Metabolomic profiling of asthma and chronic obstructive pulmonary disease: A pilot study differentiating diseases

被引:96
作者
Adamko, Darryl J. [1 ,2 ,4 ]
Nair, Parameswaran [5 ,6 ]
Mayers, Irvin [2 ]
Tsuyuki, Ross T. [2 ]
Regush, Shana [1 ]
Rowe, Brian H. [3 ]
机构
[1] Univ Alberta, Dept Pediat, Sch Publ Hlth, Edmonton, AB, Canada
[2] Univ Alberta, Dept Med, Sch Publ Hlth, Edmonton, AB, Canada
[3] Univ Alberta, Dept Emergency Med, Sch Publ Hlth, Edmonton, AB, Canada
[4] Univ Saskatchewan, Dept Pediat, Saskatoon, SK S7N OW8, Canada
[5] McMaster Univ, Dept Med, Hamilton, ON, Canada
[6] St Josephs Healthcare, Hamilton, ON, Canada
基金
加拿大健康研究院; 加拿大自然科学与工程研究理事会;
关键词
Metabolomics; asthma; chronic obstructive pulmonary disease; biomarkers; urine; nuclear magnetic resonance spectroscopy; N-METHYLHISTAMINE; NITRIC-OXIDE; HISTAMINE-RELEASE; URINARY-EXCRETION; OXIDATIVE STRESS; AMINO-ACIDS; EXACERBATIONS; FLUIDS; INFLAMMATION; NICOTINAMIDE;
D O I
10.1016/j.jaci.2015.05.022
中图分类号
R392 [医学免疫学];
学科分类号
100108 [医学免疫学];
摘要
Background: Differentiating asthma from other causes of chronic airflow limitation, such as chronic obstructive pulmonary disease (COPD), can be difficult in a typical outpatient setting. The inflammation of asthma typically is different than that of COPD, and the degree of inflammation and cellular damage varies with asthma severity. Metabolomics is the study of molecules created by cellular metabolic pathways. Objectives: We hypothesized that the metabolic activity of adults with asthma would differ from that of adults with COPD. Furthermore, we hypothesized that nuclear magnetic resonance spectroscopy (NMR) would measure such differences in urine samples. Methods: Clinical and urine-based NMR data were collected on adults meeting the criteria of asthma and COPD before and after an exacerbation (n = 133 and 38, respectively) and from patients with stable asthma or COPD (n = 54 and 23, respectively). Partial least-squares discriminant analysis was performed on the NMR data to create models of separation (86 metabolites were measured per urine sample). Some subjects' metabolomic data were withheld from modeling to be run blindly to determine diagnostic accuracy. Results: Partial least-squares discriminant analysis of the urine NMR data found unique differences in select metabolites between patients with asthma and those with COPD seen in the emergency department and even in follow-up after exacerbation. By using these select metabolomic profiles, the model could correctly diagnose blinded asthma and COPD with greater than 90% accuracy. Conclusion: This is the first report showing that metabolomic analysis of human urine samples could become a useful clinical tool to differentiate asthma from COPD.
引用
收藏
页码:571 / +
页数:13
相关论文
共 64 条
[1]
Altered Asymmetric Dimethyl Arginine Metabolism in Allergically Inflamed Mouse Lungs [J].
Ahmad, Tanveer ;
Mabalirajan, Ulaganathan ;
Ghosh, Balaram ;
Agrawal, Anurag .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 2010, 42 (01) :3-8
[2]
Characterization of the biochemical effects of 1-nitronaphthalene in rats using global metabolic profiling by NMR spectroscopy and pattern recognition [J].
Azmi, J ;
Connelly, J ;
Holmes, E ;
Nicholson, JK ;
Shore, RF ;
Griffin, JL .
BIOMARKERS, 2005, 10 (06) :401-416
[3]
Nuclear magnetic resonance spectroscopic and principal components analysis investigations into biochemical effects of three model hepatotoxins [J].
Beckwith-Hall, BM ;
Nicholson, JK ;
Nicholls, AW ;
Foxall, PJD ;
Lindon, JC ;
Connor, SC ;
Abdi, M ;
Connelly, J ;
Holmes, E .
CHEMICAL RESEARCH IN TOXICOLOGY, 1998, 11 (04) :260-272
[4]
INHIBITORY EFFECT OF NICOTINAMIDE ON ASTHMA-LIKE SYMPTOMS AND EOSINOPHILIA IN GUINEA-PIGS, ANAPHYLACTIC MAST-CELL DEGRANULATION IN MICE, AND HISTAMINE-RELEASE FROM RAT ISOLATED PERITONEAL MAST-CELLS BY COMPOUND 48-80 [J].
BEKIER, E ;
WYCZOLKOWSKA, J ;
SZYC, H ;
MASLINSKI, C .
INTERNATIONAL ARCHIVES OF ALLERGY AND APPLIED IMMUNOLOGY, 1974, 47 (05) :737-748
[5]
NICOTINAMIDE, A MISSING LINK IN THE EARLY STRESS-RESPONSE IN EUKARYOTIC CELLS - A HYPOTHESIS WITH SPECIAL REFERENCE TO OXIDATIVE STRESS IN PLANTS [J].
BERGLUND, T .
FEBS LETTERS, 1994, 351 (02) :145-149
[6]
Asymmetric dimethylarginine, and endogenous inhibitor of nitric oxide synthase, explains the "L-arginine paradox" and acts as a novel cardiovascular risk factor [J].
Böger, RH .
JOURNAL OF NUTRITION, 2004, 134 (10) :2842S-2847S
[7]
Brightling Christopher E, 2005, Treat Respir Med, V4, P309, DOI 10.2165/00151829-200504050-00002
[8]
Biomarker-based asthma phenotypes of corticosteroid response [J].
Cowan, Douglas C. ;
Taylor, D. Robin ;
Peterson, Laura E. ;
Cowan, Jan O. ;
Palmay, Rochelle ;
Williamson, Avis ;
Hammel, Jef ;
Erzurum, Serpil C. ;
Hazen, Stanley L. ;
Comhair, Suzy A. A. .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2015, 135 (04) :877-+
[9]
Receptor-Mediated Enhancement of Beta Adrenergic Drug Activity by Ascorbate In Vitro and In Vivo [J].
Dillon, Patrick F. ;
Root-Bernstein, Robert ;
Robinson, N. Edward ;
Abraham, William M. ;
Berney, Catherine .
PLOS ONE, 2010, 5 (12)
[10]
Airway purinergic responses in healthy, atopic nonasthmatic, and atopic asthmatic subjects exposed to ozone [J].
Esther, Charles R., Jr. ;
Peden, David B. ;
Alexis, Neil E. ;
Hernandez, Michelle L. .
INHALATION TOXICOLOGY, 2011, 23 (06) :324-330