Personalized medicine for patients with COPD: where are we?

References

• Collaborators GBDCoD. Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018;392(10159):1736–1788. doi:10.1016/S0140-6736(18)32203-730496103
   PubMed Web of Science ®Google Scholar
• Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med. 2006;3(11):e442. doi:10.1371/journal.pmed.003044217132052
   PubMed Web of Science ®Google Scholar
• Vogelmeier CF, Criner GJ, Martinez FJ, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease 2017 report. GOLD executive summary. Am J Respir Crit Care Med. 2017;195(5):557–582. doi:10.1164/rccm.201701-0218PP28128970
   PubMed Web of Science ®Google Scholar
• Rennard SI, Locantore N, Delafont B, et al. Identification of five chronic obstructive pulmonary disease subgroups with different prognoses in the ECLIPSE cohort using cluster analysis. Ann Am Thorac Soc. 2015;12(3):303–312. doi:10.1513/AnnalsATS.201403-125OC25642832
   PubMed Web of Science ®Google Scholar
• Duffy S, Weir M, Criner GJ. The complex challenge of chronic obstructive pulmonary disease. Lancet Respir Med. 2015;3(12):917–919. doi:10.1016/S2213-2600(15)00480-426679019
   PubMed Web of Science ®Google Scholar
• Agusti A, Calverley PM, Celli B, et al. Characterisation of COPD heterogeneity in the ECLIPSE cohort. Respir Res. 2010;11:122. doi:10.1186/1465-9921-11-6220831787
   PubMed Web of Science ®Google Scholar
• Augustin IML, Spruit MA, Houben-Wilke S, et al. The respiratory physiome: clustering based on a comprehensive lung function assessment in patients with COPD. PLoS One. 2018;13(9):e0201593. doi:10.1371/journal.pone.020159330208035
   PubMed Web of Science ®Google Scholar
• Flores M, Glusman G, Brogaard K, Price ND, Hood L. P4 medicine: how systems medicine will transform the healthcare sector and society. Per Med. 2013;10(6):565–576. doi:10.2217/pme.13.5725342952
   PubMed Web of Science ®Google Scholar
• Agusti A, Sobradillo P, Celli B. Addressing the complexity of chronic obstructive pulmonary disease: from phenotypes and biomarkers to scale-free networks, systems biology, and P4 medicine. Am J Respir Crit Care Med. 2011;183(9):1129–1137. doi:10.1164/rccm.201009-1414PP21169466
   PubMed Web of Science ®Google Scholar
• Fletcher C, Peto R. The natural history of chronic airflow obstruction. Br Med J. 1977;1(6077):1645–1648. doi:10.1136/bmj.1.6077.1645871704
   PubMed Web of Science ®Google Scholar
• Lange P, Celli B, Agustí A, et al. Lung-Function Trajectories Leading to Chronic Obstructive Pulmonary Disease. N Engl J Med. 2015;373(2):111–122. doi:10.1056/NEJMoa141153226154786
   PubMed Web of Science ®Google Scholar
• Serikov VB, Leutenegger C, Krutilina R, et al. Cigarette smoke extract inhibits expression of peroxiredoxin V and increases airway epithelial permeability. Inhal Toxicol. 2006;18(1):79–92. doi:10.1080/0895837050028250616326404
   PubMed Web of Science ®Google Scholar
• Schweitzer KS, Hatoum H, Brown MB, et al. Mechanisms of lung endothelial barrier disruption induced by cigarette smoke: role of oxidative stress and ceramides. Am J Physiol Lung Cell Mol Physiol. 2011;301(6):L836–846. doi:10.1152/ajplung.00385.201021873444
   PubMed Web of Science ®Google Scholar
• Vernooy JH, Bracke KR, Drummen NE, et al. Leptin modulates innate and adaptive immune cell recruitment after cigarette smoke exposure in mice. J Immunol. 2010;184(12):7169–7177. doi:10.4049/jimmunol.090096320488786
   PubMed Web of Science ®Google Scholar
• Hogg JC, Chu F, Utokaparch S, et al. The nature of small-airway obstruction in chronic obstructive pulmonary disease. N Engl J Med. 2004;350(26):2645–2653. doi:10.1056/NEJMoa03215815215480
   PubMed Web of Science ®Google Scholar
• Chung KF, Adcock IM. Multifaceted mechanisms in COPD: inflammation, immunity, and tissue repair and destruction. Eur Respir J. 2008;31(6):1334–1356. doi:10.1183/09031936.0001890818515558
   PubMed Web of Science ®Google Scholar
• Nunez B, Sauleda J, Anto JM, et al. Anti-tissue antibodies are related to lung function in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2011;183(8):1025–1031. doi:10.1164/rccm.201001-0029OC21097696
   PubMed Web of Science ®Google Scholar
• Brusselle GG, Joos GF, Bracke KR. New insights into the immunology of chronic obstructive pulmonary disease. Lancet. 2011;378(9795):1015–1026. doi:10.1016/S0140-6736(11)60988-421907865
   PubMed Web of Science ®Google Scholar
• Tuder RM, Petrache I. Pathogenesis of chronic obstructive pulmonary disease. J Clin Invest. 2012;122(8):2749–2755. doi:10.1172/JCI6032422850885
   PubMed Web of Science ®Google Scholar
• Klimentidis YC, Vazquez AI, de Los Campos G, Allison DB, Dransfield MT, Thannickal VJ. Heritability of pulmonary function estimated from pedigree and whole-genome markers. Front Genet. 2013;4:174. doi:10.3389/fgene.2013.0017424058366
   PubMedGoogle Scholar
• Yuan C, Chang LG, Deng X. Genetic polymorphism and chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis. 2017;12:1385–1393. doi:10.2147/COPD.S13416128546746
   PubMed Web of Science ®Google Scholar
• Janus ED, Phillips NT, Carrell RW. Smoking, lung function, and alpha 1-antitrypsin deficiency. Lancet. 1985;1(8421):152–154.2857224
   PubMed Web of Science ®Google Scholar
• Martinez FD. Early-life origins of chronic obstructive pulmonary disease. N Engl J Med. 2016;375(9):871–878. doi:10.1056/NEJMra160328727579637
   PubMed Web of Science ®Google Scholar
• Stern DA, Morgan WJ, Wright AL, Guerra S, Martinez FD. Poor airway function in early infancy and lung function by age 22 years: a non-selective longitudinal cohort study. Lancet. 2007;370(9589):758–764. doi:10.1016/S0140-6736(07)61379-817765525
   PubMed Web of Science ®Google Scholar
• Beyer D, Mitfessel H, Gillissen A. Maternal smoking promotes chronic obstructive lung disease in the offspring as adults. Eur J Med Res. 2009;14(Suppl 4):27–31.20156720
   PubMed Web of Science ®Google Scholar
• Tai A, Tran H, Roberts M, Clarke N, Wilson J, Robertson CF. The association between childhood asthma and adult chronic obstructive pulmonary disease. Thorax. 2014;69(9):805–810. doi:10.1136/thoraxjnl-2013-20481524646659
   PubMed Web of Science ®Google Scholar
• Edmond K, Scott S, Korczak V, et al. Long term sequelae from childhood pneumonia; systematic review and meta-analysis. PLoS One. 2012;7(2):e31239. doi:10.1371/journal.pone.003123922384005
   PubMed Web of Science ®Google Scholar
• Adeloye D, Chua S, Lee C, et al. Global and regional estimates of COPD prevalence: systematic review and meta-analysis. J Glob Health. 2015;5(2):020415. doi:10.7189/jogh.05.02041526755942
   PubMed Web of Science ®Google Scholar
• Salvi SS, Barnes PJ. Chronic obstructive pulmonary disease in non-smokers. Lancet. 2009;374(9691):733–743. doi:10.1016/S0140-6736(09)61303-919716966
   PubMed Web of Science ®Google Scholar
• Pauwels C, Klerx WNM, Pennings JLA, et al. Cigarette filter ventilation and smoking protocol influence aldehyde smoke yields. Chem Res Toxicol. 2018;31(6):462–471. doi:10.1021/acs.chemrestox.7b0034229727173
   PubMed Web of Science ®Google Scholar
• Centers for Disease Control and Prevention.How Tobacco Smoke Causes Disease: The Biology and Behavioral Basis for Smoking-Attributable Disease: A Report of the Surgeon General. 3, Chemistry and Toxicology of Cigarette Smoke and Biomarkers of Exposure and Harm. Atlanta, GA: Centers for Disease Control and Prevention (US); National Center for Chronic Disease Prevention and Health Promotion (US); Office on Smoking and Health (US); 2010.
