Dtsch Med Wochenschr 2013; 138(11): 541-547
DOI: 10.1055/s-0032-1332934
Übersicht | Review article
Pneumologie, Hals-Nasen-Ohrenheilkunde
© Georg Thieme Verlag KG Stuttgart · New York

Das Analgetika-Asthma-Syndrom

Aspirin-exacerbated respiratory disease
W. J. Randerath
1   Institut für Pneumologie an der Universität Witten/Herdecke, Klinik für Pneumologie und Allergologie, Zentrum für Schlaf- und Beatmungsmedizin, Krankenhaus Bethanien
› Author Affiliations
Further Information

Publication History

26 November 2012

24 January 2013

Publication Date:
05 March 2013 (online)

Zusammenfassung

Eine wichtige Differenzialdiagnose von Polyposis nasi, Intrinsic Asthma oder Urtikaria ist die Analgetika-Intoleranz. Die Begriffe „Analgetika-Asthma-Syndrom“ oder „Aspirin-exacerbated Respiratory Disease“ (AERD) fassen den Symptomenkomplex von chronischer Rhinosinusitis, Polyposis nasi, Asthma bronchiale und Unverträglichkeitsreaktion ausgelöst durch nicht-steroidale Antirheumatika (NSAR, NSAID) zusammen. Betroffen sind überwiegend Frauen ab der dritten Lebensdekade. Die Krankheitszeichen an der Nase manifestieren sich oft Jahre vor dem Asthma und einer Intoleranzreaktion. Nicht selten erfolgen wiederholt operative Entfernungen der Nasenpolypen, die jedoch meist nach kurzer Zeit rezidivieren. Das Asthma ist häufig nur schwer zu kontrollieren und steroidpflichtig. Die Erkrankung hat ihre Ursache keineswegs in der Einnahme von NSAID, die Unverträglichkeit stellt ein Epiphänomen der zugrundeliegenden biochemischen Störung dar. Sie beruht nicht auf einer allergischen, also IgE-vermittelten Reaktion, sondern auf einer Überproduktion der Cysteinyl-Leukotriene im Arachidonsäuremetabolismus der Zelle. Daher bleiben Hauttests oder spezifische Antikörper immer negativ. Es liegen neuere Daten zu In-vitro-Untersuchungen vor, die eine Analgetika-Intoleranz bestätigen und differenzieren lassen. Dennoch ist die nasale, inhalative und orale Provokationstestung weiter der diagnostische Goldstandard. Im Mittelpunkt der Therapie steht die adaptive Desaktivierung, die häufig eine Verbesserung der nasalen Symptomatik und teilweise eine Stabilisierung des Asthmas ermöglicht.

Abstract

Aspirin sensitivity is an important underlying disease in patients with nasal polyps, intrinsic asthma or urticaria. The terms “Aspirin- (or analgetics-) induced asthma” or “Aspirin-exacerbated respiratory disease“ (AERD) describe the syndrome of chronic rhinosinusititis, polyposis nasi, asthma and acute reaction after ingestion of non-steroid antiinflammatory drugs (NSAID). The disease affects mainly women in the third decade or older. Nasal symptoms often appear many years previous to asthma and acute intolerance reactions. Nasal polyps not rarely require surgical interventions. However, polyps often relapse after weeks or few months after resection. The intrinsic asthma is difficult to control and patients often require treatment with oral steroids. The disease is not caused by the ingestion of NSAID, the sensitivity represents a phenomenon of the underlying metabolic disorder. Aspirin sensitivity is not an allergic disease based on IgE-mediated reactions. In contrast it is due to a metabolic overexpression of cysteinyl leucotrienes. Thus, skin tests and specific antibodies in the blood are always negative. Recent studies indicate that NSAID sensitivity may be proven and differentiated by sophisticated in vitro tests. However, nasal, bronchial, and oral provocation testing remains the standard of diagnosis. Aspirin desensitization is the most relevant therapeutical approach which improves nasal symptoms in the majority of patients and may stabilize intrinsic asthma.

