Idiopathic pulmonary fibrosis

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Evidence last reviewed: 14 Feb 2026

Topic last updated: 25 Feb 2026

25 Feb 2026

FDA approves nerandomilast for treatment of idiopathic pulmonary fibrosis in adults

Idiopathic pulmonary fibrosis (IPF) has few treatment options and currently relies on antifibrotic agents (nintedanib and pirfenidone) and supportive therapy. Nerandomilast, an oral phosphodiesterase-4 (PDE-4) inhibitor, is the first new treatment for IPF approved by the Food and Drug Administration (FDA) in more than 10 years.

One randomized, double-blind, placebo-controlled phase 3 trial demonstrated that people with IPF taking nerandomilast had a significantly smaller decline in forced vital capacity (FVC) compared with placebo-treated groups over a period of 1 year.[84]

Nerandomilast can be used alone or in combination with antifibrotic therapy.

This treatment has the potential to impact the care of many patients, including those with:

Intolerance to an antifibrotic agent.
Continued worsening in lung function despite use of an antifibrotic agent.

See Management: approach

See Management: treatment algorithm

Original source of update

Idiopathic pulmonary fibrosis (IPF) is a rare fibrosing interstitial pneumonia of unknown cause. The disease is chronic, progressive, and ultimately fatal.

Diagnosis is suspected clinically in patients with bibasilar inspiratory crackles, older age (e.g., >60 years), and unexplained symptomatic or asymptomatic bilateral pulmonary fibrosis on a chest x-ray or high-resolution computed tomography.

In the absence of findings suggesting an alternative disease process, IPF is usually confirmed by multidisciplinary review based on the presence of a radiologic (high-resolution chest CT) pattern of usual interstitial pneumonia (UIP).

Histopathology of lung biopsy samples may be considered when radiologic and clinical data result in an uncertain diagnosis.

Initial therapy is generally with an antifibrotic agent (either pirfenidone or nintedanib), although some patients might benefit from other treatment options depending on disease severity. Important supportive measures include smoking cessation, pulmonary rehabilitation, and supplemental oxygen.

Palliative care options and referral for lung transplantation should be considered early, even if a patient is being actively treated.

Definition

IPF is a specific form of chronic, progressive fibrosing interstitial pneumonia of unknown etiology. It is defined by a radiologic and/or histopathologic pattern of UIP.[1][2]

The disease is limited to the lungs, so presentation should occur without constitutional or other symptoms that suggest a multisystem disease or an alternative diagnosis.[1]

Diagnosis requires the exclusion of other forms of interstitial pneumonia, including other idiopathic interstitial pneumonias and interstitial lung diseases associated with environmental exposures, drugs, or systemic diseases (e.g., connective tissue disease).[3][4][5]

History and exam

Key diagnostic factors

dyspnea
cough
crackles

Full details

Other diagnostic factors

weight loss, fatigue, and malaise
clubbing

Full details

Risk factors

advanced age
male sex
family history
gene mutations and nucleotide polymorphisms
cigarette smoking
occupational and environmental exposures
gastroesophageal reflux
viral infection
bacterial infection
diabetes

Full details

Diagnostic investigations

1st investigations to order

CXR
high-resolution CT (HRCT) chest
pulmonary function tests

Full details

Investigations to consider

surgical lung biopsy
bronchoalveolar lavage (BAL)
transbronchial lung biopsy and cryobiopsy
CRP
erythrocyte sedimentation rate (ESR)
antinuclear antibody immunofluorescence
rheumatoid factor
anticyclic citrullinated peptide
myositis panel

Full details

Treatment algorithm

ACUTE

acute exacerbation

ONGOING

not currently experiencing acute exacerbation

Contributors

Authors

Jake G. Natalini, MD, MS

Assistant Professor of Medicine

Pulmonary, Critical Care, and Sleep Division

NYU Grossman School of Medicine

New York University

New York

Disclosures

JGN has received consulting fees from CareDx on diagnostics in lung transplantation, not related to the article topic. There is not a contractual agreement to disseminate product information.

