Prevalence, detection, and trajectory of combined pulmonary fibrosis and emphysema

BACKGROUND: Combined pulmonary fibrosis and emphysema (CPFE) is an important phenotype in patients with fibrotic interstitial lung disease (ILD). RESEARCH QUESTION: What is the prevalence of CPFE? What is the predictive performance of the CPFE index and of physiologic airflow obstruction for CT imaging emphysema extents? Is the extent of emphysema on CT imaging associated with outcomes in patients with fibrotic ILD? STUDY DESIGN AND METHODS: Consecutive patients with idiopathic pulmonary fibrosis (IPF) and non-IPF fibrotic ILD who underwent a standardized visual assessment of the baseline high-resolution CT imaging of the chest from a prospective registry were included. CPFE was defined as emphysema extent of ≥ 15% on CT imaging, with sensitivity analyses using different thresholds: ≥ 5%, ≥ 10%, and ≥ 20%. Emphysema subtypes were categorized based on their predominant distribution: centrilobular, paraseptal, or panlobular. The CPFE index was derived using measurements of spirometry and diffusion capacity of the lungs for CO₂. RESULTS: The prevalence of CPFE at baseline was 20% for IPF (92/455) and 7% in non-IPF fibrotic ILD (84/1121). Both FEV₁ to FVC ratio less than the lower limit of normal and < 0.70 showed poor sensitivity (IPF, 11.1%-18.9%; non-IPF fibrotic ILD, 13.1%-23.7%) for detecting emphysema on CT imaging, although high specificity (IPF, 96.2%-98.8%; non-IPF fibrotic ILD, 92.8%-95.8%). The CPFE index was correlated moderately with extent of emphysema on CT imaging in both IPF (r = 0.48) and non-IPF fibrotic ILD (r = 0.41), but with poor agreement and wide limits of agreement on Bland-Altman analysis. Extent of emphysema on CT imaging of ≥ 20% was associated consistently with differences in lung function trajectories and worse transplant-free survival in IPF and non-IPF fibrotic ILD. No significant relationships were noted between emphysema subtypes and health outcomes. INTERPRETATION: Our results show that coexisting emphysema is important in both IPF and non-IPF fibrotic ILD, with extent of emphysema on CT imaging of ≥ 20% being associated with worse health outcomes. Both physiologic and radiologic assessments are needed to identify coexistent emphysema in patients with fibrotic ILD.