AUTHOR=Montuschi Paolo , Santini Giuseppe , Mores Nadia , Vignoli Alessia , Macagno Francesco , Shoreh Rugia , Tenori Leonardo , Zini Gina , Fuso Leonello , Mondino Chiara , Di Natale Corrado , D'Amico Arnaldo , Luchinat Claudio , Barnes Peter J. , Higenbottam Tim 

TITLE=Breathomics for Assessing the Effects of Treatment and Withdrawal With Inhaled Beclomethasone/Formoterol in Patients With COPD

JOURNAL=Frontiers in Pharmacology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2018.00258

DOI=10.3389/fphar.2018.00258

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> Prospective pharmacological studies on breathomics profiles in COPD patients have not been previously reported. We assessed the effects of treatment and withdrawal of an extrafine inhaled corticosteroid (ICS)-long-acting β<sub>2</sub>-agonist (LABA) fixed dose combination (FDC) using a multidimensional classification model including breathomics.</p><p><bold>Methods:</bold> A pilot, proof-of-concept, pharmacological study was undertaken in 14 COPD patients on maintenance treatment with inhaled fluticasone propionate/salmeterol (500/50 μg b.i.d.) for at least 8 weeks (visit 1). Patients received 2-week treatment with inhaled beclomethasone dipropionate/formoterol (100/6 μg b.i.d.) (visit 2), 4-week treatment with formoterol alone (6 μg b.i.d.) (visit 3), and 4-week treatment with beclomethasone/formoterol (100/6 μg b.i.d.) (visit 4). Exhaled breath analysis with two e-noses, based on different technologies, and exhaled breath condensate (EBC) NMR-based metabolomics were performed. Sputum cell counts, sputum supernatant and EBC prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) and 15-F<sub>2t</sub>-isoprostane, fraction of exhaled nitric oxide, and spirometry were measured.</p><p><bold>Results:</bold> Compared with formoterol alone, EBC acetate and sputum PGE<sub>2</sub>, reflecting airway inflammation, were reduced after 4-week beclomethasone/formoterol. Three independent breathomics techniques showed that extrafine beclomethasone/formoterol short-term treatment was associated with different breathprints compared with regular fluticasone propionate/salmeterol. Either ICS/LABA FDC vs. formoterol alone was associated with increased pre-bronchodilator FEF<sub>25−75%</sub> and FEV<sub>1</sub>/FVC (<italic>P</italic> = 0.008–0.029). The multidimensional model distinguished fluticasone propionate/salmeterol vs. beclomethasone/formoterol, fluticasone propionate/salmeterol vs. formoterol, and formoterol vs. beclomethasone/formoterol (accuracy &gt; 70%, <italic>P</italic> &lt; 0.01).</p><p><bold>Conclusions:</bold> Breathomics could be used for assessing ICS treatment and withdrawal in COPD patients. Large, controlled, prospective pharmacological trials are required to clarify the biological implications of breathomics changes. EUDRACT number: 2012-001749-42.</p>