Behandlung obstruktiver Atemwegserkrankungen - Welche Therapieoptionen stehen zur Verfügung?

Zusammenfassung

Bei der Therapie obstruktiver Atemwegserkrankungen ist eine deutliche Diskrepanz zwischen den Forderungen der Fachgesellschaften (Guidelines) und der Realität festzustellen. So erhält in Deutschland nur etwa ein Viertel der Asthmatiker inhalative Kortikoide, die sich inzwischen als Basistherapie etabliert haben. Je nach Schweregrad der Erkrankung müssen diese dann mit Beta-2-Sympathomimetika oder sogar zusätzlich auch mit oralen Kortikoiden kombiniert werden. Als Therapiestandard bei Patienten mit chronisch obstruktiver Lungenerkrankung (COPD) sind momentan bronchodilatierende Beta-2-Sympathomimetika bzw. Anticholinergika definiert. Denn anders als beim Asthma stehen bei der COPD nicht die Eosinophilen, sondern aktivierte Granulozyten im Vordergrund des Entzündungsprozesses. Granulozyten jedoch sprechen nicht auf eine Therapie mit Kortikoiden an. Bei der Behandlung akuter COPD-Exazerbationen haben orale Kortikoide aber einen hohen Stellenwert. Und laut neuen Studienergebnissen können inhalative Kortikoide insbesondere in Kombination mit lang wirksamen Beta-2-Sympathomimetika den Krankheitsverlauf der chronisch obstruktiven Lungenerkrankung positiv beeinflussen. Sie sind daher bei COPD-Patienten der Schweregrade II und III indiziert. Trotzdem lässt sich auch mit dieser Therapiestrategie das Fortschreiten des progredienten Lungenfunktionsverlustes nicht verhindern.

Summary

In the treatment of obstructive respiratory tract disease there is a clear discrepancy between the demands made by the professional associations (guidelines) and reality. Thus, for example in Germany, only about one-quarter of asthma tics receive inhalative corticoids, which have since become established basic therapy. Depending on the severity of the condition, these must then be combined with beta-2-sympathomimetic agents, or even additionally with oral corticoids. Currently accepted standard treatment in patients with chronic obstructive pulmonary disease (COPD) are bronchodilatory beta-2-sympathomimetic agents or anticholinergic agents. For, unlike asthma, it is not the eosinophils but the activated granulocytes that are prominent in the inflammatory process. However, granulocytes do not respond to treatment with corticoids. For the treatment of acute COPD exacerbations, however, oral corticoids are of great value. According to the results of new studies, inhalative corticoids, in particular in combination with long-acting beta-2-sympathomimetics, have a positive influence on the course of COPD, and are therefore indicated in COPD patients with grade II or III disease. Even with this therapeutic strategy, however, the progression of pulmonary function loss cannot be prevented.

Key Words

obstructive respiratory tract disease - chronic obstructive pulmonary disease- asthma -exacerbation - corticoids - beta-2-sympathomimetic agent - monotherapy - combination therapy

