How emphysema impacts prognostic markers of pulmonary fibrosis

Authors of a recent report in Respirology found that an emphysema extent of ≥ 10% can be used to define combined pulmonary fibrosis and emphysema (CPFE) in patients with idiopathic pulmonary fibrosis (IPF), and diffusing capacity of the lungs for carbon monoxide (DL_CO)—not forced vital capacity (FVC)—was found to be the most important prognostic factor in these patients.

“Emphysema may alter the physiological characteristics of IPF because it mitigates the impact of fibrosis on ventilatory physiology and has cumulative effects on gas exchange,” wrote the authors, led by Hee-Young Yoon, Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. “It may also delay lung function decline.”

In patients with CPFE, FVC and DL_CO are usually delayed, thus rendering these measures less clinically useful as surrogate markers for disease course. However, in IPF-only patients, these factors, along with longitudinal changes in lung function, are hypothesized to be prognostic indicators. The extent to which emphysema starts to impact the respiratory physiology and prognostic characteristics of IPF, however, is not yet fully understood.

The researchers noted that one quandary arising from these observations is that it is unclear whether patients with CPFE should be included in clinical trials of IPF patients due to challenges in monitoring disease progression and therapeutic response.

“We hypothesized that the emphysema extent that impacts both the annual decline rate and prognostic significance of lung function parameters could be used to define CPFE,” wrote the authors.

In this retrospective study, the researchers assessed the extent of emphysema in 209 patients with IPF (102 confirmed by biopsy) using high-resolution CT scans, and measured the extent of disease in these study participants using a texture-based automated quantification system. They aimed to examine the effect of differences in the extent of emphysema on the annual decline rate, as well as the prognostic significance of lung function parameters.

In the sample, the extent of emphysema was ≥ 5% in 53 patients (25%); ≥ 10% in 23 patients (11%); and ≥ 15% in 12 patients (6%).

The team found that the FVC decline rate was a significant predictor of mortality in patients with no or negligible emphysema (HR: 0.933; P < 0.001) and in patients with an extent of emphysema ≥ 5% (HR: 0.906; P < 0.001).

In contrast, DL_CO was the most significant prognostic indicator in those patients with an extent of emphysema ≥ 10% (HR: 0.972; P=0.040), as well as those patients with an extent of emphysema ≥ 15% (HR: 0.942; P=0.023).

On the basis of these results, the researchers suggested that an emphysema extent of ≥ 10% affected both the yearly decline rate and prognostic significance of FVC in patients with IPF.

“When CPFE was defined at ≥ 10% emphysema,” the researchers wrote, “one-tenth of IPF patients were classified as having CPFE, and these patients showed more preserved lung volume, lower annual FVC decline rate, and similar prognosis compared with IPF-only patients. In CPFE, DL_CO was the best surrogate for predicting subsequent mortality.”

Consequently, the authors proposed a 10% emphysema cut-off value in patients with CPFE to delineate important differences in clinical, physiologic, and prognostic features compared with IPF-only patients.

The authors acknowledged that the study had certain limitations. For example, there was a relatively small number of patients with IPF and ≥ 10% emphysema. Nonetheless, the objective measures and statistical analyses used to assess the impact of emphysema on lung function changes in this study population validated the study findings.

“Our data indicate that emphysema at an extent of ≥ 10% can be used to define CPFE in IPF patients, and that longitudinal FVC changes are imperfect predictors of subsequent mortality in these patients,” concluded the researchers. “Further investigation is needed to monitor disease course and design appropriate clinical trials in these patients.”

This study was supported by grants from the Korean Health Technology R&D Project of the Ministry of Health and Welfare, Republic of Korea and from the Basic Science Research Program through the National Research Foundation of Korea (NRF), which is funded by the Ministry of Science, ICT, and Future Planning.