Marginal decline in forced vital capacity is associated with a poor outcome in idiopathic pulmonary fibrosis

TLDR

Therapeutic studies in idiopathic pulmonary fibrosis are limited by the low prevalence of significant changes in pulmonary function tests. The study assessed whether marginal changes in pulmonary function tests predict outcomes in idiopathic pulmonary fibrosis and fibrotic non‑specific interstitial pneumonia. In 84 IPF and 72 NSIP patients, 6‑month trends in forced vital capacity and DLCO were classified as significant or marginal, and proportional‑hazards and time‑dependent ROC analyses linked these trends to mortality. Both significant and marginal declines in forced vital capacity were associated with higher mortality and worse progression‑free survival, whereas marginal changes in DLCO were not prognostic, indicating that a marginal FVC decline signals a poor outcome and can guide clinical practice and trial selection.

Abstract

In therapeutic studies in idiopathic pulmonary fibrosis (IPF), the low prevalence of significant change in pulmonary functional tests (PFTs) has been a major constraint. The prognostic value of "marginal" changes in PFTs in IPF and fibrotic non-specific interstitial pneumonia (NSIP) was evaluated. In patients with biopsy-proven IPF (n = 84) and NSIP (n = 72), forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide (D( L,CO)) trends at 6 months were categorised as "significant" (FVC >10%; D(L,CO) >15%) or "marginal" (FVC 5-10%; D(L,CO) 7.5-15%). Proportional hazards analysis and time-dependent receiver operating characteristic methodology were used to examine PFT trends against mortality. In IPF, reductions in FVC were significant in 22 cases (26%) and marginal in 19 cases (23%). Mortality was higher in patients with a significant decline in FVC (hazard ratio (HR) 2.80, 95% CI 1.54-5.06; p<0.001) and those with a marginal decline in FVC (HR 2.31, 95% CI 1.19-4.50; p = 0.01) than in those with stable disease. Progression-free survival was lower when the decline in FVC was marginal than in stable disease (HR 2.34, 95% CI 1.19-4.60; p = 0.01). Marginal changes in D(L,CO) in IPF and marginal changes in FVC and D (L,CO) in fibrotic NSIP did not provide useful prognostic information. Marginal change in FVC in IPF denotes a poor outcome. These findings are applicable to clinical practice and to the selection of patients with more progressive disease for therapeutic studies.