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.

Deepika Polineni,Rhonda G Pace,Sarah N Dalrymple,Peter R Durie,Simon C Ling,Jaclyn R Stonebraker,Annalisa V Piccorelli,Michael R Knowles,William B Hannah

doi:10.1371/journal.pone.0205257

Deepika Polineni, Rhonda G Pace + Show 7 more

Open Access

PDF Available

https://doi.org/10.1371/journal.pone.0205257

Copy DOI

Export

Save

Cite

Abstract
Highlights/Summary
Full-Text PDF
Similar Papers

Abstract

Listen

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.

Highlights

Cystic fibrosis (CF) is the most common lethal genetic disorder in Caucasians, affecting an estimated 30,000 persons in the United States [1]
We studied a large cohort of stringently phenotyped cystic fibrosis (CF) subjects with an extreme form of liver disease to rigorously test for association of CF liver disease (CFLD) with lung function decline in CF
Because lung function decline is recognized to be greatest during the adolescent age in CF [21], referencing the slope of lung function decline in severe CFLD to that of decline in the general CF population was critical

Summary

Introduction

Cystic fibrosis (CF) is the most common lethal genetic disorder in Caucasians, affecting an estimated 30,000 persons in the United States [1]. Severe CF liver disease (CFLD) with portal hypertension due to cirrhosis is the most common non-pulmonary cause of mortality in CF (after pulmonary disease and transplantation complications) [4,5,6]. While many CF patients have some degree of liver abnormality, only 5% develop severe CF liver disease with portal hypertension (CFLD) due to cirrhosis [7]. The relationship between lung function and liver disease in CF has been unclear, as previous studies have reported variable results. Other case-control studies report findings of worse FEV1 in children with liver disease compared to those without [13, 14]. The divergent findings on the relationship between hepatic disease and lung function may be due to variable definitions of CF liver disease

Methods

Results

Conclusion