Validation of Proposed Criteria for Progressive Pulmonary Fibrosis

Am J Respir Crit Care Med. 2023 Jan 1;207(1):69-76. doi: 10.1164/rccm.202201-0124OC.


Rationale: Criteria for progressive pulmonary fibrosis (PPF) have been proposed, but their prognostic value beyond categorical decline in FVC remains unclear. Objectives: To determine whether proposed PPF criteria predict transplant-free survival (TFS) in patients with non-idiopathic pulmonary fibrosis (IPF) forms of interstitial lung disease (ILD). Methods: A retrospective, multicenter cohort analysis was performed. Patients with diagnoses of fibrotic connective tissue disease-associated ILD, fibrotic hypersensitivity pneumonitis, and non-IPF idiopathic interstitial pneumonia from three U.S. centers and one UK center constituted the test and validation cohorts, respectively. Cox proportional hazards regression was used to test the association between 5-year TFS and ⩾10% FVC decline, followed by 13 additional PPF criteria satisfied in the absence of ⩾10% FVC decline. Measurements and Main Results: One thousand three hundred forty-one patients met the inclusion criteria. A ⩾10% relative FVC decline was the strongest predictor of reduced TFS and showed consistent TFS association across cohorts, ILD subtypes, and treatment groups, resulting in a phenotype that closely resembled IPF. Ten additional PPF criteria satisfied in the absence of 10% relative FVC decline were also associated with reduced TFS in the U.S. test cohort, with 6 maintaining TFS associations in the UK validation cohort. Validated PPF criteria requiring a combination of physiologic, radiologic, and symptomatic worsening performed similarly to their stand-alone components but captured a smaller number of patients. Conclusions: An FVC decline of ⩾10% and six additional PPF criteria satisfied in the absence of such decline identify patients with non-IPF ILD at increased risk for death or lung transplantation.

Keywords: idiopathic interstitial pneumonia; idiopathic pulmonary fibrosis; interstitial lung disease; progressive fibrosing interstitial lung disease; progressive pulmonary fibrosis.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Connective Tissue Diseases*
  • Disease Progression
  • Humans
  • Idiopathic Pulmonary Fibrosis* / complications
  • Idiopathic Pulmonary Fibrosis* / diagnosis
  • Lung Diseases, Interstitial* / diagnosis
  • Prognosis
  • Retrospective Studies