An IPF-like disease course in disorders other than IPF: how can this be anticipated, recognized, and managed?

ABSTRACT

Introduction

Idiopathic pulmonary fibrosis (IPF)-like chronic disease progression despite treatment cannot be predicted with confidence in interstitial lung diseases (ILDs) other than IPF at the time of diagnosis.

Areas covered

We review key determinants of a progressive fibrotic phenotype, at initial diagnosis of an ILD other than IPF. Medline literature searches (2000 to 2020) were undertaken with regard to the issues discussed in this review.

Expert opinion

The definition of the progressive fibrotic phenotype in non-IPF patients should remain real world, with a conclusion reached by an experienced clinician that progression has occurred despite the use of appropriate historical therapies, on a case by case basis. There is an urgent need for pathogenetic studies to identify pathways and genetic predilections that are common to chronic progressive fibrosis across different diseases. Efforts should also be focused on the identification of the progressive fibrotic phenotype at first presentation, potentially through a combination of CT and biopsy evaluation and the definition of a biomarker profile associated with subsequent disease progression. Recent anti-fibrotic trials of non-IPF disorders should lead to trials of combination regimens of anti-fibrotic agents and immunomodulatory or other therapies specific to individual diseases.

KEYWORDS:

• Diagnosis
• disease behavior classification
• progressive fibrotic phenotype
• treatment
• disease severity
• response to treatment

Article highlights

• In no individual ILD can a future treated course similar to IPF be expected with confidence at the first presentation. Serial monitoring plays a critical role in providing early evidence of a progressive fibrotic phenotype, especially since failure to identify responses to immunomodulation substantially increases the likelihood of subsequent disease progression.

• The identification of a UIP pattern on CT (honeycombing and/or extensive traction bronchiectasis) and/or in histological samples in patients with hypersensitivity pneumonitis has been associated with outcomes similar to IPF.

• In connective tissue disease (CTD) associated ILDs other than rheumatoid arthritis (RA)-ILD, the pulmonary function severity seems to be the key determinant of a worse outcome as opposed to the detection of UIP pattern on CT.

• In RA-associated ILD, UIP has major prognostic significance, compared with other histologic patterns, and this applies equally to the presence of UIP-like (e.g. honeycombing, severity of traction bronchiectasis) CT findings.

• The outcome in unclassifiable disease cannot usually be predicted at baseline. It is suggested that clinicians should anticipate IPF-like disease behavior in all patients with unclassifiable diseases of at least moderate severity, as judged by CT and pulmonary function tests.

Declaration of interest

AU Wells reports personal fees from Roche, Boehringer Ingelheim, Intermune, and Bayer, all of which are outside of this submitted work. 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 apart from those disclosed.

Reviewer disclosures

Peer reviewers in this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper is not funded.