   Google Scholar
• Camp PG, Ramirez-Venegas A, Sansores RH, et al. COPD phenotypes in biomass smoke- versus tobacco smoke-exposed Mexican women. Eur Respir J. 2014;43(3):725–734. doi:10.1183/09031936.0020611224114962
   PubMed Web of Science ®Google Scholar
• Aryal S, Diaz-Guzman E, Mannino DM. Influence of sex on chronic obstructive pulmonary disease risk and treatment outcomes. Int J Chron Obstruct Pulmon Dis. 2014;9:1145–1154. doi:10.2147/COPD.S5447625342899
   PubMed Web of Science ®Google Scholar
• de Torres JP, Casanova C, Hernandez C, Abreu J, Aguirre-Jaime A, Celli BR. Gender and COPD in patients attending a pulmonary clinic. Chest. 2005;128(4):2012–2016. doi:10.1378/chest.128.4.201216236849
   PubMed Web of Science ®Google Scholar
• Hanson C, Rutten EP, Wouters EF, Rennard S. Influence of diet and obesity on COPD development and outcomes. Int J Chron Obstruct Pulmon Dis. 2014;9:723–733. doi:10.2147/COPD.S5011125125974
   PubMed Web of Science ®Google Scholar
• Steell L, Ho FK, Sillars A, et al. Dose-response associations of cardiorespiratory fitness with all-cause mortality and incidence and mortality of cancer and cardiovascular and respiratory diseases: the UK Biobank cohort study. Br J Sports Med. 2019. doi:10.1136/bjsports-2018-099093
   Web of Science ®Google Scholar
• Hancox RJ, Rasmussen F. Does physical fitness enhance lung function in children and young adults? Eur Respir J. 2018;51(2):1701374. doi:10.1183/13993003.01374-201729386347
   PubMed Web of Science ®Google Scholar
• Garcia-Aymerich J, Lange P, Benet M, Schnohr P, Anto JM. Regular physical activity modifies smoking-related lung function decline and reduces risk of chronic obstructive pulmonary disease: a population-based cohort study. Am J Respir Crit Care Med. 2007;175(5):458–463. doi:10.1164/rccm.200607-896OC17158282
   PubMed Web of Science ®Google Scholar
• Garcia-Aymerich J, Lange P, Benet M, Schnohr P, Anto JM. Regular physical activity reduces hospital admission and mortality in chronic obstructive pulmonary disease: a population based cohort study. Thorax. 2006;61(9):772–778. doi:10.1136/thx.2006.06014516738033
   PubMed Web of Science ®Google Scholar
• Shukla SD, Budden KF, Neal R, Hansbro PM. Microbiome effects on immunity, health and disease in the lung. Clin Transl Immunology. 2017;6(3):e133. doi:10.1038/cti.2017.628435675
   PubMed Web of Science ®Google Scholar
• Wang Z, Bafadhel M, Haldar K, et al. Lung microbiome dynamics in COPD exacerbations. Eur Respir J. 2016;47(4):1082–1092. doi:10.1183/13993003.01406-201526917613
   PubMed Web of Science ®Google Scholar
• Agusti A, Noell G, Brugada J, Faner R. Lung function in early adulthood and health in later life: a transgenerational cohort analysis. Lancet Respir Med. 2017;5(12):935–945.29150410
   PubMed Web of Science ®Google Scholar
• Joly B, Perriot J, d’Athis P, Chazard E, Brousse G, Quantin C. Success rates in smoking cessation: psychological preparation plays a critical role and interacts with other factors such as psychoactive substances. PLoS One. 2017;12(10):e0184800. doi:10.1371/journal.pone.018480029020085
   PubMed Web of Science ®Google Scholar
• Sillen MJ, Franssen FM, Delbressine JM, et al. Heterogeneity in clinical characteristics and co-morbidities in dyspneic individuals with COPD GOLD D: findings of the DICES trial. Respir Med. 2013;107(8):1186–1194. doi:10.1016/j.rmed.2013.04.02023706780
   PubMed Web of Science ®Google Scholar
• Agusti A, Rennard S, Edwards LD, et al. Clinical and prognostic heterogeneity of C and D GOLD groups. Eur Respir J. 2015;46(1):250–254. doi:10.1183/09031936.0001221526130780
   PubMed Web of Science ®Google Scholar
• Cabrera Lopez C, Casanova Macario C, Marin Trigo JM, et al. Comparison of the 2017 and 2015 global initiative for chronic obstructive lung disease reports. impact on grouping and outcomes. Am J Respir Crit Care Med. 2018;197(4):463–469. doi:10.1164/rccm.201707-1363OC29099607
   PubMed Web of Science ®Google Scholar
• Agusti A, Bel E, Thomas M, et al. Treatable traits: toward precision medicine of chronic airway diseases. Eur Respir J. 2016;47(2):410–419. doi:10.1183/13993003.01359-201526828055
   PubMed Web of Science ®Google Scholar
• Vanfleteren LEGW, Spruit MA, Wouters EFM, Franssen FME. Management of chronic obstructive pulmonary disease beyond the lungs. Lancet Respir Med. 2016;4(11):911–924. doi:10.1016/S2213-2600(16)00097-727264777
   PubMed Web of Science ®Google Scholar
• Lindberg A, Bjerg A, Ronmark E, Larsson LG, Lundback B. Prevalence and underdiagnosis of COPD by disease severity and the attributable fraction of smoking Report from the Obstructive Lung Disease in Northern Sweden Studies. Respir Med. 2006;100(2):264–272. doi:10.1016/j.rmed.2005.04.02915975774
   PubMed Web of Science ®Google Scholar
• Zhou Y, Zhong NS, Li X, et al. Tiotropium in Early-Stage Chronic Obstructive Pulmonary Disease. N Engl J Med. 2017;377(10):923–935. doi:10.1056/NEJMoa170022828877027
   PubMed Web of Science ®Google Scholar
• Pauwels RA, Buist AS, Calverley PM, Jenkins CR, Hurd SS. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop summary. Am J Respir Crit Care Med. 2001;163(5):1256–1276. doi:10.1164/ajrccm.163.5.210103911316667
   PubMedGoogle Scholar
• Vestbo J, Lange P. Can GOLD Stage 0 provide information of prognostic value in chronic obstructive pulmonary disease? Am J Respir Crit Care Med. 2002;166(3):329–332. doi:10.1164/rccm.211204812153965
   PubMed Web of Science ®Google Scholar
• Woodruff PG, Barr RG, Bleecker E, et al. Clinical significance of symptoms in smokers with preserved pulmonary function. N Engl J Med. 2016;374(19):1811–1821. doi:10.1056/NEJMoa150597127168432
   PubMed Web of Science ®Google Scholar
• Regan EA, Lynch DA, Curran-Everett D, et al. Clinical and radiologic disease in smokers with normal spirometry. JAMA Intern Med. 2015;175(9):1539–1549. doi:10.1001/jamainternmed.2015.273526098755
   PubMed Web of Science ®Google Scholar
• Nishimura M, Makita H, Nagai K, et al. Annual change in pulmonary function and clinical phenotype in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2012;185(1):44–52. doi:10.1164/rccm.201106-0992OC22016444
   PubMed Web of Science ®Google Scholar
• Johannessen A, Skorge TD, Bottai M, et al. Mortality by level of emphysema and airway wall thickness. Am J Respir Crit Care Med. 2013;187(6):602–608. doi:10.1164/rccm.201209-1722OC23328525
   PubMed Web of Science ®Google Scholar
• Kirby M, Tanabe N, Tan WC, 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. 2018;197(1):56–65. doi:10.1164/rccm.201704-0692OC28886252
   PubMed Web of Science ®Google Scholar
• Hurst JR, Vestbo J, Anzueto A, et al. Susceptibility to exacerbation in chronic obstructive pulmonary disease. N Engl J Med. 2010;363(12):1128–1138.20843247
   PubMed Web of Science ®Google Scholar
• Han MK, Quibrera PM, Carretta EE, et al. Frequency of exacerbations in patients with chronic obstructive pulmonary disease: an analysis of the SPIROMICS cohort. Lancet Respir Med. 2017;5(8):619–626. doi:10.1016/S2213-2600(17)30207-228668356
   PubMed Web of Science ®Google Scholar
• Global Strategy for the diagnosis, managment, and prevention of chronic obstructive lung disease 2019 Report. Available from: www.goldcopd.com. Accessed June 01, 2019.