Acknowledgements

Dr Jake G. Natalini would like to gratefully acknowledge Dr Mary Elizabeth Kreider, Dr Judd David Flesch, Dr Gregory Tino, and Dr Jeffrey C. Munson, previous contributors to this topic.

Disclosures

GT has served as a consultant for InterMune. GT has served as a principal investigator for clinical trials in idiopathic pulmonary fibrosis. JCM and JDF declare that they have no competing interests.

Peer reviewers

Stephen Nathan, MD

Medical Director

Lung Transplant & Advanced Lung Disease Program

Inova Fairfax Hospital

Falls Church

Disclosures

SN is an author of a reference cited in this monograph.

Athol Wells, MD, FRCP

Professor of Respiratory Medicine

Interstitial Lung Disease Unit

Royal Brompton Hospital

London

Disclosures

AW declares that he has no competing interests.

Peer reviewer acknowledgements

BMJ Best Practice topics are updated on a rolling basis in line with developments in evidence and guidance. The peer reviewers listed here have reviewed the content at least once during the history of the topic.

Disclosures

Peer reviewer affiliations and disclosures pertain to the time of the review.

References

Our in-house evidence and editorial teams collaborate with international expert contributors and peer reviewers to ensure that we provide access to the most clinically relevant information possible.

Key articles

Raghu G, Rochwerg B, Zhang Y, et al. An official ATS/ERS/JRS/ALAT clinical practice guideline: treatment of idiopathic pulmonary fibrosis - an update of the 2011 clinical practice guideline. Am J Respir Crit Care Med. 2015 Jul 15;192(2):e3-19.Full text Abstract

Raghu G, Remy-Jardin M, Richeldi L, et al; American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Latin American Thoracic Society. Idiopathic pulmonary fibrosis (an update) and progressive pulmonary fibrosis in adults: an official ATS/ERS/JRS/ALAT clinical practice guideline. Am J Respir Crit Care Med. 2022 May 1;205(9):e18-e47.Full text Abstract

Collard HR, Ryerson CJ, Corte TJ, et al. Acute exacerbation of idiopathic pulmonary fibrosis. an international working group report. Am J Respir Crit Care Med. 2016 Aug 1;194(3):265-75.Full text Abstract

Borie R, Kannengiesser C, Antoniou K, et al. European Respiratory Society statement on familial pulmonary fibrosis. Eur Respir J. 2023 Mar;61(3):2201383.Full text Abstract

Ryerson CJ, Adegunsoye A, Piciucchi S, et al. Update of the international multidisciplinary classification of the interstitial pneumonias: an ERS/ATS statement. Eur Respir J. 2025 Dec;66(6):2500158.Full text Abstract

Reference articles

A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.

Differentials
- Nonspecific interstitial pneumonia (NSIP)
- Bronchiolocentric interstitial pneumonia (BIP)
- Organizing pneumonia
More Differentials
Guidelines
- Update of the international multidisciplinary classification of the interstitial pneumonias: an ERS/ATS statement
- ERS statement on transition of care in childhood interstitial lung diseases
More Guidelines
Videos
Late inspiratory crackles (rales)
More videos
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Idiopathic pulmonary fibrosis

FDA approves nerandomilast for treatment of idiopathic pulmonary fibrosis in adults

Summary

Definition

History and exam

Key diagnostic factors

Other diagnostic factors

Risk factors

Diagnostic investigations

1st investigations to order

Investigations to consider

Treatment algorithm

acute exacerbation

not currently experiencing acute exacerbation

Contributors

Authors

Jake G. Natalini, MD, MS

Disclosures

Acknowledgements

Disclosures

Peer reviewers

Stephen Nathan, MD

Disclosures

Athol Wells, MD, FRCP

Disclosures

Peer reviewer acknowledgements

Disclosures

References

Key articles

Reference articles

A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.

Differentials

Guidelines

Videos

Log in or subscribe to access all of BMJ Best Practice

Log in or subscribe to access all of BMJ Best Practice

Log in to access all of BMJ Best Practice