, evaluating each compartment of the lung (airway, interstitium, pleura, pulmonary vasculature) may be helpful. In complex cases, a multidisciplinary approach should be considered, potentially including the pulmonologist, rheumatologist, radiologist, pathologist, and sometimes the infectious disease specialist or oncologist. New techniques, such as quantitative computed tomography and MRI, are expected to be helpful for evaluation and management of CTD-associated thoracic disease. Copyright © 2015 Elsevier Inc. All rights reserved.
    Clinics in Chest Medicine 04/2015; 36(2). DOI:10.1016/j.ccm.2015.02.010 · 2.07 Impact Factor
  • J. Caleb Richards · David A Lynch · Jonathan H. Chung
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    ABSTRACT: Diffuse cystic and nodular lung diseases have characteristic imaging findings. The most common causes of cystic lung disease are lymphangioleiomyomatosis and Langerhans cell histiocytosis. Other less common cystic lung diseases include Birt-Hogg-Dube syndrome, lymphocytic interstitial pneumonitis, and light chain deposition disease. Computed tomography is used to differentiate cystic lung disease from emphysema, honeycombing, cavities, and bronchiectasis, which mimic cystic lung disease. Diffuse nodular lung disease are categorized as centrilobular, perilymphatic, and random types. In diffuse nodular lung disease, a specific diagnosis is achieved through a combination of history, physical examination, and imaging findings. Copyright © 2015 Elsevier Inc. All rights reserved.
    Clinics in chest medicine 04/2015; 36(2). DOI:10.1016/j.ccm.2015.02.011 · 2.07 Impact Factor
  • Tilman L. Koelsch · Jonathan H. Chung · David A. Lynch
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    ABSTRACT: The idiopathic interstitial pneumonias are a group of inflammatory and fibrosing pulmonary conditions that share many clinical, radiologic, and histologic similarities. Radiologic evaluation can often help to make a more confident diagnosis of these conditions and may help in their management. Several specific radiologic findings can suggest a single best diagnosis or can help to differentiate between similar conditions. Imaging findings can also have important prognostic implications or identify complications. This review discusses the role of radiologic findings in the setting of the idiopathic interstitial pneumonias. Copyright © 2015 Elsevier Inc. All rights reserved.
    Clinics in Chest Medicine 04/2015; 36(2). DOI:10.1016/j.ccm.2015.02.009 · 2.07 Impact Factor
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    ABSTRACT: Rationale: Former smoking history and Chronic Obstructive Pulmonary Disease (COPD) are potential risk factors for osteoporosis and fractures. Under existing guidelines for osteoporosis screening, women are included but men are not, and only current smoking is considered. Objectives: To demonstrate the impact of COPD and smoking history on the risk of osteoporosis and vertebral fracture in men and women. Measurements: Volumetric bone mineral density (vBMD) by calibrated quantitative CT (QCT), visually scored vertebral fractures and severity of lung disease were determined from chest CT scans of 3321 current and ex-smokers in COPDGene study. Low volumetric bone mineral density as a surrogate for osteoporosis was calculated from young adult normal values. Methods: Characteristics of participants with low volumetric bone mineral density were identified and associated to COPD and other risk factors. We tested associations of gender and COPD to both volumetric bone mineral density and fractures adjusting for age, race, BMI, smoking and glucocorticoid use. Main Results: Male smokers had a small but significantly greater risk of low volumetric bone mineral density (- 2.5 SD below young adult mean by calibrated quantitative CT) and more fractures than female smokers. Low volumetric bone mineral density was present in 58% of all subjects, was more frequent with worse COPD and rose to 84% of very severe COPD subjects. Vertebral fractures were present in 37% of all subjects and were associated with lower volumetric bone mineral density at each GOLD stage. Vertebral fractures were most common in the mid-thoracic region. COPD and specifically emphysema were associated with both low volumetric bone mineral density and vertebral fractures after adjustment for steroid use, age, pack years, current smoking and exacerbations. Airway disease was associated with higher bone density after adjustment for other variables. Calibrated quantitative CT identified more abnormal subjects than the standard DXA in a subset of subjects and correlated well with prevalent fractures. Conclusion: Male smokers with and without COPD, have a significant risk of low bone mineral density and vertebral fractures. COPD was associated with low volumetric bone mineral density after adjusting for race, gender, BMI, smoking, steroid use, exacerbations and increasing age. Screening for low bone mineral density in men and women smokers using quantitative CT scanning will increase opportunities to identify and treat osteoporosis in this at-risk population.
    02/2015; 12(5). DOI:10.1513/AnnalsATS.201412-591OC
