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Entwicklung und Fortschritt bei interstitiellen Lungenerkrankungen

Development and progress in interstitial lung diseases

  • Leitthema
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Zusammenfassung

Im Bereich der interstitiellen Lungenerkrankungen (ILD) waren in den letzten Jahren sehr große Fortschritte in Diagnostik und Therapie zu verzeichnen. Hierzu zählt auch ein verbessertes Verständnis interstitieller Lungenabnormalitäten (ILA). Ein wichtiger Fokus ist die Etablierung prognostischer und prädiktiver Biomarker. Bezüglich bildgebender Verfahren wird aktuell der Einsatz der Magnetresonanztomographie (MRT) sowie des FAPI („fibroblast-activation protein inhibitor“)/PET-CTs (Positronenemissionstomographie-Computertomographie) bei ILD in Studien geprüft und erscheint vielversprechend. Als ergänzendes Navigationstool könnte die konfokale Laserendoskopie dienen und so die diagnostische Ausbeute von transbronchialen Kryobiopsien erhöhen. Auch im Hinblick auf nichtmedikamentöse Therapieverfahren wurden Fortschritte erzielt und erstmals wurde eine prognostische Bedeutung der pulmonalen Rehabilitation beschrieben. Große Entwicklungen wurden im Bereich medikamentöser Therapien erzielt. So hat sich die antifibrotische Therapie auch bei progredient fibrosierenden Phänotypen als wirksam erwiesen. Auch bei der systemischen Sklerose-assoziierten ILD (SSc-ILD) ist Nintedanib effektiv; in dieser Indikation hat die Food and Drug Administration (FDA) zudem aufgrund Daten der FocuSSced-Studie Tocilizumab als erstes Biologikum zugelassen. Nachdem kürzlich ein Phase-III-Programm zum Autotaxininhibitor GLPG1690 aufgrund von Ineffektivität beendet werden musste, werden mit Pentraxin und Pamrevlumab vielversprechende neue Therapeutika zur Behandlung der idiopathischen Lungenfibrose in Phase-III-Studien getestet.

Abstract

In the field of interstitial lung disease (ILD) there have been very significant advances in the diagnostics and treatment in recent years. This includes an improved understanding of interstitial lung abnormalities (ILA). An important focus is the establishment of prognostic and predictive biomarkers. Regarding imaging modalities, the use of magnetic resonance imaging (MRI) as well as fibroblast-activation protein inhibitor/positron emission tomography-computed tomography (FAPI/PET-CT) in ILD is currently under study and appears to be promising. Confocal laser endoscopy could serve as a complementary navigation tool, increasing the diagnostic yield of transbronchial cryobiopsy. Progress has also been made with respect to nonpharmacologic treatment and a prognostic significance of pulmonary rehabilitation has been described for the first time. Major developments have been made in the area of drug treatment. For example, antifibrotic treatment has been shown to be effective even in progressively fibrosing phenotypes. Nintedanib is also effective in systemic scleroderma-associated ILD (SSc-ILD); in this indication, the FDA has also approved tocilizumab as the first biologic based on data from the FocuSSced trial. Following the recent termination of a phase III program on the autotaxin inhibitor GLPG1690 due to ineffectiveness, the promising new therapeutics for the treatment of idiopathic pulmonary fibrosis, pentraxin and pamrevlumab, are being tested in phase III trials.

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Abbreviations

ASV:

Ambulante spezialfachärztliche Versorgung

ATS:

American Thoracic Society

BAL:

Bronchoalveoläre Lavage

CLE:

Konfokale Laserendoskopie

COPD:

Chronic obstructive pulmonary disease

CT:

Computertomographie

CTGF:

Connective tissue growth factor

DLCO:

Diffusion capacity of the lungs for carbon monoxide

EAA:

Exogen allergische Alveolitis

ERS:

European Respiratory Society

FAP:

Fibroblast activation protein

FAPI:

Fibroblast activation protein inhibitor

FDA:

Food and Drug Administration

FDG:

Fluordesoxyglucose

fILD:

Fibrosierende interstitielle Lungenerkrankung

FVC:

Forcierte Vitalkapazität

HRCT:

High-Resolution-Computertomographie

Ig:

Immunglobulin

IL:

Interleukin

ILA:

Interstitielle Lungenabnormalität

ILD:

Interstitielle Lungenerkrankung

IPF:

Idiopathische Lungenfibrose

LTOT:

Langzeitsauerstofftherapie

MMRC:

Modified Medical Research Council

mRSS:

Modified Rodnan Skin Score

MRT:

Magnetresonanztomographie

NSIP:

Nichtspezifische („nonspecific“) interstitielle Pneumonie

PET:

Positronenemissionstomographie

PF-ILD:

