Early imaging biomarkers of lung cancer, COPD and coronary artery disease in the general population: rationale and design of the ImaLife (Imaging in Lifelines) Study

Congying Xia, Mieneke Rook, Gert Jan Pelgrim, Grigory Sidorenkov, Hendrik J Wisselink, Jurjen N van Bolhuis, Peter M A van Ooijen, Jiapan Guo, Matthijs Oudkerk, Harry Groen, Maarten van den Berge, Pim van der Harst, Hildebrand Dijkstra, Marleen Vonder, Marjolein A Heuvelmans, Monique D Dorrius, Peter Paul De Deyn, Geertruida H de Bock, Aafje Dotinga, Rozemarijn Vliegenthart, Congying Xia, Mieneke Rook, Gert Jan Pelgrim, Grigory Sidorenkov, Hendrik J Wisselink, Jurjen N van Bolhuis, Peter M A van Ooijen, Jiapan Guo, Matthijs Oudkerk, Harry Groen, Maarten van den Berge, Pim van der Harst, Hildebrand Dijkstra, Marleen Vonder, Marjolein A Heuvelmans, Monique D Dorrius, Peter Paul De Deyn, Geertruida H de Bock, Aafje Dotinga, Rozemarijn Vliegenthart

Abstract

Lung cancer, chronic obstructive pulmonary disease (COPD), and coronary artery disease (CAD) are expected to cause most deaths by 2050. State-of-the-art computed tomography (CT) allows early detection of lung cancer and simultaneous evaluation of imaging biomarkers for the early stages of COPD, based on pulmonary density and bronchial wall thickness, and of CAD, based on the coronary artery calcium score (CACS), at low radiation dose. To determine cut-off values for positive tests for elevated risk and presence of disease is one of the major tasks before considering implementation of CT screening in a general population. The ImaLife (Imaging in Lifelines) study, embedded in the Lifelines study, is designed to establish the reference values of the imaging biomarkers for the big three diseases in a well-defined general population aged 45 years and older. In total, 12,000 participants will undergo CACS and chest acquisitions with latest CT technology. The estimated percentage of individuals with lung nodules needing further workup is around 1-2%. Given the around 10% prevalence of COPD and CAD in the general population, the expected number of COPD and CAD is around 1000 each. So far, nearly 4000 participants have been included. The ImaLife study will allow differentiation between normal aging of the pulmonary and cardiovascular system and early stages of the big three diseases based on low-dose CT imaging. This information can be finally integrated into personalized precision health strategies in the general population.

Keywords: Cardiovascular disease; Chronic obstructive pulmonary disease; General population; Imaging biomarkers; Low-dose computed tomography; Lung cancer.

Conflict of interest statement

Rozemarijn Vliegenthart has received an institutional research grant from Siemens Healthineers. Matthijs Oudkerk is employed by iDNA B. V. Harry J. M. Groen is a board member of the NELSON screening trial and provides consultancy for BMS MERCK, PFIZER, TAKEDA, NOVARTIS. Other authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Overview of the ImaLife study. CT computed tomography, COPD chronic obstructive pulmonary disease, CAD coronary artery disease, GPs general practitioners, ID identification number

