Expertentreffen obstruktive Atemwegserkrankungen: Messen und Bewerten der COPD^[*]

Zusammenfassung

Die folgenden Beiträge einer Expertentagung im Februar 2015 behandeln die Erfassung und Bewertung der vielfältigen Dimensionen der COPD. Diese komplexe Erkrankung greift nicht nur in die Atemmechanik und den pulmonalen Gasaustausch ein. Es folgen Beeinträchtigungen der Atemmuskulatur und der kardiopulmonalen Interaktionen. Im Verlauf der Erkrankung bildet die Lunge eine zunehmende Last von Inflammation und Mikroben. Letztlich ergeben sich daraus systemische Effekte auf die Muskulatur und den Stoffwechsel.

Die Beiträge untersuchen die Wertigkeit unterschiedlichster Endpunkte in der klinischen Forschung. Quantifizierbare Kenngrößen der Atemmechanik, des Gasaustausches, der körperlichen Belastbarkeit und zirkulierende Biomarker verbessern die Messbarkeit von Effekten bei Interventionen. Aber wissen wir in einem biologischen Sinn, was sie bedeuten? Wie weit helfen Erkenntnisse über Teilaspekte der Erkrankung in der prognostischen Beurteilung?

Umgekehrt sind integrative Endpunkte wie Lebensqualität, Dyspnoe oder die spontane körperliche Aktivität auf ihren Ursprung und ihre Bedeutung zu untersuchen. Als neue Dimension wird der klinische Beitrag von morphologischen Befunden im HRCT und MRT analysiert.

Abstract

This report gives an overview on the contributions presented in an expert meeting in February, 2015. They deal with the analysis and evaluation of the multiple dimensions of COPD. This complex disease not only interferes with pulmonary mechanics and gas exchange, but also with cardiopulmonary crosstalk and the ventilator pump. A bulk of inflammatory and microbial activity develops during the progression of disease. As a consequence, systemic effects on muscles, metabolism and psyche develop.

The sections consider the value of multiple endpoints in clinical research. Quantifiable parameters of lung mechanics and gas exchange, of exercise tolerance and biomarkers improve the measurability of effects in interventions. However, do we really know in a biological sense what we are measuring? What conclusions can we draw in terms of prognosis?

Vice versa, we have to look into the origin and meaning of integrative endpoints e.g. quality or life, dyspnoea and spontaneous physical activity. As a new dimension, the clinical significance of morphological findings in HRCT and MRT is analyzed.

^* Sponsor: Boehringer Ingelheim Pharma GmbH & Co KG.