 
  • Literatur

  • 1 Adamjee J, Suh YJ, Park HS et al. Expression of 5-lipoxygenase and cyclooxygenase pathway enzymes in nasal polyps of patients with aspirin-intolerant asthma. J Pathol 2006; 209: 392-399
  • 2 Antczak A, Montuschi P, Kharitonov S et al. Increased exhaled cysteinyl-leukotrienes and 8-isoprostane in aspirin-induced asthma. Am J Respir Crit Care Med 2002; 166: 301-306
  • 3 Arm JP, Lee TH. Evidence for a specific role of leukotriene E4 in asthma and airway hyperresponsiveness. Adv Prostaglandin Thromboxane Leukotriene Res 1994; 22: 227-240
  • 4 Baenkler HW. Salicylate intolerance: pathophysiology, clinical spectrum, diagnosis and treatment. Dtsch Arztebl Int 2008; 105: 137-142
  • 5 Bochenek G, Nagraba K, Nizankowska E et al. A controlled study of 9alpha,11beta-PGF2 (a prostaglandin D2 metabolite) in plasma and urine of patients with bronchial asthma and healthy controls after aspirin challenge. J Allergy Clin Immunol 2003; 111: 743-749
  • 6 Bosso JV, Schwartz LB, Stevenson DD. Tryptase and histamine release during aspirin-induced respiratory reactions. J Allergy Clin Immunol 1991; 88: 830-837
  • 7 Cai Y, Bjermer L, Halstensen TS. Bronchial mast cells are the dominating LTC4S-expressing cells in aspirin-tolerant asthma. Am J Respir Cell Mol Biol 2003; 29: 683-693
  • 8 Christie PE, Smith CM, Lee TH. The potent and selective sulfidopeptide leukotriene antagonist, SK&F 104353, inhibits aspirin-induced asthma. Am Rev Respir Dis 1991; 144: 957-958
  • 9 Cowburn AS, Sladek K, Soja J et al. Overexpression of leukotriene C4 synthase in bronchial biopsies from patients with aspirin-intolerant asthma. J Clin Invest 1998; 101: 834-846
  • 10 Dahlen B. Treatment of aspirin-intolerant asthma with antileukotrienes. Am J Respir Crit Care Med 2000; 161: 137-141
  • 11 Dahlen SE, Malmstrom K, Nizankowska E et al. Improvement of aspirin-intolerant asthma by montelukast, a leukotriene antagonist. Am J Respir Crit Care Med 2002; 165: 9-14
  • 12 De Week AL, Sanz ML, Gamboa PM et al. Diagnosis of immediate-type beta-lactam allergy in vitro by flow-cytometric basophil activation test and sulfidoleukotriene production. J Investig Allergol Clin Immunol 2009; 19: 91-109
  • 13 Estrada Rodriguez JL, Florido Lopez JF, Belchi Hernandez J et al. Asthma in children and ASA intolerance. J Investig Allergol Clin Immunol 1993; 3: 315-320
  • 14 Ferreri NR, Howland WC, Stevenson DD et al. Release of leukotrienes, prostaglandins, and histamine into nasal secretions of aspirin-sensitive asthmatics during reaction to aspirin. Am Rev Respir Dis 1988; 137: 847-854
  • 15 Fischer AR, Rosenberg MA, Lilly CM et al. Direct evidence for a role of the mast cell in the nasal response to aspirin in aspirin-sensitive asthma. J Allergy Clin Immunol 1994; 94: 1046-1056
  • 16 Israel E, Fischer AR, Rosenberg MA et al. The pivotal role of 5-lipoxygenase products in the reaction of aspirin-sensitive asthmatics to aspirin. Am Rev Respir Dis 1993; 148: 1447-1451
  • 17 Jenkins C, Costello J, Hodge L. Systematic review of prevalence of aspirin induced asthma and its implications for clinical practice. BMJ 2004; 328: 434
  • 18 Kieff DA, Busaba NY. Efficacy of montelukast in the treatment of nasal polyposis. Ann Otol Rhinol Laryngol 2005; 114: 941-945
  • 19 Kim SH, Park HS. Genetic markers for differentiating aspirin-hypersensitivity. Yonsei Med J 2006; 47: 15-21
  • 20 Kowalski ML, Pawliczak R, Wozniak J et al. Differential metabolism of arachidonic acid in nasal polyp epithelial cells cultured from aspirin-sensitive and aspirin-tolerant patients. Am J Respir Crit Care Med 2000; 161: 391-398
  • 21 Kowalski ML, Ptasinska A, Jedrzejczak M et al. Aspirin-triggered 15-HETE generation in peripheral blood leukocytes is a specific and sensitive Aspirin-Sensitive Patients Identification Test (ASPITest). Allergy 2005; 60: 1139-1145
  • 22 Lee JY, Simon RA, Stevenson DD. Selection of aspirin dosages for aspirin desensitization treatment in patients with aspirin-exacerbated respiratory disease. J Allergy Clin Immunol 2007; 119: 157-164
