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 - Tập 61 - Trang 469-481 - 2013
Sabina Skrgat Kristan1
1University clinic of respiratory and allergic diseases, Golnik, Slovenia

Tóm tắt

Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation that is not fully reversible; this airflow limitation is both progressive and associated with an abnormal inflammatory response of the lung to noxious particles or gasses. COPD is undoubtedly an umbrella term, and it seems unlikely that all patients with COPD have the same underlying disease processes; thus, there is a need for differential treatment of different subgroups. A potential solution is to find modifiable biomarkers that can assist in drug development and distinguish subgroups of COPD. With the exception of lung function tests, there are currently no well-validated biomarkers or surrogate endpoints that can be used to establish the efficacy of a drug for COPD. This article discusses biomarkers of inflammation (fibrinogen, C-reactive protein, pulmonary and activation-regulated chemokine/CC-chemokine ligand-18, serum surfactant protein D, interleukin (IL)-6, IL-8 and tumor necrosis factor α, complement factor C5a), angiogenesis factors as a part of the pathogenetic aspect in this disease (vascular endothelial growth factor, angiogenin, and IL-8), and matrix degradation biomarkers. Troponin and natriuretic peptides are presented as biomarkers of cardiac involvement in the light of COPD comorbidities. Trials based on research on known clinical variables such as FEV1, BODE, and 6MWT in combination with biomarkers from lung and blood specimens will probably clarify part of the prognosis and natural history of the disease. This will also represent an additional step in COPD phenotyping and new treatment possibilities.

Tài liệu tham khảo

(1980) Nocturnal Oxygen Therapy Trial Group. Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive pulmonary disease: a clinical trial. Ann Intern Med 93:391–398 (1983) Intermittent positive pressure breathing therapy of chronic obstructive pulmonary disease: a clinical trial. Ann Intern Med 9:612–620 (1999) Pulmonary rehabilitation 1999. Statement of American Thoracic Society. Am J Respir Crit Care Med 159:1666–1682 Adnot S, Andrivet P, Chabrier PE (1989) Atrial natriuretic factor in chronic obstructive lung disease with pulmonary hypertension. Physiological correlates and response to peptide infusion. J Clin Invest 83:986–993 Agusti AG (2005) Systemic effects of chronic obstructive pulmonary disease. Proc Am Thorac Soc 2:367–370 Agusti A (2007) Systemic effects of chronic obstructive pulmonary disease: what we know and what we don’t know (but should). Proc Am Thorac Soc 4:522–525 Agusti AG, Noguera A, Sauleda J et al (2003) Systemic effects of chronic obstructive pulmonary disease. Eur Respir J 21:347–360 Agusti A, Edwards LD, Rennard SI et al (2012) Persistent systemic inflammation is associated with poor clinical outcomes in COPD: a novel phenotype. PLoS ONE 7:e37483 Alpert JS, Thygesen K, Antman E et al (2000) Myocardial infarction redefined: a consensus document of the Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction. J Am Coll Cardiol 36:959–969 Anthonisen NR, Connett JE, Kiley JP et al (1994) Effects of smoking intervention and the use of an inhaled anticholinergic bronchodilator on the rate of decline of FEV1: the Lung Health Study. JAMA 272:1497–1505 ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories (2002) ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med 166:111–117 Barnes PJ, Celli BR (2009) Systemic manifestations and comorbidities of COPD. Eur Respir J 33:1165–1185 Bernasconi M, Tamm M, Bingisser R et al (2011) Midregional proatrial natriuretic peptide predicts survival in exacerbations of COPD. Chest 140:91–99 Bhowmik A, Seemungal TA, Sapsford RJ et al (2000) Relation of sputum inflammatory markers to symptoms and lung function changes in COPD exacerbations. Thorax 55:114–120 Broide DH, Lotz M, Cuomo AJ et al (1992) Cytokines in symptomatic asthma airways. J Allergy Clin Immunol 89:958–967 Bucher HC, Guyatt