Prioritization of COPD protein biomarkers, based on a systematic study of the literature

Authors

  • Sara Ongay
  • Frank Klont
  • Peter Horvatovich
  • Rainer Bischoff
  • Nick HT ten Hacken

DOI:

https://doi.org/10.18063/APM.2016.01.006

Keywords:

COPD, biomarker, surrogate marker, review

Abstract

Chronic Obstructive Pulmonary Disease (COPD) is a chronic lung disease mostly due to smoking and until now diagnosed by spirometry (post bronchodilator FEV1/FVC <70%). However, in spite of the usefulness of FEV1 as diagnostic and prognostic tool, it has proven to be a weak indicator of future exacerbations, unable to predict lung function decline within COPD patients, as well as unable to identify the smokers “susceptible” to developing COPD at an early stage. Thus, there is an urgent need for biomarkers that address these questions and support clinical decision making in the diagnosis and treatment of (early) COPD. In this respect, considerable efforts have been devoted to identifying protein biomarkers that enable a better understanding of this complex disease and leading to better diagnostic and prognostic tools. However, in spite of the wide range of candidates that have been suggested as potentially useful COPD biomarkers, most remained at the level of the initial discovery, and only fibrinogen has been approved by the Food and Drug Administration (FDA) as predictor for all-cause mortality and COPD exacerbations. There is thus a need for future investigations of these biomarkers in large-scale and well characterized studies in order to prove their usefulness as surrogate endpoints. Based on this, the aim of the present review is to advance COPD biomarker development by providing a comprehensive overview of protein biomarker candidates which have been evaluated in clinical studies and prioritize them according to their potential of becoming valid, clinically useful COPD biomarkers.

References

Vestbo J, 2014, COPD: definition and phenotypes. Clinics in chest medicine, vol.35(1): 1–6.

Sin D D and Vestbo J Ã, 2009, Biomarkers in chronic obstructive pulmonary disease. Proceedings of the American Thoracic Society, vol.6(6): 543–545.

Han M K, Agusti A, Calverley P M, et al. 2010, Chronic obstructive pulmonary disease phenotypes: the future of COPD. American Journal of Respiratory and Critical Care Medicine, vol.182(5): 598–604.

MacNee W, 2013, Systemic inflammatory biomarkers and co-morbidities of chronic obstructive pulmonary disease. Annals of Medicine, vol.45(3): 291–300.

Stockley R A, 2014, Biomarkers in chronic obstructive pulmonary disease: Confusing or useful? International Journal of COPD, vol.9: 163–177.

Kristan S S, 2013, Blood specimen biomarkers of inflammation, matrix degradation, angiogenesis, and cardiac involvement: a future useful tool in assessing clinical outcomes of COPD patients in clinical practice? Archivum Immunologiae et Therapiae Experimentalis, vol.61(6): 469–481.

Russell R E, 2014, Chronic obstructive pulmonary disease: getting it right. Does optimal management of chronic obstructive pulmonary disease alter disease progression and improve survival? Current opinion in pulmonary medicine, vol.20(2): 127–131.

Faner R, Tal-Singer R, Riley J H, et al. 2014, Lessons from ECLIPSE: a review of COPD biomarkers. Thorax, vol.69(7): 666–672.

Pelaia G, Terracciano R, Vatrella A, et al. 2014, Application of proteomics and peptidomics to COPD. Biomed Research International, vol.2014(2014): 764581.

Agusti A and MacNee W, 2013, The COPD control panel: towards personalised medicine in COPD. Thorax, vol.68(7): 687–690.

Luis Lopez-Campos J, Bustamante V, Munoz X, et al. 2014, Moving towards patient-centered medicine for copd management: multidimensional approaches versus phenotype-based medicine — a critical view. Copd—Journal of Chronic Obstructive Pulmonary Disease, vol.11(5): 591–602.

Gershon A S, Campitelli M A, Croxford R, et al. 2014, Combination long-acting beta-agonists and inhaled corticosteroids compared with long-acting beta-agonists alone in older adults with chronic obstructive pulmonary disease. Jama—Journal of the American Medical Association, vol.312(11): 1114–1121.

