Pharmacological Management of Chronic Obstructive Lung Disease (COPD). Focus on Mutations - Part 1

Author(s): Patrizia Russo , Filippo Lococo , Aliaksei Kisialiou , Giulia Prinzi* , Palma Lamonaca , Vittorio Cardaci , Carlo Tomino , Massimo Fini .

Journal Name: Current Medicinal Chemistry

Volume 26 , Issue 10 , 2019

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Background: We report a comprehensive overview of current Chronic Obstructive Lung Disease (COPD) therapies and discuss the development of possible new pharmacological approaches based on “new” knowledge. Specifically, sensitivity/resistance to corticosteroids is evaluated with a special focus on the role of gene mutations in drug response.

Objective: Critically review the opportunities and the challenges occurring in the treatment of COPD.

Conclusion: Findings from “omics” trials should be used to learn more about biological targeted drugs, and to select more specific drugs matching patient’s distinctive molecular profile. Specific markers of inflammation such as the percentage of eosinophils are important in determining sensitivity/resistance to corticosteroids. Specific gene variations (Single nucleotide polymorphisms: SNPs) may influence drug sensitivity or resistance. Clinicians working in a real-world need to have a suitable interpretation of molecular results together with a guideline for the treatment and recommendations. Far more translational research is required before new results from omics techniques can be applied in personalized medicine in realworld settings.

Keywords: Classical therapy, complexity, COPD, eosinophils, personalized-medicine, real-life analysis, SNPs, systems approaches.

For, G.S. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. 2017. Available at: [Accessed: June 4, 2017].
Burden of COPD. Chronic respiratory diseases., Available at: http://www. [Accessed: June 4, 2017].
Barnes, P.J. Cellular and molecular mechanisms of chronic obstructive pulmonary disease. Clin. Chest Med., 2014, 35(1), 71-86.
Postma, D.S.; Rabe, K.F. The Asthma-COPD Overlap Syndrome. N. Engl. J. Med., 2015, 373(13), 1241-1249.
Fame, C.; Pauli, H.; Scherrer, M. [Various considerations on the classification into A and B types (“Pink puffers” and “Blue bloaters”) of chronic bronchial obstruction syndrome]. Rev. Med. Suisse Romande, 1970, 90(3), 203-218. [Article in French].
Agusti, A.G. COPD, a multicomponent disease: Implications for management. Respir. Med., 2005, 99(6), 670-682.
Rogliani, P.; Ora, J.; Puxeddu, E.; Cazzola, M. Airflow obstruction: is it asthma or is it COPD? Int. J. Chron. Obstruct. Pulmon. Dis., 2016, 11, 3007-3013.
Vestbo, J.; Hurd, S.S.; Agustí, A.G.; Jones, P.W.; Vogelmeier, C.; Anzueto, A.; Barnes, P.J.; Fabbri, L.M.; Martinez, F.J.; Nishimura, M.; Stockley, R.A.; Sin, D.D.; Rodriguez-Roisin, R. 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.
Postma, D.S.; Bush, A.; van den Berge, M. Risk factors and early origins of chronic obstructive pulmonary disease. Lancet, 2015, 385(9971), 899-909.
Schamberger, A.C.; Mise, N.; Meiners, S.; Eickelberg, O. Epigenetic mechanisms in COPD: Implications for pathogenesis and drug discovery. Expert Opin. Drug Discov., 2014, 9(6), 609-628.
Castaldi, P.J.; Cho, M.H.; San José Estépar, R.; McDonald, M.L.; Laird, N.; Beaty, T.H.; Washko, G.; Crapo, J.D.; Silverman, E.K. Genome-wide association identifies regulatory loci associated with distinct local histogram emphysema patterns. Am. J. Respir. Crit. Care Med., 2014, 190(4), 399-409.
Lococo, F.; Cesario, A.; Petracca-Ciavarella, L.; Granone, P.; Russo, P. Role of CHRNA5-A3 genetic Locus variants and developing drug for chronic obstructive pulmonary disease. Curr. Med. Chem., 2012, 19(34), 5863-5870.
Eisner, M.D.; Anthonisen, N.; Coultas, D.; Kuenzli, N.; Perez-Padilla, R.; Postma, D.; Romieu, I.; Silverman, E.K.; Balmes, J.R. An official American Thoracic Society public policy statement: Novel risk factors and the global burden of chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med., 2010, 182(5), 693-718.