• Literatur

• 1 Fleming A. On the antibacterial action of cultures of a penicillium, with special reference to their use in the isolation of B. influenzae. Br J Experim Pathol 1929; 10
• 2 Kling J. From hypertension to angina to Viagra. Mod Drug Discov 1998; 1: 31-38
• 3 Hacking I. Representing and Intervening. Introductory Topics in the Philosophy of Natural Science. 1983
• 4 Boyle R. New experiments physico-mechanicall, touching the spring of the air and its effects. Oxford: 1660
• 5 Hooke R. Micrographia: Some pysiological descriptions of minute bodies made by magnifying glasses with observations and inquiries thereupon. London: 1665
• 6 Carnap R, Gardner M. An Introduction to the Philosophy of Science. New York: Dover Publications; 1995
• 7 Popper K. Autobiography by Karl Popper. In: Schlipp PA, (Hrsg), The Philosophy of Karl Popper, in: The Library of Living Philosophers. La Salle, IL: Open Cohort Publishing Co; 1974
• 8 Kohler D, Fischer J, Raschke F et al. Usefulness of GOLD classification of COPD severity. Thorax 2003; 58: 825
• 9 Schermer TR, Smeele IJ, Thoonen BP et al. Current clinical guideline definitions of airflow obstruction and COPD overdiagnosis in primary care. Eur Respir J 2008; 32: 945-952
• 10 Banzett RB, O'Donnell CR. Should we measure dyspnoea in everyone?. Eur Respir J 2014; 43: 1547-1550
• 11 Jakeways N, McKeever T, Lewis SA et al. Relationship between FEV1 reduction and respiratory symptoms in the general population. Eur Respir J 2003; 21: 658-663
• 12 Oga T, Nishimura K, Tsukino M et al. Exercise capacity deterioration in patients with COPD: longitudinal evaluation over 5 years. Chest 2005; 128: 62-69
• 13 Oga T, Nishimura K, Tsukino M et al. Analysis of the factors related to mortality in chronic obstructive pulmonary disease: role of exercise capacity and health status. Am J Respir Crit Care Med 2003; 167: 544-549
• 14 Celli BR, Cote CG, Marin JM et al. The body-mass index, airflow obstruction, dyspnea, and exercise capacity index in chronic obstructive pulmonary disease. N Engl J Med 2004; 350: 1005-1012
• 15 Cardoso F, Tufanin AT, Colucci M et al. Replacement of the 6-min walk test with maximal oxygen consumption in the BODE Index applied to patients with COPD: an equivalency study. Chest 2007; 132: 477-482
• 16 Cote CG, Pinto-Plata VM, Marin JM et al. The modified BODE index: validation with mortality in COPD. Eur Respir J 2008; 32: 1269-1274
• 17 Oga T, Tsukino M, Hajiro T et al. Predictive properties of different multidimensional staging systems in patients with chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis 2011; 6: 521-526
• 18 Maddocks M, Shrikrishna D, Vitoriano S et al. Skeletal muscle adiposity is associated with physical activity, exercise capacity and fibre shift in COPD. Eur Respir J 2014; 44: 1188-1198
• 19 Guenette JA, Chin RC, Cheng S et al. Mechanisms of exercise intolerance in global initiative for chronic obstructive lung disease grade 1 COPD. Eur Respir J 2014; 44: 1177-1187
• 20 Lamprecht B, Vanfleteren LE, Studnicka M et al. Sex-related differences in respiratory symptoms: results from the BOLD Study. Eur Respir J 2013; 42: 858-860
• 21 Schaeffer MR, Mendonca CT, Levangie MC et al. Physiological mechanisms of sex differences in exertional dyspnoea: role of neural respiratory motor drive. Exp Physiol 2014; 99: 427-441
• 22 Chiappa GR, Vieira PJ, Umpierre D et al. Inspiratory resistance decreases limb blood flow in COPD patients with heart failure. Eur Respir J 2014; 43: 1507-1510
• 23 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: 728-735
• 24 Mannino DM, Thorn D, Swensen A et al. Prevalence and outcomes of diabetes, hypertension and cardiovascular disease in COPD. Eur Respir J 2008; 32: 962-969
• 25 Guazzi M, Adams V, Conraads V et al. EACPR/AHA Scientific Statement. Clinical recommendations for cardiopulmonary exercise testing data assessment in specific patient populations. Circulation 2012; 126: 2261-2274
