CT densitometry in emphysema: a systematic review of its clinical utility

Background The aim of the study was to assess the relationship between computed tomography (CT) densitometry and routine clinical markers in patients with chronic obstructive pulmonary disease (COPD) and alpha-1 anti-trypsin deficiency (AATD). Methods Multiple databases were searched using a combination of pertinent terms and those articles relating quantitatively measured CT densitometry to clinical outcomes. Studies that used visual scoring only were excluded, as were those measured in expiration only. A thorough review of abstracts and full manuscripts was conducted by 2 reviewers; data extraction and assessment of bias was conducted by 1 reviewer and the 4 reviewers independently assessed for quality. Pooled correlation coefficients were calculated, and heterogeneity was explored. Results A total of 112 studies were identified, 82 being suitable for meta-analysis. The most commonly used density threshold was −950 HU, and a significant association between CT density and all included clinical parameters was demonstrated. There was marked heterogeneity between studies secondary to large variety of disease severity within commonly included cohorts and differences in CT acquisition parameters. Conclusion CT density shows a good relationship to clinically relevant parameters; however, study heterogeneity and lack of longitudinal data mean that it is difficult to compare studies or derive a minimal clinically important difference. We recommend that international consensus is reached to standardize CT conduct and analysis in future COPD and AATD studies.

[1]  R H Hruban,et al.  High resolution computed tomography of inflation-fixed lungs. Pathologic-radiologic correlation of centrilobular emphysema. , 1987, The American review of respiratory disease.

[2]  N. Müller,et al.  "Density mask". An objective method to quantitate emphysema using computed tomography. , 1988, Chest.

[3]  G J Kemerink,et al.  Density resolution in quantitative computed tomography of foam and lung. , 1996, Medical physics.

[4]  P De Vuyst,et al.  Pulmonary emphysema: quantitative CT during expiration. , 1996, Radiology.

[5]  E. Hoffman,et al.  Quantification of pulmonary emphysema from lung computed tomography images. , 1997, American journal of respiratory and critical care medicine.

[6]  H A Vrooman,et al.  A randomized clinical trial of alpha(1)-antitrypsin augmentation therapy. , 1999, American journal of respiratory and critical care medicine.

[7]  H. Tanaka,et al.  Lobar distribution of emphysema in computed tomographic densitometric analysis. , 2000, Investigative radiology.

[8]  R. Stockley,et al.  High-resolution computed tomography scanning in alpha1-antitrypsin deficiency: relationship to lung function and health status. , 2001, The European respiratory journal.

[9]  L Battolla,et al.  Relationship between extent of pulmonary emphysema by high-resolution computed tomography and lung elastic recoil in patients with chronic obstructive pulmonary disease. , 2001, American journal of respiratory and critical care medicine.

[10]  H Putter,et al.  Correlation between annual change in health status and computer tomography derived lung density in subjects with α1-antitrypsin deficiency , 2003, Thorax.

[11]  Jan Stolk,et al.  Pattern of emphysema distribution in alpha1-antitrypsin deficiency influences lung function impairment. , 2004, American journal of respiratory and critical care medicine.

[12]  R. Djukanović,et al.  Relationship between peripheral airway dysfunction, airway obstruction, and neutrophilic inflammation in COPD , 2004, Thorax.

[13]  A. Field Is the meta-analysis of correlation coefficients accurate when population correlations vary? , 2005, Psychological methods.

[14]  A. Dirksen,et al.  Quantitative computed tomography and aerosol morphometry in COPD and alpha1-antitrypsin deficiency. , 2005, The European respiratory journal.

[15]  A. Dirksen,et al.  Quantitative computed tomography and aerosol morphometry in COPD and α1-antitrypsin deficiency , 2005, European Respiratory Journal.

[16]  Gianna Camiciottoli,et al.  Chronic obstructive pulmonary disease: thin-section CT measurement of airway wall thickness and lung attenuation. , 2005, Radiology.

[17]  Sharyn MacDonald,et al.  Functional impairment in emphysema: contribution of airway abnormalities and distribution of parenchymal disease. , 2005, AJR. American journal of roentgenology.

[18]  M. Mascalchi,et al.  Spirometrically gated high-resolution CT findings in COPD: lung attenuation vs lung function and dyspnea severity. , 2006, Chest.

[19]  Robert Wise,et al.  Predictors of mortality in patients with emphysema and severe airflow obstruction. , 2006, American journal of respiratory and critical care medicine.

[20]  T. Louis,et al.  Feasibility of retinoids for the treatment of emphysema study. , 2006, Chest.

[21]  Susan Murray,et al.  Sex differences in severe pulmonary emphysema. , 2007, American journal of respiratory and critical care medicine.