Vestbo J, Vogelmeier C, Small M, et al. 2014, Understanding the GOLD 2011 Strategy as applied to a real-world COPD population. Respiratory medicine, vol.108(5): 729–736.

Yang I A, Clarke M S, Sim E H A, et al. 2012, Inhaled corticosteroids for stable chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews, (7): CD002991–CD002991.

Devanarayan V, Scholand M-B, Hoidal J, et al. 2010, Identification of distinct plasma biomarker signatures in patients with rapid and slow declining forms of COPD. Copd—Journal of Chronic Obstructive Pulmonary Disease, vol.7(1): 51–58.

Higashimoto Y, Iwata T, Okada M, et al. 2009, Serum biomarkers as predictors of lung function decline in chronic obstructive pulmonary disease. Respiratory medicine, vol.103(8): 1231–1238.

Holz O, Waschki B, Roepcke S, et al. 2014, Potential prognostic value of biomarkers in lavage, sputum and serum in a five year clinical follow-up of smokers with and without COPD. Bmc Pulmonary Medicine, vol.14: 30.

Rana G S J B, York T P, Edmiston J S, et al. 2010, Proteomic biomarkers in plasma that differentiate rapid and slow decline in lung function in adult cigarette smokers with chronic obstructive pulmonary disease (COPD). Analytical and Bioanalytical Chemistry, vol.397(5): 1809–1819.

Tashkin D P, 2013, Variations in FEV1 decline over time in chronic obstructive pulmonary disease and its implications. Current opinion in pulmonary medicine, vol.19(2): 116–124.

Franciosi L, Postma D S, Van den Berge M, et al. 2014, Susceptibility to COPD: differential proteomic profiling after acute smoking. PloS one, vol.9(7): e102037.

Tzortzaki E G, Tsoumakidou M, Makris D, et al. 2006, Laboratory markers for COPD in "susceptible" smokers. Clinica Chimica Acta, vol.364(1–2): 124–138.

Kim D K, Cho M H, Hersh C P, et al. 2012, Genome- wide association analysis of blood biomarkers in chr-onic obstructive pulmonary disease. American Journal of Respiratory and Critical Care Medicine, vol.186(12): 1238–1247.

Merali S, Barrero C A, Bowler R P, et al. 2014, Analysis of the plasma proteome in COPD: novel low abundance proteins reflect the severity of lung remodeling. Copd—Journal of Chronic Obstructive Pulmonary Disease, vol.11(2): 177–189.

Pinto-Plata V, Toso J, Lee K, et al. 2007, Profiling serum biomarkers in patients with COPD: associations with clinical parameters. Thorax, vol.62(7): 595–601.

Pinto-Plata V M, Mullerova H, Toso J F, et al. 2006, C-reactive protein in patients with COPD, control smokers and non-smokers. Thorax, vol.61(1): 23–28.

Vestbo J, Edwards L D, Scanlon P D, et al. 2011, Changes in forced expiratory volume in 1 second over time in COPD. New England Journal of Medicine, vol.365(13): 1184–1192.

Agusti A, Edwards L D, Rennard S I, et al. 2012, Persistent systemic inflammation is associated with poor clinical outcomes in COPD: a novel phenotype. PloS one, vol.7(5): e37483. 10.1371/journal.pone.0037483

Eagan T M L, Eide G E, Gulsvik A, et al. 2002, Nonresponse in a community cohort study — predictors and consequences for exposure-disease associations. Journal of clinical epidemiology, vol.55(8): 775–781.

Eagan T M L, Ueland T, Wagner P D, et al. 2010, Systemic inflammatory markers in COPD: results from the Bergen COPD Cohort Study. European Respiratory Journal, vol.35(3): 540–548.

Stolz D, Kostikas K, Blasi F, et al. 2014, Adreno-medullin refines mortality prediction by the BODE index in COPD: the "BODE-A" index. European Respiratory Journal, vol.43(2): 397–408.