GH, Cook DJ et al (1999) Users’ guides to the medical literature: XIX. Applying clinical trial results. A. How to use an article measuring the effect of an intervention on surrogate end points: evidence-based medicine working group. JAMA 282:771–778 Calverley PM, Anderson JA, Celli B et al (2007) Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N Engl J Med 356:775–789 Castell JV, Gómez-Lechón MJ, David M et al (1989) Interleukin-6 is the major regulator of acute phase protein synthesis in adult human hepatocytes. FEBS Lett 242:237–239 Cazzola M, MacNee W, Martinez FJ et al (2008) Outcomes for COPD pharmacological trials: from lung function to biomarkers. Eur Respir J 31:416–468 Celli BR (2010) Predictors of mortality in COPD. Respir Med 104:773–779 Celli BR, Cote CG, Jose M et al (2004) The body-mass index, airflow obstruction, dyspnea, and exercise capacity index in chronic obstructive pulmonary disease. N Engl J Med 350:1005–1012 Celli BR, Locantore N, Yates J et al (2012) Inflammatory biomarkers improve clinical prediction of mortality in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 185:1065–1072 Chang MK, Binder CJ, Torzewski M et al (2002) C-reactive protein binds to both oxidized LDL and apoptotic cells through recognition of a common ligand: phosphorylcholine of oxidized phospholipids. Proc Natl Acad Sci USA 99:13043–13048 Chang CL, Robinson SC, Mils GD et al (2011) Biochemical markers of cardiac dysfunction predict mortality in acute exacerbation of COPD. Thorax 66:764–768 Chaouat A, Naeije R, Weitzenblum E (2008) Pulmonary hypertension in COPD. Eur Respir J 32:1371–1385 Chatila WM, Thomashow BM, Minai OA et al (2008) Comorbidities in chronic obstructive pulmonary disease. Proc Am Thorac Soc 5:549–555 Chomarat P, Banchereau J, Davoust J et al (2000) IL-6 switches the differentiation of monocytes from dendritic cells to macrophages. Nat Immunol 1:510–514 Dahl M, Nordestgaard BG (2009) Markers of early disease and prognosis in COPD. Int J Chron Obstruct Pulmon Dis 4:157–167 Dahl M, Tybjaerg-Hansen A, Vestbo J et al (2001) Elevated plasma fibrinogen associated with reduced pulmonary function and increased risk of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 164:1008–1011 Dahl M, Vestbo J, Lange P et al (2007) C-reactive protein as a predictor of prognosis in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 175:250–255 Danesh J, Lewington S, Thomson SG et al (2005) Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis. JAMA 294:1799–1809 Darnule TV, McKee M, Darnule AT et al (1982) Solid-phase radioimmunoassay for estimation of elastin peptides in human sera. Anal Biochem 122:302–307 De Gruttola VG, Clax P et al (2001) Considerations in the evaluation of surrogate endpoints in clinical trials. Summary of a national institutes of health workshop. Control Clin Trials 22:485–502 de Lemos JA, Morrow DA, Bentley JH et al (2001) The prognostic value of B-type natriuretic peptide in patients with acute coronary syndromes. N Engl J Med 345:1014–1021 de Torres JP, Cordoba-Lanus E, Lopez-Aguilar C et al (2006) C-relative protein levels and clinically important predictive outcomes in stable COPD patients. Eur Respir J 27:902–907 Di Francia M, Barbier D, Mege JL et al (1994) Tumor necrosis factor-alpha levels and weight loss in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 150:1453–1455 DiCosmo BF, Geba GP, Picarella D et al (1994) Airway epithelial cell expression of interleukin-6 in transgenic mice. Uncoupling of airway inflammation and bronchial hyperreactivity. J Clin Invest 94:2028–2035 Donaldson GC (2007) C-reactive protein. Does it predict mortality? Am J Respir Crit Care Med 175:209–210 Donaldson GC, Seemungal TA, Bhowmik A et al (2002) Relationship between exacerbation frequency and lung function decline in chronic obstructive pulmonary disease. Thorax 57:847–852 Donaldson GC, Seemungal TA, Patel IS et al (2003) Longitudinal changes in the nature, severity and frequency of COPD exacerbations. Eur Respir J 22:931–936 Donaldson GC, Seemungal TA, Patel IS et al (2005) Airway and systemic inflammation and