Benowitz, N.L. Nicotine addiction. N. Engl. J. Med., 2010, 362(24), 2295-2303.
Russo, P.; Nastrucci, C.; Alzetta, G.; Szalai, C. Tobacco habit: Historical, cultural, neurobiological, and genetic features of people’s relationship with an addictive drug. Perspect. Biol. Med., 2011, 54(4), 557-577.
Cardinale, A.; Nastrucci, C.; Cesario, A.; Russo, P. Nicotine: Specific role in angiogenesis, proliferation and apoptosis. Crit. Rev. Toxicol., 2012, 42(1), 68-89.
Salvi, S.S.; Barnes, P.J. Chronic obstructive pulmonary disease in non-smokers. Lancet, 2009, 374(9691), 733-743.
van Koeverden, I.; Blanc, P.D.; Bowler, R.P.; Arjomandi, M. Secondhand Tobacco Smoke and COPD Risk in Smokers: A COPDGene Study Cohort Subgroup Analysis. COPD, 2015, 12(2), 182-189.
Kim, W.J.; Lee, S.D. Candidate genes for COPD: Current evidence and research. Int. J. Chron. Obstruct. Pulmon. Dis., 2015, 10, 2249-2255.
Lococo, F.; Cesario, A.; Del Bufalo, A.; Ciarrocchi, A.; Prinzi, G.; Mina, M.; Bonassi, S.; Russo, P. Novel therapeutic strategy in the management of COPD: A systems medicine approach. Curr. Med. Chem., 2015, 22(32), 3655-3675.
Rigotti, N.A. Smoking cessation in patients with respiratory disease: Existing treatments and future directions. Lancet Respir. Med., 2013, 1(3), 241-250.
Rennard, S.I.; Drummond, M.B. Early chronic obstructive pulmonary disease: Definition, assessment, and prevention. Lancet, 2015, 385(9979), 1778-1788.
Gallus, S.; Tramacere, I.; La Vecchia, C.; Colombo, P.; Zuccaro, P.; Paleari, L.; Cesario, A.; Russo, P.; Apolone, G. Use of pharmacotherapy for smoking cessation in Italy. Arch. Intern. Med., 2009, 169(20), 1927-1928.
Filippo, L.; Principe, R.; Cesario, A.; Apolone, G.; Carleo, F.; Ialongo, P.; Veronesi, G.; Cardillo, G. Smoking cessation intervention within the framework of a lung cancer screening program: Preliminary results and clinical perspectives from the “Cosmos-II” Trial. Hai, 2015, 193(1), 147-149.
Field, J.K.; Oudkerk, M.; Pedersen, J.H.; Duffy, S.W. Prospects for population screening and diagnosis of lung cancer. Lancet, 2013, 382(9893), 732-741.
Parsons, A.; Daley, A.; Begh, R.; Aveyard, P. Influence of smoking cessation after diagnosis of early stage lung cancer on prognosis: systematic review of observational studies with meta-analysis. BMJ, 2010, 340, b5569.
Hajek, P.; Stead, L.F.; West, R.; Jarvis, M.; Hartmann-Boyce, J.; Lancaster, T. Relapse prevention interventions for smoking cessation. Cochrane Database Syst. Rev., 2013, 8(8)CD003999
Cahill, K.; Stevens, S.; Perera, R.; Lancaster, T. Pharmacological interventions for smoking cessation: an overview and network meta-analysis. Cochrane Database Syst. Rev., 2013, 5(5)CD009329
Cahill, K.; Stevens, S.; Lancaster, T. Pharmacological treatments for smoking cessation. JAMA, 2014, 311(2), 193-194.
Crooks, P.A.; Bardo, M.T.; Dwoskin, L.P. Nicotinic receptor antagonists as treatments for nicotine abuse. Adv. Pharmacol., 2014, 69, 513-551.
Minicã, C.C.; Mbarek, H.; Pool, R.; Dolan, C.V.; Boomsma, D.I.; Vink, J.M. Pathways to smoking behaviours: biological insights from the Tobacco and Genetics Consortium meta-analysis. Mol. Psychiatry, 2016, 22(1), 82-88.
