COPD: Eine entzündliche Erkrankung der Atemwege?

Zusammenfassung

Die COPD ist durch eine nicht vollständig reversible Begrenzung des Atemflusses charakterisiert. Die Limitation des Atemflusses ist meist fortschreitend und mit einer abnormen entzündlichen Reaktion der Lungen vergesellschaftet. Die Begrenzung des Atemflusses erfolgt in der Regel mit der Messung von FEV_1.0 . FEV_1.0 spiegelt jedoch nicht immer den Verlauf der Erkrankung wider und eignet sich nicht zur Objektivierung einer pharmakologischen oder nicht-pharmakologischen Intervention. Die Messung der forcierten Inspiration und der Belastbarkeit sollten daher in die funktionelle Diagnostik integriert werden. Die abnorme Entzündungsreaktion kann mit Hilfe verschiedener Methoden gemessen werden. Die Erhöhung der neutrophilen Granulozyten ist aber nicht mit einem therapeutischen target gleichzusetzen. Der Begriff der abnormen Entzündung der Atemwege beim Asthma bronchiale und der COPD hat zahlreiche Studien initiiert, die den Stellenwert der inhalativen Corticosteroide, ICS, bei der COPD belegen sollen. Während die ICS den Verlauf der COPD nicht verändern, reduzieren sie möglicherweise Zahl und Schwere der Exacerbationen. Die Kombination von langwirksamen β₂-Sympathatikomimetika und ICS ist den einzelnen Komponenten überlegen. Dies ist schwer mit einer antientzündlichen Wirkung zu erklären, da das langwirksame Anticholinericum Tiotropium keinen antientzündlichen Effekt aufweist, ohne jedoch den Kombinationspräparaten in der symptomatischen und funktionellen Wirkung sowie in der Beeinflussung der Exazerbationen unterlegen zu sein. Zukünftige medikamentöse Therapien müssen daher auf einem verbesserten Verständnis der funktionellen Konsequenzen der Erkrankung und ihrer Pathogenese beruhen.

Abstract

COPD is characterized by a not fully reversible airflow limitation which is progressive and associated with an abnormal inflammatory reaction of the lungs. Airflow limitation is most often assessed by FEV_1.0. However, FEV_1.0 does not always reflect the course of the disease and does not appropriately describe the functional effect of a pharmacological or non-pharmacological intervention. Measurement of inspiratory parameters, e.g. IC or FIV_1.0, as well as assessment of exercise capacity should therefore be part of functional tests. The abnormal inflammatory reaction of the lungs can be assessed by a variety of methods. However, the characteristic increase of the number of neutrophils does not indicate a new therapeutic target. The term abnormal inflammation of the airways in bronchial asthma as well as in COPD presumably prompted a number of studies investigating the effects of inhalative corticosteroids in COPD. ICS do not alter the course of the disease, however they may reduce the number and severity of exacerbations. Combination of long-acting β-agonists and ICS exert a better effect than either compound alone. This beneficial effect is difficult to explain by an anti-inflammatory action , as the long acting anticholinergic tiotropium has a comparable symptomatic and functional effect and reduces exacerbations without any known anti-inflammatory component. Future pharmacological therapies should therefore be based on a better understanding of the functional consequences of the disease and its pathogenesis.

