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

https://doi.org/10.1016/j.jaci.2015.05.022Get rights and content

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.

Section snippets

Methods

For details, see the Methods section in this article's Online Repository et al.10, 11

Baseline patients' characteristics for the metabolomic model of asthma versus COPD

The populations with COPD were both significantly older than the asthma groups, although the asthma group from McMaster was significantly older than the other asthma cohorts in Edmonton. The sex difference among these groups was similar. Subjects having an asthma exacerbation at the University of Alberta were not excluded if they currently smoked; however, the number of pack years of smoking was much lower in the asthma group compared with the COPD exacerbation group (a median of 5 compared

Discussion

We have provided proof-of-concept evidence that urine metabolites can be used to differentiate asthma from COPD. We have the metabolomic data comparing asthma and COPD before and after exacerbation, but the focus of this report was on the differentiation of asthma from COPD. A subsequent article will compare metabolites for exacerbation.

COPD and asthma involve a number of unique cellular pathways, but these pathways can still converge to produce a similar clinical outcome. Symptoms or lung

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    Supported by AllerGen, the Canadian Institutes of Health Research (CIHR), Genome Prairie, Genome Canada, an establishment grant from AHFMR, the Natural Science and Engineering Research Council of Canada (NSERC), the University of Alberta Hospital Foundation, and the Alberta Science and Research Authority (ASRA). B.H.R.'s research is supported by a Tier I Canada Research Chair in Evidence-based Emergency Medicine from the CIHR through the Government of Canada (Ottawa, Ontario, Canada). P.N. is supported by a Canada Research Chair in Airway Inflammometry through the Government of Canada (Ottawa, Ontario, Canada).

    Disclosure of potential conflict of interest: D. J. Adamko has received research support from AllerGen NCE, Alberta Heritage Foundation for Medical Research, the Women and Children's Health Research Institute, and Grand Challenges Canada; has received travel support from AllerGen NCE; has received payment for lectures from Merck and Takeda; has planned patents with the University of Alberta; and is lead on a university-based start-up company seeking to develop metabolomics as a potential diagnostic test for asthma and related airways diseases. P. Nair has consultant arrangements with Sanofi, Teva, Roche, and Boehringer Ingelheim; has received research support from GlaxoSmithKline, AstraZeneca, and Novartis; has received payment for lectures from Merck and AstraZeneca; is listed on a patent for a sputum filtration device; and has provided consultancy to a university-based start-up company seeking to develop a sputum processing kit. I. Mayers has received research support from the Public Health Agency of Canada; is a board member for Amirall Canada, Boehringer Ingelheim, and Novartis; has consultant arrangements with Boehringer Ingelheim; is employed by the Canadian Drug Expert Committee; has provided expert testimony for the Worker's Compensation Committee; and has received payment for lectures from Amirall, Boehringer Ingelheim, and Novartis. R. T. Tsuyuki has received research support from AllerGen NCE, the Canadian Institutes of Health Research, Genome Prairie, Alberta Heritage Foundation for Medical Research, the Natural Sciences and Engineering Research Council, Merck, Sanofi, and AstraZeneca; has received travel support from AllerGen NCE; and is on the pharmacy advisory board for PharmaSmart. S. Regush has received research support from AllerGen NCE, the Canadian Institutes of Health Research, Genome Prairie, Alberta Heritage Foundation for Medical Research, and the Natural Sciences and Engineering Research Council. B. H. Rowe has received research support from the University of Alabama in Hunstville Foundation, Alberta Heritage Foundation for Medical Research/Alberta Innovates: Health Solutions, and Canadian Institutes of Health Research; is chair of the International Advisory Board for SREMI–Mt. Sinai Hospital; has consultant arrangements with AlphaCore; is employed by Alberta Health Services; has received payment for lectures from AstraZeneca and Pfizer; has planned patents with the University of Alberta; and is a researcher and contributor to a university-based start-up company seeking to develop a metabolomics diagnostic test for asthma and related airways diseases.

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