Progredient fibrosierende interstitielle Lungenerkrankung

RA:

Rheumatoide Arthritis

RA-ILD:

Rheumatoide Arthritis-assoziierte interstitielle Lungenerkrankung

RNA:

Ribonukleinsäure

SSc:

Systemische Sklerose

TBB:

Transbronchiale Biopsie

UIP:

Usual interstitial pneumonia

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Authors and Affiliations

  1. Zentrum für seltene und interstitielle Lungenerkrankungen und interdisziplinäres Sarkoidosezentrum, Pneumologie, Thoraxklinik, Universitätsklinikum Heidelberg und Deutsches Zentrum für Lungenforschung (DZL), Röntgenstr. 1, 69126, Heidelberg, Deutschland

    Katharina Buschulte, Philipp Höger, Nicolas Kahn & Michael Kreuter

  2. Diagnostische und Interventionelle Radiologie mit Nuklearmedizin, Thoraxklinik, Universitätsklinikum Heidelberg und Deutsches Zentrum für Lungenforschung (DZL), Heidelberg, Deutschland

    Claus Peter Heußel

  3. Diagnostische und Interventionelle Radiologie, Universitätsklinikum Heidelberg, Heidelberg, Deutschland

    Claus Peter Heußel

Authors
  1. Katharina Buschulte
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  3. Philipp Höger
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  4. Nicolas Kahn
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Corresponding author

Correspondence to Michael Kreuter.

Ethics declarations

Interessenkonflikt

N. Kahn und M. Kreuter erhielten unabhängige Forschungsunterstützung von Roche und Boehringer Ingelheim sowie Kompensationen für Beratung. K. Buschulte und P. Höger geben an, dass kein Interessenkonflikt besteht. C.P. Heußel gibt an: Employment or Leadership Position: Head of Diagnostic and Interv Radiology with Nuclear Medicine, Thoraxklinik Heidelberg, Member of the German Center for Lung Research; Stock ownership in medical industry: GSK; Patent: Method and Device For Representing the Microstructure of the Lungs. IPC8 Class: AA61B5055FI, PAN: 20080208038 (Inventors: W Schreiber, U Wolf, AW Scholz, CP Heussel); Personal involvements—Consultation or other fees: Schering-Plough 2009, 2010, Pfizer 2008–2014, Basilea 2008, 2009, 2010, Boehringer Ingelheim 2010–2014, Novartis 2010, 2012, 2014, Roche 2010, Astellas 2011, 2012, Gilead 2011–2015, MSD 2011–2013, Lilly 2011, Intermune 2013–2014, Fresenius 2013, 2014. Expert testimony: No. Tobacco Industry: No relation. Research funding: Siemens 2012–2014, Pfizer 2012–2014, MeVis 2012, 2013, Boehringer Ingelheim 2014, German Center for Lung Research 2011ff. Lecture fees: Gilead 2008–2014, Essex 2008, 2009, 2010, Schering-Plough 2008, 2009, 2010, AstraZeneca 2008–2012, Lilly 2008, 2009, 2012, Roche 2008, 2009, MSD 2009–2014, Pfizer 2010–2014, Bracco 2010, 2011, MEDA Pharma 2011, Intermune 2011–2014, Chiesi 2012, Siemens 2012, Covidien 2012, Pierre Fabre 2012, Boehringer Ingelheim 2012, 2013, Grifols 2012, Novartis 2013–2016, Basilea 2015, 2016, Bayer 2016. Committee membership: Chest working group of the German Roentgen society. National guidelines: bronchial carcinoma, mesothelioma, COPD, screening for bronchial carcinoma, CT and MR imaging of the chest, Pneumonia. Consultant of ECIL‑3, ECCMID, EORTC/MSG. Guideline for diagnosis of infections in immunocompromized hosts. Founding member of the working team in infections in immunocompromized hosts of the German society of Hematology/Oncology. Guideline for diagnosis of infections in immunocompromized hosts. Faculty member of the European Society of Thoracic Radiology (ESTI), European Respiratory Society (ERS), and member in EIBALL (European Imaging Biomarkers Alliance). Editor of Medizinische Klinik, Intensivmedizin und Notfallmedizin, at Springer publishing.

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. Für Bildmaterial oder anderweitige Angaben innerhalb des Manuskripts, über die Patienten zu identifizieren sind, liegt von ihnen und/oder ihren gesetzlichen Vertretern eine schriftliche Einwilligung vor.

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Buschulte, K., Heußel, C.P., Höger, P. et al. Entwicklung und Fortschritt bei interstitiellen Lungenerkrankungen. Pneumologe 19, 97–103 (2022). https://doi.org/10.1007/s10405-021-00422-0

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