   Google Scholar
• Bafadhel M, McKenna S, Terry S, et al. Acute exacerbations of chronic obstructive pulmonary disease: identification of biologic clusters and their biomarkers. Am J Respir Crit Care Med. 2011;184(6):662–671. doi:10.1164/rccm.201104-0597OC21680942
   PubMed Web of Science ®Google Scholar
• Wedzicha JAE-C-C, Miravitlles M, Hurst JR, et al. Management of COPD exacerbations: a European Respiratory Society/American Thoracic Society guideline. Eur Respir J. 2017;49:3. doi:10.1183/13993003.00791-2016
   Web of Science ®Google Scholar
• Bafadhel M, McKenna S, Terry S, et al. Blood eosinophils to direct corticosteroid treatment of exacerbations of chronic obstructive pulmonary disease: a randomized placebo-controlled trial. Am J Respir Crit Care Med. 2012;186(1):48–55. doi:10.1164/rccm.201108-1553OC22447964
   PubMed Web of Science ®Google Scholar
• Ishii T, Angata T, Wan ES, et al. Influence of SIGLEC9 polymorphisms on COPD phenotypes including exacerbation frequency. Respirology. 2017;22(4):684–690. doi:10.1111/resp.1295227878892
   PubMed Web of Science ®Google Scholar
• Lee SW, Hwang HH, Hsu PW, Chuang TY, Liu CW, Wu LS. Whole-genome methylation profiling from PBMCs in acute-exacerbation COPD patients with good and poor responses to corticosteroid treatment. Genomics. 2018. doi:10.1016/j.ygeno.2018.09.010
   Web of Science ®Google Scholar
• Hillas G, Perlikos F, Tsiligianni I, Tzanakis N. Managing comorbidities in COPD. Int J Chron Obstruct Pulmon Dis. 2015;10:95–109. doi:10.2147/COPD.S5447325609943
   PubMed Web of Science ®Google Scholar
• Gershon AS, Mecredy GC, Guan J, Victor JC, Goldstein R, To T. Quantifying comorbidity in individuals with COPD: a population study. Eur Respir J. 2015;45(1):51–59. doi:10.1183/09031936.0006141425142481
   PubMed Web of Science ®Google Scholar
• Greulich T, Weist BJD, Koczulla AR, et al. Prevalence of comorbidities in COPD patients by disease severity in a German population. Respir Med. 2017;132:132–138. doi:10.1016/j.rmed.2017.10.00729229085
   PubMed Web of Science ®Google Scholar
• Kahnert K, Lucke T, Huber RM, et al. Relationship of hyperlipidemia to comorbidities and lung function in COPD: results of the COSYCONET cohort. PLoS One. 2017;12(5):e0177501. doi:10.1371/journal.pone.017750128505167
   PubMed Web of Science ®Google Scholar
• Mantoani LC, Dell’Era S, MacNee W, Rabinovich RA. Physical activity in patients with COPD: the impact of comorbidities. Expert Rev Respir Med. 2017;11(9):685–698. doi:10.1080/17476348.2017.135469928699821
   PubMed Web of Science ®Google Scholar
• Kahnert K, Alter P, Welte T, et al. Uric acid, lung function, physical capacity and exacerbation frequency in patients with COPD: a multi-dimensional approach. Respir Res. 2018;19(1):110. doi:10.1186/s12931-018-0815-y29866121
   PubMed Web of Science ®Google Scholar
• Vanfleteren LE, Spruit MA, Groenen M, et al. Clusters of comorbidities based on validated objective measurements and systemic inflammation in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2013;187(7):728–735. doi:10.1164/rccm.201209-1665OC23392440
   PubMed Web of Science ®Google Scholar
• Mullerova H, Agusti A, Erqou S, Mapel DW. Cardiovascular comorbidity in COPD: systematic literature review. Chest. 2013;144(4):1163–1178. doi:10.1378/chest.12-284723722528
   PubMed Web of Science ®Google Scholar
• Miller J, Edwards LD, Agusti A, et al. Comorbidity, systemic inflammation and outcomes in the ECLIPSE cohort. Respir Med. 2013;107(9):1376–1384. doi:10.1016/j.rmed.2013.05.00123791463
   PubMed Web of Science ®Google Scholar
• Iversen KK, Kjaergaard J, Akkan D, et al. The prognostic importance of lung function in patients admitted with heart failure. Eur J Heart Fail. 2010;12(7):685–691. doi:10.1093/eurjhf/hfq05020395261
   PubMed Web of Science ®Google Scholar
• Hawkins NM, Huang Z, Pieper KS, et al. Chronic obstructive pulmonary disease is an independent predictor of death but not atherosclerotic events in patients with myocardial infarction: analysis of the Valsartan in Acute Myocardial Infarction Trial (VALIANT). Eur J Heart Fail. 2009;11(3):292–298. doi:10.1093/eurjhf/hfp00119176539
   PubMed Web of Science ®Google Scholar
• Fisher KA, Stefan MS, Darling C, Lessard D, Goldberg RJ. Impact of COPD on the mortality and treatment of patients hospitalized with acute decompensated heart failure: the Worcester Heart Failure Study. Chest. 2015;147(3):637–645. doi:10.1378/chest.14-060725188234
   PubMed Web of Science ®Google Scholar
• Adamson PD, Anderson JA, Brook RD, et al. Cardiac troponin I and cardiovascular risk in patients with chronic obstructive pulmonary disease. J Am Coll Cardiol. 2018;72(10):1126–1137. doi:10.1016/j.jacc.2018.06.05130165984
   PubMed Web of Science ®Google Scholar
• Kawut SM, Poor HD, Parikh MA, et al. Cor pulmonale parvus in chronic obstructive pulmonary disease and emphysema: the MESA COPD study. J Am Coll Cardiol. 2014;64(19):2000–2009. doi:10.1016/j.jacc.2014.07.99125440095
   PubMed Web of Science ®Google Scholar
• Alter P, Jorres RA, Watz H, et al. Left ventricular volume and wall stress are linked to lung function impairment in COPD. Int J Cardiol. 2018;261:172–178. doi:10.1016/j.ijcard.2018.02.07429657040
   PubMed Web of Science ®Google Scholar
• Alter P, Watz H, Kahnert K, et al. Airway obstruction and lung hyperinflation in COPD are linked to an impaired left ventricular diastolic filling. Respir Med. 2018;137:14–22. doi:10.1016/j.rmed.2018.02.01129605197
   PubMed Web of Science ®Google Scholar
• Barr RG, Bluemke DA, Ahmed FS, et al. Percent emphysema, airflow obstruction, and impaired left ventricular filling. N Engl J Med. 2010;362(3):217–227. doi:10.1056/NEJMoa080883620089972
   PubMed Web of Science ®Google Scholar
• Dodd DS, Brancatisano T, Engel LA. Chest wall mechanics during exercise in patients with severe chronic air-flow obstruction. Am Rev Respir Dis. 1984;129(1):33–38. doi:10.1164/arrd.1984.129.1.336230971
   PubMed Web of Science ®Google Scholar
• Stone IS, Barnes NC, James WY, et al. Lung deflation and cardiovascular structure and function in chronic obstructive pulmonary disease. A randomized controlled trial. Am J Respir Crit Care Med. 2016;193(7):717–726. doi:10.1164/rccm.201508-1647OC26550687
