Longitudinal functional changes with clinically significant radiographic progression in idiopathic pulmonary fibrosis: are we following the right parameters?

Abstract Background. Progression of the disease in idiopathic pulmonary fibrosis (IPF) is difficult to predict, due to its variable and heterogenous course. The relationship between radiographic progression and functional decline in IPF is unclear. We sought to confirm that a simple HRCT fibrosis visual score is a reliable predictor of mortality in IPF, when longitudinally followed; and to ascertain which pulmonary functional variables best reflect clinically significant radiographic progression. Methods: One-hundred-twenty-three consecutive patients with IPF from 2 centers were followed for an average of 3 years. Longitudinal changes of HRCT fibrosis scores, forced vital capacity (FVC), total lung capacity and diffusing lung capacity for carbon monoxide were considered. HRCTs were scored by 2 chest radiologists. The primary outcome was lung transplant (LTx)-free survival after the follow-up HRCT. Results: During the follow-up period, 43 deaths and 11 LTx occurred. On average, the HRCT fibrosis score increased significantly, and a longitudinal increase >7% predicted LTx-free survival significantly, with good specificity, but limited sensitivity. The correlation between radiographic and functional progression was moderately significant. HRCT progression and FVC decline predicted LTx-free survival independently and significantly, with better sensitivity, but worse specificity for a ≥5% decline of FVC. However, the area under the curve towards LTx-survival were only 0.61 and 0.62, respectively. Conclusions: The HRCT fibrosis visual score is a reliable and responsive tool to detect clinically meaningful disease progression. Although no individual pulmonary function test closely reflects radiographic progression, a longitudinal FVC decline improves sensitivity in the detection of clinically significant disease progression. However, the accuracy of these methods remains limited, and better prognostication models need to be found.