References

    1. The top 10 causes of death. WHO. 2018. . Accessed 4 July 2018.
    1. Oudkerk M, Devaraj A, Vliegenthart R, Henzler T, Prosch H, Heussel CP, et al. European position statement on lung cancer screening. Lancet Oncol. 2017;18:e754–e766. doi: 10.1016/S1470-2045(17)30861-6.
    1. Dijkstra AE, Postma DS, van Ginneken B, Wielputz MO, Schmidt M, Becker N, et al. Novel genes for airway wall thickness identified with combined genome-wide association and expression analyses. Am J Respir Crit Care Med. 2015;191(5):547–556. doi: 10.1164/rccm.201405-0840OC.
    1. Mets OM, Schmidt M, Buckens CF, Gondrie MJ, Isgum I, Oudkerk M, et al. Diagnosis of chronic obstructive pulmonary disease in lung cancer screening computed tomography scans: independent contribution of emphysema, air trapping and bronchial wall thickening. Respir Res. 2013;14:59. doi: 10.1186/1465-9921-14-59.
    1. Heuvelmans MA, Vonder M, Rook M, Groen HJM, De Bock GH, Xie X, et al. Screening for early lung cancer, chronic obstructive pulmonary disease, and cardiovascular disease (the Big-3) using low-dose chest computed tomography: current evidence and technical considerations. J Thorac Imaging. 2018 doi: 10.1097/rti.0000000000000379.
    1. Gerhardsson de Verdier M. The big three concept: a way to tackle the health care crisis? Proc Am Thorac Soc. 2008;5(8):800–805. doi: 10.1513/pats.200806-058th.
    1. Scholtens S, Smidt N, Swertz MA, Bakker SJ, Dotinga A, Vonk JM, et al. Cohort profile: lifelines, a three-generation cohort study and biobank. Int J Epidemiol. 2015;44(4):1172–1180. doi: 10.1093/ije/dyu229.
    1. National Lung Screening Trial Research T. Aberle DR, Adams AM, Berg CD, Black WC, Clapp JD, et al. Reduced lung-cancer mortality with low-dose computed tomographic screening. New Engl J Med. 2011;365(5):395–409. doi: 10.1056/nejmoa1102873.
    1. Horeweg N, Scholten ET, de Jong PA, van der Aalst CM, Weenink C, Lammers JW, et al. Detection of lung cancer through low-dose CT screening (NELSON): a prespecified analysis of screening test performance and interval cancers. Lancet Oncol. 2014;15(12):1342–1350. doi: 10.1016/S1470-2045(14)70387-0.
    1. Horeweg N, van der Aalst CM, Thunnissen E, Nackaerts K, Weenink C, Groen HJ, et al. Characteristics of lung cancers detected by computer tomography screening in the randomized NELSON trial. Am J Respir Crit Care Med. 2013;187(8):848–854. doi: 10.1164/rccm.201209-1651OC.
    1. Kavousi M, Elias-Smale S, Rutten JH, Leening MJ, Vliegenthart R, Verwoert GC, et al. Evaluation of newer risk markers for coronary heart disease risk classification: a cohort study. Ann Intern Med. 2012;156(6):438–444. doi: 10.7326/0003-4819-156-6-201203200-00006.
    1. Oudkerk M, Stillman AE, Halliburton SS, Kalender WA, Mohlenkamp S, McCollough CH, et al. Coronary artery calcium screening: current status and recommendations from the European Society of Cardiac Radiology and North American Society for Cardiovascular Imaging. Eur Radiol. 2008;18(12):2785–2807. doi: 10.1007/s00330-008-1095-6.
    1. Elias-Smale SE, Proenca RV, Koller MT, Kavousi M, van Rooij FJ, Hunink MG, et al. Coronary calcium score improves classification of coronary heart disease risk in the elderly: the Rotterdam study. J Am Coll Cardiol. 2010;56(17):1407–1414. doi: 10.1016/j.jacc.2010.06.029.
