Emphysema

Emphysema Challenges

Complex Disease Process – Emphysema affects 14 million people in the US alone. The disease is typically caused by cigarette smoking, environmental factors, coal mining, or genetics (alpha-1). The disease begins with damage in the small distal airways and alveoli. Bronchioles collapse, leading to gas trapping, followed by an erosion in the alveolar septa (source). As more personalized therapies are developed, biopharma and device innovators are challenged to deeply understand their subjects’ emphysema characteristics (cause, form, stage).

Weak Conventional Endpoints – Traditional trial endpoints like pulmonary function tests, the 6-minute walk test, and exacerbations are all useful; however, they are often lagging indicators with limited precision when compared to quantitative imaging measures of lung anatomy and function.

Challenging Imaging Operations – Quantitative imaging provides exceptional value in emphysema trials; however, precision imaging can be especially challenging for trial sites. Strict adherence to CT protocols, staff training, scanner calibration, data management and other complexities can result in unsuccessful sites or poor/inconsistent data quality. Long onboarding times or dropout sites can add significant cost to emphysema trials.

“The interventional pulmonology field is advancing with the emergence of both novel therapies for patients with emphysema, and the essential analytics to accurately match the patient to the therapy for greater response.”

Felix Herth, MD, PhD, DSC, FCCP, FERP

Chief, Head, Associate Director, Professor
Thoraxklinik, University of Heidelberg, Germany

VIDA Lung Intelligence for Emphysema Clinical Trials

In “The Modern Art of Reading Computed Tomography Images of the Lungs” by Prof. Herth and colleagues, 25 specific QCT biomarkers are identified for emphysema, all of which (and more) are provided by VIDA from a single study. In the time since this paper was published, several novel biomarkers for emphysema, such as total airway count (TAC) and mucus scoring have gained support. Together with collaboration partners, VIDA is proud to lead the way in development and validation of new imaging biomarkers. For more information on these biomarkers, please complete this brief form 👇.

VIDA Intelligence Portal is a respiratory trial imaging orchestration platform designed to ease the imaging operations of a lung trial. Portal applies AI-powered intelligence to automate tasks that are mundane and/or prone to human error. The portal also provides eLearning, quality control, data security, drag and drop data exchange, team communications and much more. The result is clinical trial sites capable of acquiring high quality clinical trial imaging data with ease.

Intelligence services leverage imaging and operational data gold mines to maximize their value for trial sponsors. For example, retrospective data analysis services examine existing datasets to surface valuable new insights. Site performance monitoring gives sponsors dynamic operational dashboards to proactively view the health of trial sites, the data they are submitting, and more. Subject screening services assist sponsors in filtering out candidates who meet exclusion criteria.

Emphysema Biomarkers

Please complete the form below for more information on quantitative imaging biomarkers for emphysema clinical trials.

VIDA is proud to be the lead QCT imaging provider for SPIROMICS, a large multi-site COPD study for the purpose of identifying subpopulations and intermediate outcome measures.

Emphysema Studies Utilizing VIDA’s Precision Imaging

Woodruff, P. G. et al. Clinical Significance of Symptoms in Smokers with Preserved Pulmonary Function. New England Journal of Medicine 374, 1811–1821 (2016).

Smith, B. M. et al. Comparison of Spatially Matched Airways Reveals Thinner Airway Walls in COPD. The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study and the Subpopulations and Intermediate Outcomes in COPD Study (SPIROMICS). Thorax 69, 987–996 (2014).

Kirby, M. et al. A Novel Method of Estimating Small Airway Disease Using Inspiratory-to-Expiratory Computed Tomography. Respiration 94, 336–345 (2017).

Virdee, S. et al. Spatial Dependence of CT Emphysema in Chronic Obstructive Pulmonary Disease Quantified by Using Join-Count Statistics. Radiology 301, 702–709 (2021).

Armstrong, H. F. et al. Lung function, percent emphysema, and QT duration: The Multi-Ethnic Study of Atherosclerosis (MESA) lung study. Respir Med 123, 1–7 (2017).

Beiko, T. et al. Serum Proteins Associated with Emphysema Progression in Severe Alpha-1 Antitrypsin Deficiency. Chronic Obstr Pulm Dis 4, 204–216 (2017).