Bierut, L.J.; Stitzel, J.A.; Wang, J.C.; Hinrichs, A.L.; Grucza, R.A.; Xuei, X.; Saccone, N.L.; Saccone, S.F.; Bertelsen, S.; Fox, L.; Horton, W.J.; Breslau, N.; Budde, J.; Cloninger, C.R.; Dick, D.M.; Foroud, T.; Hatsukami, D.; Hesselbrock, V.; Johnson, E.O.; Kramer, J.; Kuperman, S.; Madden, P.A.; Mayo, K.; Nurnberger, J., Jr; Pomerleau, O.; Porjesz, B.; Reyes, O.; Schuckit, M.; Swan, G.; Tischfield, J.A.; Edenberg, H.J.; Rice, J.P.; Goate, A.M. Variants in nicotinic receptors and risk for nicotine dependence. Am. J. Psychiatry, 2008, 165(9), 1163-1171.
Woodruff, P.G.; Agusti, A.; Roche, N.; Singh, D.; Martinez, F.J. Current concepts in targeting chronic obstructive pulmonary disease pharmacotherapy: making progress towards personalised management. Lancet, 2015, 385(9979), 1789-1798.
Horita, N.; Goto, A.; Shibata, Y.; Ota, E.; Nakashima, K.; Nagai, K.; Kaneko, T. Long-acting muscarinic antagonist (LAMA) plus long-acting beta-agonist (LABA) versus LABA plus inhaled corticosteroid (ICS) for stable chronic obstructive pulmonary disease (COPD). Cochrane Database Syst. Rev., 2017, 2CD012066
Olland, A.; Reeb, J.; Puyraveau, M.; Hirschi, S.; Seitlinger, J.; Santelmo, N.; Collange, O.; Mertes, P.M.; Kessler, R.; Falcoz, P.E.; Massard, G. Bronchial complications after lung transplantation are associated with primary lung graft dysfunction and surgical technique. J. Heart Lung Transplant., 2017, 36(2), 157-165.
Criner, G.J. Alternatives to lung transplantation: Lung volume reduction for COPD. Clin. Chest Med., 2011, 32(2), 379-397.
Müllerova, H.; Maselli, D.J.; Locantore, N.; Vestbo, J.; Hurst, J.R.; Wedzicha, J.A.; Bakke, P.; Agusti, A.; Anzueto, A. Hospitalized exacerbations of COPD: Risk factors and outcomes in the ECLIPSE cohort. Chest, 2015, 147(4), 999-1007.
Walters, J.A.; Tan, D.J.; White, C.J.; Gibson, P.G.; Wood-Baker, R.; Walters, E.H. Systemic corticosteroids for acute exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst. Rev., 2014, 9(9)CD001288
Karner, C.; Cates, C.J. Combination inhaled steroid and long-acting beta(2)-agonist in addition to tiotropium versus tiotropium or combination alone for chronic obstructive pulmonary disease. Cochrane Database Syst. Rev., 2011, 3(3)CD008532
Mercado, N.; Ito, K.; Barnes, P.J. Accelerated ageing of the lung in COPD: New concepts. Thorax, 2015, 70(5), 482-489.
Saha, S.; Brightling, C.E. Eosinophilic airway inflammation in COPD. Int. J. Chron. Obstruct. Pulmon. Dis., 2006, 1, 39-47.
Holtzman, M.J.; Byers, D.E.; Alexander-Brett, J.; Wang, X. The role of airway epithelial cells and innate immune cells in chronic respiratory disease. Nat. Rev. Immunol., 2014, 14(10), 686-698.
Malhotra, R.; Olsson, H. Immunology, genetics and microbiota in the COPD pathophysiology: Potential scope for patient stratification. Expert Rev. Respir. Med., 2015, 9(2), 153-159.
Bafadhel, M.; McKenna, S.; Terry, S.; Mistry, V.; Pancholi, M.; Venge, P.; Lomas, D.A.; Barer, M.R.; Johnston, S.L.; Pavord, I.D.; Brightling, C.E. 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.
Pascoe, S.; Locantore, N.; Dransfield, M.T.; Barnes, N.C.; Pavord, I.D. Blood eosinophil counts, exacerbations, and response to the addition of inhaled fluticasone furoate to vilanterol in patients with chronic obstructive pulmonary disease: a secondary analysis of data from two parallel randomised controlled trials. Lancet Respir. Med., 2015, 3(6), 435-442.