Literatur

• 1 Barnes PJ. Scientific rationale for inhaled combination therapy with long acting b2-agonists and corticosteroids.  Eur Respir J. 2002;  19 182-191
• 2 Buchwald A, Hochhaus G. Pharmacokinetic and pharmacodynamic aspects of salmeterol therapy.  Int J Clin Pharm Therap. 1998;  36 652-660
• 3 Burge PS, Calverley PM, Johnes PW. et al. . Randomised, double blind, placebo controlled study of fluticasone propionate in patients with moderate to severe chronic obstructive pulmonary disease: the ISOLDE trial.  BMJ. 2000;  320 1297-1303
• 4 Calverly P, Pauwels R, Vestbo J. et al. . Combined salmeterol and fluticasone in the treatment of chronic obstructive pulmonary disease: a randomized controlled trial.  Lancet. 2003;  361 449-456
• 5 Cazzola M, Donner CF, Matera MG. Long acting beta (2) agonists and theophylline in stable chronic obstructive pulmonary disease.  Thorax. 1999;  54 730-736
• 6 Cazzola M, Donner CF. Long-acting b2-agonists in the management of stable chronic obstructive pulmonary disease.  Drugs. 2000;  60 307-320
• 7 Chapman KR. Clinical implications of anticholinergic bronchodilator therapy in COPD.  Res Clin Forums. 1991;  13 43-50
• 8 Chong LK, Cooper E, Vardey CJ, Peachell PT. Salmeterol inhibition of mediator release from human lung mast cells by beta-adrenoceptor-dependent and independent mechanisms.  Br J Pharmacol. 1998;  123 1009-1015
• 9 Derendorf H. Pharmacokinetic and pharmacodynamic properties of inhaled corticosteroids in relation to efficacy and safety.  Respir Med. 1997;  91 22-28
• 10 FitzGerald JM, Grundfeld A, Pare PD. et al. . The clinical efficacy if combination nebulized anticholinergic and adrenergic bronchodilators vs nebulized adrenergic bronchodilator alone in acute asthma.  Canadian Combivent Study Group.  Chest. 1997;  111 311-315
• 11 Haefeli WE, Seibert-Grafe M, Gleier CH. Arzneimittel-Kombinationstherapie. Sankt Augustin Kommissionsverlag Michael Itschert.  Gardez Verlag. 2002; 
• 12 Hvizdos KM, Goa KL. Tiotropium bromide.  Drugs. 2002;  62 1195-1203
• 13 Kelly WH. Comparison of inhaled corticosteroids.  Ann Pharmacother. 1998;  32 220-232
• 14 Kirsten DK, Wegner RE, Jorres RA, Magnussen H. Effects of theophylline withdrawal in severe chronic obstructive pulmonary disease.  Chest. 1993;  104 1101-1107
• 15 Laviolette M, Malmstrom K, Lu S. et al. . Montelukast added to inhaled beclomethasone in treatment of asthma.  Am J Respir Crit Care Med. 1999;  160 1862-1868
• 16 Mahler DA, Donohue JF, Barbee RA. et al. . Efficacy of salmeterol xinafoate in the treatment of COPD.  Chest. 1999;  115 957-965
• 17 Mahler DA. The effect of inhaled b2-agonists on clinical outcomes in chronic obstructive pulmonary disease.  J Allergy Clin Immunol. 2002;  110 298-202
• 18 Markham A, Faulds D. Theophylline. A review of its potential steroid sparing effects in asthma.  Drugs. 1998;  56 1081-1091
• 19 Nelson HS, Busse WW, Kerwin E. et al. . Fluticasone propionate/salmeterol combination provides more effective asthma control than low-dose inhaled corticosteroid plus montelukast.  J Allergy Clin Immunol. 2000;  106 1088-1095
• 20 Nielsen LP, Dahl R. Therapeutic ratio of inhaled corticosteroids in adult asthma.  Am J Respir Crit Care Med. 2000;  162 2053-2057
• 21 Oddera S, Silvestri M, Test R, Rossi GA. Salmeterol enhances the inhibitory activity of dexamethasone on allergen-induced blood mononuclear cell activation.  Respiration. 1998;  65 199-204
• 22 Olivieri D, Chetta A, del Donno M. et al. . Effect of short-term treatment with low-dose inhaled fluticasone propionate on airway remodeling in mild asthma: a placebo-controlled study.  Am J Respir Crit Care Med. 1997;  155 1864-1871
• 23 Pao CS, McKenzie SA. Randomized controlled trial of fluticasone in preschool children with intermittent wheeze.  Am J Respir Crit Care Med. 2002;  166 945-949
• 24 Pauwels RA, Lofdahl CG, Laitinen LA. et al. . Long-term treatment with inhaled budesonide in persons with mild chronic obstructive pulmonary disease who continue smoking. European Respiratory Society Study on Chronic Obstructive Pulmonary Disease.  N Engl J Med. 1999;  340 1948-1953
• 25 Pauwels RA, Pedersen S, Busse WW. et al. . Early intervention with budesonide in mild persistent asthma: a randomised, double-blind trial.  Lancet. 2003;  361 1071-1076
• 26 Rabe KF, Jörres R, Nowak D. et al. . Comparison of the effects of salmeterol and formoterol on airway tone and responsivness over 24 hours in bronchial asthma.  Am Rev Respir Dis. 1993;  147 1436-1441
• 27 Rabe KF, Vermeire PA, Soriano JB, Maier WC. Clinical management of asthma in 1999: the Asthma Insights and Reality in Europe (AIRE) Study.  Eur Respir J. 2000;  16 802-827
• 28 The COMBIVENT Inhalation Study Group. . Routine nebulized ipratropium and albuterol together are better than either alone in COPD.  Chest. 1997;  112 1514-1521
• 29 Seemungal T, Harper-Owen R, Bhowmik A. et al. . Respiratory viruses, symptoms, and inflammatory markers in acute exacerbations and stable chronic obstructive pulmonary disease.  Am J Respir Crit Care Med. 2001;  164 1618-1623
• 30 Szafranski W, Cukier A, Ramirez A. et al. . Efficacy and safety of budesonide/formoterol in the management of chronic obstructive pulmonary disease.  Eur Respir J. 2003;  21 74-81
• 31 Szefler SJ, Leung DYM. Glucocorticoid-resistant asthma: pathogenesis and clinical implications for management.  Eur Respir J. 1997;  10 1640-1647
• 32 The Lung Health Study Research Group . Effect of inhaled triamcinolone on the decline in pulmonary function in chronic obstructive pulmonary disease.  N Engl J Med. 2000;  343 1902-1909
• 33 Ukena D, Harnest U, Sakalauskas R. et al. . Comparison of addition of theophylline to inhaled steroid with doubling of the dose of inhaled steroid in asthma.  Eur Respir J. 1997;  10 2754-2760
• 34 van Noord JA, Smeets JJ, Raaijmakers JAM. et al. . Salmeterol versus formoterol in patients with moderately severe asthma: onset and duration of action.  Eur Respir J. 1998;  9 1684-1688
• 35 Vestbo J, Sorensen T, Lange P. et al. . Long-term effect of inhaled budesonide in mild and moderate chronic obstructive pulmonary disease: a randomised controlled trial.  Lancet. 1999;  353 1819-1823
• 36 Wettengel R, Berdel D, Hofmann D. et al. . Empfehlungen zur Asthmatherapie bei Kindern und Erwachsenen.  Pneumologie. 1998;  52 591-601
• 37 Wilson AJ, Gibson PG, Coughlan J. Long acting beta agonists versus theophylline for maintenance treatment of asthma.  Cochrane Database Syst Rev. 2000;  2
• 38 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
• 39 ZuWallack RL, Mahler DA, Reilly D. et al. . Salmeterol plus theophylline combination therapy in the treatment of COPD.  Chest. 2001;  119 1661-1670

1 global initiative for asthma

2 asthma insights and reality in Europe

3 inhaled steroid treatment as regular therapy in early asthma

4 copenhagen city lung study

5 european respiratory society study on chronic obstructive pulmonary disease

6 inhaled steroids in obstructive lung disease in europe

7 lung health study

8 trial of inhaled steroids and long acting b2 agonists

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