Non-CF-Bronchiektasen: Aktuelle therapeutische Entwicklungen

Zusammenfassung

Non-CF (NCF)-Bronchiektasen führen durch chronische Inflammation zu progredienter Zerstörung von Lungenstruktur. Die Erkrankung wird durch verbesserte Diagnostik (HR-CT) zunehmend wahrgenommen, die Prävalenz in Deutschland liegt bei 67/100 000.

Die Qualität der Therapie ist entscheidend von präziser Diagnostik bestimmt. Genetische (Mukoviszidose, Alpha-1-AT-Mangel, Rheumaerkrankungen) und immunologische Ursachen (Immundefekte, allergische bronchopulmonale Aspergillose) sind von idiopathischen NCF-Bronchiektasen zu differenzieren.

Ziel einer Therapie ist die Durchbrechung der entzündlichen Kaskade. Kombiniert werden kontinuierliche Sekretmobilisation durch Physiotherapie, immunmodulierende Verfahren und die bedarfsgerechte antibiotische Therapie. Operative Therapien bleiben speziellen Problemen vorbehalten.

Makrolide vermitteln eine Vielzahl immunmodulierender Wirkungen. Sie reduzieren Symptome und Exazerbationen bei guter Verträglichkeit, sofern kardiale Risiken ausgeschlossen werden. Die Wirkung von Statinen auf NCF-Bronchiektasen ist nicht abschließend untersucht.

Antibiotika werden resistenzgerecht bei Exazerbationen und Erstnachweis von Leitkeimen (Pseudomonas aeruginosa, MRSA) angewendet. Inhalative Antibiotikatherapien werden zunehmende Bedeutung erfahren, derzeit erfolgt die Anwendung nur in begründeten Einzelfällen.

Abstract

Non-CF (NCF)-bronchiectasis is a syndrome of chronic inflammation leading to dilatation of airways and structural lung damage. Improvements of diagnostic procedures increase its perceived frequency. In Germany, recent data suggest a prevalence of 67/100 000.

The outcome of therapeutic interventions is critically related to thorough diagnostic procedures. Genetical or immunological disorders (cystic fibrosis, alpha-1-AT deficiency, immune deficiency syndromes) require treatment options different from idiopathic NCF-bronchiectasis.

Therapy is aimed at suppression of chronic inflammation and includes continuous mobilisation of secretions, immunomodulatory strategies and antibiotic therapy, whenever required. Surgical procedures are limited to specific complications (e. g. destroyed lung after airway obstruction, uncontrolled hemorrhage)

Macrolides show a variety of immunological properties with favourable results in reduction of symptoms and frequency of exacerbations. Longtime tolerance is good, if individual risk factors are excluded.

Antibiotics are given according to resistance patterns in acute exacerbations and in first-time detection of Pseudomonas aeruginosa and MRSA. Inhaled antibiotics for NCF-bronchiectasis will gain importance, depending on future studies. Currently, they are only used in individualized concepts of therapy.

