Asthma – Geschichtliche Entwicklung, Status quo und Ausblick

Zusammenfassung

Asthma ist keine neue, aber eine der häufigsten chronischen Erkrankungen; schätzungsweise 4 – 5 % der Erwachsenen und mehr als 10 % der Kinder in Deutschland sind betroffen, was Asthma zu einer der wichtigsten Volkskrankheiten macht. Im Laufe der letzten hundert Jahre haben sich die Vorstellungen zur Pathogenese von einer neurotischen Erkrankung über eine Erkrankung der glatten Muskulatur oder der Mastzelle oder spezieller Mediatoren wie dem Platelet activating factor bzw. einer Erkrankung durch Eosinophile bzw. deren regulierende T-Zellen zu einer komplexen Störung des adaptiven Immunsystems gewandelt. Auch die Therapie unterlag einer insgesamt dramatischen Änderung: Während Asthma vor 30 Jahren noch als Anfallskrankheit häufig, vor allem des Nachts, ärztlicher Interventionen bedurfte und Patienten im Status asthmaticus entweder verstarben oder invasiv beatmet werden mussten, hat sich dies heute durch den Einsatz moderner Asthmatherapie deutlich gewandelt. Dennoch ist Asthma auch heute noch, selbst unter wirksamer Therapie, keine Bagetell-Erkrankung und Patienten sind auch unter Therapie einer erheblichen Morbidität ausgesetzt, deren weitere Verbesserung anzustreben ist. Die Entwicklungen der letzten hundert Jahre werden im Folgenden, wenn auch oft aus der besser wissenden Retrospektive betrachtet, wobei der Status quo beleuchtet und sogar ein Ausblick (ohne Gewähr) in die Zukunft gewagt wird.

Abstract

Asthma is not a new disease. It is one of the most common chronic disorders affecting approximately 4 – 5 % of adults and more than 10 % of children in Germany. This turns asthma into one of the most prevalent chronic disorders. Over the last century ideas about its pathogenesis have changed many times. While around one hundred years ago asthma was often considered a neurotic disease, changes in airway smooth muscle, mast cell accumulation and activation or specific mediators such as platelet-activating factor have since been incriminated in its pathogenesis. Eosinophils, cytokines and T-lymphocytes were favourites some time later. Nowadays, – and this is unlikely to be the end of the story – asthma is considered as a complex disorder of the adaptive immune system. Therapeutic approaches have changed dramatically, too. While until about 30 years ago asthma was still considered a Smooth muscle disorder, recurrent attacks of asthma which required frequent, mostly nocturnal interventions, status asthmaticus, or the necessity of mechanical, invasive ventilation have markedly decreased. In view of the asthma epidemic in recent years, this development suggests that current treatments are at least partially effective. In spite of this patients with asthma are often only moderately well controlled with considerable morbidity from the disease as well as its treatment. Thus, despite recent advances in diagnosis and treatment, asthma is still not a trivial disease and future attempts at improving the care of those affected are warranted. The developments of the past 100 years as well as a careful look into the future are presented in this review.