decline in lung function in patients with COPD. Chest 128:1995–2004 Eagan TML, Gabazza EC, Gabazza CA et al (2012) TNF-α is associated with loss of lean body mass only in already cachectic COPD patients. Respir Res 13:48 Espiner EA, Richards AM, Yandle TG et al (1995) Natriuretic hormones. Endocrinol Metab Clin North Am 24:481–509 Fabbri LM, Rabe KF (2007) From COPD to chronic systemic inflammatory syndrome? Lancet 370:797–799 Ferrara N (2000) VEGF: an update on biological and therapeutic aspects. Curr Opin Biotechnol 11:617–624 Fett JW, Strydom DJ, Lobb RR et al (1985) Isolation and characterisation of angiogenin, an angiogenic protein from human carcinoma cells. Biochemistry 24:5480–5486 Foster JA, Curtiss SW (1990) The regulation of lung elastin synthesis. Am J Physiol 259(2 Pt 1):L13–L23 Fukuoka Y, Xia HZ, Sanchez-Muñoz LB et al (2008) Generation of anaphylatoxins by human beta-tryptase from C3, C4, and C5. J Immunol 180:6307–6316 Gabay C, Kushner I (1999) Acute-phase proteins and other systemic responses to inflammation. N Engl J Med 340:448–454 Gan WQ, Man SF, Senthilselvan A et al (2004) Association between chronic obstructive pulmonary disease and systemic inflammation: a systematic review and a meta-analysis. Thorax 59:574–580 Garcia-Aymerich J, Monso E, Marrades RM et al (2001) Risk factors for hospitalization for a chronic obstructive pulmonary disease exacerbation: eFRAM study. Am J Respir Crit Care Med 164:1002–1007 Gerardi DA, Lovett L, Benoit-Connors ML et al (1996) Variables related to increased mortality following outpatient pulmonary rehabilitation. Eur Respir J 9:431–435 Gershov D, Kim S, Brot N et al (2000) C-reactive protein binds to apoptotic cells, protects the cells from assembly of the terminal complement components, and sustains an anti-inflammatory innate immune response: implications for systemic autoimmunity. J Exp Med 192:1353–1364 Global Initiative for Chronic Obstructive Lung Disease (GOLD) (2011) Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease (revised) Goldstein RA, Starcher BC (1978) Urinary excretion of elastin peptides containing desmosine after intratracheal injection of elastin in hamsters. J Clin Invest 61:1286–1290 Gottlieb DJ, Stone PJ, Sparrow D et al (1996) Urinary desmosine excretion in smokers with and without rapid decline of lung function: the Normative Aging Study. Am J Respir Crit Care Med 154:1290–1295 Gunther C, Bello-Fernandez C, Kopp T et al (2005) CCL18 is expressed in atopic dermatitis and mediates skin homing of human memory T cells. J Immunol 174:1723–1728 Hajiro T, Nishimura K, Tsukino M et al (1998) Comparison of discriminative properties among disease specific questionnaires for measuring health related quality of life in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 157:785–790 Harel S, Janoff A, Yu SY et al (1980) Desmosine radioimmunoassay for measuring elastin degradation in vivo. Am Rev Respir Dis 122:769–773 Harvey MG, Hancox RJ (2004) Elevation of cardiac troponins in exacerbation of chronic obstructive pulmonary disease. Emerg Med Australas 16:212–215 Hierholzer C, Kalff JC, Omert L et al (1998) Interleukin-6 production in hemorrhagic shock is accompanied by neutrophil recruitment and lung injury. Am J Physiol 275:L611–L621 Huang TJ, Chaudhuri R, Albarbarawi O et al (2012) Clinical validity of plasma and urinary desmosine as biomarkers for chronic obstructive pulmonary disease. Thorax 67:502–508 Hurst JR, Donaldson GC, Perera WR et al (2006) Use of plasma biomarkers at exacerbation of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 174:867–874 Jatakanon A, Uasuf C, Maziak W et al (1999) Neutrophilic inflammation in severe persistent asthma. Am J Respir Crit Care Med 160:1532–1539 Johnston RA, Schwartzman IN, Flynt L et al (2005) Role of interleukin-6 in murine airway responses to ozone. Am J Physiol Lung Cell Mol Physiol 288:L390–L397 Kanazawa H, Asai K, Hirata K et al (2003) Possible effects of vascular endothelial growth factor in the pathogenesis of chronic obstructive pulmonary disease. Am J Med 114:354–358 Kaner RJ, Crystal RG (2001) Compartmentalization