Literatur

• 1 Pauwels R A, Buist A S, Calverley P M. et al . Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop summary.  Am J Respir Crit Care Med. 2001;  163 1256-1276
• 2 Worth H, Buhl R, Cegla U. et al . Leitlinie der Deutschen Atemwegsliga und der Deutschen Gesellschaft für Pneumologie zur Diagnostik und Therapie von Patienten mit chronisch obstruktiver Bronchitis und Lungenemphysem (COPD).  Pneumologie. 2002;  56 704-738
• 3 Ferguson G T, Enright P L, Buist A S. et al . Office spirometry for lung health assessment in adults: A consensus statement from the National Lung Health Education Program.  Chest. 2000;  117 1146-1161
• 4 Halbert R J, Isonaka S, George D. et al . Interpreting COPD prevalence estimates: what is the true burden of disease?.  Chest. 2003;  123 1684-1692
• 5 Viegi G, Pedreschi M, Pistelli F. et al . Prevalence of airways obstruction in a general population: European Respiratory Society vs American Thoracic Society definition.  Chest. 2000;  117 339S-345S
• 6 Schermer T R, Jacobs J E, Chavannes N H. et al . Validity of spirometric testing in a general practice population of patients with chronic obstructive pulmonary disease (COPD).  Thorax. 2003;  58 861-866
• 7 Fletcher C, Peto R, Tinker C. et al .The natural history of chronic bronchitis and emphysema. Oxford University Press 1976
• 8 Pinto-Plata V M, Cote C, Cabral H. et al . The 6-min walk distance: change over time and value as a predictor of survival in severe COPD.  Eur Respir J. 2004;  23 28-33
• 9 Nishimura K, Izumi T, Tsukino M. et al . Dyspnea is a better predictor of 5-year survival than airway obstruction in patients with COPD.  Chest. 2002;  121 1434-1440
• 10 O'Donnell D E, Lam M, Webb K A. Measurement of symptoms, lung hyperinflation, and endurance during exercise in chronic obstructive pulmonary disease.  Am J Respir Crit Care Med. 1998;  158 1557-1565
• 11 O'Donnell D E. Assessment of bronchodilator efficacy in symptomatic COPD: is spirometry useful?.  Chest. 2000;  117 42S-47S
• 12 O'Donnell D E, Revill S M, Webb K A. Dynamic hyperinflation and exercise intolerance in chronic obstructive pulmonary disease.  Am J Respir Crit Care Med. 2001;  164 770-777
• 13 O'Donnell D E, Flüge T, Gerken F. et al . Effects of Tiotropium on lung hyperinflation, dyspnoea and exercise tolerance in COPD.  Eur Respir J. 2004;  in press
• 14 Taube C, Lehnigk B, Paasch K. et al . Factor analysis of changes in dyspnea and lung function parameters after bronchodilation in chronic obstructive pulmonary disease.  Am J Respir Crit Care Med. 2000;  162 216-220
• 15 Taube C, Kanniess F, Gronke L. et al . Reproducibility of forced inspiratory and expiratory volumes after bronchodilation in patients with COPD or asthma.  Respir Med. 2003;  97 568-577
• 16 Saetta M, Turato G, Maestrelli P. et al . Cellular and structural bases of chronic obstructive pulmonary disease.  Am J Respir Crit Care Med. 2001;  163 1304-1309
• 17 Turato G, Zuin R, Miniati M. et al . Airway inflammation in severe chronic obstructive pulmonary disease: relationship with lung function and radiologic emphysema.  Am J Respir Crit Care Med. 2002;  166 105-110
• 18 Retamales I, Elliott W M, Meshi B. et al . Amplification of inflammation in emphysema and its association with latent adenoviral infection.  Am J Respir Crit Care Med. 2001;  164 469-473
• 19 Agusti A, MacNee W, Donaldson K. et al . Hypothesis: Does COPD have an autoimmune component?.  Thorax. 2003;  58 832-834
• 20 Holz O, Zühlke I, Jaksztat E. et al . Lung fibroblasts from patients with emphysema show a reduced proliferation rate in culture.  Eur Respir J. 2004;  submitted
• 21 Kips J C, Peleman R A, Pauwels R A. Methods of examining induced sputum: do differences matter?.  Eur Respir J. 1998;  11 529-533
• 22 Tsoumakidou M, Tzanakis N, Siafakas N M. Induced sputum in the investigation of airway inflammation of COPD.  Respir Med. 2003;  97 863-871
• 23 Taube C, Holz O, Mücke M. et al . Airway Response to Inhaled Hypertonic Saline in Patients with Moderate to Severe Chronic Obstructive Pulmonary Disease.  Am J Respir Crit Care Med. 2001;  164 1810-1815
• 24 Keatings V M, Barnes P J. Granulocyte activation markers in induced sputum: comparison between chronic obstructive pulmonary disease, asthma, and normal subjects.  Am J Respir Crit Care Med. 1997;  155 449-453
