Breathomics for assessing the effects of treatment and withdrawal with inhaled beclomethasone/formoterol in patients with COPD

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

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Article number258
JournalFrontiers in Pharmacology
Volume9
Issue numberAPR
DOIs
Publication statusPublished - Apr 17 2018

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Beclomethasone
Chronic Obstructive Pulmonary Disease
Sputum
Therapeutics
Adrenal Cortex Hormones
Dinoprostone
Formoterol Fumarate
Electronic Nose
Pharmacology
Metabolomics
Bronchodilator Agents
Spirometry
Nitric Oxide
Acetates
Cell Count

Keywords

  • Breathomics
  • COPD
  • Inhaled corticosteroids
  • Long-acting ß2-agonists
  • Pharmacotherapy

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

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.

In: Frontiers in Pharmacology, Vol. 9, No. APR, 258, 17.04.2018.

Research output: Contribution to journalArticle

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 2018, 'Breathomics for assessing the effects of treatment and withdrawal with inhaled beclomethasone/formoterol in patients with COPD', Frontiers in Pharmacology, vol. 9, no. APR, 258. https://doi.org/10.3389/fphar.2018.00258
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. In: Frontiers in Pharmacology. 2018 ; Vol. 9, No. APR.
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T1 - Breathomics for assessing the effects of treatment and withdrawal with inhaled beclomethasone/formoterol in patients with COPD

AU - Montuschi, Paolo

AU - Santini, Giuseppe

AU - Mores, Nadia

AU - Vignoli, Alessia

AU - Macagno, Francesco

AU - Shoreh, Rugia

AU - Tenori, Leonardo

AU - Zini, Gina

AU - Fuso, Leonello

AU - Mondino, Chiara

AU - Di Natale, Corrado

AU - D'Amico, Arnaldo

AU - Luchinat, Claudio

AU - Barnes, Peter J.

AU - Higenbottam, Tim

PY - 2018/4/17

Y1 - 2018/4/17

N2 - 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.

AB - 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.

KW - Breathomics

KW - COPD

KW - Inhaled corticosteroids

KW - Long-acting ß2-agonists

KW - Pharmacotherapy

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DO - 10.3389/fphar.2018.00258

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JO - Frontiers in Pharmacology

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