Background: 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 β2-agonist (LABA) fixed dose combination (FDC) using a multidimensional classification model including breathomics. Methods: 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 E2 (PGE2) and 15-F2t-isoprostane, fraction of exhaled nitric oxide, and spirometry were measured. Results: Compared with formoterol alone, EBC acetate and sputum PGE2, 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 FEF25-75% and FEV1/FVC (P = 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 > 70%, P < 0.01). Conclusions: 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.
Montuschi, P., Santini, G., Mores, N., Vignoli, A., Macagno, F., Shoreh, R., et al. (2018). Breathomics for assessing the effects of treatment and withdrawal with inhaled beclomethasone/formoterol in patients with COPD. FRONTIERS IN PHARMACOLOGY, 9(APR), 258 [10.3389/fphar.2018.00258].
|Tipologia:||Articolo su rivista|
|Citazione:||Montuschi, P., Santini, G., Mores, N., Vignoli, A., Macagno, F., Shoreh, R., et al. (2018). Breathomics for assessing the effects of treatment and withdrawal with inhaled beclomethasone/formoterol in patients with COPD. FRONTIERS IN PHARMACOLOGY, 9(APR), 258 [10.3389/fphar.2018.00258].|
|IF:||Con Impact Factor ISI|
|Settore Scientifico Disciplinare:||Settore ING-INF/01 - Elettronica|
|Revisione (peer review):||Esperti anonimi|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.3389/fphar.2018.00258|
|Stato di pubblicazione:||Pubblicato|
|Data di pubblicazione:||2018|
|Titolo:||Breathomics for assessing the effects of treatment and withdrawal with inhaled beclomethasone/formoterol in patients with COPD|
|Autori:||Montuschi, P; Santini, G; Mores, N; Vignoli, A; Macagno, F; Shoreh, R; Tenori, L; Zini, G; Fuso, L; Mondino, C; Di Natale, C; D'Amico, A; Luchinat, C; Barnes, Pj; Higenbottam, T|
|Appare nelle tipologie:||01 - Articolo su rivista|