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.

Effect of genotype on the disease course in idiopathic pulmonary fibrosis despite antifibrotic treatment

“…As cases of rapid IPF progression have been described and longitudinal data were available for most of the enrolled subjects, data from months 6 and 18 were also included into the study protocol. IPF is the most aggressive form of progressive fibrosing interstitial lung disease, and a 6-month interval and 10% decline in FVC were found to be meaningful in a previous study ( 29 ). A Dlco decline of >15% was incorporated as a marker of disease progression.…”

“…The reason for including Dlco is explained in the study by Nathan et al ( 30 ); an FVC decline during the first year of follow-up may not be predictive of further progression of the disease. Despite the Dlco limitations, adding this parameter to the FVC decline is a reasonable means of defining the progression of IPF ( 29 ).…”

Radiological and Physiological Predictors of IPF Mortality

“…In this retrospective study, both soft tissue thickness and %FRC were identified as predictors of IPF mortality in this cohort. The physiological and radiological parameters such as FVC, DLco, traction bronchiectasis, and honeycombing are routinely used [ 22 , 23 ]. The chest radiograph is easy to use and cost effective in clinical practice, as an alternative to HRCT, and provides useful new information for clinicians.…”

Validation of the risk stratification score in idiopathic pulmonary fibrosis: study protocol of a prospective, multi-centre, observational, 3-year clinical trial

“…A 2nd HRCT will be obtained at the 2-year visit, or sooner if clinically indicated, and as per clinicians’ discretion. The HRCT fibrosis score [ 12 ] will be then recalculated on the 2nd scan. Deaths, LTx, AEs and hospitalizations due to respiratory causes will be recorded.…”

“…The current approach to the detection of progression of disease in IPF is largely based on forced vital capacity (FVC) changes and high-resolution chest CT scan (HRCT). We recently demonstrated that the prognostic accuracy of a decline of FVC combined with an increase of the extent fibrosis on HRCT (visual score) is far from being optimal, although the 2 variables are independent from each other [ 12 ]. This finding further strengthens the rationale for pursuing the development and validation of an integrated, multi-dimensional prognostic tool for IPF.…”