[22]  R. Wise,et al.  The role of NETT in emphysema research. , 2008, Proceedings of the American Thoracic Society.

[23]  Eric A. Hoffman,et al.  Computed Tomographic-Based Quantification of Emphysema and Correlation to Pulmonary Function and Mechanics , 2008, COPD.

[24]  G. Bastarrika,et al.  Low-dose Volumetric Computed Tomography for Quantification of Emphysema in Asymptomatic Smokers Participating in an Early Lung Cancer Detection Trial , 2009, Journal of thoracic imaging.

[25]  A. Dirksen,et al.  Exploring the optimum approach to the use of CT densitometry in a randomised placebo-controlled study of augmentation therapy in alpha 1-antitrypsin deficiency , 2009, Respiratory research.

[26]  Yoshikazu Inoue,et al.  Quantitative CT in chronic obstructive pulmonary disease: inspiratory and expiratory assessment. , 2009, AJR. American journal of roentgenology.

[27]  P. Leander,et al.  Validity of apparent diffusion coefficient hyperpolarized 3He-MRI using MSCT and pulmonary function tests as references. , 2009, European journal of radiology.

[28]  R. Stockley,et al.  Mortality in alpha-1-antitrypsin deficiency in the United Kingdom. , 2009, Respiratory medicine.

[29]  本橋 典久 Emphysema on imaging is associated with quality of life in elderly patients with chronic obstructive pulmonary disease , 2009 .

[30]  A. Dirksen,et al.  Exploring the role of CT densitometry: a randomised study of augmentation therapy in α1-antitrypsin deficiency , 2009, European Respiratory Journal.

[31]  B. Stoel,et al.  The Effect of Inhaled Corticosteroids on the Development of Emphysema in Smokers Assessed by Annual Computed Tomography , 2009, COPD.

[32]  S. Muro,et al.  Relationship between peripheral airway function and patient-reported outcomes in COPD: a cross-sectional study , 2010, BMC pulmonary medicine.

[33]  B. Stoel,et al.  Retinoid treatment of Emphysema in Patients on the Alpha-1 International Registry. The REPAIR study: study design, methodology and quality control of study assessments , 2010, Therapeutic advances in respiratory disease.

[34]  J. Seo,et al.  Slope of emphysema index: an objective descriptor of regional heterogeneity of emphysema and an independent determinant of pulmonary function. , 2010, AJR. American journal of roentgenology.

[35]  E. Regan,et al.  Genetic Epidemiology of COPD (COPDGene) Study Design , 2011, COPD.

[36]  Yasutaka Nakano,et al.  CT scan findings of emphysema predict mortality in COPD. , 2010, Chest.

[37]  J. Seo,et al.  Responses to inhaled long-acting beta-agonist and corticosteroid according to COPD subtype. , 2010, Respiratory medicine.

[38]  Raúl San José Estépar,et al.  Airway count and emphysema assessed by chest CT imaging predicts clinical outcome in smokers. , 2010, Chest.

[39]  Jason C Woods,et al.  Effects of CT section thickness and reconstruction kernel on emphysema quantification relationship to the magnitude of the CT emphysema index. , 2010, Academic radiology.

[40]  Bram van Ginneken,et al.  CT-quantified emphysema in male heavy smokers: association with lung function decline , 2011, Thorax.

[41]  Jae Seung Lee,et al.  Predictors of Pulmonary Function Response to Treatment with Salmeterol/fluticasone in Patients with Chronic Obstructive Pulmonary Disease , 2011, Journal of Korean medical science.

[42]  Jae Seung Lee,et al.  Comparison of Clinico-Physiologic and CT Imaging Risk Factors for COPD Exacerbation , 2011, Journal of Korean medical science.

[43]  H. D. de Koning,et al.  NELSON lung cancer screening study , 2011, Cancer imaging : the official publication of the International Cancer Imaging Society.

[44]  Gorka Bastarrika,et al.  Emphysema presence, severity, and distribution has little impact on the clinical presentation of a cohort of patients with mild to moderate COPD. , 2011, Chest.

[45]  Susan Mallett,et al.  QUADAS-2: A Revised Tool for the Quality Assessment of Diagnostic Accuracy Studies , 2011, Annals of Internal Medicine.

[46]  B. Stoel,et al.  CT lung densitometry in young adults with alpha-1-antitrypsin deficiency. , 2011, Respiratory Medicine.

[47]  Nicola A Hanania,et al.  Chronic obstructive pulmonary disease exacerbations in the COPDGene study: associated radiologic phenotypes. , 2011, Radiology.

[48]  Susan Murray,et al.  Relationship between quantitative CT metrics and health status and BODE in chronic obstructive pulmonary disease , 2012, Thorax.

