Abstract
This observational study catalogues the overlap in metabolites between matched bronchoalveolar lavage fluid (BALF) and plasma, identifies the degree of congruence between these metabolomes in human and mouse, and determines how molecules may change in response to cigarette smoke (CS) exposure. Matched BALF and plasma was collected from mice (ambient air or CS-exposed) and humans (current or former smokers), and analyzed using mass spectrometry. There were 1155 compounds in common in all 4 sample types; fatty acyls and glycerophospholipids strongly overlapped between groups. In humans and mice, more than half of the metabolites present in BALF were also present in plasma. Mouse BALF and human BALF had a strong positive correlation with 2040 metabolites in common, suggesting that mouse models can be used to interrogate human lung metabolome changes. While power was affected by small sample size in the mouse study, the BALF metabolome appeared to be more affected by CS than plasma. CS-exposed mice showed increased plasma and BALF glycerolipids and glycerophospholipids. This is the first report cataloguing the metabolites present across mouse and human, BALF and plasma. Findings are relevant to translational studies where mouse models are used to examine human disease, and where plasma may be interrogated in lieu of BALF or lung tissue.
Highlights
Plasma and serum are often utilized in biomarker discovery studies; collection is relatively non-invasive and sufficient volume can be obtained
This situation is of particular interest in biomarker studies focusing on lung disease, where bronchoalveolar lavage fluid (BALF), sputum, exhaled breath condensate, and saliva have all been used as proxies for lung epithelial lining fluid and tissue[1,2,3,4]
The current study aims to fill this gap by using metabolomics to investigate the overlap between BALF and plasma in both humans and mice; further, it explores how metabolites can change upon exposure to cigarette smoke
Summary
Plasma and serum are often utilized in biomarker discovery studies; collection is relatively non-invasive and sufficient volume can be obtained. No discovery-based proteomics study has shown a significant correlation between markers found in both plasma and lung in the context of COPD severity[6] This is partially due to the challenges inherent in plasma proteomics, which include poor sensitivity and wide dynamic range. While significant in terms of plasma and tissue biomarkers that relate to COPD, none of these studies examined metabolites from both plasma and BALF and examined the overlap between mice and humans. The authors found a significant relationship between lung-specific L-carnitine and lung function; lung function was restored upon supplementation with L-carnitine These studies illustrate the utility of animal models; no comparison between animal and human samples was performed. The current study aims to fill this gap by using metabolomics to investigate the overlap between BALF and plasma in both humans and mice; further, it explores how metabolites can change upon exposure to cigarette smoke. Our long-term goal is to determine if specific compounds or classes of compounds in plasma reflect lung health status
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