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Was ist gesichert in der Therapie der Mukoviszidose?

Evidence-based treatment of cystic fibrosis

  • Schwerpunkt: Was ist gesichert in der Therapie?
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Zusammenfassung

Mukoviszidose (zystische Fibrose, „cystic fibrosis“ [CF]) ist die häufigste autosomal-rezessiv vererbte Multisystemerkrankung mit fatalem Verlauf. Sie wird durch Mutationen im Cystic-fibrosis-transmembrane-conductance-regulator-Gen (CFTR) verursacht, die zu einer unzureichenden Funktion des Chloridkanals CFTR führen. Infolge dessen kommt es durch unzureichende Hydratisierung des epithelialen Flüssigkeitsfilms zu einer Retention zähen Sekrets in etlichen lebenswichtigen Organen, vor allem in Lunge und Atemwegen, Pankreas, Leber und Gallengängen sowie dem Darm. Dadurch kommt es zu Inflammation und Infektion, Fibrose und progredienter Organdestruktion. Die Mortalität wird im Wesentlichen durch die respiratorische und ventilatorische Insuffizienz bedingt. In den gerade einmal 30 Jahren, die seit der molekularen Charakterisierung des CF-verursachenden CFTR-Basisdefekts vergangen sind, hat sich die Langzeitprognose der betroffenen Patienten enorm verbessert. Diese Prognoseverbesserung ist einerseits auf eine kooperative, sehr aktive und gut vernetzte internationale CF-Forschungsgemeinschaft zurückzuführen, andererseits auf eine standardisierte Behandlung durch ein interdisziplinäres und multiprofessionelles klinisches CF-Team, das die dadurch erfreulicherweise in zahlreichen Aspekten der CF-Therapie vorhandene Evidenz konsequent und gemeinsam mit dem Patienten in Behandlungsstandards umsetzt. Der vorliegende narrative Übersichtsbeitrag zeigt die Evidenz in ausgewählten Bereichen der CF-Therapie auf und würdigt hierbei insbesondere die jüngste Entwicklung der hocheffektiven CFTR-Modulator-Therapie, die in naher Zukunft voraussichtlich etwa 90 % der Betroffenen zur Verfügung stehen wird und die die CF durch ihren Einfluss auf die Pathophysiologie und den Langzeitverlauf in eine gut behandelbare chronische Erkrankung der Inneren Medizin transformieren wird.

Abstract

Mucoviscidosis (cystic fibrosis [CF]) is the most common autosomal recessive inherited multisystem disease with fatal outcome. It is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which lead to a dysfunctional chloride channel and a defective CFTR protein. As a consequence, retention of insufficiently hydrated mucus affects multiple essential organs, mainly the lungs and airways, pancreas, liver, biliary tract and intestines. This leads to inflammation and infection, fibrosis and progressive tissue destruction. Respiratory failure is the major cause of mortality; however, in the no more than 30 years since the molecular characterization of the basic CFTR defect causing CF, tremendous success has been made with respect to the long-term prognosis of people with CF. This improvement in the prognosis was achieved by the cooperative spirit and networking of the very active and international CF research community and by establishing a multidisciplinary clinical CF team that implements the existing evidence in various aspects of standardized care together with the CF patient. This narrative review article presents the evidence in selected aspects of CF treatment, with special consideration of the most recent development of highly effective CFTR modulator treatment. This treatment will soon become available for more than 90% of the global CF patients and transform the pathophysiology as well as the course of disease towards a treatable chronic condition in internal medicine.

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Abbreviations

ABPA:

Allergische bronchopulmonale Aspergillose

BAL:

Bronchoalveoläre Lavage

BMI:

Body-Mass-Index

CF:

„Cystic fibrosis“ (zystische Fibrose, Mukoviszidose)

CFF:

Cystic Fibrosis Foundation

CFQ‑R:

Cystic Fibrosis Questionnaire Revised

CFTR:

„Cystic fibrosis transmembrane conductance regulator“

ECFS:

European Cystic Fibrosis Society

EKG:

Elektrokardiogramm

EMA:

European Medicines Agency

FDA:

US Food and Drug Administration

FEV1 :

„Forced expiratory volume in 1 s“ (exspiratorische Einsekundenkapazität)

GKV:

Gesetzliche Krankenversicherung

LCI:

Lung Clearance Index

MF:

Minimalfunktion

NTM:

Nichttuberkulöse Mykobakterien

PA:

Pseudomonas aeruginosa

PEP:

„Positive expiratory pressure“

RF:

Restfunktion

rhDNase:

Rekombinante humane DNase

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Correspondence to F. C. Ringshausen.

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F. C. Ringshausen bzw. seine Institution hat in den letzten 3 Jahren Forschungsförderung von Bayer, Chiesi, InfectoPharm, Insmed, Grifols, Novartis und Polyphor, Entgelte für die Teilnahme an klinischen Studien von Boehringer Ingelheim, Celtaxsys, Corbus, Insmed, Novartis, Parion Sciences, Polyphor, Vertex und Zambon und finanzielle Unterstützung für die Durchführung von Patienteninformations- und Fortbildungsveranstaltungen von APOSAN, Bayer, Chiesi, InfectoPharm, Insmed, MSD, Novartis, PARI und Vertex erhalten. Darüber hinaus hat F.C. Ringshausen Honorare für Beratungstätigkeiten und Vorträge von AstraZeneca, Bayer, Boehringer Ingelheim, Chiesi, Grifols, Insmed, Novartis, Parion Sciences und Zambon erhalten. T. Hellmuth hat eine Forschungsförderung durch das Mukoviszidose Institut gGmbH, Bonn, den Forschungs- und Entwicklungsbereich von Mukoviszidose e. V., erhalten. A.-M. Dittrich bzw. ihre Institution hat in den letzten 3 Jahren Forschungsförderung von Vertex erhalten.

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

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H. Haller, Hannover

F.C. Ringshausen und A.-M. Dittrich sind Mitglieder des Deutschen Zentrums für Lungenforschung (DZL), Hannover, Deutschland.

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Ringshausen, F.C., Hellmuth, T. & Dittrich, A. Was ist gesichert in der Therapie der Mukoviszidose?. Internist 61, 1212–1229 (2020). https://doi.org/10.1007/s00108-020-00896-9

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