Predictors of Disease Progression in Idiopathic Pulmonary Fibrosis Under Antifibrotic Therapy: A Retrospective Study

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing lung disease with a low median survival of three to five years. Antifibrotic agents, pirfenidone and nintedanib, slow but do not reverse disease progression, and treatment response varies. Identifying baseline predictors of progression may help personalize care.

We retrospectively analyzed consecutive IPF patients treated at Okinawa Chubu Hospital between 2012 and 2020. Eligible patients received antifibrotics for ≥3 months and had baseline and follow-up pulmonary function tests (PFTs). Clinical, laboratory, PFT, and high-resolution computed tomography (HRCT) data were collected. Disease progression within one year was defined as ≥2 of: worsening symptoms, ≥5% decline in forced vital capacity (FVC), or radiologic progression. Predictors were evaluated using exact logistic regression; survival was assessed with Kaplan-Meier analysis.

Forty-seven patients (mean age 73.3 years, 32 men) were included; 63.8% were ever-smokers. Mean baseline FVC was 1.93 L, %FVC 67.6%, % peak expiratory flow (PEF) 75.0%, %total leucocyte count (TLC) 72.4%, %diffusing capacity of the lungs for carbon monoxide (DLCO) 63.7%. HRCT showed definite usual interstitial pneumonia (UIP) in 20 patients, probable UIP in 19, and indeterminate UIP in eight. Progression occurred in 29 patients (61.7%). Lower baseline %PEF (OR 0.977, p=0.097) and %TLC (OR 0.953, p=0.071) were associated with early progression. Median survival was 47 months; patients with preserved %PEF and %TLC had a slower decline.

Lower %PEF and %TLC may predict poorer response to antifibrotics in IPF. These readily available PFT indices could serve as practical markers for risk stratification and early intervention. Prospective, multicenter studies are warranted to confirm predictive value.