• 25 Richter K, Holz O, Jorres R A. et al . Sequentially induced sputum in patients with asthma or chronic obstructive pulmonary disease.  Eur Respir J. 1999;  14 697-701
• 26 Jayaram L, Parameswaran K, Sears M R. et al . Induced sputum cell counts: their usefulness in clinical practice.  Eur Respir J. 2000;  16 150-158
• 27 Hargreave F E, Leigh R. Induced sputum, eosinophilic bronchitis, and chronic obstructive pulmonary disease.  Am J Respir Crit Care Med. 1999;  160 S53-S57
• 28 Kelly M M, Keatings V, Leigh R. et al . Analysis of fluid-phase mediators.  Eur Respir J Suppl. 2002;  37 24s-39s
• 29 Kharitonov S A, Robbins R A, Yates D. et al . Acute and chronic effects of cigarette smoking on exhaled nitric oxide.  Am J Respir Crit Care Med. 1995;  152 609-612
• 30 Repine J E, Bast A, Lankhorst I. Oxidative stress in chronic obstructive pulmonary disease. Oxidative Stress Study Group.  Am J Respir Crit Care Med. 1997;  156 341-357
• 31 Hunt J. Exhaled breath condensate: an evolving tool for noninvasive evaluation of lung disease.  J Allergy Clin Immunol. 2002;  110 28-34
• 32 Schleiss M B, Holz O, Behnke M. et al . The concentration of hydrogen peroxide in exhaled air depends on expiratory flow rate.  Eur Respir J. 2000;  16 1115-1118
• 33 Rahman I. Reproducibility of oxidative stress biomarkers in breath condensate: are they reliable?.  Eur Respir J. 2004;  23 183-184
• 34 Magnussen H, Richter K, Taube C. Are chronic obstructive pulmonary disease (COPD) and asthma different diseases?.  Clin Exp Allergy. 1998;  28 Suppl 5 187-194
• 35 Decramer M, de B V, Dom R. Functional and histologic picture of steroid-induced myopathy in chronic obstructive pulmonary disease.  Am J Respir Crit Care Med. 1996;  153 1958-1964
• 36 Singh J M, Palda V A, Stanbrook M B. et al . Corticosteroid therapy for patients with acute exacerbations of chronic obstructive pulmonary disease: a systematic review.  Arch Intern Med. 2002;  162 2527-2536
• 37 Loppow D, Schleiss M B, Kanniess F. et al . In patients with chronic bronchitis a four week trial with inhaled steroids does not attenuate airway inflammation.  Respir Med. 2001;  95 115-121
• 38 Culpitt S V, Maziak W, Loukidis S. et al . Effect of high dose inhaled steroid on cells, cytokines, and proteases in induced sputum in chronic obstructive pulmonary disease.  Am J Respir Crit Care Med. 1999;  160 1635-1639
• 39 Niewoehner D E, Erbland M L, Deupree R H. et al . Effect of systemic glucocorticoids on exacerbations of chronic obstructive pulmonary disease. Department of Veterans Affairs Cooperative Study Group.  N Engl J Med. 1999;  340 1941-1947
• 40 Sutherland E R, Allmers H, Ayas N T. et al . Inhaled corticosteroids reduce the progression of airflow limitation in chronic obstructive pulmonary disease: a meta-analysis.  Thorax. 2003;  58 937-941
• 41 Highland K B, Strange C, Heffner J E. Long-term effects of inhaled corticosteroids on FEV1 in patients with chronic obstructive pulmonary disease. A meta-analysis.  Ann Intern Med. 2003;  138 969-973
• 42 Sin D D, McAlister F A, Man S F. et al . Contemporary management of chronic obstructive pulmonary disease: scientific review.  JAMA. 2003;  290 2301-2312
• 43 Sin D D, Man S F. Inhaled corticosteroids and survival in chronic obstructive pulmonary disease: does the dose matter?.  Eur Respir J. 2003;  21 260-266
• 44 Fan V S, Bryson C L, Curtis J R. et al . Inhaled corticosteroids in chronic obstructive pulmonary disease and risk of death and hospitalization: time-dependent analysis.  Am J Respir Crit Care Med. 2003;  168 1488-1494
• 45 Suissa S. Effectiveness of inhaled corticosteroids in chronic obstructive pulmonary disease: immortal time bias in observational studies.  Am J Respir Crit Care Med. 2003;  168 49-53
• 46 Rabe K F. Combination therapy for chronic obstructive pulmonary disease: one size fits all?.  Eur Respir J. 2003;  22 874-875
• 47 Nannini L, Lasserson T, Poole P. Combined corticosteroid and longacting beta-agonist in one inhaler for chronic obstructive pulmonary disease.  Cochrane Database Syst Rev. 2003;  4 CD003794
• 48 Calverley P M, Burge P S, Spencer S. et al . Bronchodilator reversibility testing in chronic obstructive pulmonary disease.  Thorax. 2003;  58 659-664
• 49 Tashkin D P, Cooper C B. The role of long-acting bronchodilators in the management of stable COPD.  Chest. 2004;  125 249-259