    1. Vliegenthart R, Oudkerk M, Hofman A, Oei HH, van Dijck W, van Rooij FJ, et al. Coronary calcification improves cardiovascular risk prediction in the elderly. Circulation. 2005;112(4):572–577. doi: 10.1161/CIRCULATIONAHA.104.488916.
    1. Schmermund A, Mohlenkamp S, Berenbein S, Pump H, Moebus S, Roggenbuck U, et al. Population-based assessment of subclinical coronary atherosclerosis using electron-beam computed tomography. Atherosclerosis. 2006;185(1):177–182. doi: 10.1016/j.atherosclerosis.2005.06.003.
    1. McClelland RL, Chung H, Detrano R, Post W, Kronmal RA. Distribution of coronary artery calcium by race, gender, and age: results from the Multi-Ethnic Study of Atherosclerosis (MESA) Circulation. 2006;113(1):30–37. doi: 10.1161/CIRCULATIONAHA.105.580696.
    1. Vonder M, van der Aalst CM, Vliegenthart R, van Ooijen PMA, Kuijpers D, Gratama JW, et al. Coronary artery calcium imaging in the ROBINSCA trial: rationale, design, and technical background. Acad Radiol. 2018;25(1):118–128. doi: 10.1016/j.acra.2017.07.010.
    1. Oei HH, Vliegenthart R, Hofman A, Oudkerk M, Witteman JC. Risk factors for coronary calcification in older subjects: the Rotterdam coronary calcification study. Eur Heart J. 2004;25(1):48–55. doi: 10.1016/j.ehj.2003.10.008.
    1. Mets OM, Buckens CF, Zanen P, Isgum I, van Ginneken B, Prokop M, et al. Identification of chronic obstructive pulmonary disease in lung cancer screening computed tomographic scans. JAMA. 2011;306(16):1775–1781. doi: 10.1001/jama.2011.1531.
    1. Oelsner EC, Hoffman EA, Folsom AR, Carr JJ, Enright PL, Kawut SM, et al. Association between emphysema-like lung on cardiac computed tomography and mortality in persons without airflow obstruction: a cohort study. Ann Intern Med. 2014;161(12):863–873. doi: 10.7326/m13-2570.
    1. Sanchez-Salcedo P, Wilson DO, de-Torres JP, Weissfeld JL, Berto J, Campo A, et al. Improving selection criteria for lung cancer screening: the potential role of emphysema. Am J Respir Crit Care Med. 2015;191(8):924–931. doi: 10.1164/rccm.201410-1848oc.
    1. Lynch DA, Moore CM, Wilson C, Nevrekar D, Jennermann T, Humphries SM, et al. CT-based visual classification of emphysema: association with mortality in the COPD gene study. Radiology. 2018;288(3):859–866. doi: 10.1148/radiol.2018172294.
    1. Klijs B, Scholtens S, Mandemakers JJ, Snieder H, Stolk RP, Smidt N. Representativeness of the LifeLines Cohort Study. PLoS ONE. 2015;10(9):e0137203. doi: 10.1371/journal.pone.0137203.
    1. Boudewijn IM, Postma DS, Telenga ED, ten Hacken NHT, Timens W, Oudkerk M, et al. Effects of ageing and smoking on pulmonary computed tomography scans using parametric response mapping. Eur Respir J. 2015;46(4):1193–1196. doi: 10.1183/09031936.00009415.
    1. Hoff JA, Chomka EV, Krainik AJ, Daviglus M, Rich S, Kondos GT. Age and gender distributions of coronary artery calcium detected by electron beam tomography in 35,246 adults. Am J Cardiol. 2001;87(12):1335–1339. doi: 10.1016/S0002-9149(01)01548-X.
    1. Lung cancer figures and context| current situation public . . Accessed 4 July 2018.
    1. van Klaveren RJ, Oudkerk M, Prokop M, Scholten ET, Nackaerts K, Vernhout R, et al. Management of lung nodules detected by volume CT scanning. New Engl J Med. 2009;361(23):2221–2229. doi: 10.1056/NEJMoa0906085.