Literatur

• 1 Diamant Z, Boot J D, Virchow J C. Summing up 100 years of asthma.  Respir Med. 2007;  101 378-388
• 2 Nolte D. Asthma. 7 ed. München; Elsevier 1998
• 3 Virchow C. Intrinsic Asthma: Symptomatik, Serum-IgE-Spiegel und Pathophysiologie.  Prax Pneumol. 1973;  27 578-591
• 4 Evans D J, Barnes P J, Cluzel M. et al . Effects of a potent platelet-activating factor antagonist, SR27417A, on allergen-induced asthmatic responses.  Am J Respir Crit Care Med. 1997;  156 11-16
• 5 Walker C, Bode E, Boer L. et al . Allergic and nonallergic asthmatics have distinct patterns of T-cell activation and cytokine production in peripheral blood and bronchoalveolar lavage.  Am Rev Respir Dis. 1992;  146 109-115
• 6 Wenzel S, Wilbraham D, Fuller R. et al . Effect of an interleukin-4 variant on late phase asthmatic response to allergen challenge in asthmatic patients: results of two phase 2a studies.  Lancet. 2007;  370 1422-1431
• 7 Haldar P, Brightling C E, Hargadon B. et al . Mepolizumab and exacerbations of refractory eosinophilic asthma.  N Engl J Med. 2009;  360 973-984
• 8 Ellul-Micallef R. Airway smooth muscle in health and in asthma.  Br J Dis Chest. 1973;  67 107-113
• 9 Laitinen L A, Heino M, Laitinen A. et al . Damage of the airway epithelium and bronchial reactivity in patients with asthma.  Am Rev Respir Dis. 1985;  131 599-606
• 10 Braun A, Lommatzsch M, Renz H. The role of neurotrophins in allergic bronchial asthma.  Clin Exp Allergy. 2000;  30 178-186
• 11 Virchow J C, Julius P, Lommatzsch M. et al . Neurotrophins are increased in bronchoalveolar lavage fluid after segmental allergen provocation.  Am J Respir Crit Care Med. 1998;  158 2002-2005
• 12 Castro M, Rubin A S, Laviolette M. et al . Effectiveness and safety of bronchial thermoplasty in the treatment of severe asthma: a multicenter, randomized, double-blind, sham-controlled clinical trial.  Am J Respir Crit Care Med. 2010;  181 116-124
• 13 Ross I. Bronchial asthma in Malaysia.  Br J Dis Chest. 1984;  78 369-375
• 14 Ulrik C S, Backer V, Dirksen A. et al . Extrinsic and intrinsic asthma from childhood to adult age: a 10-yr follow-up.  Respir Med. 1995;  89 547-554
• 15 Walker C, Virchow Jr. J C, Bruijnzeel P L. et al . T cell subsets and their soluble products regulate eosinophilia in allergic and nonallergic asthma.  J Immunol. 1991;  146 1829-1835
• 16 Ogilvie A G. The treatment of patients with severe asthma and chronic bronchitis.  Br J Tuberc Dis Chest. 1958;  52 126-133
• 17 Contoli M, Message S D, Laza-Stanca V. et al . Role of deficient type III interferon-lambda production in asthma exacerbations.  Nat Med. 2006;  12 1023-1026
• 18 Barnes P J, Woolcock A J. Difficult asthma.  Eur Respir J. 1998;  12 1209-1218
• 19 Garden G M, Ayres J G. Psychiatric and social aspects of brittle asthma.  Thorax. 1993;  48 501-505
• 20 Virchow Jr J C, Kroegel C, Luttmann W, Kortsik C. et al . Leukotrien-Rezeptorantagonisten, 5-Lipoxygenase- und 5-Lipoxygenase-aktivierendes Protein (FLAP)-Inhibitoren. Neue Therapieform inder Behandlung des Asthma bronchiale?.  Allergologie. 1996;  19 3-14
• 21 Haldar P, Pavord I D, Shaw D E. et al . Cluster analysis and clinical asthma phenotypes.  Am J Respir Crit Care Med. 2008;  178 218-224
• 22 Orie N G. The relationship between asthma and chronic obstructive and restrictive pulmonary diseases; lessons from the past century.  Ned Tijdschr Geneeskd. 2002;  146 1504-1508
• 23 Wardman A G, Binns V, Clayden A D. et al . The diagnosis and treatment of adults with obstructive airways disease in general practice.  Br J Dis Chest. 1986;  80 19-26
