Metabolomic endotype of asthma

SAA Comhair, J McDunn, C Bennett… - The Journal of …, 2015 - journals.aai.org
SAA Comhair, J McDunn, C Bennett, J Fettig, SC Erzurum, SC Kalhan
The Journal of Immunology, 2015journals.aai.org
Metabolomics, the quantification of small biochemicals in plasma and tissues, can provide
insight into complex biochemical processes and enable the identification of biomarkers that
may serve as therapeutic targets. We hypothesized that the plasma metabolome of asthma
would reveal metabolic consequences of the specific immune and inflammatory responses
unique to endotypes of asthma. The plasma metabolomic profiles of 20 asthmatic subjects
and 10 healthy controls were examined using an untargeted global and focused …
Abstract
Metabolomics, the quantification of small biochemicals in plasma and tissues, can provide insight into complex biochemical processes and enable the identification of biomarkers that may serve as therapeutic targets. We hypothesized that the plasma metabolome of asthma would reveal metabolic consequences of the specific immune and inflammatory responses unique to endotypes of asthma. The plasma metabolomic profiles of 20 asthmatic subjects and 10 healthy controls were examined using an untargeted global and focused metabolomic analysis. Individuals were classified based on clinical definitions of asthma severity or by levels of fraction of exhaled NO (F E NO), a biomarker of airway inflammation. Of the 293 biochemicals identified in the plasma, 25 were significantly different among asthma and healthy controls (p< 0.05). Plasma levels of taurine, lathosterol, bile acids (taurocholate and glycodeoxycholate), nicotinamide, and adenosine-5-phosphate were significantly higher in asthmatics compared with healthy controls. Severe asthmatics had biochemical changes related to steroid and amino acid/protein metabolism. Asthmatics with high F E NO, compared with those with low F E NO, had higher levels of plasma branched-chain amino acids and bile acids. Asthmatics have a unique plasma metabolome that distinguishes them from healthy controls and points to activation of inflammatory and immune pathways. The severe asthmatic and high F E NO asthmatic have unique endotypes that suggest changes in NO-associated taurine transport and bile acid metabolism.
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