A new study published in the American Journal of Respiratory and Critical Care Medicine shows that forced vital capacity (FVC) measurements may be inappropriate when assessing disease progression in patients with emphysema extent ≥15% and idiopathic pulmonary fibrosis (IPF).
“The aim of this analysis was to characterize the relationship between emphysema extent and changes in pulmonary function over time in patients with IPF enrolled in the GIPF-001 and GIPF-007 clinical trials,” wrote Vincent Cottin, MD, PhD, Department of Respiratory Medicine, National Reference Center for Rare Pulmonary Diseases, Louis Pradel Hospital, Lyon, France.
FVC is typically used to monitor clinical decline in patients with IPF, with serial decline in FVC values predicting death in IFC cohorts. Although emphysema with comorbid IPF presents in one-third of patients, few researchers have looked at the effect of both IPF and emphysema on serial FVC trends.
Importantly, in patients with both IPF and emphysema, FVC levels are higher than in patients with IPF alone, which holds true even when fibrosis extent is visualized using high-resolution computed tomography (HRCT).
“These observations provide strong indirect support for the hypothesis that, in patients with IPF, coexisting emphysema has a significant attenuating effect on serial FVC decline,” wrote the authors. “This would have major implications for routine monitoring and use of serial FVC as a primary endpoint in IPF treatment trials.”
In this post hoc analysis, researchers sampled data from two phase 3, double-blind, randomized placebo-controlled clinical trials (GIPF-001 and GIPF-007) examining interferon gamma-1b treatment in patients with IPF. Neither clinical trial demonstrated treatment efficacy for the outcomes measured; thus, the researchers combined patients from the treatment and placebo groups during their analysis.
The research team included patients with lung function data at week 48 and baseline HRCT scans. From GIPF-001, they selected patients with FEV1/FVC ratios < 0.8 or > 0.9, and from GIPF-007 they selected patients with FEV1/FVC ratios of < 0.7 or > 0.9. Finally, they included randomly selected patients with FEV1/FVC ratios of between 0.8 and 0.9 or between 0.7 and 0.8.
The association between emphysema extents and fibrosis was examined using baseline HRCT. Specifically, the team analyzed changes in FVC, FEV1, diffusing capacity of the lung for carbon monoxide (DLCO), and Composite Physiological Index (CPI) by quartile of emphysema extent. They used multivariate linear regression to ascertain the association between emphysema and fibrosis extents and change in pulmonary function between baseline and week 48.
Of 1,156 IPF patients included in GIPF-001 and GIPF-007, Dr. Cottin and colleagues included 455 patients in their post hoc analysis. In total, they found emphysema using HRCT in 174 patients (38%).
The team found a negative association between fibrosis and emphysema extents (r =–0.232; P < 0.001). Using quartile analysis, they found that patients with the greatest emphysema extent (28% to 65%) showed the smallest FVC declines compared with patients with no emphysema (P=0.047).
During multivariate analysis, the team found that emphysema extent ≥15% was associated with significantly decreased FVC decline over 48 weeks when compared with patients without emphysema or an emphysema extent <15%.
The team did not observe an association between emphysema extent and DLCO or CPI.
Although no treatment effects (ie, progression-free survival, pulmonary function, quality of life or mortality) were observed during the GIPF-001 and GIPF-007 clinical trials, it is possible that interferon gamma-1b may have influenced the progression of emphysema in study participants, thus serving as a limitation in the analysis.
“Serial FVC measurements may not capture IPF progression, and other endpoints, including DLCO and CPI, should be considered in patients with combined IPF and emphysema,” concluded the researchers. “These important observations require deliberation by expert groups with regard to routine monitoring of IPF and need to be taken into account in the design of IPF clinical trials.”
To read more about this study, click here.