• 26 Kanner RE, Renzetti Jr AD, Klauber MR et al. Variables associated with changes in spirometry in patients with obstructive lung diseases. Am J Med 1979; 67: 44-50
• 27 Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. NHLBI/WHO Workshop Report, Executive Summary. 2701A. National Institutes of Health. National Heart, Lung, and Blood Institute. World Health Organisation; 2001
• 28 Seemungal TA, Hurst JR, Wedzicha JA. Exacerbation rate, health status and mortality in COPD--a review of potential interventions. Int J Chron Obstruct Pulmon Dis 2009; 4: 203-223
• 29 Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global Strategy for the Diagnosis,Management and Prevention of COPD. Update. 2015
• 30 Gunen H, Hacievliyagil SS, Kosar F et al. Factors affecting survival of hospitalised patients with COPD. Eur Respir J 2005; 26: 234-241
• 31 Suissa S, Dell'Aniello S, Ernst P. Long-term natural history of chronic obstructive pulmonary disease: severe exacerbations and mortality. Thorax 2012; 67: 957-963
• 32 Hoogendoorn M, Hoogenveen RT, Rutten-van Molken MP et al. Case fatality of COPD exacerbations: a meta-analysis and statistical modelling approach. Eur Respir J 2011; 37: 508-515
• 33 Seemungal TA, Donaldson GC, Bhowmik A et al. Time course and recovery of exacerbations in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2000; 161: 1608-1613
• 34 Donaldson GC, Seemungal TA, Bhowmik A et al. Relationship between exacerbation frequency and lung function decline in chronic obstructive pulmonary disease. Thorax 2002; 57: 847-852
• 35 Chang CL, Robinson SC, Mills GD et al. Biochemical markers of cardiac dysfunction predict mortality in acute exacerbations of COPD. Thorax 2011; 66: 764-768
• 36 Singanayagam A, Schembri S, Chalmers JD. Predictors of mortality in hospitalized adults with acute exacerbation of chronic obstructive pulmonary disease. Ann Am Thorac Soc 2013; 10: 81-89
• 37 Piquet J, Chavaillon JM, David P et al. High-risk patients following hospitalisation for an acute exacerbation of COPD. Eur Respir J 2013; 42: 946-955
• 38 Soler-Cataluna JJ, Martinez-Garcia MA, Roman SP et al. Severe acute exacerbations and mortality in patients with chronic obstructive pulmonary disease. Thorax 2005; 60: 925-931
• 39 Beeh KM, Glaab T, Stowasser S et al. Characterisation of exacerbation risk and exacerbator phenotypes in the POET-COPD trial. Respir Res 2013; 14: 116
• 40 Jenkins CR, Jones PW, Calverley PM et al. Efficacy of salmeterol/fluticasone propionate by GOLD stage of chronic obstructive pulmonary disease: analysis from the randomised, placebo-controlled TORCH study. Respir Res 2009; 10: 59
• 41 Tashkin DP, Celli B, Senn S et al. A 4-year trial of tiotropium in chronic obstructive pulmonary disease. N Engl J Med 2008; 359: 1543-1554
• 42 Groenewegen KH, Schols AM, Wouters EF. Mortality and mortality-related factors after hospitalization for acute exacerbation of COPD. Chest 2003; 124: 459-467
• 43 Kohnlein T, Windisch W, Kohler D et al. Non-invasive positive pressure ventilation for the treatment of severe stable chronic obstructive pulmonary disease: a prospective, multicentre, randomised, controlled clinical trial. Lancet Respir Med 2014; 2: 698-705
• 44 Lepper PM, Ott S, Nuesch E et al. Serum glucose levels for predicting death in patients admitted to hospital for community acquired pneumonia: prospective cohort study. BMJ 2012; 344: e3397
• 45 Pass HI, Levin SM, Harbut MR et al. Fibulin-3 as a blood and effusion biomarker for pleural mesothelioma. N Engl J Med 2012; 367: 1417-1427
• 46 Hersh CP, DeMeo DL, Silverman EK. National Emphysema Treatment Trial state of the art: genetics of emphysema. Proc Am Thorac Soc 2008; 5: 486-493
• 47 de Torres JP, Cordoba-Lanus E, Lopez-Aguilar C et al. C-reactive protein levels and clinically important predictive outcomes in stable COPD patients. Eur Respir J 2006; 27: 902-907
• 48 Lomas DA, Silverman EK, Edwards LD et al. Evaluation of serum CC-16 as a biomarker for COPD in the ECLIPSE cohort. Thorax 2008; 63: 1058-1063
• 49 Dickens JA, Miller BE, Edwards LD et al. COPD association and repeatability of blood biomarkers in the ECLIPSE cohort. Respir Res 2011; 12: 146
