CPFE: Why Spirometry Alone Misses Emphysema in Fibrotic ILD

Coexisting emphysema may be an important phenotype in patients with fibrotic interstitial lung disease (ILD), tied to worsening outcomes and divergent lung function trajectories between idiopathic pulmonary fibrosis (IPF) and non-IPF fibrotic ILD.¹

The findings, published in Chest, underscore the significance of combined pulmonary fibrosis and emphysema (CPFE) and how the CPFE index, alongside CT imaging, predicts outcomes in fibrotic ILD. The study builds on clinician insights on tools needed to flag worsening disease, especially in IPF.² Emphysema commonly overlaps with fibrotic ILD, but most research has focused on IPF, excluding other subtypes despite the overlap. Researchers used a large multicenter cohort to evaluate CPFE prevalence and the predictive performance of airflow obstruction and the CPFE index for extent of emphysema on CT imaging.¹

The study included 455 patients with IPF and 1121 patients with non-IPF fibrotic ILD. Baseline CPFE, defined as emphysema extent of 15% or greater, was present in 20% of the IPF cohort and 7% of the non-IPF cohort, varying by subtype: 6% in connective tissue disease-associated ILD, 5% in fibrotic hypersensitivity pneumonitis, and 11% in unclassifiable ILD.

Patients with CPFE were more often ever-smokers, with higher forced vital capacity (FVC) and lower diffusing capacity for carbon monoxide (DLCO) percentage predicted, versus patients with emphysema extent below 15%.

Spirometry and the CPFE Index Show Limited Sensitivity

A fixed forced expiratory volume in 1 second (FEV1) to FVC ratio below 0.70 showed poor sensitivity for an emphysema extent of 15% or greater: 18.9% in IPF and 23.7% in non-IPF fibrotic ILD, though specificity was high (96.2% and 92.8%, respectively). A ratio below the lower limit of normal was even less sensitive (11.1% in IPF; 13.1% in non-IPF fibrotic ILD) but more specific (98.8% and 95.8%, respectively).

The CPFE index, derived from percent-predicted FEV1, FVC, and DLCO, correlated moderately with CT-measured emphysema extent in IPF (r = 0.48) and non-IPF fibrotic ILD (r = 0.41). Agreement was weak, with concordance correlation coefficients of 0.52 and 0.40, respectively, and the index tended to overestimate emphysema extent at high values. At the 15% threshold, it showed 47.7% sensitivity and 93.9% specificity in IPF and 50.7% sensitivity and 92.8% specificity in non-IPF fibrotic ILD.

20% Emphysema Threshold Linked to Worse Survival

Patients with IPF and CPFE had smaller annualized declines in FVC (-1.47% vs -2.12%; P = .008) and DLCO (-1.91% vs -2.88%; P = .001) than those without CPFE. The pattern reversed in non-IPF fibrotic ILD, where CPFE brought larger declines in FVC (-1.26% vs -0.66%; P = .008) and DLCO (-1.70% vs -0.62%; P < .001).

An emphysema extent of 20% or greater was tied to worse transplant-free survival in both cohorts (IPF: HR, 1.51; 95% CI, 1.06-2.15; P = .02; non-IPF fibrotic ILD: HR, 1.51; 95% CI, 1.07-2.14; P = .02). CPFE and lower thresholds were independently linked to survival in non-IPF fibrotic ILD, while IPF showed only a trend. Neither CPFE nor the emphysema subtype was tied to 1-year progressive pulmonary fibrosis or new pulmonary hypertension in either cohort.

“More severe emphysema was associated with slower decline in FVC and DLCO in IPF, with the contrary observed for non-IPF fibrotic ILD,” the study authors wrote.

Patients came from specialized ILD centers, limiting generalizability. Visual CT scoring is subject to interobserver variability, though a subgroup of 112 patients showed good intraclass correlation (0.82; 95% CI, 0.75-0.87). The CPFE index relies on FEV1 and FVC, and prebronchodilator spirometry use was not accounted for. Suspected pulmonary hypertension and progressive pulmonary fibrosis were assessed in only 50% to 62% of the cohorts, which may have overestimated time to their development.

“Our findings suggest that the extent of emphysema on CT imaging of
[greater than or equal to] 20% may be appropriate for defining CPFE clinical syndrome in fibrotic ILD, given its consistent associations with health outcomes across both IPF and non-IPF subtypes, and further highlight the challenges in using a fixed FEV1 to FVC ratio as a clinical trial exclusion criterion,” the study authors concluded.

References

1. Khor YH, Marinescu DC, Manganas H, et al. Prevalence, detection, and trajectory of combined pulmonary fibrosis and emphysema. CHEST. Published online July 7, 2026. doi:10.1016/j.chest.2026.05.051

2. McCrear S. Gaps persist in interstitial lung disease care. AJMC®. August 7, 2026. Accessed August 31, 2026. https://www.ajmc.com/view/gaps-persist-in-interstitial-lung-disease-care