    1. Xu DM, Gietema H, de Koning H, Vernhout R, Nackaerts K, Prokop M, et al. Nodule management protocol of the NELSON randomised lung cancer screening trial. Lung Cancer. 2006;54(2):177–184. doi: 10.1016/j.lungcan.2006.08.006.
    1. Human exposure to ionising radiation for clinical and research purposes: radiation dose and risk estimates. Netherlands Commission on Radiation Dosimetry. 2016. 10.25030/ncs-026. Accessed 4 July 2018.
    1. Population Screening Act: calcium score and the risk of cardiovascular disease| Health Council of the Netherlands. 2018. . Accessed 4 July 2018.
    1. van der Ende MY, Hartman MH, Hagemeijer Y, Meems LM, de Vries HS, Stolk RP, et al. The LifeLines Cohort Study: prevalence and treatment of cardiovascular disease and risk factors. Int J Cardiol. 2017;228:495–500. doi: 10.1016/j.ijcard.2016.11.061.
    1. Coronaire hartziekten| Cijfers and Context| Huidige situatie| . 2018. . Accessed 4 July 2018.
    1. COPD| Cijfers and Context| Huidige situatie| . 2018. . Accessed 4 July 2018.
    1. International Early Lung Cancer Action Program I. Henschke CI, Yankelevitz DF, Libby DM, Pasmantier MW, Smith JP, et al. Survival of patients with stage I lung cancer detected on CT screening. New Engl J Med. 2006;355(17):1763–1771. doi: 10.1056/nejmoa060476.
    1. Pedersen JH, Ashraf H, Dirksen A, Bach K, Hansen H, Toennesen P, et al. The Danish randomized lung cancer CT screening trial–overall design and results of the prevalence round. J Thorac Oncol Off Publ Int Assoc Study Lung Cancer. 2009;4(5):608–614. doi: 10.1097/JTO.0b013e3181a0d98f.
    1. Pastorino U, Rossi M, Rosato V, Marchiano A, Sverzellati N, Morosi C, et al. Annual or biennial CT screening versus observation in heavy smokers: 5-year results of the MILD trial. Eur J Cancer Prev. 2012;21(3):308–315. doi: 10.1097/CEJ.0b013e328351e1b6.
    1. Takx RA, Isgum I, Willemink MJ, van der Graaf Y, de Koning HJ, Vliegenthart R, et al. Quantification of coronary artery calcium in nongated CT to predict cardiovascular events in male lung cancer screening participants: results of the NELSON study. J Cardiovasc Comput Tomogr. 2015;9(1):50–57. doi: 10.1016/j.jcct.2014.11.006.
    1. Chiles C, Duan F, Gladish GW, Ravenel JG, Baginski SG, Snyder BS, et al. Association of coronary artery calcification and mortality in the national lung screening trial: a comparison of three scoring methods. Radiology. 2015;276(1):82–90. doi: 10.1148/radiol.15142062.
    1. Sverzellati N, Cademartiri F, Bravi F, Martini C, Gira FA, Maffei E, et al. Relationship and prognostic value of modified coronary artery calcium score, FEV1, and emphysema in lung cancer screening population: the MILD trial. Radiology. 2012;262(2):460–467. doi: 10.1148/radiol.11110364.
    1. Shemesh J, Henschke CI, Shaham D, Yip R, Farooqi AO, Cham MD, et al. Ordinal scoring of coronary artery calcifications on low-dose CT scans of the chest is predictive of death from cardiovascular disease. Radiology. 2010;257(2):541–548. doi: 10.1148/radiol.10100383.
    1. Rasmussen T, Kober L, Abdulla J, Pedersen JH, Wille MM, Dirksen A, et al. Coronary artery calcification detected in lung cancer screening predicts cardiovascular death. Scand Cardiovasc J. 2015;49(3):159–167. doi: 10.3109/14017431.2015.1039572.
    1. Williams MC, Murchison JT, Edwards LD, Agusti A, Bakke P, Calverley PM, et al. Coronary artery calcification is increased in patients with COPD and associated with increased morbidity and mortality. Thorax. 2014;69(8):718–723. doi: 10.1136/thoraxjnl-2012-203151.
