Deep Learning Assessment of Progression of Emphysema and Fibrotic Interstitial Lung Abnormality

Abstract

Rationale: Although studies have evaluated emphysema and fibrotic interstitial lung abnormality individually, less is known about their combined progression. Objectives: To define clinically meaningful progression of fibrotic interstitial lung abnormality in smokers without interstitial lung disease and evaluate the effects of fibrosis and emphysema progression on mortality. Methods: Emphysema and pulmonary fibrosis were assessed on the basis of baseline and 5-year follow-up computed tomography scans of 4,450 smokers in the COPDGene Study using deep learning algorithms. Emphysema was classified as absent, trace, mild, moderate, confluent, or advanced destructive. Fibrosis was expressed as a percentage of lung volume. Emphysema progression was defined as an increase by at least one grade. A hybrid distribution and anchor-based method was used to determine the minimal clinically important difference in fibrosis. The relationship between progression and mortality was evaluated using multivariable shared frailty models using an age timescale. Measurements and Main Results: The minimal clinically important difference for fibrosis was 0.58%. On the basis of this threshold, 2,822 (63%) had progression of neither emphysema nor fibrosis, 841 (19%) had emphysema progression alone, 512 (12%) had fibrosis progression alone, and 275 (6.2%) had progression of both. Compared with nonprogressors, hazard ratios for mortality were 1.42 (95% confidence interval, 1.11-1.82) in emphysema progressors, 1.49 (1.14-1.94) in fibrosis progressors, and 2.18 (1.58-3.02) in those with progression of both emphysema and fibrosis. Conclusions: In smokers without known interstitial lung disease, small changes in fibrosis may be clinically significant, and combined progression of emphysema and fibrosis is associated with increased mortality.

Keywords: emphysema; mortality; pulmonary fibrosis.

Figure 1.

CONSORT (Consolidated Standards of Reporting Trials) diagram.

Figure 2.

Example of combined progression of emphysema and fibrosis progression. Progressive emphysema and interstitial lung abnormality in a 64-year-old cigarette smoker. (A–C) Baseline computed tomographic images through upper and lower lungs show moderate centrilobular emphysema and mild subpleural basal interstitial abnormality. (D) The data-driven texture analysis (DTA) fibrotic score at baseline was 4.5%. (E–G) Follow-up examination 6 years later shows that the emphysema has increased by one grade, to confluent emphysema, and the basal interstitial abnormality has increased. (H) The basal interstitial abnormality has increased, and the DTA fibrotic score has increased to 8.2%. (F) Areas of emphysema progression circled in yellow. (D, H) DTA fibrosis highlighted in red.

Figure 3.

Survival by emphysema/fibrosis progression category. (A) Entire cohort. (B) Subgroup of cohort with stable lung function. DTA = data-driven texture analysis; LSTM = long short-term memory layer.