Short-Term Pulmonary Function Trends Are Predictive of Mortality in Interstitial Lung Disease Associated With Systemic Sclerosis.

Abstract

To determine the prognostic value of pulmonary function test (PFT) trends at 1 and 2 years in interstitial lung disease (ILD) associated with systemic sclerosis (SSc). The prognostic significance of PFT trends at 1 year (n = 162) and 2 years (n = 140) was examined against 15-year survival in patients with SSc-associated ILD. PFT trends, expressed as continuous change and as categorical change in separate analyses, were examined against mortality in univariate and multivariate models. SSc-associated ILD was defined at presentation as either limited lung fibrosis or extensive lung fibrosis, using the United Kingdom Raynaud's and Scleroderma Association severity staging system. One-year PFT trends were predictive of mortality only in patients with extensive lung fibrosis: categorical change in the forced vital capacity (FVC), alone or in combination with categorical change in the diffusing capacity for carbon monoxide (DLco), had greater prognostic significance than continuous change in the FVC or trends in other PFT variables. Taking into account both prognostic value and sensitivity to change, the optimal definition of progression for trial purposes was an FVC and DLco composite end point, consisting of either an FVC decline from baseline of ≥10% or an FVC decline of 5-9% in association with a DLco decline of ≥15%. At 2 years, gas transfer trends had the greatest prognostic significance, in the whole cohort and in those with limited lung fibrosis. However, in patients with extensive lung fibrosis, the above-defined FVC and DLco composite end point was the strongest prognostic determinant. Larger changes in the FVC:DLco ratio than in the carbon monoxide transfer coefficient were required to achieve prognostic significance. Based on linkages to long-term outcomes, these findings provide support for use of routine spirometry and gas transfer monitoring in patients with SSc-associated ILD, with further evaluation of a composite FVC and DLco end point warranted for trial purposes.