   PubMed Web of Science ®Google Scholar
• Hohlfeld JM, Vogel-Claussen J, Biller H, et al. Effect of lung deflation with indacaterol plus glycopyrronium on ventricular filling in patients with hyperinflation and COPD (CLAIM): a double-blind, randomised, crossover, placebo-controlled, single-centre trial. Lancet Respir Med. 2018;6(5):368–378. doi:10.1016/S2213-2600(18)30054-729477448
   PubMed Web of Science ®Google Scholar
• Vogel-Claussen J, Schonfeld CO, Kaireit TF, et al. Effect of indacaterol/glycopyrronium on pulmonary perfusion and ventilation in hyperinflated patients with Chronic Obstructive Pulmonary Disease (CLAIM). A double-blind, randomized, crossover trial. Am J Respir Crit Care Med. 2019;199(9):1086–1096. doi:10.1164/rccm.201805-0995OC30641027
   PubMed Web of Science ®Google Scholar
• Rutten FH, Cramer MJ, Grobbee DE, et al. Unrecognized heart failure in elderly patients with stable chronic obstructive pulmonary disease. Eur Heart J. 2005;26(18):1887–1894. doi:10.1093/eurheartj/ehi29115860516
   PubMed Web of Science ®Google Scholar
• Triest FJ, Franssen FM, Spruit MA, Groenen MT, Wouters EF, Vanfleteren LE. Poor agreement between chart-based and objectively identified comorbidities of COPD. Eur Respir J. 2015;46(5):1492–1495. doi:10.1183/13993003.00667-201526341984
   PubMed Web of Science ®Google Scholar
• Rodriguez-Roisin R, Rabe KF, Vestbo J, et al. Global Initiative for Chronic Obstructive Lung Disease (GOLD) 20th Anniversary: a brief history of time. Eur Respir J. 2017;50:1. doi:10.1183/13993003.00711-2017
   Web of Science ®Google Scholar
• Rabe KF, Hurd S, Anzueto A, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2007;176(6):532–555. doi:10.1164/rccm.200703-456SO17507545
   PubMed Web of Science ®Google Scholar
• Calverley P, Pauwels R, Vestbo J, et al. Combined salmeterol and fluticasone in the treatment of chronic obstructive pulmonary disease: a randomised controlled trial. Lancet. 2003;361(9356):449–456. doi:10.1016/S0140-6736(03)12459-212583942
   PubMed Web of Science ®Google Scholar
• Szafranski W, Cukier A, Ramirez A, et al. Efficacy and safety of budesonide/formoterol in the management of chronic obstructive pulmonary disease. Eur Respir J. 2003;21(1):74–81.12570112
   PubMed Web of Science ®Google Scholar
• Vestbo J, Hurd SS, Agusti AG, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2013;187(4):347–365. doi:10.1164/rccm.201204-0596PP22878278
   PubMed Web of Science ®Google Scholar
• Haughney J, Gruffydd-Jones K, Roberts J, Lee AJ, Hardwell A, McGarvey L. The distribution of COPD in UK general practice using the new GOLD classification. Eur Respir J. 2014;43(4):993–1002. doi:10.1183/09031936.0006501324176990
   PubMed Web of Science ®Google Scholar
• Kopsaftis Z, Wood-Baker R, Poole P. Influenza vaccine for chronic obstructive pulmonary disease (COPD). Cochrane Database Syst Rev. 2018;6:CD002733.29943802
   PubMed Web of Science ®Google Scholar
• Bekkat-Berkani R, Wilkinson T, Buchy P, et al. Seasonal influenza vaccination in patients with COPD: a systematic literature review. BMC Pulm Med. 2017;17(1):79. doi:10.1186/s12890-017-0500-928468650
   PubMed Web of Science ®Google Scholar
• Walters JA, Smith S, Poole P, Granger RH, Wood-Baker R. Injectable vaccines for preventing pneumococcal infection in patients with chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2010;(11):CD001390.21069668
   PubMed Web of Science ®Google Scholar
• Celli BR, Decramer M, Wedzicha JA, et al. An official American Thoracic Society/European Respiratory Society statement: research questions in COPD. Eur Respir J. 2015;45(4):879–905. doi:10.1183/09031936.0000901525829431
   PubMed Web of Science ®Google Scholar
• Spruit MA, Wouters EFM. Organizational aspects of pulmonary rehabilitation in chronic respiratory diseases. Respirology. 2019. doi:10.1111/resp.13512
   PubMed Web of Science ®Google Scholar
• Spruit MA, Singh SJ, Garvey C, et al. An official American Thoracic Society/European Respiratory Society statement: key concepts and advances in pulmonary rehabilitation. Am J Respir Crit Care Med. 2013;188(8):e13–64. doi:10.1164/rccm.201309-1634ST24127811
   PubMed Web of Science ®Google Scholar
• Andrianopoulos V, Klijn P, Franssen FM, Spruit MA. Exercise training in pulmonary rehabilitation. Clin Chest Med. 2014;35(2):313–322. doi:10.1016/j.ccm.2014.02.01324874127
   PubMed Web of Science ®Google Scholar
• Rocha A, Arbex FF, Sperandio PA, et al. Exercise intolerance in comorbid COPD-heart failure: the role of impaired aerobic function. Eur Respir J. 2019;53:1802386. doi:10.1183/13993003.02386-201830765506
   PubMed Web of Science ®Google Scholar
• Garrod R, Marshall J, Barley E, Jones PW. Predictors of success and failure in pulmonary rehabilitation. Eur Respir J. 2006;27(4):788–794. doi:10.1183/09031936.06.0013060516481381
   PubMed Web of Science ®Google Scholar
• Spruit MA, Augustin IM, Vanfleteren LE, et al. Differential response to pulmonary rehabilitation in COPD: multidimensional profiling. Eur Respir J. 2015;46(6):1625–1635. doi:10.1183/13993003.00350-201526453626
   PubMed Web of Science ®Google Scholar
• Janssen R, Piscaer I, Franssen FM, Wouters EF. Emphysema: looking beyond alpha-1 antitrypsin deficiency. Expert Rev Respir Med. 2019;13:381–397. doi:10.1080/17476348.2019.158057530761929
   PubMed Web of Science ®Google Scholar
• van Geffen WH, Slebos DJ, Herth FJ, Kemp SV, Weder W, Shah PL. Surgical and endoscopic interventions that reduce lung volume for emphysema: a systemic review and meta-analysis. Lancet Respir Med. 2019;7(4):313–324. doi:10.1016/S2213-2600(18)30431-430744937
   PubMed Web of Science ®Google Scholar
• Fishman A, Martinez F, Naunheim K, et al. A randomized trial comparing lung-volume-reduction surgery with medical therapy for severe emphysema. N Engl J Med. 2003;348(21):2059–2073. doi:10.1056/NEJMoa03028712759479
   PubMed Web of Science ®Google Scholar
• Klooster K, Ten Hacken NH, Hartman JE, Kerstjens HA, van Rikxoort EM, Slebos DJ. Endobronchial valves for emphysema without interlobar collateral ventilation. N Engl J Med. 2015;373(24):2325–2335. doi:10.1056/NEJMoa150780726650153
