Performance Characteristics for Physiological Measures of Progressive Pulmonary Fibrosis

Abstract

Rationale: Clinical measures of progressive pulmonary fibrosis (PPF) have been proposed, but their clinical utility remains unclear. Objectives: To determine performance characteristics of lung function-based PPF measures, including new guideline criteria for discriminating clinically relevant outcomes. Methods: A multicenter retrospective cohort analysis was performed to assess the performance characteristics of eight categorical measures of FVC and Dl_CO decline, together with PPF guideline criteria (requiring two of the following: worsening respiratory symptoms, absolute decline in FVC ⩾5% or Dl_CO ⩾15%, or radiological progression) for discriminating 2-year death or lung transplant among patients fibrotic interstitial lung disease from the United States, United Kingdom, and Canada (n = 2,727). The net benefit of the top-performing measures to inform treatment initiation were compared using decision curves. Measurements and Main Results: PPF classified according to relative decline in FVC of ⩾10%, relative decline in Dl_CO of ⩾15%, and PPF guideline criteria displayed the best overall test performance, with area under the receiver operating characteristic curves of 0.67-0.68. Specificity was higher than sensitivity for all evaluated measures, with relative measures of lung function decline outperforming absolute measures. The net benefit of standalone relative decline in FVC ⩾10% and Dl_CO ⩾15% was similar to PPF guideline criteria across the range of treatment probability thresholds. Conclusions: Classifying PPF by standalone measures of FVC and Dl_CO decline provides clinical utility similar to PPF guideline criteria. Top-performing physiology-based measures of PPF discriminate outcomes with high specificity but low sensitivity.

Keywords: idiopathic pulmonary fibrosis; interstitial lung disease; progressive fibrosing interstitial lung disease; progressive pulmonary fibrosis; test performance characteristics.