The Detection of Bile Acids in the Lungs of Paediatric Cystic Fibrosis Patients Is Associated with Altered Inflammatory Patterns.

Jose A Caparrós-Martín,Stephanie Flynn,Fergal O’Gara,F Jerry Reen,David F Woods,Stephen M Stick,Patricia Agudelo-Romero,Sarath C Ranganathan

doi:10.3390/diagnostics10050282

Abstract

Background: Cystic fibrosis (CF) is a hereditary disorder in which persistent unresolved inflammation and recurrent airway infections play major roles in the initiation and progression of the disease. Little is known about triggering factors modulating the transition to chronic microbial infection and inflammation particularly in young children. Cystic fibrosis respiratory disease starts early in life, with the detection of inflammatory markers and infection evident even before respiratory symptoms arise. Thus, identifying factors that dysregulate immune responsiveness at the earliest stages of the disease will provide novel targets for early therapeutic intervention. Methods: We evaluated the clinical significance of bile acid detection in the bronchoalveolar lavage fluid of clinically stable preschool-aged children diagnosed with CF. Results: We applied an unbiased classification strategy to categorize these specimens based on bile acid profiles. We provide clear associations linking the presence of bile acids in the lungs with alterations in the expression of inflammatory markers. Using multiple regression analysis, we also demonstrate that clustering based on bile acid profiles is a meaningful predictor of the progression of structural lung disease. Conclusions: Altogether, our work has identified a clinically relevant host-derived factor that may participate in shaping early events in the aetiology of CF respiratory disease.

Highlights

Cystic fibrosis (CF) is an autosomal recessive condition caused by pathogenic genetic variants that compromise the function of the cystic fibrosis conductance transmembrane regulator (CFTR) gene product [1]
The aim of this study was to evaluate whether the presence of bile acids (BAs) in the bronchoalveolar lavage fluid (BALF) of clinically stable preschool-aged children diagnosed with CF, was associated with markers of inflammation and clinical outcomes
A cohort of 88 randomly selected bronchoalveolar lavage fluid (BALF) samples biobanked at the Australian Respiratory Surveillance Team for Cystic Fibrosis (AREST-CF) in Perth (WA, Australia) were used in this study

Summary

Introduction

Cystic fibrosis (CF) is an autosomal recessive condition caused by pathogenic genetic variants that compromise the function of the cystic fibrosis conductance transmembrane regulator (CFTR) gene product [1]. Cystic fibrosis lung disease is characterized by chronic neutrophilic inflammation and infection, which progressively lead to the development of bronchiectasis, lung function decline and respiratory failure [5,6]. This progressive course is marked by a succession of unpredictable episodic clinical deteriorations known as acute pulmonary exacerbations, the aetiology of which is not well understood [7,8,9]. Delineating the factors predisposing CF patients to airway inflammation and infection in early life is a necessary prerequisite for improvements in the clinical management of respiratory lung disease in children. Identifying factors that dysregulate immune responsiveness at the earliest stages of the disease will provide novel targets for early therapeutic intervention

Objectives

Methods

Results

Conclusion