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Asthma pp 71-88 | Cite as

Structural and inflammatory changes in the airways of asthmatics

  • P. K. Jeffery

Summary

These studies support the role of airway wall inflammation in bronchial asthma, confirm the involvement of eosinophils and their degranulation and implicate, further, T lymphocytes and interleukin 5 as controllers of the eosinophilic response. Several factors may contribute to apparent airways hyperresponsiveness including fragility of surface epithelium, thickening of the airway wall, uncoupling of airway wall and parenchyma or loss of lung elastic recoil. Thickening of the airway wall may be due to bronchial vessel dilatation and oedema, or enlargement of the mass of bronchial smooth muscle or mucus-secretory glands. Each of these changes may be induced by the inflammatory cells which infiltrate the airway wall in both mild and severe asthma: their predominant cytokine products can clearly influence the characteristic profile of cell phenotypes, their activation and the chronicity of the inflammatory response. In this regard, mast cells and lymphocytes may be important initiators and controllers, whilst activated eosinophils are key reactor cells whose increased presence is associated with increased airways responsiveness.

Keywords

Mast Cell Allergy Clin Immunol Airway Wall Mild Asthma Status Asthmaticus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Zusammenfassung

Strukturelle und entzündliche Veränderungen in den Atemwegen von Asthmatikern. Das tödliche Asthma zeigt histologisch drei Charakteristika: Die Abschilferung und Zerstörung des Epithels der Atemwegsoberfläche, die Verdickung seiner retikulären Basalmembran und die Entzündung der Mukosa. Wir haben die Ultrastruktur und die Immunhistologie der Bronchialmukosa an Autopsiepräparaten von Personen, die im Status asthmatikus gestorben waren (n = 15), analysiert, sowie von Bronchialbiopsien, welche durch fiberoptische Bronchoskopie von Patienten mit relativ mildem atopischen Asthma gewonnen worden waren (n = 33). Bei ersteren (fatale Asthmafälle) wurde ein Vergleich mit den Befunden von plötzlich verstorbenen nicht asthmatischen Kontrollen (n = 10) durchgeführt, bei den milden Asthmatikern wurde ein Vergleich sowohl mit atopischen Nicht-Asthmatikern als auch normalen gesunden Personen durchgeführt (n = 32). Beim milden Asthma korrelierte der Verlust von Oberflächenepithel mit dem Grad der Hyperreaktivität auf Metacholin, als Hinweis auf die Brüchigkeit des Atemwegsepithels. Die Verdickung der retikulären Basalmembran und die Schleimhautentzündung, welche beim fatalen Asthma beobachtet wurde, sind ebenso beim milden atopischen Asthma nachzuweisen. Hier besteht ein Trend zu größeren Zahlen von CD45+ Leukozyten, sowohl beim fatalen als auch beim milden Asthma, wobei hier CD3+ (T) Lymphozyten und Eosinophile, aber nicht Neutrophile betroffen sind. Die Aktivitätsmarker für Lymphozyten und Eosinophile (CD25 bzw. EG2) sind signifikant erhöht und bei symptomatischen Patienten mit dem Auftreten von unregelmäßig gestalteten lymphozytenähnlichen Zellen verquickt. Je größer die Zahl der aktivierten Eosinophilen, desto größer ist auch der Grad der Hyperreaktivität. Ähnliche Veränderungen können beim intrinsischen und Berufsasthma beobachtet werden. Unter Verwendung von in situ Hybridisation können spezifische Zytokinsignale für IL-5 und für IL-5 und GM- CSF mRNA nachgewiesen werden, und zwar innerhalb der Bronchialmukosa von symptomatischen atopischen Asthmatikern, bzw. in der Folge von Allergenprovokation. Kurzfristige (4 Wochen) und langfristige Behandlung durch inhalative Kortikosteroide reduzierte die charakteristische Eosinophilie signifikant. Die Untersuchung der BAL bestätigt das Vorhandensein von Eosinophilen, die Freisetzung von ECP und die vermehrte Expression von T-Zell-Genen, mit den Codes für IL4, IL5 und GM-CSF. Diese Ergebnisse stützen die Annahme, daß pro-inflammatorische Zytokine (insbesondere Interleukin 4 und 5) an der durch Eosinophile mediierten Epithelzerstörung sogar bei milden atopischen Asthmatikern beteiligt sind.

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Copyright information

© Springer-Verlag/Wien 1995

Authors and Affiliations

  • P. K. Jeffery
    • 1
  1. 1.Lung Pathology, Department of HistopathologyRoyal Brompton National Heart & Lung InstituteGB-LondonUK

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