    1. Bhatt SP, Kazerooni EA, Newell JD, Jr, Hokanson JE, Budoff MJ, Dass CA, et al. Visual estimate of coronary artery calcium predicts cardiovascular disease in COPD. Chest. 2018 doi: 10.1016/j.chest.2018.05.037.
    1. Program in Epidemiology of Chronic Pulmonary Diseases. 2018. . Accessed 9 July 2018.
    1. Leng S, Hruska CB, McCollough CH. Use of ionizing radiation in screening examinations for coronary artery calcium and cancers of the lung, colon, and breast. Semin Roentgenol. 2015;50(2):148–160. doi: 10.1053/j.ro.2014.10.012.
    1. Bergstrom G, Berglund G, Blomberg A, Brandberg J, Engstrom G, Engvall J, et al. The Swedish cardiopulmonary bioimage study: objectives and design. J Intern Med. 2015;278(6):645–659. doi: 10.1111/joim.12384.
    1. Gierada DS, Guniganti P, Newman BJ, Dransfield MT, Kvale PA, Lynch DA, et al. Quantitative CT assessment of emphysema and airways in relation to lung cancer risk. Radiology. 2011;261(3):950–959. doi: 10.1148/radiol.11110542.
    1. Zulueta JJ, Wisnivesky JP, Henschke CI, Yip R, Farooqi AO, McCauley DI, et al. Emphysema scores predict death from COPD and lung cancer. Chest. 2012;141(5):1216–1223. doi: 10.1378/chest.11-0101.
    1. Lopes Pegna A, Picozzi G, Mascalchi M, Maria Carozzi F, Carrozzi L, Comin C, et al. Design, recruitment and baseline results of the ITALUNG trial for lung cancer screening with low-dose CT. Lung Cancer. 2009;64(1):34–40. doi: 10.1016/j.lungcan.2008.07.003.
    1. Camiciottoli G, Cavigli E, Grassi L, Diciotti S, Orlandi I, Zappa M, et al. Prevalence and correlates of pulmonary emphysema in smokers and former smokers: a densitometric study of participants in the ITALUNG trial. Eur Radiol. 2009;19(1):58–66. doi: 10.1007/s00330-008-1131-6.
    1. Wilson DO, Weissfeld JL, Fuhrman CR, Fisher SN, Balogh P, Landreneau RJ, et al. The Pittsburgh Lung Screening Study (PLuSS): outcomes within 3 years of a first computed tomography scan. Am J Respir Crit Care Med. 2008;178(9):956–961. doi: 10.1164/rccm.200802-336OC.
    1. Wilson DO, Leader JK, Fuhrman CR, Reilly JJ, Sciurba FC, Weissfeld JL. Quantitative computed tomography analysis, airflow obstruction, and lung cancer in the pittsburgh lung screening study. J Thorac Oncol Offic Publ Int Assoc Study Lung Cancer. 2011;6(7):1200–1205. doi: 10.1097/JTO.0b013e318219aa93.
    1. Coxson HO, Dirksen A, Edwards LD, Yates JC, Agusti A, Bakke P, et al. The presence and progression of emphysema in COPD as determined by CT scanning and biomarker expression: a prospective analysis from the ECLIPSE study. Lancet Respir Med. 2013;1(2):129–136. doi: 10.1016/S2213-2600(13)70006-7.
    1. Regan EA, Hokanson JE, Murphy JR, Make B, Lynch DA, Beaty TH, et al. Genetic epidemiology of COPD (COPDGene) study design. COPD J Chronic Obstr Pulm Dis. 2010;7(1):32–43. doi: 10.3109/15412550903499522.
    1. Hoffmann U, Massaro JM, Fox CS, Manders E, O’Donnell CJ. Defining normal distributions of coronary artery calcium in women and men (from the Framingham Heart Study) Am J Cardiol. 2008;102(9):1136–1141. doi: 10.1016/j.amjcard.2008.06.038.
    1. Rice M. Air pollution exposure and COPD in the Framingham Heart Study. @Grantome. 2018. . Accessed 4 Sept 2018.

Source: PubMed

스폰서 및 공동 작업자

건강 상태

약물 개입

3
구독하다