Lipid phenotyping of lung epithelial lining fluid in healthy human volunteers

Joost Brandsma,Ana R Sousa,Ratko Djukanović,Thomas Sandström,Pascal Chanez,Dominick Shaw ,Per Bakke ,Norbert Krug,Sven‐Erik Dahlén ,Massimo Caruso,Xian Yang,Louise Fleming ,Marek Sanak,Peter J Sterk,Victoria Goss ,Aruna T Bansal,Ioannis Pandis,Stephen J Fowler,Ildikó Horváth ,Paolo Montuschi,Florian Singer,Kian Fan Chung,Anthony D Postle

doi:10.1007/s11306-018-1412-2

Abstract

BackgroundLung epithelial lining fluid (ELF)—sampled through sputum induction—is a medium rich in cells, proteins and lipids. However, despite its key role in maintaining lung function, homeostasis and defences, the composition and biology of ELF, especially in respect of lipids, remain incompletely understood.ObjectivesTo characterise the induced sputum lipidome of healthy adult individuals, and to examine associations between different ELF lipid phenotypes and the demographic characteristics within the study cohort.MethodsInduced sputum samples were obtained from 41 healthy non-smoking adults, and their lipid compositions analysed using a combination of untargeted shotgun and liquid chromatography mass spectrometry methods. Topological data analysis (TDA) was used to group subjects with comparable sputum lipidomes in order to identify distinct ELF phenotypes.ResultsThe induced sputum lipidome was diverse, comprising a range of different molecular classes, including at least 75 glycerophospholipids, 13 sphingolipids, 5 sterol lipids and 12 neutral glycerolipids. TDA identified two distinct phenotypes differentiated by a higher total lipid content and specific enrichments of diacyl-glycerophosphocholines, -inositols and -glycerols in one group, with enrichments of sterols, glycolipids and sphingolipids in the other. Subjects presenting the lipid-rich ELF phenotype also had significantly higher BMI, but did not differ in respect of other demographic characteristics such as age or gender.ConclusionsWe provide the first evidence that the ELF lipidome varies significantly between healthy individuals and propose that such differences are related to weight status, highlighting the potential impact of (over)nutrition on lung lipid metabolism.

Highlights

Epithelial lining fluid (ELF) is the thin layer of biofluid that covers the apical surface of the respiratory epithelium, from the alveoli up through to the large airways
A total of 1364 positive and 1031 negative ions were detected in the 41 analysed sputum samples, the majority being present in a small number of samples but absent or below the limit of detection in the remainder
This study shows that epithelial lining fluid (ELF), as sampled by sputum induction, has a diverse lipidome comprising a range of different lipid molecular classes, including glycerophospholipids (PC, PE, PG, PI and glycerophosphoserine (PS) and PI), sphingolipids (SM, Cer and HexCer) sterol lipids and glycerolipids (DG, TG)

Summary

Introduction

Epithelial lining fluid (ELF) is the thin layer of biofluid that covers the apical surface of the respiratory epithelium, from the alveoli up through to the large airways. Extended author information available on the last page of the article prime target for molecular studies of lung disease. Sputum samples may contain secretions from the upper airways or the gastroesophageal tract, inhaled aerosols and microbes. These additional sources can affect the concentrations of lower airways biomarkers, principally through dilution of the sample with saliva, and may influence its molecular composition. Objectives To characterise the induced sputum lipidome of healthy adult individuals, and to examine associations between different ELF lipid phenotypes and the demographic characteristics within the study cohort. Subjects presenting the lipid-rich ELF phenotype had significantly higher BMI, but did not differ in respect of other demographic characteristics such as age or gender. Conclusions We provide the first evidence that the ELF lipidome varies significantly between healthy individuals and propose that such differences are related to weight status, highlighting the potential impact of (over)nutrition on lung lipid metabolism

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