[49]  M. Mascalchi,et al.  BODE-index, modified BODE-index and ADO-score in Chronic Obstructive Pulmonary Disease: Relationship with COPD phenotypes and CT lung density changes , 2012, COPD.

[50]  Jae Seung Lee,et al.  Contributors of the Severity of Airflow Limitation in COPD Patients , 2012 .

[51]  R. Stockley,et al.  Relationship between frequency, length, and treatment outcome of exacerbations to baseline lung function and lung density in alpha-1 antitrypsin-deficient COPD , 2012, International journal of chronic obstructive pulmonary disease.

[52]  B. van Ginneken,et al.  Computed tomography-quantified emphysema distribution is associated with lung function decline , 2012, European Respiratory Journal.

[53]  J. Higgins,et al.  Cochrane Handbook for Systematic Reviews of Interventions, Version 5.1.0. The Cochrane Collaboration , 2013 .

[54]  Joyce D. Schroeder,et al.  Chronic obstructive pulmonary disease: lobe-based visual assessment of volumetric CT by Using standard images--comparison with quantitative CT and pulmonary function test in the COPDGene study. , 2013, Radiology.

[55]  Carla G. Wilson,et al.  Relationships between airflow obstruction and quantitative CT measurements of emphysema, air trapping, and airways in subjects with and without chronic obstructive pulmonary disease. , 2013, AJR. American journal of roentgenology.

[56]  L. Edwards,et al.  Impact of emphysema and airway wall thickness on quality of life in smoking-related COPD. , 2013, Respiratory medicine.

[57]  Sang Min Lee,et al.  Detailed analysis of the density change on chest CT of COPD using non-rigid registration of inspiration/expiration CT scans , 2015, European Radiology.

[58]  B. Ginneken,et al.  Contribution of CT Quantified Emphysema, Air Trapping and Airway Wall Thickness on Pulmonary Function in Male Smokers With and Without COPD , 2014, COPD.

[59]  Hans-Ulrich Kauczor,et al.  Variation of Densitometry on Computed Tomography in COPD – Influence of Different Software Tools , 2014, PloS one.

[60]  J. Austin,et al.  Emphysema Predicts Hospitalisation and Incident Airflow Obstruction among Older Smokers: A Prospective Cohort Study , 2014, PloS one.

[61]  S. Matsumoto,et al.  Airflow limitation in chronic obstructive pulmonary disease: ratio and difference of percentage of low-attenuation lung regions in paired inspiratory/expiratory computed tomography. , 2014, Academic radiology.

[62]  Jae Seung Lee,et al.  Study Design and Outcomes of Korean Obstructive Lung Disease (KOLD) Cohort Study , 2014, Tuberculosis and respiratory diseases.

[63]  B. van Ginneken,et al.  Airway wall thickness associated with forced expiratory volume in 1 second decline and development of airflow limitation , 2015, European Respiratory Journal.

[64]  I. Horváth,et al.  Clinically relevant subgroups in COPD and asthma , 2015, European Respiratory Review.

[65]  Berend C Stoel,et al.  Intravenous augmentation treatment and lung density in severe α1 antitrypsin deficiency (RAPID): a randomised, double-blind, placebo-controlled trial , 2015, The Lancet.

[66]  H. Wan,et al.  Obvious emphysema on computed tomography during an acute exacerbation of chronic obstructive pulmonary disease predicts a poor prognosis , 2015, Internal medicine journal.

[67]  M. Pistolesi,et al.  Chronic Obstructive Pulmonary Disease: Pulmonary Function and CT Lung Attenuation Do Not Show Linear Correlation. , 2015, Radiology.

[68]  Xian-tao Zeng,et al.  The methodological quality assessment tools for preclinical and clinical studies, systematic review and meta‐analysis, and clinical practice guideline: a systematic review , 2015, Journal of evidence-based medicine.

[69]  Joyce D. Schroeder,et al.  Relationships between diffusing capacity for carbon monoxide (DLCO), and quantitative computed tomography measurements and visual assessment for chronic obstructive pulmonary disease. , 2015, European journal of radiology.

[70]  H. Coxson,et al.  Diffusing capacity for carbon monoxide correlates best with tissue volume from quantitative CT scanning analysis. , 2015, Chest.

[71]  P. Gøtzsche,et al.  Intravenous alpha-1 antitrypsin augmentation therapy for treating patients with alpha-1 antitrypsin deficiency and lung disease. , 2016, The Cochrane database of systematic reviews.

[72]  E. Sapey,et al.  Treatment of lung disease in alpha-1 antitrypsin deficiency: a systematic review , 2017, International journal of chronic obstructive pulmonary disease.