Omics approaches in cystic fibrosis research: a focus on oxylipin profiling in airway secretions

Abstract

Cystic fibrosis (CF) is associated with abnormal lipid metabolism, intense respiratory tract (RT) infection, and inflammation, eventually resulting in lung tissue destruction and respiratory failure. The CF RT inflammatory milieu, as reflected by airway secretions, includes a complex array of inflammatory mediators, bacterial products, and host secretions. It is dominated by neutrophils and their proteolytic and oxidative products and includes a wide spectrum of bioactive lipids produced by both host and presumably microbial metabolic pathways. The fairly recent advent of "omics" technologies has greatly increased capabilities of further interrogating this easily obtainable RT compartment that represents the apical culture media of the underlying RT epithelial cells. This paper discusses issues related to the study of CF omics with a focus on the profiling of CF RT oxylipins. Challenges in their identification/quantitation in RT fluids, their pathways of origin, and their potential utility for understanding CF RT inflammatory and oxidative processes are highlighted. Finally, the utility of oxylipin metabolic profiling in directing optimal therapeutic approaches and determining the efficacy of various interventions is discussed.

Figure 1

Generalized and lipid-specific scheme to illustrate omics pathways from gene to phenotype with regard to understanding CF airway biology and pathobiology.

Figure 2

Generalized scheme illustrating an LC/MS/MS metabolomic approach to comprehensively evaluate bioactive oxylipin profiles in CF RT secretions.

Figure 3

Summary of oxylipins detected in adult CF sputum as a function of the parent unsaturated fatty acid.