New targets in idiopathic pulmonary fibrosis: from inflammation and immunity to remodeling and repair

ABSTRACT

Introduction: Idiopathic pulmonary fibrosis (IPF) is a chronic respiratory disease whose incidence and prevalence are increasing. Recent evidence has led to a change of paradigm regarding understanding of the underlying pathophysiology. In parallel, we have witnessed the development and rise of the first anti-fibrotic drugs, namely pirfenidone and nintedanib. However, with clinical results being below expectations there is a clear need for new medications in this field.

Areas covered: After covering new mechanisms involved in IPF pathogenesis, the present review discusses current clinical trials and deciphers potential new targets in light of in vitro and in vivo experimental studies.

Expert Opinion: All in all, we believe that future development will require (1) a significant improvement in experimental models, (2) a proper selection and characterization of patients, allowing us to foresee which will respond to a given treatment and (3) an evaluation of combined therapies, targeting different pathways.

KEYWORDS:

• Idiopathic pulmonary fibrosis
• fibrogenesis
• lung remodeling
• antifibrotic drugs

Article highlights

• IPF is an epithelial-derived disease resulting from chronic lung injury.

• The recent comprehension of several mechanisms underlying IPF development led to the development of anti-fibrotic drugs.

• Drugs targeting remodeling and inflammation are currently tested in randomized control trials.

• Current research will lead to the development of new molecules targeting remodeling, abnormal repair, and inflammation.

• Unmet needs in IPF include new experimental models, improved patient clustering, and the evaluation of combined treatments.

This box summarizes key points contained in the article.

Declaration of interest

B Crestani reports receiving consulting fees, speaker fees, grants for research and/or honoraria from AstraZeneca, Boehringer Ingelheim, Intermune, Roche, Sanofi, and is the principal investigator of therapeutic trials for IPF. A Froidure has received a joint ERS-EMBO long term fellowship and support from the Société Belge de Pneumologie – Belgische Vereniging voor Pneumologie (SBP-VBP). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

AF is funded by a joint European Respiratory Society-European Molecular Biology Organization Long-term fellowship (ERS-EMBO LTFR 2015 - 4476) and by the Société belge de pneumologie-Belgische vereniging voor pneumologie (SBP-BVP). This work was supported by the ‘ Agence Nationale pour la Recherche’ (ANR-11-BSV1-0011), the LABEX ‘Inflamex’, the European COST Action BM1201, the ‘ Association pour la fibrose pulmonaire idiopathique Pierre ENJALRAN’ and by a generous donation from Mr and Mrs Angelucci.