• 50 Celli BR, Locantore N, Yates J et al. Inflammatory biomarkers improve clinical prediction of mortality in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2012; 185: 1065-1072
• 51 Sukkar MB, Wood LG, Tooze M et al. Soluble RAGE is deficient in neutrophilic asthma and COPD. Eur Respir J 2012; 39: 721-729
• 52 Cheng SL, Wang HC, Yu CJ et al. Increased expression of placenta growth factor in COPD. Thorax 2008; 63: 500-506
• 53 Stolz D, Meyer A, Rakic J et al. Mortality risk prediction in COPD by a prognostic biomarker panel. Eur Respir J 2014; 44: 1557-1570
• 54 Galban CJ, Han MK, Boes JL et al. Computed tomography-based biomarker provides unique signature for diagnosis of COPD phenotypes and disease progression. Nat Med 2012; 18: 1711-1715
• 55 Karlsson FH, Fak F, Nookaew I et al. Symptomatic atherosclerosis is associated with an altered gut metagenome. Nat Commun 2012; 3: 1245
• 56 Partridge MR, Karlsson N, Small IR. Patient insight into the impact of chronic obstructive pulmonary disease in the morning: an internet survey. Curr Med Res Opin 2009; 25: 2043-2048
• 57 Jones PW, Lamarca R, Chuecos F et al. Characterisation and impact of reported and unreported exacerbations: results from ATTAIN. Eur Respir J 2014; 44: 1156-1165
• 58 Oba Y, Lone NA. Comparative efficacy of long-acting muscarinic antagonists in preventing COPD exacerbations: a network meta-analysis and meta-regression. Ther Adv Respir Dis 2015; 3: 9-15
• 59 Agusti A, Fabbri LM. Inhaled steroids in COPD: when should they be used?. Lancet Respir Med 2014; 2: 869-871
• 60 Buhl R, Gessner C, Schuermann W et al. Efficacy and safety of once-daily QVA149 compared with the free combination of once-daily tiotropium plus twice-daily formoterol in patients with moderate-to-severe COPD (QUANTIFY): a randomised, non-inferiority study. Thorax 2015; 70: 311-319
• 61 White WB, Cooke GE, Kowey PR et al. Cardiovascular Safety In Patients Receiving Roflumilast for the Treatment of Chronic Obstructive Pulmonary Disease. Chest 2013; 1244: 758-765
• 62 Kuhnigk JM, Dicken V, Zidowitz S et al. Informatics in radiology (infoRAD): new tools for computer assistance in thoracic CT. Part 1. Functional analysis of lungs, lung lobes, and bronchopulmonary segments. Radiographics 2005; 25: 525-536
• 63 Owsijewitsch M, Ley-Zaporozhan J, Kuhnigk JM et al. Quantitative Emphysema Distribution in Anatomic and Non-anatomic Lung Regions. COPD 2014; 12: 257-266
• 64 Washko GR. The role and potential of imaging in COPD. Med Clin North Am 2012; 96: 729-743
• 65 Hansell DM, Bankier AA, MacMahon H et al. Fleischner Society: glossary of terms for thoracic imaging. Radiology 2008; 246: 697-722
• 66 Coxson HO, Dirksen A, Edwards LD et al. The presence and progression of emphysema in COPD as determined by CT scanning and biomarker expression: a prospective analysis from the ECLIPSE study. Lancet Respir Med 2013; 1: 129-136
• 67 Barr RG, Berkowitz EA, Bigazzi F et al. A combined pulmonary-radiology workshop for visual evaluation of COPD: study design, chest CT findings and concordance with quantitative evaluation. COPD 2012; 9: 151-159
• 68 Lynch DA, Austin JHM, Hogg JC et al. CT definable subtypes of COPD: A statement of the Fleischner society. Radiology 2015; Mai 11:141579 [Epub ahead of print]; http://dx.doi.org/10.1148/radiol.2462070712
• 69 Han MK, Kazerooni EA, Lynch DA et al. Chronic obstructive pulmonary disease exacerbations in the COPDGene study: associated radiologic phenotypes. Radiology 2011; 261: 274-282
• 70 Biederer J. Untersuchungsprotokolle. Fortschr Röntgenstr 2008; 180 RK_306_1
• 71 Gompelmann D, Eberhardt R, Slebos DJ et al. Diagnostic performance comparison of the Chartis System and high-resolution computerized tomography fissure analysis for planning endoscopic lung volume reduction. Respirology 2014; 19: 524-530
• 72 Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global Strategy for the Diagnosis, Management and Prevention of COPD. 2015
