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

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 β(2)-agonist (LABA) fixed dose combination (FDC) using a multidimen...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5914154/
https://www.ncbi.nlm.nih.gov/pubmed/29719507
http://dx.doi.org/10.3389/fphar.2018.00258
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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
author_facet 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
author_sort Montuschi, Paolo
collection PubMed
description 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 β(2)-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 E(2) (PGE(2)) and 15-F(2t)-isoprostane, fraction of exhaled nitric oxide, and spirometry were measured. Results: Compared with formoterol alone, EBC acetate and sputum PGE(2), 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(25−75%) and FEV(1)/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.
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spelling pubmed-59141542018-05-01 Breathomics for Assessing the Effects of Treatment and Withdrawal With Inhaled Beclomethasone/Formoterol in Patients With COPD 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 Front Pharmacol Pharmacology 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 β(2)-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 E(2) (PGE(2)) and 15-F(2t)-isoprostane, fraction of exhaled nitric oxide, and spirometry were measured. Results: Compared with formoterol alone, EBC acetate and sputum PGE(2), 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(25−75%) and FEV(1)/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. Frontiers Media S.A. 2018-04-17 /pmc/articles/PMC5914154/ /pubmed/29719507 http://dx.doi.org/10.3389/fphar.2018.00258 Text en Copyright © 2018 Montuschi, Santini, Mores, Vignoli, Macagno, Shoreh, Tenori, Zini, Fuso, Mondino, Di Natale, D'Amico, Luchinat, Barnes and Higenbottam. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
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
Breathomics for Assessing the Effects of Treatment and Withdrawal With Inhaled Beclomethasone/Formoterol in Patients With COPD
title Breathomics for Assessing the Effects of Treatment and Withdrawal With Inhaled Beclomethasone/Formoterol in Patients With COPD
title_full Breathomics for Assessing the Effects of Treatment and Withdrawal With Inhaled Beclomethasone/Formoterol in Patients With COPD
title_fullStr Breathomics for Assessing the Effects of Treatment and Withdrawal With Inhaled Beclomethasone/Formoterol in Patients With COPD
title_full_unstemmed Breathomics for Assessing the Effects of Treatment and Withdrawal With Inhaled Beclomethasone/Formoterol in Patients With COPD
title_short Breathomics for Assessing the Effects of Treatment and Withdrawal With Inhaled Beclomethasone/Formoterol in Patients With COPD
title_sort breathomics for assessing the effects of treatment and withdrawal with inhaled beclomethasone/formoterol in patients with copd
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5914154/
https://www.ncbi.nlm.nih.gov/pubmed/29719507
http://dx.doi.org/10.3389/fphar.2018.00258
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