Celli B R, Cote C G, Marin J M, et al. 2004, The body- mass index, airflow obstruction, dyspnea, and exercise capacity index in chronic obstructive pulmonary disease. New England Journal of Medicine, vol.350(10): 1005– 1012.

Hankinson J L, Kawut S M, Shahar E, et al. 2010, Performance of American Thoracic Society —recom-mended spirometry reference values in a multiethnic sample of adults: the multi-ethnic study of atheroscle-rosis (MESA) lung study. Chest, vol.137(1): 138–145.

Vestbo J, Anderson W, Coxson H O, et al. 2008, Eva-luation of COPD longitudinally to identify predictive surrogate end-points (ECLIPSE). European Respiratory Journal, vol.31(4): 869–873.

Vogelmeier C, Aquino T O, O'Brien C D, et al. 2012, A randomised, placebo-controlled, dose-finding study of AZD9668, an oral inhibitor of neutrophil elastase, in patients with chronic obstructive pulmonary disease tre-ated with tiotropium. Copd—Journal of Chronic Obstructive Pulmonary Disease, vol.9(2): 111–120.

Ohar J A, Crater G D, Emmett A, et al. 2014, Fluticasone propionate/salmeterol 250/50 mu g versus salm-eterol 50 mu g after chronic obstructive pulmonary disease exacerbation. Respiratory Research, vol.15: 105.

Holmgaard D B, Mygind L H, Titlestad I, et al. 2013, Calprotectin — a marker of mortality in COPD? Results from a prospective cohort study. Copd—Journal of Chronic Obstructive Pulmonary Disease vol.10(5): 581–587.

Holmgaard D B, Mygind L H, Titlestad I L, et al. 2013, Plasma YKL-40 and all-cause mortality in patients with chronic obstructive pulmonary disease. Bmc Pulmonary Medicine, vol.13: 77.

Criner G J, Connett J E, Aaron S D, et al. 2014, Simvastatin for the prevention of exacerbations in moderate-to-severe COPD. New England Journal of Medicine, vol.370(23): 2201–2210.

Albert R K, 2012, Azithromycin for prevention of exacerbations of COPD (vol 365, pg 689, 2011). New England Journal of Medicine, vol.366(14): 1356.

Pauwels R A, Lofdahl C G, Laitinen L A, et al. 1999, Long-term treatment with inhaled budesonide in persons with mild chronic obstructive pulmonary disease who continue smoking. New England Journal of Medicine, vol.340(25): 1948–1953.

Connett J E, Kusek J W, Bailey W C, et al. 1993, Design of the lung health study — a randomized clinical-trial of early intervention for chronic obstructive pulmonary-disease. Controlled Clinical Trials vol.14(2): S3–S19.

Altose M D, Redline S, Deitz C D, et al. 2000, Effect of inhaled triamcinolone on the decline in pulmonary function in chronic obstructive pulmonary disease. New England Journal of Medicine, vol.343(26): 1902–1909.

Ackermann-Liebrich U, Kuna-Dibbert B, Probst-Hensch N M, et al. 2005, Follow-up of the Swiss cohort study on air pollution and lung diseases in adults (SAPALDIA 2) 1991–2003: methods and characterization of parti-cipants. Sozial-Und Praventivmedizin, vol.50(4): 245– 263.

Martin B W, Ackermann-Liebrich U, Leuenberger P, et al., 1997, SAPALDIA: methods and participation in the cross-sectional part of the Swiss study on air pollution and lung diseases in adults. Sozial-Und Praventiv-medizin, vol.42(2): 67–84.

Burney P G J, Luczynska C, Chinn S, et al. 1994, The European Community Respiratory Health Survey. European Respiratory Journal, vol.7(5): 954–960.

European Community Respiratory Health Survey II Steering Commitee, 2002, The European Community Respiratory Health Survey II. European Respiratory Journal, vol.20(5): 1071–1079.

Bujarski S, Parulekar A D, Sharafkhaneh A, et al. 2015, The asthma COPD overlap syndrome (ACOS). Current Allergy and Asthma Reports, vol.15(3): 509.

