Journal
JOURNAL OF PROTEOME RESEARCH
Volume 19, Issue 1, Pages 64-74Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jproteome.9b00345
Keywords
metabolomics; nuclear magnetic resonance spectroscopy; COPD; long-acting beta(2)-agonists; inhaled corticosteroids; pharmacotherapy
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Funding
- Chiesi Farmaceutici
- Catholic University of the Sacred Heart, Rome, Italy
- AIRC fellowship for Italy
- Instruct-ERIC, a Landmark ESFRI project
- CERM/CIRMMP Italy Centre
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The aim of this proof-of-concept, pilot study was the evaluation of the effects of steroid administration and suspension of an inhaled corticosteroid (ICS)-long-acting beta(2)-agonist (LABA) extrafine fixed dose combination (FDC) on metabolomic fingerprints in subjects with chronic obstructive pulmonary disease (COPD). We hypothesized that a comprehensive metabolomics approach discriminates across inhaled pharmacotherapies and that their effects on metabolomic signatures depend on the biological fluids analyzed. We performed metabolomics via nuclear magnetic resonance (NMR) spectroscopy in exhaled breath condensate (EBC), sputum supernatants, serum, and urine. Fourteen patients suffering from COPD who were on regular inhaled fluticasone propionate/salmeterol therapy (visit 1) were consecutively treated with 2-week beclomethasone dipropionate/formoterol (visit 2), 4-week formoterol alone (visit 3), and 4-week beclomethasone/formoterol (visit 4). The comprehensive NMR-based metabolomics approach showed differences across all pharmacotherapies and that different biofluids provided orthogonal information. Serum formate was lower at visits 1 versus 3 (P = 0.03), EBC formate was higher at visit 1 versus 4 (P = 0.03), and urinary 1-methyl-nicotinamide was lower at 3 versus 4 visit (P = 0.002). NMR-based metabolomics of different biofluids distinguishes across inhaled pharmacotherapies, provides complementary information on the effects of an extrafine ICS/LABA FDC on metabolic fingerprints in COPD patients, and might be useful for elucidating the ICS mechanism of action.
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