Updated Practice Guideline: IPF and Progressive Pulmonary Fibrosis

A recent update of IPF clinical practice guideline addresses the progression of pulmonary fibrosis in patients with interstitial lung diseases other than IPF.

An update of the 2018 idiopathic pulmonary fibrosis (IPF) clinical practice guidelines, recently published in the American Journal of Respiratory and Critical Care Medicine, addresses the progression of pulmonary fibrosis in adult patients with interstitial lung diseases (ILDs) other than IPF. The guideline update was developed collaboratively by the American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana de Tórax.1

The updated guideline includes1:

  • A conditional recommendation to regard transbronchial lung cryobiopsy (TBLC) as an alternative to surgical lung biopsy (SLB) for IPF in certain circumstances.
  • Conditional recommendations against antacid medication and antireflux surgery for the treatment of IPF.
  • New diagnostic criteria for progressive pulmonary fibrosis (PPF).
  • A conditional recommendation for treatment of PPF with nintedanib.
  • A recommendation for additional research into pirfenidone as a potential treatment for PPF.

Notably, the updated guideline does not include a recommendation for or against genomic classifier testing for IPF.

Recommendations and updates were developed by a committee of multidisciplinary experts in ILD, methodologists, and patient representatives, who conducted systematic reviews and issued evidence-based recommendations utilizing the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.1

IPF Diagnosis: TBLC vs SLB

The recommendation that TBLC be regarded as an acceptable alternative to surgical lung biopsy for making a histopathologic diagnosis in patients with ILD of undetermined type was a conditional recommendation based on “very low-quality evidence.” This recommendation also includes the stipulation that TBLC be done in medical centers that have experience in performing and interpreting TBLC — thus emphasizing the importance of the chosen facility and of the clinician’s experience in performing the TBLC and interpreting the samples. In explaining this update, the guideline authors noted that TBLC is less invasive and less costly than SLB; however, guideline authors also cautioned that TBLC may not be appropriate for all patients.1

Genomic Classifier Testing

The committee made no recommendation regarding the addition of genomic classifier testing for diagnosing usual interstitial pneumonia (UIP) in patients with ILD of undetermined type who are undergoing transbronchial forceps biopsy. Members who favored genomic classifier testing believed that the high specificity provided important diagnostic information that could be useful in multidisciplinary discussion and could reduce the need for additional sampling for histopathology diagnosis. Other members believed that a recommendation in favor of testing was premature.1

HRCT Pattern of Probable UIP

In a key change to the diagnostic algorithm, the committee noted that patients with a high-resolution computed tomography (HRCT) pattern of probable UIP are now managed similarly to patients with UIP, as lung sampling after initial multidisciplinary discussion is less likely. Also, an HRCT pattern that is suggestive of an alternative diagnosis combined with a histopathology pattern of probable UIP is now considered indeterminate for IPF rather than non-IPF.1

Antacid Medication and Reflux Update

The committee recommends not treating patients with IPF with antacid medication to improve respiratory outcomes (conditional recommendation, very low-quality evidence). “Antacid medication and other interventions may be appropriate for patients with both IPF and symptoms of gastroesophageal reflux disease (GERD) for the purpose of improving gastroesophageal reflux (GER)–related outcomes in accordance with GER-specific guidelines,” the group stated.1

The committee also recommends not referring patients with IPF for antireflux surgery to improve respiratory outcomes (conditional recommendation, very low-quality evidence).1

Diagnosing Progressive Pulmonary Fibrosis

Among patients with ILD of known or unknown etiology other than IPF and radiologic evidence of pulmonary fibrosis, the guideline committee defined progressive pulmonary fibrosis (PPF) as having at least 2 of the following criteria occurring within the past year with no alternative explanation: (1) worsening respiratory symptoms; (2) physiologic evidence of disease progression; and (3) radiologic evidence of disease progression.1

Pirfenidone and PPF

The committee recommends that further research is necessary regarding the efficacy and safety of pirfenidone in non-IPF ILD manifesting PPF in general and for specific types of non-IPF ILD manifesting PPF.1

Pirfenidone is a promising therapy for non-IPF PPF, according to the committee. However, committee members were concerned that the estimated effects were derived from 1 trial with only 127 patients who had PPF owing to an ILD other than fibrotic unclassifiable ILD (uILD), which was not precisely defined.2 Also, they were concerned that if they made a recommendation specifically for patients with uILD, it may discourage clinicians from trying to identify the underlying type of ILD before beginning therapy, and the data were insufficient to warrant such a paradigm shift.1

Nintedanib and PPF

The committee recommends nintedanib (NCT02999178)3 for the treatment of PPF in patients who have failed standard management for fibrotic ILD, other than IPF (conditional recommendation, low-quality evidence). Standard management will be different for each patient, noted the committee. “In many patients it will be immunosuppressive treatment in an attempt to stabilize or reverse initial disease, but this is not a prerequisite, as in some patients, standard management could be antigen remediation or observation,” the group stated. “Besides this, it should be acknowledged that in many ILDs, evidence-based guidance for standard of care is lacking; hence, standard of care may vary from region to region.”1

The committee also recommends that research is needed regarding the efficacy and safety of nintedanib in specific types of non-IPF ILD manifesting PPF.1

The effects of therapy may differ depending on the type of underlying ILD and management may be based on the underlying ILD in the future, noted the committee. However, the committee concluded that the data are insufficient to support such a targeted approach and made a research recommendation to investigate the efficacy and safety of nintedanib in patients with PPF owing to specific types of ILD.1

Recommendations, Not Performance Measures

“These recommendations are not mandates, because they cannot account for all unique clinical circumstances, and they should be revisited as new evidence is published,” the guideline authors concluded. “It was determined that none of the recommendations are appropriate targets for performance measures.”1

Disclosure: Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


1. Raghu G, Remy-Jardin M, Richeldi L, et al. 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;205(9):e18-e47. doi:10.1164/rccm.202202-0399ST

2. Behr J, Prasse A, Kreuter M, et al. Pirfenidone in patients with progressive fibrotic interstitial lung diseases other than idiopathic pulmonary fibrosis (RELIEF): a double-blind, randomised, placebo-controlled, phase 2b trial. Lancet Respir Med. 2021;9(5):476-486. doi:10.1016/S2213-2600(20)30554-3

3. ClinicalTrials.gov. Efficacy and safety of nintedanib in patients with progressive fibrosing interstitial lung disease (PF-ILD) (INBUILD®). Accessed May 18, 2022. https://clinicaltrials.gov/ct2/show/NCT02999178