   PubMed Web of Science ®Google Scholar
• Maier D. Applying systems medicine in the clinic. Curr Opin Syst Biol. 2017;3:77–87. doi:10.1016/j.coisb.2017.04.014
   Google Scholar
• Apweiler R, Beissbarth T, Berthold MR, et al. Whither systems medicine? Exp Mol Med. 2018;50(3):e453. doi:10.1038/emm.2017.29029497170
   PubMed Web of Science ®Google Scholar
• Schmeck B, Bertrams W, Lai X, Vera J. Systems medicine for lung diseases: phenotypes and precision medicine in cancer, infection, and allergy. Methods Mol Biol. 2016;1386:119–133. doi:10.1007/978-1-4939-3283-2_826677183
   PubMedGoogle Scholar
• Charron CE, Russell P, Ito K, et al. RV568, a narrow-spectrum kinase inhibitor with p38 MAPK-alpha and -gamma selectivity, suppresses COPD inflammation. Eur Respir J. 2017;50:4. doi:10.1183/13993003.00711-2017
   Web of Science ®Google Scholar
• Pavord ID, Chanez P, Criner GJ, et al. Mepolizumab for eosinophilic chronic obstructive pulmonary disease. N Engl J Med. 2017;377(17):1613–1629. doi:10.1056/NEJMoa170820828893134
   PubMed Web of Science ®Google Scholar
• Leung JM, Obeidat M, Sadatsafavi M, Sin DD. Introduction to precision medicine in COPD. Eur Respir J. 2019;53:4. doi:10.1183/13993003.01184-2018
   Web of Science ®Google Scholar
• Eberhardt M, Lai X, Tomar N, et al. Third-kind encounters in biomedicine: immunology meets mathematics and informatics to become quantitative and predictive. Methods Mol Biol. 2016;1386:135–179. doi:10.1007/978-1-4939-3283-2_926677184
   PubMedGoogle Scholar
• Reyfman PA, Walter JM, Joshi N, et al. Single-cell transcriptomic analysis of human lung provides insights into the pathobiology of pulmonary fibrosis. Am J Respir Crit Care Med. 2018. doi:10.1164/rccm.201712-2410OC
   Web of Science ®Google Scholar
• Castaldi PJ, Guo F, Qiao D, et al. Identification of functional variants in the FAM13A chronic obstructive pulmonary disease genome-wide association study locus by massively parallel reporter assays. Am J Respir Crit Care Med. 2019;199(1):52–61. doi:10.1164/rccm.201802-0337OC30079747
   PubMed Web of Science ®Google Scholar
• Seimetz M, Parajuli N, Pichl A, et al. Inducible NOS inhibition reverses tobacco-smoke-induced emphysema and pulmonary hypertension in mice. Cell. 2011;147(2):293–305. doi:10.1016/j.cell.2011.08.03522000010
   PubMed Web of Science ®Google Scholar
• Jia J, Conlon TM, Sarker RS, et al. Cholesterol metabolism promotes B-cell positioning during immune pathogenesis of chronic obstructive pulmonary disease. EMBO Mol Med. 2018;10:5. doi:10.15252/emmm.201708349
   Web of Science ®Google Scholar
• Uhl FE, Vierkotten S, Wagner DE, et al. Preclinical validation and imaging of Wnt-induced repair in human 3D lung tissue cultures. Eur Respir J. 2015;46(4):1150–1166. doi:10.1183/09031936.0018321425929950
   PubMed Web of Science ®Google Scholar
• Yang J, Zuo WL, Fukui T, et al. Smoking-dependent distal-to-proximal repatterning of the adult human small airway epithelium. Am J Respir Crit Care Med. 2017;196(3):340–352. doi:10.1164/rccm.201608-1672OC28345955
   PubMed Web of Science ®Google Scholar
• Gkatzis K, Taghizadeh S, Huh D, Stainier DYR, Bellusci S. Use of three-dimensional organoids and lung-on-a-chip methods to study lung development, regeneration and disease. Eur Respir J. 2018;52:5. doi:10.1183/13993003.01675-2018
   Web of Science ®Google Scholar
• Benedikter BJ, Volgers C, van Eijck PH, et al. Cigarette smoke extract induced exosome release is mediated by depletion of exofacial thiols and can be inhibited by thiol-antioxidants. Free Radic Biol Med. 2017;108:334–344. doi:10.1016/j.freeradbiomed.2017.03.02628359953
   PubMed Web of Science ®Google Scholar
• Agusti A, Compte A, Faner R, et al. The EASI model: A first integrative computational approximation to the natural history of COPD. PLoS One. 2017;12(10):e0185502. doi:10.1371/journal.pone.018550229016620
   PubMed Web of Science ®Google Scholar
• Loeppky JA, Icenogle MV, Caprihan A, Vidal Melo MF, Altobelli SA. CO2 rebreathing model in COPD: blood-to-gas equilibration. Eur J Appl Physiol. 2006;98(5):450–460. doi:10.1007/s00421-006-0288-416960726
   PubMed Web of Science ®Google Scholar
• Cox LAT. A mathematical model of protease-antiprotease homeostasis failure in chronic obstructive pulmonary disease (COPD). Risk Anal. 2009;29(4):576–586. doi:10.1111/j.1539-6924.2008.01152.x19000077
   PubMed Web of Science ®Google Scholar
• Cox LAT. A causal model of chronic obstructive pulmonary disease (COPD) risk. Risk Anal. 2011;31(1):38–62. doi:10.1111/j.1539-6924.2010.01487.x20846171
   PubMed Web of Science ®Google Scholar
• Jolley CJ, Moxham J. A physiological model of patient-reported breathlessness during daily activities in COPD. Eur Respir Rev. 2009;18(112):66–79. doi:10.1183/09059180.0000080920956127
   PubMedGoogle Scholar
• Zhang B, Qi S, Yue Y, et al. Particle disposition in the realistic airway tree models of subjects with tracheal bronchus and COPD. Biomed Res Int. 2018;2018:7428609.30155481
   PubMed Web of Science ®Google Scholar
• De Backer LA, Vos W, De Backer J, Van Holsbeke C, Vinchurkar S, De Backer W. The acute effect of budesonide/formoterol in COPD: a multi-slice computed tomography and lung function study. Eur Respir J. 2012;40(2):298–305. doi:10.1183/09031936.0007251122183484
   PubMed Web of Science ®Google Scholar
• De Backer JW, Vanderveken OM, Vos WG, et al. Functional imaging using computational fluid dynamics to predict treatment success of mandibular advancement devices in sleep-disordered breathing. J Biomech. 2007;40(16):3708–3714. doi:10.1016/j.jbiomech.2007.06.02217663990
   PubMed Web of Science ®Google Scholar
• Burrowes KS, Doel T, Brightling C. Computational modeling of the obstructive lung diseases asthma and COPD. J Transl Med. 2014;12(Suppl 2):S5. doi:10.1186/1479-5876-12-S2-S525471125
   PubMed Web of Science ®Google Scholar
• Burrowes KS, De Backer J, Smallwood R, et al. Multi-scale computational models of the airways to unravel the pathophysiological mechanisms in asthma and chronic obstructive pulmonary disease (AirPROM). Interface Focus. 2013;3(2). doi:10.1098/rsfs.2012.0057.