of vascular endothelial growth factor to the epithelial surface of the human lung. Mol Med 7:240–246 Kasahara Y, Tuder RM, Taraseviciene-Stewart L et al (2000) Inhibition of VEGF receptors causes lung cell apoptosis and emphysema. J Clin Invest 106:1311–1319 Kazi AS, Lotfi S, Goncharova EA et al (2004) Vascular endothelial growth factor-induced secretion of fibronectin is ERK dependent. Am J Physiol Lung Cell Mol Physiol 286:L539–L545 Kessler R, Faller M, Fourgaut G et al (1999) Predictive factors of hospitalization for acute exacerbation in a series of 64 patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 159:158–164 Kishimoto K, Liu S, Tsui T et al (2005) Endogenous angiogenin in endothelial cells is a general requirement for cell proliferation and angiogenesis. Oncogene 24:445–456 Kishore U, Greenhough TJ, Waters P et al (2006) Surfactant proteins SP-A and SP-D: structure, function and receptors. Mol Immunol 43:1293–1315 Köhl J (2001) Anaphylatoxins and infectious and non-infectious inflammatory diseases. Mol Immunol 38:175–187 Kony S, Zureik M, Driss F et al (2004) Association of bronchial hyperresponsiveness and lung function with C-reactive protein (CRP): a population based study. Thorax 59:892–896 Kraaijeveld AO, de Jager SC, de Jager WJ et al (2007) CC chemokine ligand-5 (CCL5/RANTES) and CC chemokine ligand-18 (CCL18/PARC) are specific markers of refractory unstable angina pectoris and are transiently raised during severe ischemic symptoms. Circulation 116:1931–1941 Kragelund C, Gronning B, Kober L et al (2005) N-terminal pro-B-type natriuretic peptide and long-term mortality in stable coronary heart disease. N Engl J Med 352:666–675 Kranenburg AR, de Boer WI, Alagappan VK et al (2005) Enhanced bronchial expression of vascular endothelial growth factor and receptors (Flk-1 and Flt-1) in patients with chronic obstructive pulmonary disease. Thorax 60:106–113 Kristan SS, Malovrh MM, Silar M et al (2009) Airway angiogenesis in patients with rhinitis and controlled asthma. Clin Exp Allergy 39:354–360 Kristan SS, Marc MM, Kern I et al (2012) Airway angiogenesis in stable and exacerbated chronic obstructive pulmonary disease. Scand J Immunol 75:109–114 Lainscak M, von Haehling S, Anker SD (2009) Natriuretic peptides and other biomarkers in chronic heart failure: from BNP, NT-proBNP, and MR-proANP to routine biochemical markers. Int J Cardiol 132:303–311 Lomas DA, Silverman EK, Edwards LD et al (2009) Serum surfactant protein D is steroid sensitive and associated with exacerbations of COPD. Eur Respir J 34:95–102 Loza MJ, Watt R, Baribaud F et al (2012) Systemic inflammatory profile and response to anti-tumor necrosis factor therapy in chronic obstructive pulmonary disease. Respir Res 13:12 Luisetti M, Ma S, Iadarola P et al (2008) Desmosine as a biomarker of elastin degradation in COPD: current status and future directions. Eur Respir J 32:1146–1157 Ma S, Lieberman S, Turino GM et al (2003) The detection and quantitation of free desmosine and isodesmosine in human urine and their peptide-bound forms in sputum. Proc Natl Acad Sci USA 100:12941–12943 Macie C, Wooldrage K, Manfreda J et al (2006) Inhaled corticosteroids and mortality in COPD. Chest 130:640–646 Mahajan N, Mehta Y, Rose M et al (2006) Elevated troponin level is not synonymous with myocardial infarction. Int J Cardiol 111:442–449 Mahler DA, Criner GJ (2007) Assessment tools for chronic obstructive pulmonary disease: do newer metrics allow for disease modification? Proc Am Thorac Soc 4:507–511 Mahler DA, Weinberg DH, Wells CK et al (1984) The measurement of dyspnea: contents, interobserver agreement, and physiologic correlates of two new clinical indexes. Chest 85:751–758 Malhotra S, Man SF, Sin DD (2006) Emerging drugs for the treatment of chronic obstructive pulmonary disease. Expert Opin Emerg Drugs 11:275–291 Man SF, Connett JE, Anthonisen NR et al (2006) C-reactive protein and mortality in mild to chronic obstructive pulmonary disease. Thorax 61:849–853 Marc MM, Korosec P, Kosnik M et al (2004) Complement factors c3a, c4a, and c5a in chronic obstructive