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    ABSTRACT: We aimed to estimate the prevalence of combined pulmonary fibrosis and emphysema (CPFE) and describe the follow-up CT results of CPFE in asymptomatic smokers. This study was retrospective, and approved by an institutional review board. CT images of 2,016 current or previous male smokers who underwent low-dose chest CT at our healthcare centre were reviewed. Quantitative CT analysis was used to assess the extent of emphysema, and two radiologists visually analyzed the extent of fibrosis. Changes in fibrosis (no change, improvement, or progression) were evaluated on follow-up CT imaging (n = 42). Kaplan-Meier survival analysis, multivariate logistic regression and its ROC curve were used for survival and progression analysis. The prevalence of CPFE among asymptomatic male smokers was 3.1 % (63/2,016). The median follow-up period was 50.4 months, and 72.7 % (16/22) of continued smoker had progressing fibrosis on follow-up CT. CPFE progressed more rapidly in continuous smokers than in former smokers (p = 0.002). The 3.5-year follow-up period after initial CPFE diagnosis maximized the sum of sensitivity and specificity of CPFE progression prediction in continuous smokers. The prevalence of CPFE turned out not to be inconsiderable in asymptomatic male smokers, but serial CT follow-up would be helpful in recognizing disease progression. • The prevalence of CPFE in asymptomatic smokers is 3.1 % (63/2,016). • Progression of CPFE is associated with smoking status. • 3.5 years of follow-up period would be needed to identify CPFE progression.
    European Radiology 02/2015; 25(8). DOI:10.1007/s00330-015-3617-3 · 4.01 Impact Factor
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    ABSTRACT: To evaluate the relationships between DLCO, and Quantitative CT (QCT) measurements and visual assessment of pulmonary emphysema and to test the relative roles of visual and quantitative assessment of emphysema. The subjects included 199 current and former cigarette smokers from the COPDGene cohort who underwent inspiratory and expiratory CT and also had diffusing capacity for carbon monoxide corrected for alveolar volume (DLCO/VA). Quantitative CT measurements included % low attenuation areas (%LAA-950ins=voxels ≤-950Hounsfield unit (HU), % LAA-910ins, and % LAA-856ins), mean CT attenuation and 15th percentile HU value on inspiratory CT, and %LAA-856exp (voxels ≤-856HU on expiratory CT). The extent of emphysema was visually assessed using a 5-point grading system. Univariate and multiple variable linear regression analyses were employed to evaluate the correlations between DLCO/VA and QCT parameters and visual extent of emphysema. The DLCO/VA correlated most strongly with 15th percentile HU (R(2)=0.440, p<0.001) closely followed by % LAA-950ins (R(2)=0.417, p<0.001) and visual extent of emphysema (R(2)=0.411, p<0.001). Multiple variable analysis showed that visual extent of emphysema and 15th percentile HU were independent significant predictors of DLCO/VA at an R(2) of 0.599. 15th percentile HU seems the best parameter to represent the respiratory condition of COPD. Visual and Quantitative CT assessment of emphysema provide complementary information to QCT analysis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    European Journal of Radiology 01/2015; 84(5). DOI:10.1016/j.ejrad.2015.01.010 · 2.37 Impact Factor
  • Christian W Cox · David A Lynch
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    ABSTRACT: The purpose of this review is to provide an up-to-date summary of developments in medical imaging in the diagnosis, surveillance, treatment, and screening of occupational and environmental lung diseases, focusing on articles published within the past 2 years. Many new exposures resulting in lung disease have been described worldwide; medical imaging, particularly computed tomography (CT), is often pivotal in recognition and characterization of these new patterns of lung injury. Chest radiography remains important to surveillance studies tracking the long-term evolution of disease and effectiveness of air quality regulation. Finally, studies are proving the utility of screening with low-dose CT, and technical advances offer the prospect of further CT dose reduction with ultra-low-dose CT. In understanding the best practices and new developments in medical imaging, the occupational and environmental medicine clinician can optimize diagnosis and management of related lung diseases.
    Current opinion in pulmonary medicine 01/2015; 21(2). DOI:10.1097/MCP.0000000000000139 · 2.76 Impact Factor

Publication Stats

8k Citations
1,213.35 Total Impact Points


  • 2009–2015
    • National Jewish Health
      • Division of Radiology
      Denver, Colorado, United States
  • 2007–2015
    • Kingsbrook Jewish Medical Center
      Brooklyn, New York, United States
  • 2007–2014
    • National Research Center (CO, USA)
      Boulder, Colorado, United States
  • 2001–2014
    • University of Colorado
      • • Division of Pulmonary Sciences and Critical Care Medicine
      • • Department of Radiology
      Denver, Colorado, United States
    • University of Alabama at Birmingham
      • Department of Medicine
      Birmingham, Alabama, United States
  • 2011–2012
    • University of Iowa
      • Department of Radiology
      Iowa City, Iowa, United States
  • 2004
    • Yamaguchi University
      • Division of Radiology
      Yamaguti, Yamaguchi, Japan