   Web of Science ®Google Scholar
• Hiorns JE, Jensen OE, Brook BS. Static and dynamic stress heterogeneity in a multiscale model of the asthmatic airway wall. J Appl Physiol. 2016;121(1):233–247. doi:10.1152/japplphysiol.00715.201527197860
   PubMed Web of Science ®Google Scholar
• Bordas R, Lefevre C, Veeckmans B, et al. Development and analysis of patient-based complete conducting airways models. PLoS One. 2015;10(12):e0144105. doi:10.1371/journal.pone.014410526656288
   PubMed Web of Science ®Google Scholar
• Walters M, Wells AK, Jones IP, et al. Patient-specific simulation of tidal breathing. Paper presented at: Medical Imaging 2016: Biomedical Applications in Molecular, Structural, and Functional Imaging; 3 29;2016; San Diego, CA.
   Google Scholar
• Chernyavsky IL, Russell RJ, Saunders RM, et al. In vitro, in silico and in vivo study challenges the impact of bronchial thermoplasty on acute airway smooth muscle mass loss. Eur Respir J. 2018;51(5):1701680. doi:10.1183/13993003.01680-201729700102
   PubMed Web of Science ®Google Scholar
• Marín de Mas I, Fanchon E, Papp B, Kalko S, Roca J, Cascante M. Molecular mechanisms underlying COPD-muscle dysfunction unveiled through a systems medicine approach. Bioinformatics. 2017;33(1):95–103.
   Web of Science ®Google Scholar
• Cano I, Roca J, Wagner PD. Effects of lung ventilation-perfusion and muscle metabolism-perfusion heterogeneities on maximal O2 transport and utilization. J Physiol (Lond). 2015;593(8):1841–1856. doi:10.1113/jphysiol.2014.28649225640017
   PubMedGoogle Scholar
• Selivanov VA, Cascante M, Friedman M, Schumaker MF, Trucco M, Votyakova TV. Multistationary and oscillatory modes of free radicals generation by the mitochondrial respiratory chain revealed by a bifurcation analysis. PLoS Comput Biol. 2012;8(9):e1002700. doi:10.1371/journal.pcbi.100270023028295
   PubMed Web of Science ®Google Scholar
• Selivanov VA, Votyakova TV, Pivtoraiko VN, et al. Reactive oxygen species production by forward and reverse electron fluxes in the mitochondrial respiratory chain. PLoS Comput Biol. 2011;7(3):e1001115. doi:10.1371/journal.pcbi.100224421483483
   PubMed Web of Science ®Google Scholar
• Clarke K, Ricciardi S, Pearson T, et al. The role of Eif6 in skeletal muscle homeostasis revealed by endurance training co-expression networks. Cell Rep. 2017;21(6):1507–1520. doi:10.1016/j.celrep.2017.10.04029117557
   PubMed Web of Science ®Google Scholar
• Esteva A, Kuprel B, Novoa RA, et al. Dermatologist-level classification of skin cancer with deep neural networks. Nature. 2017;542:115–118. doi:10.1038/nature2105628117445
   PubMed Web of Science ®Google Scholar
• Abràmoff MD, Lavin PT, Birch M, Shah N, Folk JC. Pivotal trial of an autonomous AI-based diagnostic system for detection of diabetic retinopathy in primary care offices. NPJ Digit Med. 2018;1:39. doi:10.1038/s41746-018-0040-631304320
   PubMed Web of Science ®Google Scholar
• Bellos CC, Papadopoulos A, Rosso R, Fotiadis DI. Identification of COPD patients’ health status using an intelligent system in the CHRONIOUS wearable platform. IEEE J Biomed Health Inform. 2014;18:731–738. doi:10.1109/JBHI.2013.229317224808219
   PubMed Web of Science ®Google Scholar
• Er O, Sertkaya C, Temurtas F, Tanrikulu AC. A comparative study on chronic obstructive pulmonary and pneumonia diseases diagnosis using neural networks and artificial immune system. J Med Syst. 2009;33:485–492.20052900
   PubMed Web of Science ®Google Scholar
• Er O, Yumusak N, Temurtas F. Chest diseases diagnosis using artificial neural networks. Expert Syst Appl. 2010;37:7648–7655. doi:10.1016/j.eswa.2010.04.078
   Web of Science ®Google Scholar
• Fernández-Granero MA, Sánchez-Morillo D, León-Jiménez A, Crespo LF. Automatic prediction of chronic obstructive pulmonary disease exacerbations through home telemonitoring of symptoms. Biomed Mater Eng. 2014;24:3825–3832. doi:10.3233/BME-14121225227099
   PubMed Web of Science ®Google Scholar
• Deep Neural Networks for Prediction of Exacerbations of Patients with Chronic Obstructive Pulmonary Disease. Cham: Springer International Publishing; 19th International Conference, EANN 2018, September 3-5, 2018; Bristol, UK.
   Google Scholar
• van der Heijden M, Lucas PJF, Lijnse B, Heijdra YF, Schermer TRJ. An autonomous mobile system for the management of COPD. J Biomed Inform. 2013;46:458–469. doi:10.1016/j.jbi.2013.03.00323500485
   PubMed Web of Science ®Google Scholar
• Ying J, Dutta J, Guo N, et al. Classification of exacerbation frequency in the COPDGene cohort using deep learning with deep belief networks. IEEE J Biomed Health Inform. 2016;1. doi:10.1109/JBHI.2016.2642944
   Web of Science ®Google Scholar
• Amalakuhan B, Kiljanek L, Parvathaneni A, Hester M, Cheriyath P, Fischman D. A prediction model for COPD readmissions: catching up, catching our breath, and improving a national problem. J Community Hosp Intern Med Perspect. 2012;2(1).