pulmonary disease and asthma. Am J Respir Cell Mol Biol 31:216–219 Marc MM, Kristan SS, Rozman A et al (2010) Complement factor C5a in acute exacerbation of chronic obstructive pulmonary disease. Scand J Immunol 71:386–391 Marcun R, Sustic A, Brguljan PM et al (2012) Cardiac biomarkers predict outcome after hospitalisation for an acute exacerbation of chronic obstructive pulmonary disease. Int J Cardiol 161:156–159 Martin LD, Rochelle LG, Fischer BM et al (1997) Airway epithelium as an effector of inflammation: molecular regulation of secondary mediators. Eur Respir J 10:2139–2146 Mazzarella G, Grella E, D’Auria D et al (2000) Phenotypic features of alveolar monocytes/macrophages and IL-8 gene activation by IL-1 and TNF-a in asthmatic patients. Allergy 55(Suppl 61):36–41 Mecham RP (1997) Elastin fibers in the lung. In: Crystal RG, West JB, Weibel ER, Barnes PJ (eds) Scientific foundations. Lippincott-Raven, Philadelphia, pp 729–736 Mold C, Rodic-Polic B, Du Clos TW (2002) Protection from Streptococcus pneumoniae infection by C-reactive protein and natural antibody requires complement but not Fc receptors. J Immunol 168:6375–6381 Mori K, Kurihara N, Hayashida S et al (2002) The intrauterine expression of surfactant protein D in the terminal airways of human fetuses compared with surfactant protein A. Eur J Pediatr 161:431–434 Mura M, dos Santos CC, Stewart D et al (2004) Vascular endothelial growth factor and related molecules in acute lung injury. J Appl Physiol 97:1605–1617 Nagaya N, Nishikimi T, Uematsu M et al (2000) Plasma brain natriuretic peptide as a prognostic indicator in patients with primary pulmonary hypertension. Circulation 102:865–870 Neas LM, Schwartz J (1998) Pulmonary function levels as predictors of mortality in a national sample of US adults. Am J Epidemiol 147:1011–1018 Nussbaumer-Ochsner Y, Rabe KF (2011) Systemic manifestations of COPD. Chest 139:165–173 Oostenbrink JB, Rutten-van Molken MP (2004) Resource use and risk factors in high-cost exacerbations of COPD. Respir Med 98:883–891 Ordonez CL, Shaughnessy TE, Matthay MA et al (2000) Increased neutrophil numbers and IL-8 levels in airway secretions in acute severe asthma. Am J Respir Crit Care Med 161:1185–1190 Papaioannou AI, Kostikas K, Kollia P et al (2006) Clinical implications for vascular endothelial growth factor in the lung: a friend or foe? Respir Res 7:128 Pauwels R, Buist A, Calverley P et al (2001) 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 163:1256–1276 Pinto-Plata VM, Mullerova H, Toso JF et al (2006) C-reactive protein in patients with COPD, control smokers and non-smokers. Thorax 61:23–28 Pinto-Plata V, Toso J, Lee K et al (2007) Profiling serum biomarkers in patients with COPD: associations with clinical parameters. Thorax 62:595–601 Polverini PJ (1995) The pathophysiology of angiogenesis. Crit Rev Oral Biol Med 6:230–247 Puxeddu I, Ribatti D, Crivellato E et al (2005) Mast cells and eosinophils: a novel link between inflammation and angiogenesis in allergic diseases. J Allergy Clin Immunol 116:531–536 Racki S, Zaputovic L, Mavric Z et al (2006) C-reactive protein is a strong predictor of mortality in hemodialysis patients. Ren Fail 28:427–433 Rennard SI, Fogarty C, Kelsen S et al (2007) The safety and efficacy of infliximab in moderate to severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med 175:926–934 Rovina N, Papapetropoulos A, Kollintza A et al (2007) Vascular endothelial growth factor reflecting airway inflammation in healthy smokers and in patients with bronchitis type of chronic obstructive pulmonary disease? Respir Res 8:53 Sandberg LB, Soskel NT, Leslie JG (1981) Elastin structure, biosynthesis, and relation to disease states. N Engl J Med 304:566–579 Sapey E, Bayley D, Ahmad A et al (2008) Interrelationships between inflammatory markers in patients with stable COPD with bronchitis: intra-patient and inter-patient variability. Thorax 63:493–499 Schols AM, Slangen J, Volovics L et al (1998) Weight loss is a reversible factor in the prognosis of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 157:1791–1797 