• 24 Hirsch S. Klinischer und experimenteller Beitrag zur krampflösenden Wirkung der Purinderivate.  Klin Wochenschr. 1922;  1 615-618
• 25 http://www.ginasthma.com; Stand: 2007
• 26 Inman W H, Adelstein A M. Rise and fall of asthma mortality in England and Wales in relation to use of pressurised aerosols.  Lancet. 1969;  2 279-285
• 27 Hasford J, Virchow J C. Excess mortality in patients with asthma on long-acting beta2-agonists.  Eur Respir J. 2006;  28 900-902
• 28 Kramer J M. Balancing the benefits and risks of inhaled long-acting beta-agonists – the influence of values.  N Engl J Med. 2009;  360 1592-1595
• 29 Haahtela T, Jarvinen M, Kava T. et al . Comparison of a beta 2-agonist, terbutaline, with an inhaled corticosteroid, budesonide, in newly detected asthma.  N Engl J Med. 1991;  325 388-392
• 30 Guilbert T W, Morgan W J, Zeiger R S. et al . Long-term inhaled corticosteroids in preschool children at high risk for asthma.  N Engl J Med. 2006;  354 1985-1997
• 31 Virchow Jr. J C, Faehndrich S, Nassenstein C. et al . Effect of a specific cysteinyl leukotriene-receptor 1-antagonist (montelukast) on the transmigration of eosinophils across human umbilical vein endothelial cells.  Clin Exp Allergy. 2001;  31 836-844
• 32 Lane S J. Leukotriene antagonism in asthma and rhinitis.  Respir Med. 1998;  92 795-809
• 33 Virchow J C, Lommatzsch M. Anticholinergic agents in asthma. In: Polosa R, Holgate ST, ed. Asthma: Current Strategies: Clinical Publishing. 2007: 79-90
• 34 Church M K, Hiroi J. Inhibition of IgE-dependent histamine release from human dispersed lung mast cells by anti-allergic drugs and salbutamol.  Br J Pharmacol. 1987;  90 421-429
• 35 Pearce F L. Effect of nedocromil sodium on mediator release from mast cells.  J Allergy Clin Immunol. 1993;  92 155-158
• 36 Humbert M, Beasley R, Ayres J. et al . Benefits of omalizumab as add-on therapy in patients with severe persistent asthma who are inadequately controlled despite best available therapy (GINA 2002 step 4 treatment): INNOVATE.  Allergy. 2005;  60 309-316
• 37 Vignola A M, Humbert M, Bousquet J. et al . Efficacy and tolerability of anti-immunoglobulin E therapy with omalizumab in patients with concomitant allergic asthma and persistent allergic rhinitis: SOLAR.  Allergy. 2004;  59 709-717
• 38 Leckie M J. Anti-interleukin-5 monoclonal antibodies: preclinical and clinical evidence in asthma models.  Am J Respir Med. 2003;  2 245-259
• 39 Pavord I D, Haldar P, Bradding P. et al . Mepolizumab in refractory eosinophilic asthma.  Thorax. 2010;  65 370
• 40 Luttmann W, Knoechel B, Foerster M. et al . Activation of human eosinophils by IL-13. Induction of CD69 surface antigen, its relationship to messenger RNA expression, and promotion of cellular viability.  J Immunol. 1996;  157 1678-1683
• 41 Nassenstein C, Braun A, Erpenbeck V J. et al . The neurotrophins nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4 are survival and activation factors for eosinophils in patients with allergic bronchial asthma.  J Exp Med. 2003;  198 455-467
• 42 Jacobsen L, Niggemann B, Dreborg S. et al . Specific immunotherapy has long-term preventive effect of seasonal and perennial asthma: 10-year follow-up on the PAT study.  Allergy. 2007;  62 943-948
• 43 Hasford J, Uricher J, Tauscher M. et al . Persistence with asthma treatment is low in Germany especially for controller medication – a population based study of 483,051 patients.  Allergy. 2010;  65 347-354
• 44 Buhl R, Berdel D, Criée C P. et al . Leitlinie zur Diagnostik und Therapie von Patienten mit Asthma.  Pneumologie. 2006;  60 139-177