Buchan A, Bennett R, Coad A, et al. 2015, The role of cardiac biomarkers for predicting left ventricular dysfunction and cardiovascular mortality in acute exacerbations of COPD. Open Heart, vol.2(1): e000052.

The Atherosclerosis Risk in Communities (ARIC) Study: design and objectives. The ARIC investigators. 1989, American Journal of Epidemiology, vol.129(4): 687– 702.

Berglund G, Eriksson K F, Israelsson B, et al. 1996, Cardiovascular risk groups and mortality in an urban Swedish male population: The Malmo Preventive Project. Journal of internal medicine, vol.239(6): 489–497.

Schnohr P, Jensen G, Nyboe J, et al. 1977, [The Copenhagen City Heart Study. A prospective cardiovascular population study of 20,000 men and women]. Ugeskrift for laeger, vol.139(32): 1921–1923.

Dahl M, Vestbo J, Zacho J, et al. 2011, C reactive protein and chronic obstructive pulmonary disease: a Mendelian randomisation approach. Thorax, vol.66(3): 197–204.

Hofman A, Breteler M M B, van Duijn C M, et al. 2007, The Rotterdam Study: objectives and design update. European journal of epidemiology, vol.22(11): 819–829.

Hofman A, van Duijn C M, Franco O H, et al. 2011, The Rotterdam Study: 2012 objectives and design update. European journal of epidemiology, vol.26(8): 657–686.

van Durme Y M T A, Verhamme K M C, Stijnen T, et al. 2009, Prevalence, incidence, and lifetime risk for the development of COPD in the elderly: the Rotterdam Study. Chest, vol.135(2): 368–377.

Plan and operation of the Third National Health and Nutrition Examination Survey, 1988–94. Series 1: programs and collection procedures. 1994, Vital and Health Statistics. Series 1, Programs and Collection Procedures, (32): 1–407.

Ezzati T M, Massey J T, Waksberg J, et al. 1992, Sample design: Third National Health and Nutrition Examination Survey. Vital and health Statistics. Series 2, Data Evaluation and Methods Research, (113): 1–35.

Liang B and Feng Y, 2012, The association of low bone mineral density with systemic inflammation in clinically stable COPD. Endocrine, vol.42(1): 190–195.

Fischer B M, Pavlisko E and Voynow J A, 2011, Pathogenic triad in COPD: oxidative stress, protease-anti-protease imbalance, and inflammation. International Journal of Chronic Obstructive Pulmonary Disease, vol.6: 413–421.

Rovina N, Koutsoukou A and Koulouris N G, 2013, Inflammation and immune response in COPD: where do we stand? Mediators of inflammation, vol.2013(2013): 413735.

Sethi S, Mahler D A, Marcus P, et al. 2012, Inflammation in COPD: implications for management. Amer-ican Journal of Medicine, vol.125(12): 1162–1170.

Aaron C P, Schwartz J E, Bielinski S J, et al. 2015, Intercellular adhesion molecule 1 and progression of percent emphysema: the MESA Lung Study. Respiratory medicine, vol.109(2): 255–264.

Albert R K, Connett J, Curtis J L, et al. 2012, Mannose-binding lectin deficiency and acute exacerbations of chronic obstructive pulmonary disease. International Journal of Chronic Obstructive Pulmonary Disease, vol.7: 767–777.

Breyer M-K, Rutten E P A, Locantore N W, et al. 2012, Dysregulated adipokine metabolism in chronic obstructive pulmonary disease. European journal of clinical investigation, vol.42(9): 983–991.

Cheng D T, Kim D K, Cockayne D A, et al. 2013, Systemic soluble receptor for advanced glycation end-products is a biomarker of emphysema and associated with AGER genetic variants in patients with chronic obstructive pulmonary disease. American Journal of Respiratory and Critical Care Medicine, vol.188(8): 948–957.

Dickens J A, Miller B E, Edwards L D, et al. 2011, COPD association and repeatability of blood biomarkers in the ECLIPSE cohort. Respiratory Research, vol.12: 146.

