Zusammenfassung
Die chronisch obstruktive Lungenerkrankung (COPD) ist durch verminderten Atemfluss und eine Entzündungsreaktion im Bereich der kleinen und grösseren Atemwege gekennzeichnet. Eine Entzündung der kleinen Atemwege, ausgelöst durch inhalierte Partikel und Gase steht nach aktuellem Verständnis im Mittelpunkt der Pathogenese der COPD. Daneben kommt auch oxidativem Stress eine Bedeutung zu, da bekannt ist, dass reaktive Sauerstoffmetabolite die Inflammationsreaktion verstärken können. Ein wesentlicher weiterer pathophysiologischer Faktor ist eine Störung des Gleichgewichts von Proteasen und Antiproteasen, was im kausalen Zusammenhang mit der Ausbildung eines Emphysems gesehen wird. Aktuell wird diskutiert, dass der durch Apoptose bedingte Verlust von Alveolarzellen zur Emphysembildung beitragen kann. Es gibt zunehmend Daten, die die COPD als Erkrankung mit systemischen Konsequenzen ausweisen. Nicht nur Hinweise auf eine systemische Entzündungzeichen werden gefunden, sondern es finden sich auch Zeichen kardiovaskulärer, neurologischer - psychiatrischer, muskuloskeletaler und auch endokrinologischer mit der COPD assoziierte Dysfunktionen. Unterschiedlichste innovative Therapiekonzepte sollen versuchen, auf dem Boden der neuen pathophysiologischen Erkenntnisse Verbesserungen in Überlebenszeit, Krankheitskontrolle und Befindlichkeit der Patienten zu erbringen.
Summary
Chronic obstructive pulmonary disease (COPD) is a chronic disease of the lungs that is characterised by a decreased air flow and an abnormal inflammatory response. Inflammation of the small airways caused by inhaled particles and gases is believed to be a major factor in the pathogenesis of chronic obstructive pulmonary disease. Oxidative stress may be an additional important pathogenetic factor and may enhance the inflammatory process. In that context a disturbance of the physiologic balance between proteases and antiproteases develops, which may cause lung emphysema. Currently it is also discussed that the loss of alveolar cells by apoptosis contributes to the development of emphysema. There is growing awareness of the systemic consequences of this disease. It has been demonstrated that markers of systemic inflammation are increased in COPD. Furthermore, cardiovascular, neurologic, psychiatric, muscoloskeletal and endocrine manifestations have been described. New therapy concepts based on these findings will hopefully result in improvements of morbidity, disease control and quality of life.
Schlüsselwörter
COPD - Pathophysiologie - Therapie - Inflammation
Key words
COPD - pathophysiology - therapy - inflammation
Literatur
-
1
Nocturnal Oxygen Therapy Trial Group .
Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: a clinical trial.
Ann Intern Med.
1980;
93
391-398
-
2
Barnes P J, Stockley R A.
COPD: current therapeutic interventions and future approaches.
Eur Respir J.
2005;
25
1084-1106
-
3
Beeh K M, Derom E, Kanniess F. et al .
Indacaterol, a novel inhaled beta2-agonist, provides sustained 24-h bronchodilation in asthma.
Eur Respir J.
2007;
29
871-878
-
4
Churg A, Dai J, Tai H, Xie C, Wright J L.
Tumor necrosis factor-alpha is central to acute cigarette smoke-induced inflammation and connective tissue breakdown.
Am J Respir Crit Care Med.
2002;
166
849-854
-
5
Churg A, Wang R D, Tai H, Wang X, Xie C, Dai J, Shapiro S D, Wright J L.
Macrophage metalloelastase mediates acute cigarette smoke-induced inflammation via tumor necrosis factor-alpha release.
Am J Respir Crit Care Med.
2003;
167
1083-1089
-
6
Churg A, Wang R D, Tai H, Wang X, Xie C, Wright J L.
Tumor necrosis factor-alpha drives 70 % of cigarette smoke-induced emphysema in the mouse.
Am J Respir Crit Care Med.
2004;
170
492-498
-
7
Cydulka R K, Emerman C L.
Effects of combined treatment with glycopyrrolate and albuterol in acute exacerbation of chronic obstructive pulmonary disease.
Ann Emerg Med.
1995;
25
470-473
-
8
FM, Barbier D, Mege J L, Orehek J.
Tumor necrosis factor-alpha levels and weight loss in chronic obstructive pulmonary disease.
Am J Respir Crit Care Med.
1994;
150
1453-1455
-
9
Gamble E, Grootendorst D C, Brightling C E, Troy S, Qiu Y, Zhu J, Parker D, Matin D, Majumdar S, Vignola A M, Kroegel C, Morell F, Hansel T T, Rennard S I, Compton C, Amit O, Tat T, Edelson J, Pavord I D, Rabe K F, Barnes N C, Jeffery P K.
Antiinflammatory effects of the phosphodiesterase-4 inhibitor cilomilast (Ariflo) in chronic obstructive pulmonary disease.
Am J Respir Crit Care Med.
2003;
168
976-982
-
10
Glover E D, Laflin M T, Schuh K J, Schuh L M, Nides M, Christen A G, Glover P N, Strnad J V.
A randomized, controlled trial to assess the efficacy and safety of a transdermal delivery system of nicotine/mecamylamine in cigarette smokers.
Addiction.
2007;
102
795-802
-
11
Gotfried M H.
Macrolides for the treatment of chronic sinusitis, asthma, and COPD.
Chest.
2004;
125
52S-60S
-
12
Hansel T T, Neighbour H, Erin E M, Tan A J, Tennant R C, Maus J G, Barnes P J.
