Real-World Findings Suggest New Look at Thresholds for IPF Progression

Even small drops in lung function can predict poor outcomes for patients with chronic lung disease, suggests a new real-world study.¹ Detailing their findings in Chest, the researchers say their study can help steer treatment guidelines for managing the progressive lung disease.

Data from this new study show that cutoffs as low as 2% were associated with poor outcomes in IPF, even when accounting for other known prognostic factors. | Image Credit: Crystal light - stock.adobe.com

After following the 1000 patients with idiopathic pulmonary fibrosis (IPF) for a median of 38.4 months, the researchers found significant associations between declines in lung function, measured by forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (DLco), and the risk of death or lung transplant.

While reductions larger than 5% or 10% in FVC predicted value and a 15% or larger reduction in DLco % are generally accepted cutoffs for determining IPF worsening, data from this new study show that cutoffs as low as 2% were associated with poor outcomes, even when accounting for other known prognostic factors.

“Our data add to a body of literature demonstrating that the threshold of decline in FVC % predicted that is associated with an increased risk of mortality in patients with IPF may be much lower than the threshold of 5% or 10% that is generally regarded as indicating progression,” wrote the researchers, noting that current thresholds are based on clinical data. Literature has defined IPF progression as a decline in FVC ≥10% predicted and a decline in DLco ≥15% predicted.²

Adjusted analyses showed that a 2% or greater decline in FVC predicted value resulted in a 1.8-fold increase in risk of death or lung transplant. This risk increased with increasing reductions in function, with a threshold of 5% having a 2.3-fold increased risk and 10% having a 2.7-fold increased risk.

The researchers found similar results in adjusted analyses of DLco %, with a 2-fold increase of death or lung transplant associated with a ≥2% threshold, a 1.4-fold increase associated with a ≥5% threshold, and a 1.9-fold increase associated with a ≥15% threshold.

Throughout the follow-up period, the researchers found that within the first 6 months, approximately 1 in 4 patients had a relative decline in FVC% predicted of at least 2% and nearly 1 in 5 (18%) had a similar relative decline in DLco%, suggesting that these small declines in lung function happen quickly.

Patients included in the study were mostly male (74.6%), White (94.9%), and current or former smokers (66.9%). The median age was 71 years (range, 66-75).

Notably, for DLco only, using a threshold based on relative risk generally showed bigger increases in risk of poor outcomes, with larger hazard ratios seen for patients who met thresholds based on relative risk versus absolute decline. Hazard ratios for absolute versus relative decline were similar for FVC % predicted.

“The question of whether declines in lung function should be considered as absolute or relative values remains open to debate,” explained the researchers, noting that their study is the first to report on the prognostic value of absolute vs relative risk. They wrote, “Our finding that a relative decline in DLco % predicted provides more prognostic information than an absolute decline adds to the evidence base that will inform future trial design and clinical practice guidelines.”

References

1. Oldham JM, Neely ML, Wojdyla DM, et al. Changes in lung function and mortality risk in patients with idiopathic pulmonary fibrosis. Chest. Published online February 18, 2025. doi:10.1016/j.chest.2025.02.018
2. Wuyts WA, Wijsenbeek M, Bondue B, et al. Idiopathic pulmonary fibrosis: Best practice in monitoring and managing a relentless fibrotic disease. Respiration. 2019;99(1):73-82. doi:10.1159/000504763