Brusselle, G.G.; Bracke, K.; Lahousse, L. Targeted therapy with inhaled corticosteroids in COPD according to blood eosinophil counts. Lancet Respir. Med., 2015, 3(6), 416-417.
Pavord, I.D.; Lettis, S.; Locantore, N.; Pascoe, S.; Jones, P.W.; Wedzicha, J.A.; Barnes, N.C. Blood eosinophils and inhaled corticosteroid/long-acting β-2 agonist efficacy in COPD. Thorax, 2016, 71(2), 118-125.
Liao, W.; Long, H.; Chang, C.C.; Lu, Q. The eosinophil in health and disease: from bench to bedside and back. Clin. Rev. Allergy Immunol., 2016, 50(2), 125-139.
Furuta, G.T.; Atkins, F.D.; Lee, N.A.; Lee, J.J. Changing roles of eosinophils in health and disease. Ann. Allergy Asthma Immunol., 2014, 113(1), 3-8.
Broughton, S.E.; Dhagat, U.; Hercus, T.R.; Nero, T.L.; Grimbaldeston, M.A.; Bonder, C.S.; Lopez, A.F.; Parker, M.W. The GM-CSF/IL-3/IL-5 cytokine receptor family: from ligand recognition to initiation of signaling. Immunol. Rev., 2012, 250(1), 277-302.
Powell, C.; Milan, S.J.; Dwan, K.; Bax, L.; Walters, N. Mepolizumab versus placebo for asthma. Cochrane Database Syst. Rev., 2015, 7(7)CD010834
GSK announces start of phase III programme for mepolizumab in patients with COPD [news release]. 2014 April 29. Available at: [Accessed: February 4, 2016].
[54] Mepolizumab in chronic obstructive pulmonary diseases (COPD) with eosinophilic bronchitis. Available at: [Accessed: February 4, 2016].
[55] Efficacy and safety of mepolizumab as an add-on treatment in chronic obstructive pulmonary disease (COPD). Available at: [Accessed: February 4, 2016].
Lu, T.X.; Lim, E.J.; Besse, J.A.; Itskovich, S.; Plassard, A.J.; Fulkerson, P.C.; Aronow, B.J.; Rothenberg, M.E. MiR-223 deficiency increases eosinophil progenitor proliferation. J. Immunol., 2013, 190(4), 1576-1582.
Hua, L.; Zheng, W.; Xia, H.; Zhou, P.; An, L. Integration of multi-microarray datasets to identify chronic obstructive pulmonary disease-related miRNAs. Biomed. Mater. Eng., 2015, 26(26)(Suppl. 1), S1903-S1915.
Ezzie, M.E.; Crawford, M.; Cho, J.H.; Orellana, R.; Zhang, S.; Gelinas, R.; Batte, K.; Yu, L.; Nuovo, G.; Galas, D.; Diaz, P.; Wang, K.; Nana-Sinkam, S.P. Gene expression networks in COPD: MicroRNA and mRNA regulation. Thorax, 2012, 67(2), 122-131.
Wong, C.K.; Lau, K.M.; Chan, I.H.; Hu, S.; Lam, Y.Y.; Choi, A.O.; Lam, C.W. MicroRNA-21* regulates the prosurvival effect of GM-CSF on human eosinophils. Immunobiology, 2013, 218(2), 255-262.
Lu, T.X.; Sherrill, J.D.; Wen, T.; Plassard, A.J.; Besse, J.A.; Abonia, J.P.; Franciosi, J.P.; Putnam, P.E.; Eby, M.; Martin, L.J.; Aronow, B.J.; Rothenberg, M.E. MicroRNA signature in patients with eosinophilic esophagitis, reversibility with glucocorticoids, and assessment as disease biomarkers. J. Allergy Clin. Immunol., 2012, 129(4), 1064-75.e9.
Tantisira, K.G.; Lasky-Su, J.; Harada, M.; Murphy, A.; Litonjua, A.A.; Himes, B.E.; Lange, C.; Lazarus, R.; Sylvia, J.; Klanderman, B.; Duan, Q.L.; Qiu, W.; Hirota, T.; Martinez, F.D.; Mauger, D.; Sorkness, C.; Szefler, S.; Lazarus, S.C.; Lemanske, R.F., Jr; Peters, S.P.; Lima, J.J.; Nakamura, Y.; Tamari, M.; Weiss, S.T. Genomewide association between GLCCI1 and response to glucocorticoid therapy in asthma. N. Engl. J. Med., 2011, 365(13), 1173-1183.
