Analysis of a large cohort of cystic fibrosis patients with severe liver disease indicates lung function decline does not significantly differ from that of the general cystic fibrosis population

Abstract

Previous reports of lung function in cystic fibrosis (CF) patients with liver disease have shown worse, similar, or even better forced expiratory volume in 1 second (FEV1), compared to CF patients without liver disease. Varying definitions of CF liver disease likely contribute to these inconsistent relationships reported between CF lung function and liver disease. We retrospectively evaluated spirometric data in 179 subjects (62% male; 58% Phe508del homozygous) with severe CF liver disease (CFLD; defined by presence of portal hypertension due to cirrhosis). FEV1 values were referenced to both a normal population (FEV1% predicted) and CF population (CF-specific FEV1 percentile). We utilized a linear mixed model with repeated measures to assess changes in lung function (before and after diagnosis of CFLD), relative to both the normal and CF populations. At diagnosis of CFLD, the mean FEV1 was 81% predicted, or at the 53rd percentile referenced to CF patients without CFLD. There was a significant difference in post-CFLD slope compared to pre-CFLD slope (post-pre) using FEV1% predicted (-1.94, p-value < 0.0001). However, there was insignificant evidence of this difference using the CF-specific FEV1 percentile measure (-0.99, p-value = 0.1268). Although FEV1% predicted values declined in patients following CFLD diagnosis, there was not significant evidence of lung function decline in CF-specific FEV1 percentiles. Thus, the observed study cohort indicates diagnosis of severe CFLD was not associated with worsened CF lung disease when compared to a large CF reference population.

Fig 1. Plot of average slope decline in lung function in CFLD subjects.

(A) Points are estimated mean values (±SE), of outcome plotted at t = -5 years (before CFLD diagnosis), t = 0 years (time of CFLD diagnosis), and t = 5 years (after CFLD diagnosis) for a patient age 13.3 years (average age at CFLD diagnosis). CF-specific FEV₁ percentile (solid line) and FEV₁% predicted (dashed line) are shown in 118 CFLD subjects with lung function values before and after CFLD diagnosis. (B) Averaged data at t = 0 and t = 5 years (±SE), including an additional 61 patients with post-CFLD diagnosis lung function values (total subjects, n = 179).