title: Metabolomic Endotype of Asthma.
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 (FENO), 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 FENO, compared with those with low FENO, 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 FENO asthmatic have unique endotypes that suggest changes in NO-associated taurine transport and bile acid metabolism.
authors.affiliation: Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195; Cleveland Clinic, Lerner College of Medicine, Case Western Reserve University, Cleveland, OH 44195;
authors.forename: Suzy A A
authors.initials: SA
authors.lastname: Comhair
authors.affiliation: Metabolon, Inc., Durham, NC 27713; and.
authors.forename: Jonathan
authors.initials: J
authors.lastname: McDunn
authors.affiliation: Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195;
authors.forename: Carole
authors.initials: C
authors.lastname: Bennett
authors.affiliation: Cleveland Clinic, Lerner College of Medicine, Case Western Reserve University, Cleveland, OH 44195;
authors.forename: Jade
authors.initials: J
authors.lastname: Fettig
authors.affiliation: Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195; Cleveland Clinic, Lerner College of Medicine, Case Western Reserve University, Cleveland, OH 44195; Respiratory Institute, Cleveland Clinic, Cleveland, OH 44195.
authors.forename: Serpil C
authors.initials: SC
authors.lastname: Erzurum
authors.affiliation: Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195; Cleveland Clinic, Lerner College of Medicine, Case Western Reserve University, Cleveland, OH 44195; sck@case.edu.
authors.forename: Satish C
authors.initials: SC
authors.lastname: Kalhan
mesh_terms: D000249:Adenosine Monophosphate / Q000097:blood; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001249:Asthma / Q000097:blood* / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology; D001647:Bile Acids and Salts / Q000097:blood; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002784:Cholesterol / Q000097:blood; D045853:Exhalation; D005260:Female; D006002:Glycodeoxycholic Acid / Q000097:blood; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D055442:Metabolome; D055432:Metabolomics; D009536:Niacinamide / Q000097:blood; D009569:Nitric Oxide / Q000378:metabolism*; D012129:Respiratory Function Tests; D012720:Severity of Illness Index; D013654:Taurine / Q000097:blood; D013656:Taurocholic Acid / Q000097:blood
chemical_list: D000305:Adrenal Cortex Hormones; D000893:Anti-Inflammatory Agents; D001647:Bile Acids and Salts; D015415:Biomarkers; D013654:Taurine; D009536:Niacinamide; D009569:Nitric Oxide; D006002:Glycodeoxycholic Acid; D000249:Adenosine Monophosphate; D013656:Taurocholic Acid; C001521:lathosterol; D002784:Cholesterol