Schlüsselwörter

Bronchiektasen - Therapie - Makrolide - Antibiotika - inhalative Antibiotika

Keywords

bronchiectasis - therapy - macrolide - antibiotic - inhaled antibiotic

• Literatur

• 1 Bronchiectasis. In: Gibson J, Loddenkemper R, Sibille Y, Lundbäck B, (eds.): The European Lung White Book: Respiratory Health and Disease in Europe. Lausanne: European Respiratory Society; 2013: 176-183
• 2 Seitz AE, Olivier KN, Steiner CA et al. Trends and Burden of Bronchiectasis-Associated Hospitalizations in the United States, 1993–2006. Chest 2010; 138: 944-949
• 3 Seitz AE, Olivier KN, Adjemian J et al. Trends in Bronchiectasis Among Medicare Beneficiaries in the United States, 2000 to 2007. Chest 2012; 142: 432-439
• 4 Ringshausen FC, de Roux A, Diel R et al. Bronchiectasis in Germany: a population-based estimation of disease prevalence. Eur Respir J 2015; 46: 1805-1807
• 5 Quint JK, Millett ER, Joshi M et al. Changes in the incidence, prevalence and mortality of bronchiectasis in the UK from 2004 to 2013: a population-based cohort study. Eur Respir J 2016; 47: 186-193
• 6 Martínez-García MÁ, Soler-Cataluña JJ, Donat Sanz Y et al. Factors associated with bronchiectasis in patients with COPD. Chest 2011; 140: 1130-1137
• 7 Lonni S, Chalmers JD, Goeminne PC et al. Etiology of Non-Cystic Fibrosis Bronchiectasis in Adults and Its Correlation to Disease Severity. Ann Am Thorac Soc 2015; 12: 1764-1770
• 8 de Roux A. Versorgung von Patienten mit Non-CF-Bronchiektasen in der niedergelassenen Praxis. Der Pneumologe 2014; 11: 330-336
• 9 Li AM, Sonnappa S, Lex C et al. Non-CF bronchiectasis: does knowing the aetiology lead to changes in management?. Eur Respir J 2005; 26: 8-14
• 10 Loebinger MR, Wells AU, Hansell DM et al. Mortality in bronchiectasis: a long-term study assessing the factors influencing survival. Eur Respir J 2009; 34: 843-849
• 11 Bös L, Schönfeld N, Schaberg T. Non tuberculous mycobacteria – a short review about epidemiology, diagnosis and treatment. Pneumologie 2015; 69: 287-294
• 12 Griffith DE, Aksamit T, Brown-Elliott BA et al. An Official ATS / IDSA Statement: Diagnosis, Treatment, and Prevention of Nontuberculous Mycobacterial Diseases. www.thoracic.org/statements/resources/mtpi/nontuberculous-mycobacterial-diseases.pdf (Letzter Zugriff: 16. 3. 2016)
• 13 Goyal V, Chang AB. Combination inhaled corticosteroids and long-acting beta2-agonists for children and adults with bronchiectasis. Cochrane Database Syst Rev 2014; 6: CD010327
• 14 Martinez-Garcia MA, Soler-Cataluna JJ, Catalan-Serra P et al. Clinical efficacy and safety of budesonide-formoterol in non-cystic fibrosis bronchiectasis. Chest 2012; 141: 461-468
• 15 Kanoh S, Rubin BK. Mechanisms of Action and Clinical Application of Macrolides as Immunomodulatory Medications. Clin Microbiol Rev 2010; 23: 590-615
• 16 Li-Chao Fan, Hai-Wen Lu, Ping Wei et al. Effects of long-term use of macrolides in patients with non-cystic fibrosis bronchiectasis: a meta-analysis of randomized controlled trials. BMC Infect Dis 2015; 15: 160-170
• 17 Wong C, Jayaram L, Karalus N. Azithromycin for prevention of exacerbations in non-cystic fibrosis bronchiectasis (EMBRACE): a randomised, double-blind, placebo-controlled trial. Lancet 2012; 380: 660
• 18 Altenburg J, de Graaff CS, Stienstra Y. Effect of azithromycin maintenance treatment on infectious exacerbations among patients with non-cystic fibrosis bronchiectasis: the BAT randomized controlled trial. JAMA 2013; 309: 1251
• 19 Serisier DJ, Martin ML, McGuckin MA. Effect of long-term, low-dose erythromycin on pulmonary exacerbations among patients with non-cystic fibrosis bronchiectasis: the BLESS randomized controlled trial. JAMA 2013; 309: 1260
• 20 Albert RK, Schuller JL COPD Clinical Research Network. Macrolide antibiotics and the risk of cardiac arrhythmias. Am J Respir Crit Care Med 2014; 189: 1173-1180
• 21 Mandal P, Chalmers JD, Graham C, Harley C et al. Atorvastatin as a stable treatment in bronchiectasis: a randomised controlled trial. Lancet Respir Med 2014; 2: 455-463
• 22 Martin C, Burgel PR, Lepage P et al. Host–microbe interactions in distal airways: relevance to chronic airway disease. Europ Respir Rev 2015; 135: 78-91
• 23 Green H, Jones AM. The microbiome and emerging pathogens in cystic fibrosis and non–cystic fibrosis bronchiectasis. Semin Respir Crit Care Med 2015; 36: 225-235
• 24 Miao XY, Ji XB, Lu HW at al. Distribution of major pathogens from sputum and bronchoalveolar lavage fluid in patients with noncystic fibrosis bronchiectasis: a systematic review. Chin Med J 2015; 128: 2792-2797
• 25 Judson MA, Chaudhry H, Compa DR, O’Donnell AE. A Delphi study of pharmacotherapy for noncystic fibrosis bronchiectasis. Am J Med Sci 2014; 348: 387-393
• 26 Pasteur MC, Bilton D, Hill AT. British Thoracic Society guideline for non-CF bronchiectasis. Thorax 2010; 65 (Supplement 1)
• 27 Finch S, McDonnell MJ, Abo-Leyah H et al. A comprehensive analysis of the impact of pseudomonas aeruginosa colonization on prognosis in adult bronchiectasis. Ann Am Thorac Soc 2015; 12: 1602-1611
• 28 Suresh Babu K, Kastelik J, Morjaria JB. Role of long term antibiotics in chronic respiratory diseases. Respir Med 2013; 107: 800-815
• 29 Brodt AM, Stovold E, Zhang L. Inhaled antibiotics for stable non-cystic fibrosis bronchiectasis: a systematic review. Eur Respir J 2014; 44: 382-393
• 30 Tay GTP, Reid DW, Bell SC. Inhaled antibiotics in cystic fibrosis (CF) and non-CF bronchiectasis. Semin Respir Crit Care Med 2015; 36: 267-286
• 31 Serisier DJ, Bilton D, De Soyza A. Inhaled, dual release liposomal ciprofloxacin in non-cystic fibrosis bronchiectasis (ORBIT-2): a randomised, double-blind, placebo-controlled trial. Thorax 2013; 68: 812
• 32 Lee AL, Burge AT, Holland AE. Airway clearance techniques for bronchiectasis. Cochrane Database Syst Rev 2015; 11: CD008351
• 33 Wilkinson M, Sugumar K, Milan SJ et al. Mucolytics for bronchiectasis. Cochrane Database Syst Rev 2014; 5: CD001289
• 34 Ringshausen FC, Welte T. Bronchiektasen. Pneumologe 2014; 11: 299-300
• 35 PROspective German NOn-CF BronchiectaSIS Patient Registry (PROGNOSIS). www.bronchiektasen-register.de (Letzter Zugriff: 16. 03. 2016)