Eagan T M L, Gabazza E C, D'Alessandro-Gabazza C, et al. 2012, TNF-alpha is associated with loss of lean body mass only in already cachectic COPD patients. Respiratory Research, vol.13: 48.

Engstrom G, Segelstorm N, Ekberg-Aronsson M, et al., 2009, Plasma markers of inflammation and incidence of

hospitalisations for COPD: results from a population-based cohort study. Thorax, vol.64(3): 211–215.

Man S F P, Xing L, Connett J E, et al. 2008, Circulating fibronectin to C-reactive protein ratio and mortality: a biomarker in COPD? European Respiratory Journal, vol.32(6): 1451–1457.

Miller J, Edwards L D, Agusti A, et al. 2013, Comorbidity, systemic inflammation and outcomes in the ECLIPSE cohort. Respiratory Medicine, vol.107(9): 1376–1384.

Park H Y, Man S F P, Tashkin D, et al. 2013, The relation of serum myeloperoxidase to disease progression and mortality in patients with chronic obstructive pulmonary disease (COPD). PloS one, vol.8(4): e61315.

Pinto-Plata V, Casanova C, Muellerova H, et al. 2012, Inflammatory and repair serum biomarker pattern. Association to clinical outcomes in COPD. Respiratory Research, vol.13: 71.

Sin D D, Miller B E, Duvoix A, et al. 2011, Serum PARC/CCL-18 concentrations and health outcomes in chronic obstructive pulmonary disease. American Journal of Respiratory and Critical Care Medicine, vol.183(9): 1187–1192.

Wells J M, O'Reilly P J, Szul T, et al. 2014, An aberrant leukotriene A(4) hydrolase-proline-glycine-proline path-way in the pathogenesis of chronic obstructive pulmonary disease. American Journal of Respiratory and Critical Care Medicine, vol.190(1): 51–61.

Fischer B M, Voynow J A and Ghio A J, 2015, COPD: balancing oxidants and antioxidants. International Jour-nal of Chronic Obstructive Pulmonary Disease, vol.10: 261–76.

Duvoix A, Miranda E, Perez J, et al. 2011, Evaluation of full-length, cleaved and nitrosylated serum surfactant protein D as biomarkers for COPD. Copd—Journal of Chronic Obstructive Pulmonary Disease, vol.8(2): 79–95.

Foreman M G, Kong X, DeMeo D L, et al. 2011, Polymorphisms in surfactant protein-D are associated with chronic obstructive pulmonary disease. American Journal of Respiratory Cell and Molecular Biology, vol.44(3): 316–322.

Lomas D A, Silverman E K, Edwards L D, et al. 2008, Evaluation of serum CC-16 as a biomarker for COPD in the ECLIPSE cohort. Thorax, vol.63(12): 1058–1063.

Park H Y, Churg A, Wright J L, et al. 2013, Club cell protein 16 and disease progression in chronic obstru-ctive pulmonary disease. American Journal of Respir-atory and Critical Care Medicine, vol.188(12): 1413– 1419.

Lomas D A, Silverman E K, Edwards L D, et al. 2009, Serum surfactant protein D is steroid sensitive and associated with exacerbations of COPD. European Respiratory Journal, vol.34(1): 95–102.

Johnell O, Pauwels R, Lofdahl C G, et al. 2002, Bone mineral density in patients with chronic obstructive pulmonary disease treated with budesonide Turbuhaler (R). European Respiratory Journal, vol.19(6): 1058– 1063.

Scanlon P D, Connett J E, Wise R A, et al. 2004, Loss of bone density with inhaled triamcinolone in Lung Health Study II. American Journal of Respiratory and Critical Care Medicine, vol.170(12): 1302–1309.

Mannino D M, Valvi D, Mullerova H, et al. 2012, Fibrinogen, COPD and mortality in a nationally rep-resentative U.S. cohort. Copd—Journal of Chronic Obstructive Pulmonary Disease, vol.9(4): 359–366.

Romme E A P M, Murchison J T, Edwards L D, et al. 2013, CT-measured bone attenuation in patients with chronic obstructive pulmonary disease: relation to clinical features and outcomes. Journal of Bone and Mineral Research, vol.28(6): 1369–1377.