Seemungal TA, Donaldson GC, Bhowmik A et al (2000) Time course and recovery of exacerbations in patients with chronic obstructive pulmonary disease. Am J Respir Crit Med 161:1608–1613 Sin DD, Vestbo J (2009) Biomarkers in obstructive pulmonary disease. Proc Am Thorac Soc 6:543–545 Sin DD, Lacy P, York E et al (2004) Effects of fluticasone on systemic markers of inflammation in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 170:760–765 Sin DD, Miller BE, Duvoix A (2011) Serum PARC/CCL-18 concentrations and health outcomes in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 183:1187–1192 Soler N, Torres A, Ewig S et al (1998) Bronchial microbial patterns in severe exacerbations of chronic obstructive pulmonary disease (COPD) requiring mechanical ventilation. Am J Respir Crit Care Med 157:1498–1505 Stone PJ, Gottlieb DJ, O’Connor GT et al (1995) Elastin and collagen degradation products in urine of smokers with and without chronic obstructive pulmonary disease. Am J Respir Crit Care Med 151:952–959 Sutherland ER, Cherniack RM (2004) Management of chronic obstructive pulmonary disease. N Engl J Med 350:2689–2697 Suwa T, Hogg JC, Klut ME et al (2001) Interleukin-6 changes deformability of neutrophils and induces their sequestration in the lung. Am J Respir Crit Care Med 163:970–976 Swedberg K, Cleland J, Dargie H et al (2005) Guidelines for the diagnosis and treatment of chronic heart failure: full text (update 2005). Eur Heart J 26:1115–1140 Thomason MJ, Strachan DP (2000) Which spirometric indices best predict subsequent death from chronic obstructive pulmonary disease? Thorax 55:785–788 Tulevski II, Hirsch A, Sanson BJ et al (2001) Increased brain natriuretic peptide as a marker for right ventricular dysfunction in acute pulmonary embolism. Thromb Haemost 86:1193–1196 Turino GM, Ma S, Lin YY et al (2011) Matrix elastin. A promising biomarker for chronic obstructive pulmonary disease. Am J Respir Crit Care Med 184:637–641 US Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) (2007) Guidance for industry chronic obstructive pulmonary disease: developing drugs for treatment. Available via http://www.fda.gov/CDER/GUIDANCE/7875dft.pdf. Accessed 14 April 2009 Valipour A, Schreder M, Wolzt M et al (2008) Circulating vascular endothelial growth factor and systemic inflammatory markers in patients with stable and exacerbated chronic obstructive pulmonary disease. Clin Sci 115:225–232 van Tits L, de Graaf J, Toenhake H et al (2005) C-reactive protein and annexin A5 bind to distinct sites of negatively charged phospholipids present in oxidized low-density lipoprotein. Arterioscler Thromb Vasc Biol 25:717–722 Vestbo J, Edvards LD, Scanlon PD et al (2011) Changes in forced expiratory volume in 1 second over time in COPD. N Engl J Med 365:1184–1192 Vignola AM, Rennar SI, Hargreave FE et al (2002) Standardised methodology of sputum induction and processing: future directions. Eur Respir J Suppl 37:51s–55s Walters EH, Reid D, Soltani A et al (2008) Angiogenesis: a potentially critical part of remodelling in chronic airway diseases? Pharmacol Ther 118:128–137 Weiser JN, Pan N, McGowan KL et al (1998) Phosphorylcholine on the lipopolysaccharide of Haemophilus influenzae contributes to persistence in the respiratory tract and sensitivity to serum killing mediated by C-reactive protein. J Exp Med 187:631–640 Wills-Karp M (2007) Complement activation pathways: a bridge between innate and adaptive immune responses in asthma. Proc Am Thorac Soc 4:247–251 Witte KK, Ford SJ, Preston T et al (2008) Fibrinogen synthesis is increased in cachectic patients with chronic heart failure. Int J Cardiol 129:363–367 World Health Organization (2008) Global burden of disease 2004: update part 2, causes of death. Available via http://www.who.int/healthinfo/global_burden_disease/GBD_report_2004update_part2.pdf. Accessed 14 Feb 2012 Wouters EF (2006) The systemic face of airway diseases: the role of C-reactive protein. Eur Respir J 27:877–879 Wright RR (1961) Elastic tissue of normal and emphysematous lungs—a tridimensional histologic study. Am J Pathol 39:355–367