Izuhara, Y.; Matsumoto, H.; Kanemitsu, Y.; Izuhara, K.; Tohda, Y.; Horiguchi, T.; Kita, H.; Kuwabara, K.; Tomii, K.; Otsuka, K.; Fujimura, M.; Ohkura, N.; Tomita, K.; Yokoyama, A.; Ohnishi, H.; Nakano, Y.; Oguma, T.; Hozawa, S.; Nagasaki, T.; Ito, I.; Oguma, T.; Inoue, H.; Tajiri, T.; Iwata, T.; Ono, J.; Ohta, S.; Tamari, M.; Hirota, T.; Yokoyama, T.; Niimi, A.; Mishima, M. GLCCI1 variant accelerates pulmonary function decline in patients with asthma receiving inhaled corticosteroids. Allergy, 2014, 69(5), 668-673.
The National Human Genome Research Institute (NHGRI) Catalog of Published Genome-Wide Association Studies.
Kim, W.J.; Lee, S.D. Candidate genes for COPD: Current evidence and research. Int. J. Chron. Obstruct. Pulmon. Dis., 2015, 10, 2249-2255.
Hobbs, B.D.; Parker, M.M.; Chen, H.; Lao, T.; Hardin, M.; Qiao, D.; Hawrylkiewicz, I.; Sliwinski, P.; Yim, J.J.; Kim, W.J.; Kim, D.K.; Castaldi, P.J.; Hersh, C.P.; Morrow, J.; Celli, B.R.; Pinto-Plata, V.M.; Criner, G.J.; Marchetti, N.; Bueno, R.; Agusti, A.; Make, B.J.; Crapo, J.D.; Calverley, P.M.; Donner, C.F.; Lomas, D.A.; Wouters, E.F.; Vestbo, J.; Paré, P.D.; Levy, R.D.; Rennard, S.I.; Zhou, X.; Laird, N.M.; Lin, X.; Beaty, T.H.; Silverman, E.K.; Cho, M.H. NETT Genetics; ECLIPSE; COPD Gene; International COPD Genetics Network Investigators. Exome array analysis identifies a common variant in IL27 associated with chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med., 2016, 194(1), 48-57.
Lamonaca, P.; Prinzi, G.; Kisialiou, A.; Cardaci, V.; Fini, M.; Russo, P. Metabolic disorder in chronic obstructive pulmonary disease (COPD) patients: Towards a personalized approach using marine drug derivatives. Mar. Drugs, 2017, 15(3), 3-15.
Hardin, M.; Cho, M.H.; McDonald, M.L.; Wan, E.; Lomas, D.A.; Coxson, H.O.; MacNee, W.; Vestbo, J.; Yates, J.C.; Agusti, A.; Calverley, P.M.; Celli, B.; Crim, C.; Rennard, S.; Wouters, E.; Bakke, P.; Bhatt, S.P.; Kim, V.; Ramsdell, J.; Regan, E.A.; Make, B.J.; Hokanson, J.E.; Crapo, J.D.; Beaty, T.H.; Hersh, C.P. A genome-wide analysis of the response to inhaled β2-agonists in chronic obstructive pulmonary disease. Pharmacogenomics J., 2016, 16(4), 326-335.
Rabe, K.F.; Fabbri, L.M.; Israel, E.; Kögler, H.; Riemann, K.; Schmidt, H.; Glaab, T.; Vogelmeier, C.F. Effect of ADRB2 polymorphisms on the efficacy of salmeterol and tiotropium in preventing COPD exacerbations: A prespecified substudy of the POET-COPD trial. Lancet Respir. Med., 2014, 2(1), 44-53.
Nielsen, A.O.; Jensen, C.S.; Arredouani, M.S.; Dahl, R.; Dahl, M. Variants of the ADRB2 gene in COPD: Systematic review and meta-analyses of disease risk and treatment response. COPD, 2017, 14(4), 451-460.
Emeryk-Maksymiuk, J.; Emeryk, A.; Krawczyk, P.; Wojas-Krawczyk, K.; Milanowski, J. Beta-2-adrenoreceptor polymorphism at position 16 determines the clinical severity of chronic obstructive pulmonary disease. Pulm. Pharmacol. Ther., 2017, 43, 1-5.
