Abstract
Cystic fibrosis is a mono-genetic multi-system disease; however, respiratory manifestations cause the main morbidity and mortality where chronic bacterial infections lead to bronchiectasis and ultimately respiratory failure. Metabolomics allows a relatively complete snapshot of metabolic processes in a sample using different mass spectrometry methods. Sample types used for discovery of biomarkers or pathomechanisms in cystic fibrosis (CF) have included blood, respiratory secretions, and exhaled breath to date. Metabolomics has shown distinction of CF vs. non-CF for matrices of blood, exhaled breath, and respiratory epithelial cultures, each showing different pathways. Severity of lung disease has been addressed by studies in bronchoalveolar lavage and exhaled breath condensate showing separation by metabolites that the authors of each study related to inflammation; e.g., ethanol, acetone, purines. Lipidomics has been applied to blood and sputum samples showing associations with lung function and Pseudomonas aeruginosa infection status. Finally, studies of bacteria grown in vitro showed differences of bacterial metabolites to be associated with clinical parameters. Metabolomics, in the sense of global metabolomic profiling, is a powerful technique that has allowed discovery of pathways that had not previously been implicated in CF. These may include purines, mitochondrial pathways, and different aspects of glucose metabolism besides the known differences in lipid metabolism in CF. However, targeted studies to validate such potential metabolites and pathways of interest are necessary. Studies evaluating metabolites of bacterial origin are in their early stages. Thus further well-designed studies could be envisioned.
Highlights
Cystic fibrosis (CF) or mucoviscidosis is a multi-system monogenetic disease caused by mutation of the cystic fibrosis transmembrane regulator (CFTR) gene leading to abnormal folding and function of the CFTR protein, which is a chloride/bicarbonate channel
Metabolomic technology in CF has been used for biomarker detection and identification of potential pathomechanistic changes to advance novel therapeutic approaches
The same group of authors more recently reported discriminatory nuclear magnetic resonance (NMR) spectra of exhaled breath condensate (EBC) in CF compared to primary ciliary dyskinesia (PCD) [20]
Summary
Cystic fibrosis (CF) or mucoviscidosis is a multi-system monogenetic disease caused by mutation of the cystic fibrosis transmembrane regulator (CFTR) gene leading to abnormal folding and function of the CFTR protein, which is a chloride/bicarbonate channel. The study provided careful control measures including within day and between-day repeatability in disease and healthy subjects and external validation in a set of patients from a different CF center. The same group of authors more recently reported discriminatory NMR spectra of EBC in CF compared to primary ciliary dyskinesia (PCD) [20] Both the discovery and the validation group of CF and control subjects had been included in the prior analyses, but repeat measures confirmed identification of the same metabolites. Principal component analyses (PCA) of the NMR spectra identified three dominant clusters Analyses of these clusters relative to bacterial growth characteristics and patient outcomes showed significant associations between cluster membership and both, lung function and pH of the spent culture medium. Examining results from both approaches allows researchers to look at the data from different perspectives and extract the best possible amount of information from the data
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