Waschki B, Spruit M A, Watz H, et al. 2012, Physical activity monitoring in COPD: compliance and assoc-iations with clinical characteristics in a multicenter study. Respiratory medicine, vol.106(4): 522–530.

Celli B R, Locantore N, Yates J, et al. 2012, Inflammatory biomarkers improve clinical prediction of mortality in chronic obstructive pulmonary disease. American Journal of Respiratory and Critical Care Medicine, vol.185(10): 1065–1072.

Hurst J R, Vestbo J, Anzueto A, et al. 2010, Susceptibility to exacerbation in chronic obstructive pulmonary disease. New England Journal of Medicine, vol.363(12): 1128–1138.

Mullerova H, Maselli D J, Locantore N, et al. 2015, Hospitalized exacerbations of COPD: risk factors and outcomes in the ECLIPSE cohort. Chest, vol.147(4): 999–1007.

Parker D R, Liu J, Roberts M B, et al. 2014, Is inflammatory chronic obstructive pulmonary disease a cor-onary heart disease risk equivalent? A longitudinal analysis of the third National Health and Nutrition Examination Survey (NHANES III), 1988–1994. Bmc Pulmonary Medicine, vol.14: 195.

Thomsen M, Ingebrigtsen T S, Marott J L, et al. 2013, Inflammatory biomarkers and exacerbations in chronic obstructive pulmonary disease. Jama—Journal of the American Medical Association, vol.309(22): 2353–2361.

Williams M C, Murchison J T, Edwards L D, et al. 2014, Coronary artery calcification is increased in patients with COPD and associated with increased morbidity and mortality. Thorax, vol.69(8): 718–723.

Casaburi R, Celli B, Crapo J, et al. 2013, The COPD Biomarker Qualification Consortium (CBQC). Copd—Journal of Chronic Obstructive Pulmonary Disease, vol.10(3): 367–377.

Lahousse L, Loth D W, Joos G F, et al. 2013, Statins, systemic inflammation and risk of death in COPD: the Rotterdam study. Pulmonary pharmacology & therapeutics, vol.26(2): 212–217.

Man S F P, Connett J E, Anthonisen N R, et al. 2006, C-reactive protein and mortality in mild to moderate chronic obstructive pulmonary disease. Thorax, vol.61(10): 849–853.

van Durme Y M T A, Verhamme K M C, Aarnoudse A-J L H J, et al. 2009, C-reactive protein levels, haplotypes, and the risk of incident chronic obstructive pulmonary disease. American Journal of Respiratory and Critical Care Medicine, vol.179(5): 375–382.

Madsen J, Kliem A, Tornoe I, et al. 2000, Localization of lung surfactant protein D on mucosal surfaces in human tissues. Journal of Immunology, vol.164(11): 5866–5870.

Voorhout W F, Veenendaal T, Kuroki Y, et al. 1992, Immunocytochemical localization of surfactant protein- D (SP-D) in type II cells, Clara cells, and alveolar macrophages of rat lung. Journal of Histochemistry & Cytochemistry, vol.40(10): 1589–1597.

Crouch E and Wright J R, 2001, Surfactant proteins A and D and pulmonary host defense. Annual Review of Physiology, vol.63: 521–554.

Singh G, Singh J, Katyal S L, et al. 1988, Identification, cellular-localization, isolation, and characterization of human Clara cell-specific 10-Kd protein. Journal of Histochemistry & Cytochemistry, vol.36(1): 73–80.

Lakind J S, Holgate S T, Ownby D R, et al. 2007, A critical review of the use of Clara cell secretory protein (CC16) as a biomarker of acute or chronic pulmonary effects. Biomarkers, vol.12(5): 445–467.

Buckley S T and Ehrhardt C, 2010, The receptor for advanced glycation end products (RAGE) and the lung. Journal of Biomedicine and Biotechnology, vol.2010: 917108.