   PubMedGoogle Scholar
• Raudys SJ, Jain AK. Small sample size effects in statistical pattern recognition: recommendations for practitioners. IEEE Trans Pattern Anal Mach Intell. 1991;13:252–264. doi:10.1109/34.75512
   Web of Science ®Google Scholar
• Gurbeta L, Badnjevic A, Maksimovic M, Omanovic-Miklicanin E, Sejdic E. A telehealth system for automated diagnosis of asthma and chronical obstructive pulmonary disease. J Am Med Inform Assoc. 2018;25(9):1213–1217. doi:10.1093/jamia/ocy05529788482
   PubMed Web of Science ®Google Scholar
• Badnjevic A, Cifrek M, Koruga D, Osmankovic D. Neuro-fuzzy classification of asthma and chronic obstructive pulmonary disease. BMC Med Inform Decis Mak. 2015;15(Suppl 3):S1. doi:10.1186/1472-6947-15-S3-S1
   Web of Science ®Google Scholar
• Amaral JLM, Lopes AJ, Jansen JM, Faria ACD, Melo PL. Machine learning algorithms and forced oscillation measurements applied to the automatic identification of chronic obstructive pulmonary disease. Comput Methods Programs Biomed. 2012;105:183–193. doi:10.1016/j.cmpb.2011.09.00922018532
   PubMed Web of Science ®Google Scholar
• Amaral JLM, Lopes AJ, Faria ACD, Melo PL. Machine learning algorithms and forced oscillation measurements to categorise the airway obstruction severity in chronic obstructive pulmonary disease. Comput Methods Programs Biomed. 2015;118:186–197. doi:10.1016/j.cmpb.2014.11.00225435077
   PubMed Web of Science ®Google Scholar
• Badnjevic A, Gurbeta L, Custovic E. An expert diagnostic system to automatically identify asthma and chronic obstructive pulmonary disease in clinical settings. Sci Rep. 2018;8:11645. doi:10.1038/s41598-018-30116-230076356
   PubMed Web of Science ®Google Scholar
• Spathis D, Vlamos P. Diagnosing asthma and chronic obstructive pulmonary disease with machine learning. Health Informatics J. 2017;146045821772316. doi:10.1177/1460458217723169
   Web of Science ®Google Scholar
• Topalovic M, Laval S, Aerts J-M, Troosters T, Decramer M, Janssens W. Automated interpretation of pulmonary function tests in adults with respiratory complaints. Respiration. 2017;93:170–178. doi:10.1159/00045495628088797
   PubMed Web of Science ®Google Scholar
• Bodduluri S, Newell JD Jr, Hoffman EA, Reinhardt JM. Registration-based lung mechanical analysis of Chronic Obstructive Pulmonary Disease (COPD) using a supervised machine learning framework. Acad Radiol. 2013;20:527–536. doi:10.1016/j.acra.2013.01.01923570934
   PubMed Web of Science ®Google Scholar
• Classification of COPD with Multiple Instance Learning. IEEE; 2014.22nd International Conference on Pattern Recognition, Stockholm, Sweden
   Google Scholar
• Mets OM, Buckens CFM, Zanen P, et al. Identification of chronic obstructive pulmonary disease in lung cancer screening computed tomographic scans. JAMA. 2011;306:1775–1781. doi:10.1001/jama.2011.153122028353
   PubMed Web of Science ®Google Scholar
• Murphy K, Pluim JPW, van Rikxoort EM, et al. Toward automatic regional analysis of pulmonary function using inspiration and expiration thoracic CT. Med Phys. 2012;39:1650–1662. doi:10.1118/1.368789122380397
   PubMed Web of Science ®Google Scholar
• Sørensen L, Loog M, Lo P, et al. Image dissimilarity-based quantification of lung disease from CT. Medical Image Computing and Computer-Assisted Intervention – MICCAI 2010; 2010:37–44.
   Google Scholar
• Sørensen L, Nielsen M, Lo P, Ashraf H, Pedersen JH, de Bruijne M. Texture-based analysis of COPD: A data-driven approach. IEEE Trans Med Imaging. 2012;31:70–78. doi:10.1109/TMI.2011.216493121859615
   PubMed Web of Science ®Google Scholar
• Van Rikxoort EM, de Jong PA, Mets OM,van Ginneken B. Automatic classication of pulmonary function in COPD patients using trachea analysis in chest CT scans. SPIE Medical Imaging. 2012; 8315: MI. doi.org/10.1117/12.911603
   Google Scholar
• Kuncheva LI, Rodriguez JJ, Syed YI, Phillips CO, Lewis KE. Classifier ensemble methods for diagnosing COPD from volatile organic compounds in exhaled air. Int J Knowledge Discovery Bioinf. 2012;3:1–15. doi:10.4018/jkdb.2012040101
   Google Scholar
• Mieloszyk RJ, Verghese GC, Deitch K, et al. Automated quantitative analysis of capnogram shape for COPD–normal and COPD–CHF classification. IEEE Trans Biomed Eng. 2014;61:2882–2890. doi:10.1109/TBME.2014.233295424967981
   PubMed Web of Science ®Google Scholar
• Phillips CO, Syed Y, Parthaláin NM, Zwiggelaar R, Claypole TC, Lewis KE. Machine learning methods on exhaled volatile organic compounds for distinguishing COPD patients from healthy controls. J Breath Res. 2012;6:036003. doi:10.1088/1752-7155/6/3/03600322759349
   PubMed Web of Science ®Google Scholar
• Van Berkel JJBN, Dallinga JW, Möller GM, et al. A profile of volatile organic compounds in breath discriminates COPD patients from controls. Respir Med. 2010;104:557–563. doi:10.1016/j.rmed.2009.10.01819906520
   PubMed Web of Science ®Google Scholar
• Bermejo-Peláez D, Estepar RSJ, Ledesma-Carbayo MJ. Emphysema classification using a multi-view convolutional network. 2018 IEEE 15th International Symposium on Biomedical Imaging (ISBI 2018), Washington, DC;2018;519–522. doi:10.1109/ISBI.2018.8363629
   Google Scholar
• Coppini G, Miniati M, Paterni M, Monti S, Ferdeghini EM. Computer-aided diagnosis of emphysema in COPD patients: neural-network-based analysis of lung shape in digital chest radiographs. Med Eng Phys. 2007;29:76–86. doi:10.1016/j.medengphy.2006.02.00116540362
   PubMed Web of Science ®Google Scholar
• Friman O, Borga M, Lundberg M, Tylen U, Knutsson H. Recognizing emphysema - a neural network approach. Object recognition supported by user interaction for service robots. Quebec City, Quebec; 2002;1: 512-515. doi:10.1109/ICPR.2002.1044781.
   Google Scholar
• Karabulut EM and Ibrikci T. Emphysema discrimination from raw HRCT images by convolutional neural networks. 9th International Conference on Electrical and Electronics Engineering (ELECO), Bursa, 2015, pp. 705-708. doi:10.1109/ELECO.2015.7394441
   Google Scholar
• Mendoza CS, Washko GR, Ross JC, et al. Emphysema quantificaion in a multi-scanner HRCT cohort using local intensity distributions. Proceedings IEEE International Symposium on Biomedical Imaging; 2012:474–477.