Choi, S. et al. Differentiation of quantitative CT imaging phenotypes in asthma versus COPD. BMJ Open Respiratory Research 4, e000252 (2017).

Herth, F. J. F. et al. The Modern Art of Reading Computed Tomography Images of the Lungs: Quantitative CT. Respiration 95, 8–17 (2018).

Smith, B. M. et al. Human airway branch variation and chronic obstructive pulmonary disease. Proceedings of the National Academy of Sciences 115, E974–E981 (2018).

Washko, G. R., Coxson, H. O., O'Donnell, D. E. & Aaron, S. D. CT imaging of chronic obstructive pulmonary disease: insights, disappointments, and promise. The Lancet Respiratory Medicine 5, 903–908 (2017).

Belchi, F. et al. Lung Topology Characteristics in patients with Chronic Obstructive Pulmonary Disease. Sci Rep 8, 5341 (2018).

Bhatt, S. P. et al. Comparison of spirometric thresholds in diagnosing smoking-related airflow obstruction: authors' response. Thorax 69, 1147–1148 (2014).

Gietema, H. A. et al. Quantifying the Extent of Emphysema:: Factors Associated with Radiologists' Estimations and Quantitative Indices of Emphysema Severity Using the ECLIPSE Cohort. Academic Radiology 18, 661–671 (2011).

Ostridge, K. et al. Using Novel Computed Tomography Analysis to Describe the Contribution and Distribution of Emphysema and Small Airways Disease in Chronic Obstructive Pulmonary Disease. Annals ATS 16, 990–997 (2019).

Valipour, A. et al. Endobronchial Valve Therapy in Patients with Homogeneous Emphysema. Results from the IMPACT Study. Am J Respir Crit Care Med 194, 1073–1082 (2016).

Gompelmann, D. et al. The minimal important difference for target lobe volume reduction after endoscopic valve therapy. Int J Chron Obstruct Pulmon Dis 13, 465–472 (2018).

Khauli, S., Bolukbas, S., Reed, R. M. & Eberlein, M. Interlobar collateral ventilation in severe emphysema. Thorax 71, 1168–1169 (2016).

Yablonskiy, D. A. Air Trapping - Insights from CT and In Vivo Lung Morphometry with Hyperpolarized 3He MRI. American Thoracic Society International Conference Meetings Abstracts American Thoracic Society International Conference Meetings Abstracts.

Valipour, A. et al. Expert Statement: Pneumothorax Associated with Endoscopic Valve Therapy for Emphysema - Potential Mechanisms, Treatment Algorithm, and Case Examples. Respiration 87, 513–521 (2014).

Schuhmann, M. et al. Computed Tomography Predictors of Response to Endobronchial Valve Lung Reduction Treatment. Comparison with Chartis. Am J Respir Crit Care Med 191, 767–774 (2015).

Valipour, A. et al. Patterns of Emphysema Heterogeneity. Respiration 90, 402–411 (2015).

de Oliveira, H. G. et al. Combined Bone Marrow‐Derived Mesenchymal Stromal Cell Therapy and One‐Way Endobronchial Valve Placement in Patients with Pulmonary Emphysema: A Phase I Clinical Trial. Stem Cells Transl Med 6, 962–969 (2017).

de Oliveira, H. G., de Oliveira, S. M., Rambo, R. R. & de Macedo Neto, A. V. Fissure Integrity and Volume Reduction in Emphysema: A Retrospective Study. Respiration 91, 471–479 (2016).

Lo Cascio, C. M. et al. Percent Emphysema and Daily Motor Activity Levels in the General Population. Chest 151, 1039–1050 (2017).

Oelsner, E. C. et al. Per cent emphysema is associated with respiratory and lung cancer mortality in the general population: a cohort study. Thorax 71, 624–632 (2016).

Adar, S. D. et al. Air Pollution and Percent Emphysema Identified by Computed Tomography in the Multi-Ethnic Study of Atherosclerosis. Environ Health Perspect 123, 144–151 (2015).

Oelsner, E. C. et al. Association between emphysema-like lung on cardiac computed tomography and mortality in persons without airflow obstruction: a cohort study. Ann Intern Med 161, 863–873 (2014).

Smith, B. M. et al. Not all measures of hyperinflation are created equal: lung structure and clinical correlates of gas trapping and hyperexpansion in COPD: the Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study. Chest 145, 1305–1315 (2014).