Glycopyrrolate causes prolonged bronchoprotection and bronchodilatation in patients with asthma.
Chest.
2005;
128
1974-1979
-
13
Healy D P.
Macrolide immunomodulation of chronic respiratory diseases.
Curr Infect Dis Rep.
2007;
9
7-13
-
14
Ishida W, Kajiwara T, Ishii M, Fujiwara F, Taneichi H, Takebe N, Takahashi K, Kaneko Y, Segawa I, Inoue H, Satoh J.
Decrease in mortality rate of chronic obstructive pulmonary disease (COPD) with statin use: a population-based analysis in Japan.
Tohoku J Exp Med.
2007;
212
265-273
-
15
Keatings V M, Jatakanon A, Worsdell Y M, Barnes P J.
Effects of inhaled and oral glucocorticoids on inflammatory indices in asthma and COPD.
Am J Respir Crit Care Med.
1997;
155
542-548
-
16
Laurell C B, Eriksson S.
Hypo-alpha-1-Antitrypsinämie.
Verh Dtsch Ges Inn Med.
1964;
70
537-539
-
17
Laurell C B, Eriksson S.
The serum alpha-1-antitrypsin in families with hypo-alpha-1-antitrypsinemia.
Clin Chim Acta.
1965;
11
395-398
-
18
Mahler D A, Huang S, Tabrizi M, Bell G M.
Efficacy and safety of a monoclonal antibody recognizing interleukin-8 in COPD: a pilot study.
Chest.
2004;
126
926-934
-
19
Massaro G D, Massaro D.
Retinoic acid treatment abrogates elastase-induced pulmonary emphysema in rats.
Nat Med.
1997;
3
675-677
-
20
Matera M G, Cazzola M.
Ultra-long-acting beta2-adrenoceptor agonists: an emerging therapeutic option for asthma and COPD?.
Drugs.
2007;
67
503-515
-
21
Ong D E, Chytil F.
Changs in levels of cellular retinol- and retinoic-acid-binding proteins of liver and lung during perinatal development of rat.
Proc Nat Acad Sci USA.
1976;
73
3976-3978
-
22
Rennard S I, Fogarty C, Kelsen S. et al .
The safety and efficacy of infliximab in moderate to severe chronic obstructive pulmonary disease.
Am J Respir Crit Care Med.
2007;
175
926-934
-
23
Roth M D, Connett J E. et al .
Feasibility of retinoids for the treatment of emphysema study.
Chest.
2006;
130
1334-1345
-
24
Russell R E, Culpitt S V, DeMatos C, Donnelly L, Smith M, Wiggins J, Barnes P J.
Release and activity of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 by alveolar macrophages from patients with chronic obstructive pulmonary disease.
Am J Respir Cell Mol Biol.
2002;
26
602-609
-
25
Smith S J, Fenwick P S, Nicholson A G. et al .
Inhibitory effect of p38 mitogen-activated protein kinase inhibitors on cytokine release from human macrophages.
Br J Pharmacol.
2006;
149
393-404
-
26
Soyseth V, Brekke P H, Smith P, Omland T.
Statin use is associated with reduced mortality in COPD.
Eur Respir J.
2007;
29
279-283
-
27
Steinberg M B, Foulds J.
Rimonabant for treating tobacco dependence.
Vasc Health Risk Manag.
2007;
3
307-311
-
28
van der Vaart H, Koeter G H, Postma D S. et al .
First study of infliximab treatment in patients with chronic obstructive pulmonary disease.
Am J Respir Crit Care Med.
2005;
172
465-469
-
29
Vestbo J, Hogg J C.
Convergence of the epidemiology and pathology of COPD.
Thorax.
2006;
61
86-88
-
30
Voelkel N F, Douglas I S, Nicolls M.
Angiogenesis in chronic lung disease.
Chest.
2007;
131
874-879
-
31
Vogelmeier C. et al .
Guidelines for the Diagnosis and Therapy of COPD Issued by Deutsche Atemwegsliga and Deutsche Gesellschaft fur Pneumologie und Beatmungsmedizin.
Pneumologie.
2007;
61
517
-
32
Vogelmeier C, Koczulla R, Fehrenbach H, Bals R.
Pathogenese der chronisch obstruktiven Lungenerkrankung.
Internist .
2006;
47
885-892
-
33
Watz H, Kanniess F, Magnussen H.
Neue pharmakologische Optionen in der Therapie der COPD.
Pneumologie.
2007;
61
365-373
-
34
Yao J S, Shen F, Young W L, Yang G Y.
Comparison of doxycycline and minocycline in the inhibition of VEGF-induced smooth muscle cell migration.
Neurochem Int.
2007;
50
524-530
-
35
Zhen G, Park S W, Nguyenvu T L, Rodriguez M W, Barbeau R, Paquet A C, Erle D J.
IL-13 and epidermal growth factor receptor have critical but distinct roles in epithelial cell mucin production.
Am J Respir Cell Mol Biol.
2007;
36
244-253
-
36
Schultz K, Bergmann KC, Kenn K et al.
Effektivität der pneumologischen Anschluss-Heilbehandlung (AHB).
Dtsch Med Wochenschr.
2006;
131
1793-1798
-
37
Schultz K, Taube K, Lang S M.
Stellenwert der COPD in der Langzeitrehabilitation bei COPD.
Dtsch Med Wochenschr .
2007;
132
508-512
Dr. A. R. Koczulla
Universitätsklinikum Gießen und Marburg, Abteilung für Pulmonologie, Standort Marburg
Baldingerstraße 1
35042 Marburg
Email: koczulla@uni-marburg.de