  • 23 Lewis RA, Austen KF, Soberman RJ. Leukotrienes and other products of the 5-lipoxygenase pathway. Biochemistry and relation to pathobiology in human diseases. N Engl J Med 1990; 323: 645-655
  • 24 Loewen PS. Review of the selective COX-2 inhibitors celecoxib and rofecoxib: focus on clinical aspects. CJEM 2002; 4: 268-75
  • 25 Marquette CH, Saulnier F, Leroy O et al. Long-term prognosis of near-fatal asthma. A 6-year follow-up study of 145 asthmatic patients who underwent mechanical ventilation for a near-fatal attack of asthma. Am Rev Respir Dis 1992; 146: 76-81
  • 26 Mostafa BE, Abdel Hay H, Mohammed HE et al. Role of leukotriene inhibitors in the postoperative management of nasal polyps. ORL J Otorhinolaryngol Relat Spec 2005; 67: 148-153
  • 27 Nasser S, Christie PE, Pfister R et al. Effect of endobronchial aspirin challenge on inflammatory cells in bronchial biopsy samples from aspirin-sensitive asthmatic subjects. Thorax 1996; 51: 64-70
  • 28 Nasser SM, Bell GS, Foster S et al. Effect of the 5-lipoxygenase inhibitor ZD2138 on aspirin-induced asthma. Thorax 1994; 49: 749-756
  • 29 Nizankowska E, Bestynska-Krypel A, Cmiel A et al. Oral and bronchial provocation tests with aspirin for diagnosis of aspirin-induced asthma. Eur Respir J 2000; 15: 863-869
  • 30 Oosting E, Kardaun SH, Doeglas HM et al. Increased urinary excretion of the histamine metabolite N tau-methylhistamine during acetylsalicylic acid provocation in chronic urticaria patients. Agents Actions 1990; 30: 254-257
  • 31 Park HS. Early and late onset asthmatic responses following lysine-aspirin inhalation in aspirin-sensitive asthmatic patients. Clin Exp Allergy 1995; 25: 38-40
  • 32 Patriarca G, Nucera E et al. Nasal provocation test with lysine acetylsalicylate in aspirin-sensitive patients. Ann Allergy 1991; 67: 60-62
  • 33 Picado C, Fernandez-Morata JC, Juan M et al. Cyclooxygenase-2 mRNA is downexpressed in nasal polyps from aspirin-sensitive asthmatics. Am J Respir Crit Care Med 1999; 160: 291-296
  • 34 Pierzchalska M, Szabo Z, Sanak M et al. Deficient prostaglandin E2 production by bronchial fibroblasts of asthmatic patients, with special reference to aspirin-induced asthma. J Allergy Clin Immunol 2003; 111: 1041-1048
  • 35 Pleskow WW, Stevenson DD et al. Aspirin desensitization in aspirin-sensitive asthmatic patients: clinical manifestations and characterization of the refractory period. J Allergy Clin Immunol 1982; 69: 11-19
  • 36 Randerath W, Galetke W. Differentialdiagnose der rezidivierenden Polyposis nasi: Das Analgetika-Asthma-Syndrom. Dtsch Ärztebl 2007; 46: 3178-3183
  • 37 Randerath W. Das Analgetika-Asthma-Syndrom. In: Randerath W, Hrsg. Bronchialtherapeutika. Medizinisch-Pharmakologisches Kompendium. Stuttgart: Wissenschaftliche Verlagsgesellschaft; 2007: 123-133
  • 38 Schafer D, Maune S. Pathogenic mechanisms and In vitro diagnosis of AERD. J Allergy 2012; 2012: 789232
  • 39 Schapowal AG, Simon HU, Schmitz-Schumann M. Phenomenology, pathogenesis, diagnosis and treatment of aspirin-sensitive rhinosinusitis. Acta Otorhinolaryngol Belg 1995; 49: 235-250
  • 40 Sestini P, Armetti L, Gambaro G et al. Inhaled PGE2 prevents aspirin-induced bronchoconstriction and urinary LTE4 excretion in aspirin-sensitive asthma. Am J Respir Crit Care Med 1996; 153: 572-575
  • 41 Sousa AR, Parikh A, Scadding G et al. Leukotriene-receptor expression on nasal mucosal inflammatory cells in aspirin-sensitive rhinosinusitis. N Engl J Med 2002; 347: 1493-1499
  • 42 Stevenson DD, Simon RA, Lumry WR et al. Adverse reactions to tartrazine. J Allergy Clin Immunol 1986; 78: 182-191
  • 43 Szczeklik A, Gryglewski RJ, Czerniawska-Mysik G. Relationship of inhibition of prostaglandin biosynthesis by analgesics to asthma attacks in aspirin-sensitive patients. Br Med J 1975; 1: 67-69
  • 44 Tintinger GR, Feldman C, Theron AJ et al. Montelukast: more than a cysteinyl leukotriene receptor antagonist?. Sci World J 2010; 10: 2403-2413
  • 45 Widal MF, Abramin P, Lermoyez J. Anaphylaxie et idiosyncrasie. Presse Méd 1922; 30: 189