   Google Scholar
• Prasad M, Sowmya A, Wilson P. Multi-level classification of emphysema in HRCT lung images. Pattern Anal Appl. 2009;12:9–20. doi:10.1007/s10044-007-0093-7
   Web of Science ®Google Scholar
• Sørensen L, Shaker SB, de Bruijne M. Quantitative analysis of pulmonary emphysema using local binary patterns. IEEE Trans Med Imaging. 2010;29:559–569.20129855
   PubMed Web of Science ®Google Scholar
• Xu Y, Sonka M, McLennan G, Guo J, Hoffman EA. MDCT-based 3-D texture classification of emphysema and early smoking related lung pathologies. IEEE Trans Med Imaging. 2006;25:464–475. doi:10.1109/TMI.2006.87088916608061
   PubMed Web of Science ®Google Scholar
• Fernandez-Granero MA, Sanchez-Morillo D, Leon-Jimenez A. Computerised analysis of telemonitored respiratory sounds for predicting acute exacerbations of COPD. Sensors. 2015;15:26978–26996. doi:10.3390/s15102697826512667
   PubMed Web of Science ®Google Scholar
• Fernandez-Granero MA, Sanchez-Morillo D, Leon-Jimenez A. An artificial intelligence approach to early predict symptom-based exacerbations of COPD. Biotechnol Biotechnol Equip. 2018;32:778–784. doi:10.1080/13102818.2018.1437568
   Web of Science ®Google Scholar
• Mohktar MS, Redmond SJ, Antoniades NC, et al. Predicting the risk of exacerbation in patients with chronic obstructive pulmonary disease using home telehealth measurement data. Artif Intell Med. 2015;63:51–59. doi:10.1016/j.artmed.2014.12.00325704112
   PubMed Web of Science ®Google Scholar
• McHeick H, Saleh L, Ajami H, Mili H. Context relevant prediction model for COPD domain using bayesian belief network. Sensors (Basel). 2017;17(7). doi:10.3390/s17050968
   Web of Science ®Google Scholar
• He H, Sun Y, Sun B, Zhan Q. Application of a parametric model in the mortality risk analysis of ICU patients with severe COPD. Clin Respir J. 2018;12(2):491–498. doi:10.1111/crj.1254927606821
   PubMed Web of Science ®Google Scholar
• Moore E, Chatzidiakou L, Jones RL, et al. Linking e-health records, patient-reported symptoms and environmental exposure data to characterise and model COPD exacerbations: protocol for the COPE study. BMJ Open. 2016;6(7):e011330. doi:10.1136/bmjopen-2016-011330
   Web of Science ®Google Scholar
• Risebrough NA, Briggs A, Baker TM, et al. Validating A model to predict disease progression outcomes in patients with COPD. Value Health. 2014;17(7):A560–A561. doi:10.1016/j.jval.2014.08.1852
   PubMed Web of Science ®Google Scholar
• Briggs AH, Baker T, Risebrough NA, et al. Development of the Galaxy Chronic Obstructive Pulmonary Disease (COPD) model using data from ECLIPSE: internal validation of a linked-equations cohort model. Med Decis Making. 2017;37(4):469–480. doi:10.1177/0272989X1665311827317436
   PubMed Web of Science ®Google Scholar
• Hoogendoorn M, Corro Ramos I, Baldwin M, Gonzalez-Rojas Guix N, Rutten-van Molken M. Broadening the perspective of cost-effectiveness modeling in chronic obstructive pulmonary disease: a new patient-level simulation model suitable to evaluate stratified medicine. Value Health. 2019;22(3):313–321. doi:10.1016/j.jval.2018.10.00830832969
   PubMed Web of Science ®Google Scholar
• Altenburg WA, Bossenbroek L, de Greef MHG, Kerstjens HAM, Ten Hacken NHT, Wempe JB. Functional and psychological variables both affect daily physical activity in COPD: a structural equations model. Respir Med. 2013;107(11):1740–1747. doi:10.1016/j.rmed.2013.06.00223810269
   PubMed Web of Science ®Google Scholar
• Nwaru BI, Simpson CR, Sheikh A, Kotz D. External validation of a COPD prediction model using population-based primary care data: a nested case-control study. Sci Rep. 2017;7:44702. doi:10.1038/srep4470228304375
   PubMed Web of Science ®Google Scholar
• Kotz D, Simpson CR, Viechtbauer W, van Schayck OCP, Sheikh A. Development and validation of a model to predict the 10-year risk of general practitioner-recorded COPD. NPJ Prim Care Respir Med. 2014;24:14011. doi:10.1038/npjpcrm.2014.1124841327
   PubMed Web of Science ®Google Scholar
• Lode H, Allewelt M, Balk S, et al. A prediction model for bacterial etiology in acute exacerbations of COPD. Infection. 2007;35(3):143–149. doi:10.1007/s15010-007-6078-z17565454
   PubMed Web of Science ®Google Scholar
• Dal Negro RW, Micheletto C, Tognella S, Visconti M, Guerriero M, Sandri MF. A two-stage logistic model based on the measurement of pro-inflammatory cytokines in bronchial secretions for assessing bacterial, viral, and non-infectious origin of COPD exacerbations. COPD. 2005;2(1):7–16.17136956
   PubMedGoogle Scholar
• Erdemir A, Hunter PJ, Holzapfel GA, et al. Perspectives on sharing models and related resources in computational biomechanics research. J Biomech Eng. 2018;140(2):024701. doi:10.1115/1.4038768
   Web of Science ®Google Scholar
• Schneeweiss S, Eichler HG, Garcia-Altes A, et al. Real world data in adaptive biomedical innovation: a framework for generating evidence fit for decision-making. Clin Pharmacol Ther. 2016;100(6):633–646. doi:10.1002/cpt.51227627027
   PubMed Web of Science ®Google Scholar
• Ryan D, Blakey J, Chisholm A, et al. Use of electronic medical records and biomarkers to manage risk and resource efficiencies. Eur Respir J. 2017;4(1):1293386. doi:10.1080/20018525.2017.1293386
   Web of Science ®Google Scholar
• Agusti A, MacNee W. The COPD control panel: towards personalised medicine in COPD. Thorax. 2013;68(7):687–690. doi:10.1136/thoraxjnl-2012-20277223117977
   PubMed Web of Science ®Google Scholar
• Mattila J, Koikkalainen J, Virkki A, van Gils M, Lötjönen J. Design and application of a generic clinical decision support system for multiscale data. IEEE Trans Biomed Eng. 2012;59(1):234–240. doi:10.1109/TBME.2011.217098621990325
   PubMed Web of Science ®Google Scholar
• Sim I, Gorman P, Greenes RA, et al. Clinical decision support systems for the practice of evidence-based medicine. J Am Med Inform Assoc. 2001;8(6):527–534.11687560
   PubMed Web of Science ®Google Scholar
• Burgos F, Melia U, Vallverdú M, et al. Clinical decision support system to enhance quality control of spirometry using information and communication technologies. JMIR Med Inform. 2014;2(2):e29. doi:10.2196/medinform.317925600957
   PubMedGoogle Scholar
• Roca J, Cano I, Gomez-Cabrero D, Tegnér J. From systems understanding to personalized medicine: lessons and recommendations based on a multidisciplinary and translational analysis of COPD. Methods Mol Biol. 2016;1386:283–303. doi:10.1007/978-1-4939-3283-2_1326677188
   PubMedGoogle Scholar
• Velickovski F, Ceccaroni L, Roca J, et al. Clinical Decision Support Systems (CDSS) for preventive management of COPD patients. J Transl Med. 2014;12(Suppl 2):S9. doi:10.1186/1479-5876-12-S2-S925471545
   PubMed Web of Science ®Google Scholar
• Goldman AW, Burmeister Y, Cesnulevicius K, et al. Bioregulatory systems medicine: an innovative approach to integrating the science of molecular networks, inflammation and systems biology with the patient’s autoregulatory capacity? Front Physiol. 2015;6:225. doi:10.3389/fphys.2015.0009826347656
   PubMed Web of Science ®Google Scholar
• Gustafson C, Kara N. Fitzgerald, ND: case reports-informing the practice of systems medicine. Integr Med (Encinitas). 2015;14(6):36–39.26807070
   PubMedGoogle Scholar
• Belard A, Buchman T, Forsberg J, et al. Precision diagnosis: a view of the clinical decision support systems (CDSS) landscape through the lens of critical care. J Clin Monit Comput. 2017;31(2):261–271. doi:10.1007/s10877-016-9849-126902081
   PubMed Web of Science ®Google Scholar
• McGinn T. Putting meaning into meaningful use: a roadmap to successful integration of evidence at the point of care. JMIR Med Inform. 2016;4(2):e16. doi:10.2196/medinform.585327199223
   PubMed Web of Science ®Google Scholar