Beclomethasone dipropionate, formoterol fumarate and glycopyrronium bromide: Synergy of triple combination therapy on human airway smooth muscle <i>ex vivo</i>

Rogliani, Paola; Matera, Maria Gabriella; Facciolo, Francesco; Page, Clive; Cazzola, Mario; Calzetta, Luigino

doi:10.1111/bph.14909

Cited by 48 publications

(48 citation statements)

References 37 publications

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“…Further, in an ex-vivo experimental setting the triple ICS/LABA/LAMA combination of beclometasone dipropionate, formoterol fumarate and glycopyrronium (BDP/FF/G) synergistically relaxed both medium and small airways; in particular, the 100:6:10 concentration ratio resulted in a very strong synergistic bronchorelaxant effect. Such a synergistic interaction was related to the activation of intracellular glucocorticoid receptors and the Gsα subunit G protein of β 2 -adrenoceptors, leading to modulation of the protein kinase A pathway dependent on cyclic adenosine monophosphate [31].…”

Section: Potential Mechanisms Of Action Of Lamas In Asthmamentioning

confidence: 99%

Inhaled long-acting muscarinic antagonists in asthma – A narrative review

Papi

Fabbri

Kerstjens

et al. 2021

European Journal of Internal Medicine

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Long-acting muscarinic antagonists (LAMAs) have a recognised role in the management of chronic obstructive pulmonary disease. In asthma, muscarinic antagonists (both short-and long-acting) were historically considered less effective than β 2 -agonists; only relatively recently have studies been conducted to evaluate the efficacy of LAMAs, as add-on to either inhaled corticosteroid (ICS) monotherapy or ICS/long-acting β 2 -agonist (LABA) combinations. These studies led to the approval of the first LAMA, tiotropium, as an add-on therapy in patients with poorly controlled asthma. Subsequently, a number of single-inhaler ICS/LABA/LAMA triple therapies have been approved or are in clinical development for the management of asthma. There is now substantial evidence of the efficacy and safety of LAMAs in asthma that is uncontrolled despite treatment with an ICS/LABA combination. This regimen is recommended by GINA as an optimisation step for patients with severe asthma before any biologic or systemic corticosteroid treatment is initiated.This narrative review summarises the potential mechanisms of action of LAMAs in asthma, together with the initial clinical evidence supporting this use. We also discuss the studies that led to the approval of tiotropium for asthma and the data evaluating the efficacy and safety of the various triple therapies, before considering other potential uses for triple therapy.

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Section: Potential Mechanisms Of Action Of Lamas In Asthmamentioning

confidence: 99%

Inhaled long-acting muscarinic antagonists in asthma – A narrative review

Papi

Fabbri

Kerstjens

et al. 2021

European Journal of Internal Medicine

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“… 65 Recent evidence further supports the beneficial synergistic interaction at the level of human medium bronchi and small airways not only when TIO is combined with the long-acting β 2 adrenoceptor agonist (LABA) olodaterol (OLO) as LABA/LAMA fixed-dose combination (FDC), 67 but also when a LAMA is combined with an inhaled corticosteroid (ICS), 68 and when ICSs, LABAs and LAMAs are combined in triple FDCs. 69 Overall, the currently available data on the anti-inflammatory effect of LAMAs support the evidence coming from studies performed ex vivo concerning the release of non-neurogenic Ach in the airways. 9 …”

Section: Discussionmentioning

confidence: 53%

The Impact of Muscarinic Receptor Antagonists on Airway Inflammation: A Systematic Review

Calzetta¹,

Coppola²,

Ritondo³

et al. 2021

COPD

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Long-acting muscarinic receptor antagonists (LAMAs) are the cornerstone for the treatment of chronic obstructive pulmonary disease (COPD); furthermore, tiotropium is approved as add-on therapy in severe asthmatic patients. Accumulating evidence suggests that LAMAs may modulate airway contractility and airway hyperresponsiveness not only by blocking muscarinic acetylcholine receptors (mAchRs) expressed on airway smooth muscle but also via anti-inflammatory mechanisms by blocking mAchRs expressed on inflammatory cells, submucosal glands, and epithelial cells. The aim of this systematic review, performed according to the PRISMA-P guidelines, was to provide a synthesis of the literature on the anti-inflammatory impact of muscarinic receptor antagonists in the airways. Most of the current evidence originates from studies on tiotropium, that demonstrated a reduction in synthesis and release of cytokines and chemokines, as well as the number of total and differential inflammatory cells, induced by different pro-inflammatory stimuli. Conversely, few data are currently available for aclidinium and glycopyrronium, whereas no studies on the potential anti-inflammatory effect of umeclidinium have been reported. Overall, a large body of evidence supports the beneficial impact of tiotropium against airway inflammation. Further well-designed randomized controlled trials are needed to better elucidate the anti-inflammatory mechanisms leading to the protective effect of LAMAs against exacerbations via identifying suitable biomarkers.

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“…Недавно было опубликовано интересное исследование, целью которого было изучение ex vivo возможного синергизма действия беклометазона дипропионата, формотерола фумарата и гликопиррония бромида, которые входят в состав экстрамелкодисперсного комбинированного препарата, предназначенного для лечения ХОБЛ и бронхиальной астмы [22]. Авторы использовали бронхи человека, которые выделяли из образцов ткани легкого, полученной во время лобэктомии по поводу рака у больных с ХОБЛ.…”

Section: фармакологическое обоснование тройной комбинированной терапииunclassified

Clinical and pharmacological justification of triple therapy with two long-acting bronchodilators and inhaled corticosteroid in patients with COPD

Titova¹,

Моисеев²

2021

CPT

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Long-acting β 2 adrenoceptor agonists (LABA) and/or longacting muscarinic antagonists (LAMA) should be used as monotherapy or in combination for the initial treatment in patients with chronic obstructive pulmonary disease (COPD). Triple inhaled therapy with LABA, LAMA, and inhaled corticosteroid (ICS) has been recommended for COPD patients who still have clinically significant symptoms following the use of a dual inhaler with LABA plus LAMA, particularly for those who present with frequent exacerbations, blood eosinophilia and/or concomitant bronchial asthma. Experimental studies on human isolated airways suggested that LABA, LAMA, and ICS synergistically relax the medium and small bronchi probably as a result of enhanced elevation of the cyclic adenosine monophosphate (cAMP) that mediates relaxation of airway smooth muscle cells. Synergy of LABA and LAMA was also shown in a few clinical studies, whereas in the randomized controlled trials triple therapy with two long-acting bronchodilatators and ICS was more effective than various dual combinations (LABA/LAMA or ICS/LABA) in patients with severe COPD. These findings justify triple therapy in patients with severe COPD who have frequent exacerbations and do not respond to dual therapy. Recently, a single inhalers containing ICS, LABA, and LAMA have been developed as a more practical alternative, which may improve therapy compliance.

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Beclomethasone dipropionate, formoterol fumarate and glycopyrronium bromide: Synergy of triple combination therapy on human airway smooth muscle ex vivo

Cited by 48 publications

References 37 publications

Inhaled long-acting muscarinic antagonists in asthma – A narrative review

Inhaled long-acting muscarinic antagonists in asthma – A narrative review

The Impact of Muscarinic Receptor Antagonists on Airway Inflammation: A Systematic Review

Clinical and pharmacological justification of triple therapy with two long-acting bronchodilators and inhaled corticosteroid in patients with COPD

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