Cherubini, E.; Esposito, M.C.; Scozzi, D.; Terzo, F.; Osman, G.A.; Mariotta, S.; Mancini, R.; Bruno, P.; Ricci, A. Genetic Polymorphism of CHRM2 in COPD: Clinical Significance and Therapeutic Implications. J. Cell. Physiol., 2016, 231(8), 1745-1751.
Tantisira, K.G.; Lasky-Su, J.; Harada, M.; Murphy, A.; Litonjua, A.A.; Himes, B.E.; Lange, C.; Lazarus, R.; Sylvia, J.; Klanderman, B.; Duan, Q.L.; Qiu, W.; Hirota, T.; Martinez, F.D.; Mauger, D.; Sorkness, C.; Szefler, S.; Lazarus, S.C.; Lemanske, R.F., Jr; Peters, S.P.; Lima, J.J.; Nakamura, Y.; Tamari, M.; Weiss, S.T. Genomewide association between GLCCI1 and response to glucocorticoid therapy in asthma. N. Engl. J. Med., 2011, 365(13), 1173-1183.
van den Berge, M.; Hiemstra, P.S.; Postma, D.S. Genetics of glucocorticoids in asthma. N. Engl. J. Med., 2011, 365(25), 2434-2435.
Mosteller, M.; van den Berge, M.; Hosking, L.; Timens, W.; Hiemstra, P.S.; Crim, C. Genetic evaluation of the effect of GLCCI1 rs37973 on corticosteroid response in chronic obstructive pulmonary disease. COPD Res. Pract., 2017, 3, 2.
Lei, Y.; Gao, Y.; Chen, J.; Li, M.; Wu, X.; Ning, Q.; Zhao, J.; Xiong, W.; Xu, Y.; Xie, J. GLCCI1 rs37973: a potential genetic predictor of therapeutic response to inhaled corticosteroids in Chinese chronic obstructive pulmonary disease patients. Sci. Rep., 2017, 7, 42552.
Priyadharshini, V.S.; Teran, L.M. Personalized medicine in respiratory disease: role of proteomics. Adv. Protein Chem. Struct. Biol., 2016, 102, 115-146.
Paone, G.; Leone, V.; Conti, V.; De Marchis, L.; Ialleni, E.; Graziani, C.; Salducci, M.; Ramaccia, M.; Munafò, G. Blood and sputum biomarkers in COPD and asthma: A review. Eur. Rev. Med. Pharmacol. Sci., 2016, 20(4), 698-708.
Terracciano, R.; Pelaia, G.; Preianò, M.; Savino, R. Asthma and COPD proteomics: current approaches and future directions. Proteomics Clin. Appl., 2015, 9(1-2), 203-220.
Paone, G.; Leone, V.; Conti, V.; De Marchis, L.; Ialleni, E.; Graziani, C.; Salducci, M.; Ramaccia, M.; Munafò, G. Blood and sputum biomarkers in COPD and asthma: a review. Eur. Rev. Med. Pharmacol. Sci., 2016, 20(4), 698-708.
Nicholson, J.K.; Lindon, J.C. Systems biology: Metabonomics. Nature, 2008, 455(7216), 1054-1056.
Arakaki, A.K.; Skolnick, J.; McDonald, J.F. Marker metabolites can be therapeutic targets as well. Nature, 2008, 456(7221), 443.
Nobakht, M.; Gh, B.F.; Aliannejad, R.; Rezaei-Tavirani, M.; Taheri, S.; Oskouie, A.A.; Oskouie, A.A. The metabolomics of airway diseases, including COPD, asthma and cystic fibrosis. Biomarkers, 2015, 20(1), 5-16.
Adamko, D.J.; Nair, P.; Mayers, I.; Tsuyuki, R.T.; Regush, S.; Rowe, B.H. Metabolomic profiling of asthma and chronic obstructive pulmonary disease: A pilot study differentiating diseases. J. Allergy Clin. Immunol., 2015, 136(3), 571-580.e3.