Lindsey J B, Cipollone F, Abdullah S M, et al. 2009, Receptor for advanced glycation end-products (RAGE) and soluble RAGE (sRAGE): cardiovascular implications. Diabetes & Vascular Disease Research, vol.6(1): 7–14.

Selvin E, Halushka M K, Rawlings A M, et al. 2013, sRAGE and risk of diabetes, cardiovascular disease, and death. Diabetes, vol.62(6): 2116–2121.

Ferhani N, Letuve S, Kozhich A, et al. 2010, Expression of high-mobility group box 1 and of receptor for advanced glycation end products in chronic obstructive pulmonary disease. American Journal of Respiratory and Critical Care Medicine, vol.181(9): 917–927.

Prioritization of COPD protein biomarkers, based on a systematic study of the literature

Advances in Precision Medicine, vol 1, issue 1, 2016

Yoon H I, Li Y, Man S F P, et al. 2012, The complex relationship of serum adiponectin to COPD outcomes. Chest, vol.142(4): 893–899.

Berg I, Hanson C, Sayles H, et al. 2013, Vitamin D, vitamin D binding protein, lung function and structure in COPD. Respiratory medicine, vol.107(10): 1578–1588.

Hanania N A, Muellerova H, Locantore N W, et al. 2011, Determinants of depression in the ECLIPSE chronic obstructive pulmonary disease cohort. American Journal of Respiratory and Critical Care Medicine, vol.183(5): 604–611.

Donaldson G C, Muellerova H, Locantore N, et al. 2013, Factors associated with change in exacerbation frequency in COPD. Respiratory Research, vol.14: 79– 79.

Ólafsdóttir I S, Gíslason T, Thjóðleifsson B, et al. 2007, Gender differences in the association between Creative protein, lung function impairment, and COPD. International Journal of Chronic Obstructive Pulmonary Disease, vol.2(4): 635.

Bridevaux P O, Gerbase M W, Schindler C, et al. 2009, Sex-specific effect of body weight gain on systemic inflammation in subjects with COPD: results from the SAPALDIA cohort study 2. European Respiratory Journal, vol.34(2): 332–339.

Diaz A A, Zhou L, Young T P, et al. 2014, Chest CT measures of muscle and adipose tissue in COPD: gender-based differences in content and in relationships with blood biomarkers. Academic Radiology, vol.21(10): 1255–1261.

Eagan T M L, Aukrust P, Ueland T, et al. 2010, Body composition and plasma levels of inflammatory biomarkers in COPD. European Respiratory Journal, vol.36(5): 1027–1033.

Husebo G R, Bakke P S, Aanerud M, et al. 2014, Predictors of exacerbations in chronic obstructive pulmonary disease — results from the Bergen COPD cohort study. PloS One, vol.9(10): e109721.

Janssen D J A, Muellerova H, Agusti A, et al. 2014, Persistent systemic inflammation and symptoms of depression among patients with COPD in the ECLIPSE cohort. Respiratory Medicine, vol.108(11): 1647–1654.

Singh D, Edwards L, Tal-Singer R, et al. 2010, Sputum neutrophils as a biomarker in COPD: findings from the ECLIPSE study. Respiratory Research, vol.11: 77.

Mannino D M, Tal-Singer R, Lomas D A, et al. 2015, Plasma fibrinogen as a biomarker for mortality and hospitalized exacerbations in people with COPD. Chronic Obstructive Pulmonary Diseases: Journal of the COPD Foundation, vol.2(1): 23–34.

Eagan T M, Aukrust P, Bakke P S, et al. 2010, Systemic mannose-binding lectin is not associated with chronic obstructive pulmonary disease. Respiratory Medicine, vol.104(2): 283–290.

Eagan T M, Damas J K, Ueland T, et al. 2010, Neutrophil gelatinase-associated lipocalin: a biomarker in COPD. Chest, vol.138(4): 888–895.

Kunisaki K M, Niewoehner D E, Connett J E, et al. 2012, Vitamin D levels and risk of acute exacerbations of chronic obstructive pulmonary disease: a prospective cohort study. American Journal of Respiratory and Critical Care Medicine, vol.185(3): 286–290.

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2016-03-16

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