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
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
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
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
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
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
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
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
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
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
