Abstract
BACKGROUND: AP01, a novel formulation of inhaled pirfenidone, has demonstrated potential for improved efficacy and safety for idiopathic pulmonary fibrosis (IPF) vs. oral pirfenidone. A 72-week phase 1b study, ATLAS, suggested reliable correlations between structural changes revealed by high-resolution computed tomography (HRCT) and functional changes in forced vital capacity (FVC). Correlations between symptom improvement and structural changes are less established. Using ATLAS data, this study aims to investigate correlations between quantitative HRCT scores and changes in patient-reported outcomes (PROs) in AP01-treated patients with IPF. METHODS: Patients (N = 91) received AP01 50 mg qd or 100 mg bid. FVC, quantitative lung fibrosis (QLF), and PRO measures including King’s Brief Interstitial Lung Disease questionnaire (KBILD) assessed functional, structural, and symptomatic changes over 48 weeks. Non-contrast HRCTs were performed at baseline and 24 weeks; improvement was defined as > 2% decrease in QLF score. RESULTS: Among 69 patients with sufficient quality HRCT scans, similar proportions on both regimens exhibited QLF improvement (50 mg qd: 16%; 100 mg bid:16%) and QLF stabilisation (-2% ≤ ∆QLF ≤ 2%) (50 mg qd: 47%; 100 mg bid: 55%). 100-mg bid subjects with improved QLF exhibited increased mean KBILD total scores from baseline beginning week 8 (8 points) through week 48 (> 20 points) (minimal clinically important difference = 5 points). CONCLUSIONS: A strong and lasting association between structural and symptomatic improvements confirms functional changes with AP01 and supports evaluation of the 100(-)mg bid dose. CLINICAL TRIAL REGISTRATION: AustralianNew Zealand Clinical Trials Registry Identifier ACTRN 12,618,001,838,202 URL: https://www.anzctr.org.au the trial registration took place before the first patient enrolled trial registration was 12 November 2018 and first patient enrolled on 06 January 2019. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12890-026-04234-x.