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Molecular approach to the classification of chronic fibrosing lung disease—there and back again

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Abstract

Chronic diffuse parenchymal lung disease (DPLD) is an umbrella term for a very heterogeneous group of lung diseases. Over the last decades, clinical, radiological and histopathological criteria have been established to define and separate these entities. More recently the clinical utility of this approach has been challenged as a unifying concept of pathophysiological mechanisms and a shared response to therapy across the disease spectrum have been described. In this review, we discuss molecular motifs for subtyping and the prediction of prognosis focusing on genetics and markers found in the blood, lavage and tissue. As a purely molecular classification so far lacks sufficient sensitivity and specificity for subtyping, it is not routinely used and not implemented in international guidelines. However, a better molecular characterization of lung disease with a more precise identification of patients with, for example, a risk for rapid disease progression would facilitate more accurate treatment decisions and hopefully contribute to better patients’ outcomes.

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Abbreviations

CA:

Carbohydrate antigen

CCL18:

Chemokine ligand-18

ChP:

Chronic hypersensitivity pneumonitis

DPLD:

Diffuse parenchymal lung disease

FIP:

Familial interstitial fibrosis

FVC:

Forced vital capacity

IGFBP-1:

Insulin-like growth factor-binding protein

ILD:

Interstitial lung disease

IPF:

Idiopathic pulmonary fibrosis

KL-6:

Krebs von den Lungen-6

ME:

Metaplastic epithelium

MM:

Myogenic metaplasia

MMP-7:

Matrix metalloproteinase-7

MO:

Alveolar macrophages

NAC:

N-Acetylcysteine

NSIP:

Nonspecific interstitial pneumonia

PARN:

Poly(A)-specific ribonuclease

PF-ILD:

Progressive-fibrosing ILD

RTEL1:

Regulator of telomere elongation helicase 1

SNP:

Single nucleotide polymorphisms

SP-D:

Surfactant protein-D

TERC:

Telomerase RNA component

TERT:

Telomerase reverse transcriptase

TNFRSF-1A:

Tumour necrosis factor superfamily

UIP:

Usual interstitial pneumonia

VATS:

Video-assisted thoracoscopic surgery

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Acknowledgement

The authors would like to thank Vincent Schmidt for his excellent technical support and Thia Hoffman for editing the manuscript.

Funding

SEV is a postdoctoral fellow of the Fonds wetenschappelijk onderzoek (12G8718N, V441019N) and acknowledges KU Leuven for their financial support (C24/18/073). DJ is supported by the grant of the European Research Council (ERC); European Consolidator Grant, XHale (ref. no.771883).

Author information

Authors and Affiliations

  1. Institute of Pathology, Hannover Medical School, Hannover, Germany

    Stijn E. Verleden, Peter Braubach, Mark Kuehnel, Emily Brouwer, Pauline Tittmann, Florian Laenger & Danny Jonigk

  2. BREATHE Lab, Department of CHROMETA, KU Leuven, Leuven, Belgium

    Stijn E. Verleden

  3. Member of the German Center for Lung Research, Biomedical Research in End-Stage and Obstructive Lung Disease (BREATH), Hannover, Germany

    Peter Braubach, Mark Kuehnel, Emily Brouwer, Pauline Tittmann, Florian Laenger & Danny Jonigk

  4. Department of Respiratory Medicine and Thoracic Oncology, Ibbenbueren General Hospital, Ibbenbueren, Germany

    Nicolas Dickgreber

Authors
  1. Stijn E. Verleden
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  2. Peter Braubach
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  3. Mark Kuehnel
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  4. Nicolas Dickgreber
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  5. Emily Brouwer
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  6. Pauline Tittmann
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  7. Florian Laenger
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  8. Danny Jonigk
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Contributions

Assisting in conception/design of the paper: SEV, PB, MR, ND, EB, PT, FL, DJ. Critical revision of the paper: SEV, PB, MR, ND, EB, PT, FL, DJ

Corresponding author

Correspondence to Stijn E. Verleden.

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Verleden, S.E., Braubach, P., Kuehnel, M. et al. Molecular approach to the classification of chronic fibrosing lung disease—there and back again. Virchows Arch 478, 89–99 (2021). https://doi.org/10.1007/s00428-020-02964-9

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  • DOI: https://doi.org/10.1007/s00428-020-02964-9

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