Evidence map›Paper›PMID 27296533›Full record

ArticleRespiratory research2016

Pharmacological characterisation of the interaction between glycopyrronium bromide and indacaterol fumarate in human isolated bronchi, small airways and bronchial epithelial cells.

Mario Cazzola, Luigino Calzetta, Ermanno Puxeddu, Josuel Ora, Francesco Facciolo, Paola Rogliani, Maria Gabriella Matera

Open access · goldAbstract read
In one paragraph

Article in Respiratory research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed, 3 pooled it
8.4field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

30 citing papers in PubMed, 3 syntheses or guidelines pooled it, 98 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. The Impact of Muscarinic Receptor Antagonists on Airway Inflammation: A Systematic Review.International journal of chronic obstructive pulmonary disease
    Pooled it
  4. Trial
  5. Article
  6. Review
  7. Article
  8. Review
  9. Review
  10. Review
  11. Article
  12. Drug interaction and chronic obstructive respiratory disorders.Current research in pharmacology and drug discovery · 2021
    Review
  13. Article
  14. Cholinergic receptors on intestine cells of Ascaris suum and activation of nAChRs by levamisole.International journal for parasitology. Drugs and drug resistance · 2020
    Article
  15. Day and Night Control of COPD and Role of Pharmacotherapy: A Review.International journal of chronic obstructive pulmonary disease · 2020
    Review
  16. Review
  17. Article
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  20. Involvement of Allosteric Effect and KInternational journal of molecular sciences · 2018
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Mario CazzolaDepartment of Systems Medicine, Chair of Respiratory Medicine, University of Rome Tor Vergata, Rome, Italy.
Luigino CalzettaDepartment of Systems Medicine, Respiratory Pharmacology Research Unit, University of Rome Tor Vergata, Via Montpellier 1, 00133, Rome, Italy. luigino.calzetta@uniroma2.it.
Ermanno PuxedduDepartment of Systems Medicine, Chair of Respiratory Medicine, University of Rome Tor Vergata, Rome, Italy.
Josuel OraDivision of Respiratory Medicine, University Hospital Tor Vergata, Rome, Italy.
Francesco FaccioloRegina Elena National Cancer Institute, Thoracic Surgery Unit, Rome, Italy.
Paola RoglianiDepartment of Systems Medicine, Chair of Respiratory Medicine, University of Rome Tor Vergata, Rome, Italy.
Maria Gabriella MateraDepartment of Experimental Medicine, Unit of Pharmacology, Second University of Naples, Naples, Italy.
University of Rome Tor Vergata · ITUniversity of Campania "Luigi Vanvitelli" · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundNowadays, there is a considerable gap in knowledge concerning the mechanism(s) by which long-acting β2-agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) interact to induce bronchodilation. This study aimed to characterise the pharmacological interaction between glycopyrronium bromide and indacaterol fumarate and to identify the mechanism(s) leading to the bronchorelaxant effect of this interaction.

methodsThe effects of glycopyrronium plus indacaterol on the contractile tone of medium and small human isolated bronchi were evaluated, and acetylcholine and cAMP concentrations were quantified. The interaction was assessed by Bliss Independence approach.

resultsGlycopyrronium plus indacaterol synergistically inhibited the bronchial tone (medium bronchi, +32.51 % ± 7.86 %; small bronchi, +28.46 % ± 5.35 %; P < 0.05 vs. additive effect). The maximal effect was reached 140 min post-administration. A significant (P < 0.05) synergistic effect was observed during 9 h post-administration on the cholinergic tone, but not on the histaminergic contractility. Co-administration of glycopyrronium and indacaterol reduced the release of acetylcholine from the epithelium but not from bronchi, and enhanced cAMP levels in bronchi and epithelial cells (P < 0.05 vs. control), an effect that was inhibited by the selective KCa(++) channel blocker iberiotoxin. The role of cAMP-dependent pathway was confirmed by the synergistic effect elicited by the adenylate cyclase activator forskolin on glycopyrronium (P < 0.05 vs. additive effect), but not on indacaterol (P > 0.05 vs. additive effect), with regard of the bronchial relaxant response and cAMP increase.

conclusionsGlycopyrronium/indacaterol co-administration leads to a synergistic improvement of bronchodilation by increasing cAMP concentrations in both airway smooth muscle and bronchial epithelium, and by decreasing acetylcholine release from the epithelium.

Indexed as

AcetylcholineAdenylyl CyclasesAdrenergic beta-2 Receptor AgonistsAgedBronchiBronchoconstrictionBronchodilator AgentsCells, CulturedCyclic AMPDose-Response Relationship, DrugDrug SynergismEpithelial CellsFemaleGlycopyrrolateHumansIndansAcetylcholineAdenylyl CyclasesAdrenergic beta-2 Receptor AgonistsBronchodilator AgentsCyclic AMPGlycopyrrolateindacaterolIndansMuscarinic AntagonistsQuinolonesGlycopyrronium bromideHuman bronchiIndacaterol fumarateSynergistic interaction

Identifiers

PMID27296533
PMCPMC4906998
OpenAlexW2434767947

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.