Idiopathic Pulmonary Fibrosis: The Association between the Adaptive Multiple Features Method and Fibrosis Outcomes

Abstract

Rationale: Adaptive multiple features method (AMFM) lung texture analysis software recognizes high-resolution computed tomography (HRCT) patterns.

Objectives: To evaluate AMFM and visual quantification of HRCT patterns and their relationship with disease progression in idiopathic pulmonary fibrosis.

Methods: Patients with idiopathic pulmonary fibrosis in a clinical trial of prednisone, azathioprine, and N-acetylcysteine underwent HRCT at study start and finish. Proportion of lung occupied by ground glass, ground glass-reticular (GGR), honeycombing, emphysema, and normal lung densities were measured by AMFM and three radiologists, documenting baseline disease extent and postbaseline change. Disease progression includes composite mortality, hospitalization, and 10% FVC decline.

Measurements and main results: Agreement between visual and AMFM measurements was moderate for GGR (Pearson's correlation r = 0.60, P < 0.0001; mean difference = -0.03 with 95% limits of agreement of -0.19 to 0.14). Baseline extent of GGR was independently associated with disease progression when adjusting for baseline Gender-Age-Physiology stage and smoking status (hazard ratio per 10% visual GGR increase = 1.98, 95% confidence interval [CI] = 1.20-3.28, P = 0.008; and hazard ratio per 10% AMFM GGR increase = 1.36, 95% CI = 1.01-1.84, P = 0.04). Postbaseline visual and AMFM GGR trajectories were correlated with postbaseline FVC trajectory (r = -0.30, 95% CI = -0.46 to -0.11, P = 0.002; and r = -0.25, 95% CI = -0.42 to -0.06, P = 0.01, respectively).

Conclusions: More extensive baseline visual and AMFM fibrosis (as measured by GGR densities) is independently associated with elevated hazard for disease progression. Postbaseline change in AMFM-measured and visually measured GGR densities are modestly correlated with change in FVC. AMFM-measured fibrosis is an automated adjunct to existing prognostic markers and may allow for study enrichment with subjects at increased disease progression risk.

Keywords: idiopathic pulmonary fibrosis; multidetector computed tomography; prognosis.

Figure 1.

Expert radiologist labeling of volumes of interest for adaptive multiple features method training. Shown is an example of ground glass–reticular opacity. The boxed area within the lung parenchyma corresponds to the double-outlined box (upper right corner) in the associated black panel.

Figure 2.

Kaplan-Meier event-free survival analysis stratified by visual and adaptive multiple features method (AMFM) ground glass reticular (GGR) density scores of 10% or greater, or less than 10%. Shown are Kaplan-Meier event-free (events of interest are FVC % predicted decline >10%, hospitalization, or death) survival estimates in subjects stratified by visual and AMFM GGR scores of 10% or greater total lung involvement versus less than 10%. The crosses denote censoring and the steps are events. Subjects having 10% or more total lung occupied by GGR densities at baseline have significantly worse event-free survival than those with less than 10% (log-rank visual, P = 0.002; AMFM, P = 0.0003).