Ceiling effect of beclomethasone/formoterol/glycopyrronium triple fixed-dose combination in COPD: A translational bench-to-bedside study.
Administration, Inhalation
Beclomethasone
/ therapeutic use
Bronchodilator Agents
/ therapeutic use
Drug Combinations
Formoterol Fumarate
/ therapeutic use
Glycopyrrolate
/ therapeutic use
Humans
Muscarinic Antagonists
/ therapeutic use
Pulmonary Disease, Chronic Obstructive
/ drug therapy
Treatment Outcome
Airway resistance
Ceiling effect
Severe COPD
Small airways
Translational study
Triple therapy
Journal
Pulmonary pharmacology & therapeutics
ISSN: 1522-9629
Titre abrégé: Pulm Pharmacol Ther
Pays: England
ID NLM: 9715279
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
received:
12
04
2021
revised:
14
05
2021
accepted:
09
06
2021
pubmed:
16
6
2021
medline:
25
2
2023
entrez:
15
6
2021
Statut:
ppublish
Résumé
Currently, data on the possible synergy of adding a LAMA to ICS/LABA combination are missing and no studies assessed whether triple therapy may induce ceiling bronchodilator effect. A translational study was performed to investigate the interaction between glycopyrronium bromide (GB) and beclomethasone dipropionate (BDP)/formoterol fumarate (FF) combination in human isolated airways and the effect on FEV The interaction of adding GB to BDP/FF combination was tested in vitro in medium and small airways via Bliss, Loewe, and Highest Single Agent models. The peak and trough effect on FEV GB plus BDP/FF elicited significant synergistic bronchorelaxation in medium and small isolated airways (overall maximal effect: +32% vs. additive effect). No significant (P > 0.05) improvement in R5-R19 was detected when salbutamol was administered on top of BDP/FF/GB 100/6/12.5 μg FDC (peak -0.12 ± 0.22 cmH The synergistic interaction detected in vitro when adding GB to BDP/FF combination may lead to ceiling bronchorelaxation of small airways in vivo, an effect that may improve hyperinflation in subjects with small airway disease and, thus, explain the substantial clinical benefits of triple combination therapy administered via extrafine formulation in severe COPD patients. ISRCTN94089001.
Sections du résumé
BACKGROUND
Currently, data on the possible synergy of adding a LAMA to ICS/LABA combination are missing and no studies assessed whether triple therapy may induce ceiling bronchodilator effect. A translational study was performed to investigate the interaction between glycopyrronium bromide (GB) and beclomethasone dipropionate (BDP)/formoterol fumarate (FF) combination in human isolated airways and the effect on FEV
METHODS
The interaction of adding GB to BDP/FF combination was tested in vitro in medium and small airways via Bliss, Loewe, and Highest Single Agent models. The peak and trough effect on FEV
RESULTS
GB plus BDP/FF elicited significant synergistic bronchorelaxation in medium and small isolated airways (overall maximal effect: +32% vs. additive effect). No significant (P > 0.05) improvement in R5-R19 was detected when salbutamol was administered on top of BDP/FF/GB 100/6/12.5 μg FDC (peak -0.12 ± 0.22 cmH
CONCLUSION
The synergistic interaction detected in vitro when adding GB to BDP/FF combination may lead to ceiling bronchorelaxation of small airways in vivo, an effect that may improve hyperinflation in subjects with small airway disease and, thus, explain the substantial clinical benefits of triple combination therapy administered via extrafine formulation in severe COPD patients.
STUDY REGISTRATION
ISRCTN94089001.
Identifiants
pubmed: 34129945
pii: S1094-5539(21)00062-6
doi: 10.1016/j.pupt.2021.102050
pii:
doi:
Substances chimiques
Bronchodilator Agents
0
Drug Combinations
0
Muscarinic Antagonists
0
Beclomethasone
KGZ1SLC28Z
Glycopyrrolate
V92SO9WP2I
Formoterol Fumarate
W34SHF8J2K
Banques de données
ISRCTN
['ISRCTN94089001']
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
102050Informations de copyright
Copyright © 2021 Elsevier Ltd. All rights reserved.