Gompelmann, D. et al. Lung Volume Reduction with Vapor Ablation in the Presence of Incomplete Fissures: 12-Month Results from the STEP-UP Randomized Controlled Study. Respiration 92, 397–403 (2016).

Martinez, C. H. et al. Age and Small Airway Imaging Abnormalities in Subjects with and without Airflow Obstruction in SPIROMICS. Am J Respir Crit Care Med 195, 464–472 (2017).

Hoffman, E. A. et al. Variation in the Percent of Emphysema-like Lung in a Healthy, Nonsmoking Multiethnic Sample. The MESA Lung Study. Ann Am Thorac Soc 11, 898–907 (2014).

Newell, J. D., Sieren, J. & Hoffman, E. A. Development of quantitative computed tomography lung protocols. J Thorac Imaging 28, 266–271 (2013).

McAllister, D. et al. Pulmonary Function is Associated with Distal Aortic Calcium, not Proximal Aortic Distensibility. MESA Lung Study. COPD 8, 71–78 (2011).

Han, M. K. et al. Prevalence and clinical correlates of bronchoreversibility in severe emphysema. Eur Respir J 35, 1048–1056 (2010).

Hoffman, E. A. et al. Reproducibility and validity of lung density measures from cardiac CT scans – the Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study. Acad Radiol 16, 689–699 (2009).

Genetic determinants of emphysema distribution in the national emphysema treatment trial | Cochrane Library.

Martinez, F. J. et al. Sex differences in severe pulmonary emphysema. AM.REV.RESPIR.DIS. 176, 243–252 (2007).

Burkart, K. M. et al. APOM and High-Density Lipoprotein are associated with Lung Function and Percent Emphysema. Eur Respir J 43, 1003–1017 (2014).

Powell, R. et al. Genetic ancestry and the relationship of cigarette smoking to lung function and per cent emphysema in four race/ethnic groups: a cross-sectional study. Thorax 68, 634–642 (2013).

Lovasi, G. S. et al. Socioeconomic status is positively associated with percent emphysema on CT scan: The MESA lung study. Acad Radiol 18, 199–204 (2011).

Barr, R. G. et al. Percent Emphysema, Airflow Obstruction, and Impaired Left Ventricular Filling. N Engl J Med 362, 217–227 (2010).

Martinez, F. J. et al. Predictors of Mortality in Patients with Emphysema and Severe Airflow Obstruction. Am J Respir Crit Care Med 173, 1326–1334 (2006).

Krachman, S. L. et al. Effect of Emphysema Severity on the Apnea-Hypopnea Index in Smokers with Obstructive Sleep Apnea. Ann Am Thorac Soc 13, 1129–1135 (2016).

Parikh, M. A. et al. Angiotensin-Converting Inhibitors and Angiotensin II Receptor Blockers and Longitudinal Change in Percent Emphysema on Computed Tomography. The Multi-Ethnic Study of Atherosclerosis Lung Study. Ann Am Thorac Soc 14, 649–658 (2017).

Uppaluri, R., Mitsa, T., Hoffman, E. A., McLennan, G. & Sonka, M. Texture analysis of pulmonary parenchyma in normal and emphysematous lung. 2709, 456–467 (1996).

Uppaluri, R. et al. Computer recognition of regional lung disease patterns. Am J Respir Crit Care Med 160, 648–654 (1999).

Xu, Y., Sonka, M., McLennan, G., Guo, J. & Hoffman, E. A. MDCT-based 3-D texture classification of emphysema and early smoking related lung pathologies. IEEE Trans Med Imaging 25, 464–475 (2006).

Uppaluri, R., Mitsa, T., Sonka, M., Hoffman, E. A. & McLennan, G. Quantification of pulmonary emphysema from lung computed tomography images. Am J Respir Crit Care Med 156, 248–254 (1997).

Elbehairy, A. F. et al. Pulmonary Vascular Volume by Quantitative CT in Dyspneic Smokers with Minor Emphysema. COPD: Journal of Chronic Obstructive Pulmonary Disease 20, 135–143 (2023).

Kirby, M. et al. Total Airway Count on Computed Tomography and the Risk of Chronic Obstructive Pulmonary Disease Progression. Findings from a Population-based Study. Am J Respir Crit Care Med 197, 56–65 (2018).