Naz, S.; Kolmert, J.; Yang, M.; Reinke, S.N.; Kamleh, M.A.; Snowden, S.; Heyder, T.; Levänen, B.; Erle, D.J.; Sköld, C.M.; Wheelock, Å.M.; Wheelock, C.E. Metabolomics analysis identifies sex-associated metabotypes of oxidative stress and the autotaxin-lysoPA axis in COPD. Eur. Respir. J., 2017, 49(6)1602322
Singh, B.; Jana, S.K.; Ghosh, N.; Das, S.K.; Joshi, M.; Bhattacharyya, P.; Chaudhury, K. Metabolomic profiling of doxycycline treatment in chronic obstructive pulmonary disease. J. Pharm. Biomed. Anal., 2017, 132, 103-108.
Barabási, A.L.; Gulbahce, N.; Loscalzo, J. Network medicine: a network-based approach to human disease. Nat. Rev. Genet., 2011, 12(1), 56-68.
Janjić, V.; Pržulj, N. Przulj, N. The core diseasome. Mol. Biosyst., 2012, 8(10), 2614-2625.
Suratanee, A.; Plaimas, K. DDA: A novel network-based scoring method to identify disease-disease associations. Bioinform. Biol. Insights, 2015, 9, 175-186.
Glass, K.; Quackenbush, J.; Silverman, E.K.; Celli, B.; Rennard, S.I.; Yuan, G.C.; DeMeo, D.L. Sexually-dimorphic targeting of functionally-related genes in COPD. BMC Syst. Biol., 2014, 8, 118.
Ng, C.T.; Mendoza, J.L.; Garcia, K.C.; Oldstone, M.B. Alpha and beta type 1 interferon signaling: Passage for diverse biologic outcomes. Cell, 2016, 164(3), 349-352.
Barcelona Respiratory Network. 82. Available at: [Accesse:d February 4, 2016]
Agustí, A.; Barberà, J.A.; Wouters, E.F.; Peinado, V.I.; Jeffery, P.K. Lungs, bone marrow, and adipose tissue. A network approach to the pathobiology of chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med., 2013, 188(12), 1396-1406.
Castaldi, P.J.; Benet, M.; Petersen, H.; Rafaels, N.; Finigan, J.; Paoletti, M. MarikeBoezen, H.; Vonk, J.M.; Bowler, R.; Pistolesi, M.; Puhan, M.A.; Anto, J.; Wauters, E.; Lambrechts, D.; Janssens, W.; Bigazzi, F.; Camiciottoli, G.; Cho, M.H.; Hersh, C.P.; Barnes, K.; Rennard, S.; Boorgula, M.P.; Dy, J.; Hansel, N.N.; Crapo, J.D.; Tesfaigzi, Y.; Agusti, A.; Silverman, E.K.; Garcia-Aymerich, J. Do COPD subtypes really exist? COPD heterogeneity and clustering in 10 independent cohorts. Thorax, 2017, 72(11), 998-1006.
Agusti, A.; Bel, E.; Thomas, M.; Vogelmeier, C.; Brusselle, G.; Holgate, S.; Humbert, M.; Jones, P.; Gibson, P.G.; Vestbo, J.; Beasley, R.; Pavord, I.D. Treatable traits: Toward precision medicine of chronic airway diseases. Eur. Respir. J., 2016, 47(2), 410-419.
Shrimanker, R.; Choo, X.N.; Pavord, I.D. A new approach to the classification and management of airways diseases: Identification of treatable traits. Clin. Sci. (Lond.), 2017, 131(10), 1027-1043.
Fragoso, C.A. Epidemiology of Chronic Obstructive Pulmonary Disease (COPD) in aging populations. COPD, 2016, 13(2), 125-129.
Vetrano, D.L.; Bianchini, E.; Onder, G.; Cricelli, I.; Cricelli, C.; Bernabei, R.; Bettoncelli, G.; Lapi, F. Poor adherence to chronic obstructive pulmonary disease medications in primary care: Role of age, disease burden and polypharmacy. Geriatr. Gerontol. Int., 2017, 17(12), 2500-2506. Epub ahead of print
Andrews, A. ASCO and NCI launch largest precision medicine trials using real-world evidence. Am. Health Drug Benefits, 2015, 8(Spec Issue), 37.
Price, D.; Brusselle, G.; Roche, N.; Freeman, D.; Chisholm, A. Real-world research and its importance in respiratory medicine. Breathe (Sheff.), 2015, 11(1), 26-38.

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Year: 2019
Page: [1721 - 1733]
Pages: 13
DOI: 10.2174/0929867325666180601100235
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