• 73 Curtis JR, Patrick DL. The assessment of health status among patients with COPD. Eur Respir J Suppl 2003; 41: 36s-45s
• 74 Jones PW, Quirk FH, Baveystock CM. The St George's Respiratory Questionnaire. Respir Med 1991; 85 Suppl B 25-31
• 75 Cazzola M, MacNee W, Martinez FJ et al. Outcomes for COPD pharmacological trials: from lung function to biomarkers. Eur Respir J 2008; 31: 416-469
• 76 Engstrom CP, Persson LO, Larsson S et al. Health-related quality of life in COPD: why both disease-specific and generic measures should be used. Eur Respir J 2001; 18: 69-76
• 77 Watz H, Waschki B, Meyer T et al. Physical activity in patients with chronic obstructive pulmonary disease. Eur Respir J 2009; 33: 262-272
• 78 Ferrer M, Alonso J, Morera J et al. Chronic obstructive pulmonary disease stage and health-related quality of life. The Quality of Life of Chronic Obstructive Pulmonary Disease Study Group. Ann Intern Med 1997; 127: 1072-1079
• 79 Burgel PR, Escamilla R, Perez T et al. Impact of comorbidities on COPD-specific health-related quality of life. Respir Med 2013; 107: 233-241
• 80 Jorres RA, Welte T, Bals R et al. [Systemic manifestations and comorbidities in patients with chronic obstructive pulmonary disease (COPD) and their effect on clinical state and course of the disease - an overview of the cohort study COSYCONET]. Dtsch Med Wochenschr 2010; 135: 446-449
• 81 Jones PW, Singh D, Bateman ED et al. Efficacy and safety of twice-daily aclidinium bromide in COPD patients: the ATTAIN study. Eur Respir J 2012; 40: 830-836
• 82 Trivedi R, Richard N, Mehta R et al. Umeclidinium in patients with COPD: a randomised, placebo-controlled study. Eur Respir J 2014; 43: 72-81
• 83 Decramer M, Anzueto A, Kerwin E et al. Efficacy and safety of umeclidinium plus vilanterol versus tiotropium, vilanterol, or umeclidinium monotherapies over 24 weeks in patients with chronic obstructive pulmonary disease: results from two multicentre, blinded, randomised controlled trials. Lancet Respir Med 2014; 2: 472-486
• 84 Bateman ED, Ferguson GT, Barnes N et al. Dual bronchodilation with QVA149 versus single bronchodilator therapy: the SHINE study. Eur Respir J 2013; 42: 1484-1494
• 85 D'Urzo AD, Rennard SI, Kerwin EM et al. Efficacy and safety of fixed-dose combinations of aclidinium bromide/formoterol fumarate: the 24-week, randomized, placebo-controlled AUGMENT COPD study. Respir Res 2014; 15: 123
• 86 Singh D, Jones PW, Bateman ED et al. Efficacy and safety of aclidinium bromide/formoterol fumarate fixed-dose combinations compared with individual components and placebo in patients with COPD (ACLIFORM-COPD): a multicentre, randomised study. BMC Pulm Med 2014; 14: 178
• 87 Buhl R, Maltais F, Abrahams R et al. Tiotropium and olodaterol fixed-dose combination versus mono-components in COPD (GOLD 2-4). Eur Respir J 2015; 45: 969-979
• 88 Vogelmeier CF, Bateman ED, Pallante J et al. Efficacy and safety of once-daily QVA149 compared with twice-daily salmeterol-fluticasone in patients with chronic obstructive pulmonary disease (ILLUMINATE): a randomised, double-blind, parallel group study. Lancet Respir Med 2013; 1: 51-60
• 89 Prescott JW. Quantitative imaging biomarkers: the application of advanced image processing and analysis to clinical and preclinical decision making. J Digit Imaging 2013; 26: 97-108
• 90 Sullivan DC, Obuchowski NA, Kessler LG et al. RSNA-QIBA Metrology Working Group. Metrology Standards for Quantitative Imaging Biomarkers. Radiology. COPD 2015; Aug 12:142202 [Epub ahead of print]; http://dx.doi.org/10.1148/radiol.2015142202
• 91 Kim SS, Yagihashi K, Stinson DS et al. Visual Assessment of CT Findings in Smokers With Nonobstructed Spirometric Abnormalities in The COPDGene^® Study. Chronic Obstr Pulm Dis (Miami) 2014; 1: 88-96
• 92 Wilke S, Watz H, Bals R et al. Impact of Peripheral Artery Disease on Functional Capacity and Health Status in Patients with Chronic Obstructive Pulmonary Disease: Results of the COSYCONET Study. COPD Am J Respir Crit Care Med 2015; 191 A6204