Das akute Lungenversagen – Pulmonale Reparatur und therapeutische Optionen

Zusammenfassung

Das akute respiratorische distress syndrome (ARDS) ist charakterisiert durch inflammatorisch bedingtes Lungenödem, hyaline Membranen, diffusen endothelialen und epithelialen Schaden sowie Fibrose. Ein Überleben impliziert Lungenreparatur. Diese Übersicht fast den aktuellen Wissenstand in Bezug auf Reparatur sowie genetische Faktoren zusammen, die Einfluss nehmen auf Letalität und Schweregrad des ARDS.

Summary

The acute respiratory distress syndrome (ARDS) is characterized by inflammation evoked pulmonary edema, hyaline membranes, diffuse endothelial and epithelial injury, and fibrosis. For survival to occur lung repair is required. This review explores recent advances in the field of fibroproliferation with emphasis on cellular and soluble factors, mechanisms involved in lung repair, and genetic factors which influence severity and survival in ARDS.

Schlüsselwörter:

ARDS - extrazelluläres Proteasom - Lungenumbau - Polymorphismen - Lungenreparatur - Therapie

Keywords:

ARDS - extracellular proteasome - lung repair - polymorphisms - prognosis - therapy

Kernaussagen

• 30–70  % der ARDS–Patienten überleben unter qualifizierter Therapie einschließlich extrakorporalem Lungenersatz in spezialisierten Zentren.

• Überleben Patienten das ARDS, sind im Langzeitverlauf in vielen Fällen nur noch geringe pulmonale Veränderungen und Funktionseinschränkungen nachweisbar.

• Es gibt bislang keine kausale bzw. spezifische Therapie, pulmonale Reparaturmechanismen positiv zu beeinflussen – das ist jedoch Ziel aktueller Forschung.

• Migration, Proliferation und Regeneration von Pneumozyten Typ II und deren Sekretion von extrazellulären Enzymen in den Alveolarraum sind essenzielle Elemente pulmonaler Reparatur.

• Die Einwanderung atemwegsresidenter, transdifferenzierter mesenchymaler Zellen sowie pluripotenter Knochenmarkszellen in den Alveolarraum und Apoptose von Pneumozyten trägt wesentlich zur Wiederherstellung alveolärer Integrität bei.

• In der Reparaturphase des ARDS gelangen enzymatische „Fressmaschinen” in den geschädigten Alveolarraum, um dort hyaline Membranen abzuräumen.

• Alveolarmakrophagen sezernieren Mediatoren und Wachstumsfaktoren, die zu einer proliferativen Antwort von Fibroblasten und glatten Muskelzellen führen.

• Wesentliches Schlüsselelement in der Lungenfibrose ist TGF–β.

• Auch das lokale Gerinnungssystem an der Alveolaroberfläche spielt eine wichtige Rolle in der Entwicklung der Lungenfibrose.

• Inzidenz und Krankheitsverlauf werden durch die individuelle genetische Konstellation erheblich beeinflusst.

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