Bridging the GAP: Prognostic stratification by longitudinal FVC changes in IPF

Idiopathic pulmonary fibrosis (IPF) carries a poor prognosis despite antifibrotic therapy. The Gender-Age-Physiology (GAP) index enables baseline risk assessment but does not capture longitudinal disease behavior. To determine whether combining baseline GAP score with early change in forced vital capacity (Δ1YFVC%) improves prediction of 2-year mortality in IPF.

A prospective, multicenter observational cohort study conducted across three hospitals in Taiwan between 2018 and 2023. Patients with IPF receiving reimbursed antifibrotic therapy were enrolled. Individuals who died within six months, were lost to follow-up, or lacked one-year pulmonary function data were excluded. The primary outcome was 2-year mortality. Baseline GAP score and Δ1YFVC% were evaluated using a survival-tree model to determine prognostic cutoffs. Survival was analyzed using Kaplan-Meier curves and Cox proportional-hazards regression.

Among 156 patients included (median age 77 years; 76.3% male; median baseline FVC 73.5% predicted). 23 (14.7%) died within 2 years. The survival-tree model identified a key prognostic split by GAP (<5 vs ≥5) and Δ1YFVC%. A decline in predicted FVC% greater than 10.5 percentage points (Δ1YFVC% declined > 10.5 percentage points) was associated with increased mortality, even among patients with lower GAP scores (adjusted HR 3.30, p=0.010). Among patients with GAP ≥5, relatively stable lung function (Δ1YFVC% improved > 1.5 percentage points) was associated with lower mortality risk. Stratification based on GAP score and Δ1YFVC% significantly discriminated mortality risk groups (log-rank p<0.0001, concordance index 0.761).

Integrating Δ1YFVC% with the GAP score provides a clinically applicable approach for risk stratification and may support the identification of high-risk patients during antifibrotic therapy.