AISI as a Potential Prognostic Marker for Progressive Pulmonary Fibrosis in Autoimmune-Associated ILD: A Prospective Real-World Cohort Study

Background/Objectives: Progressive pulmonary fibrosis (PPF) is an important outcome in autoimmune-associated ILD, but practical biomarkers for identifying patients at increased risk before overt progression remain limited. We investigated the incidence and timing of PPF and evaluated the prognostic value of the aggregate index of systemic inflammation (AISI), a routinely evaluated blood count-derived marker. Methods: In this prospective real-world cohort, 222 patients with autoimmune-associated ILD, including patients with systemic autoimmune rheumatic disease-associated interstitial lung disease (SARD-ILD) and interstitial pneumonia with autoimmune features (IPAFs), were consecutively enrolled at West China Hospital between July 2019 and September 2024, with follow-up approximately every 6 months. PPF was defined according to the 2022 ATS/ERS/JRS/ALAT criteria. Associations between baseline AISI and time to first PPF event documented during follow-up were assessed using Cox regression, time-dependent receiver operating characteristic analysis, Kaplan–Meier analysis, and bootstrap validation. Results: Over a median follow-up of 2.05 years, 58 patients (26.1%) had a first PPF event documented during follow-up. Among these patients, the median time to the first documented PPF event was 1.92 years, and 70.7% of first events were documented within 1–3 years after enrollment. After multivariable adjustment for the included covariates, each doubling of baseline AISI was associated with a 39% higher hazard of first PPF documented during follow-up (adjusted hazard ratio, 1.39; 95% confidence interval, 1.09–1.76; p = 0.008). Baseline AISI showed an area under the curve of 0.791 (95% CI, 0.669–0.906) for 1-year PPF, and bootstrap analysis supported internal stability. Conclusions: PPF was frequent in this autoimmune-associated ILD, with most first events documented within the first 1–3 years. Higher baseline AISI remained associated with the first PPF event documented during follow-up after adjustment for the included covariates and may provide a simple, inexpensive adjunct for risk stratification. External validation is required before clinical implementation.