Loss of bronchoprotection with ICS plus LABA treatment, β-receptor dynamics, and the effect of alendronate.

Administration, Inhalation Adrenal Cortex Hormones / administration & dosage Adult Alendronate / administration & dosage Asthma / drug therapy Double-Blind Method Female Fluticasone / administration & dosage Humans Male Proof of Concept Study Receptors, Adrenergic, beta-2 / metabolism Salmeterol Xinafoate / administration & dosage
bisphosphonate bronchoprotection controller therapy downregulation loss of bronchoprotection salmeterol β(2)-Adrenergic receptor β(2)-agonists

Journal

The Journal of allergy and clinical immunology
ISSN: 1097-6825
Titre abrégé: J Allergy Clin Immunol
Pays: United States
ID NLM: 1275002

Informations de publication

Date de publication:
08 2019
Historique:
received: 02 05 2018
revised: 14 12 2018
accepted: 23 01 2019
pubmed: 16 3 2019
medline: 20 5 2020
entrez: 16 3 2019
Statut: ppublish

Résumé

Loss of bronchoprotection (LOBP) with a regularly used long-acting β We sought to determine whether alendronate can reduce LABA-associated LOBP in inhaled corticosteroid (ICS)-treated patients. We conducted a randomized, double-blind, placebo-controlled, parallel-design, proof-of-concept trial. Seventy-eight participants with persistent asthma receiving 250 μg of fluticasone twice daily for 2 weeks were randomized to receive alendronate or placebo while initiating salmeterol for 8 weeks. Salmeterol-protected methacholine challenges (SPMChs) and PBMC B2AR numbers (radioligand binding assay) and signaling (cyclic AMP ELISA) were assessed before randomization and after 8 weeks of ICS plus LABA treatment. LOBP was defined as a more than 1 doubling dose reduction in SPMCh PC The mean doubling dose reduction in SPMCh PC This study did not find evidence that alendronate reduces LABA-associated LOBP, which relates to the occurrence of LOBP in only one third of participants. LOBP appears to be less common than presumed in concomitant ICS plus LABA-treated asthmatic patients. B2AR downregulation measured in PBMCs does not appear to reflect LOBP.

Sections du résumé

BACKGROUND
Loss of bronchoprotection (LOBP) with a regularly used long-acting β
OBJECTIVE
We sought to determine whether alendronate can reduce LABA-associated LOBP in inhaled corticosteroid (ICS)-treated patients.
METHODS
We conducted a randomized, double-blind, placebo-controlled, parallel-design, proof-of-concept trial. Seventy-eight participants with persistent asthma receiving 250 μg of fluticasone twice daily for 2 weeks were randomized to receive alendronate or placebo while initiating salmeterol for 8 weeks. Salmeterol-protected methacholine challenges (SPMChs) and PBMC B2AR numbers (radioligand binding assay) and signaling (cyclic AMP ELISA) were assessed before randomization and after 8 weeks of ICS plus LABA treatment. LOBP was defined as a more than 1 doubling dose reduction in SPMCh PC
RESULTS
The mean doubling dose reduction in SPMCh PC
CONCLUSION
This study did not find evidence that alendronate reduces LABA-associated LOBP, which relates to the occurrence of LOBP in only one third of participants. LOBP appears to be less common than presumed in concomitant ICS plus LABA-treated asthmatic patients. B2AR downregulation measured in PBMCs does not appear to reflect LOBP.

Identifiants

DOI: 10.1016/j.jaci.2019.01.049 PMID: 30872116 PMC: PMC6950766
pubmed: 30872116
pii: S0091-6749(19)30347-1
doi: 10.1016/j.jaci.2019.01.049
pmc: PMC6950766
mid: NIHMS1064376
pii:
doi:

Substances chimiques

Adrenal Cortex Hormones 0
Receptors, Adrenergic, beta-2 0
Salmeterol Xinafoate 6EW8Q962A5
Fluticasone CUT2W21N7U
Alendronate X1J18R4W8P

Banques de données

ClinicalTrials.gov
['NCT02230332']

Types de publication

Journal Article Randomized Controlled Trial Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

416-425.e7

Subventions

Organisme : NCATS NIH HHS
ID : UL1 TR000430
Pays : United States
Organisme : NHLBI NIH HHS
ID : U10 HL098075
Pays : United States
Organisme : NHLBI NIH HHS
ID : U10 HL098102
Pays : United States
Organisme : NHLBI NIH HHS
ID : U10 HL098115
Pays : United States
Organisme : NHLBI NIH HHS
ID : U10 HL098177
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000439
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002003
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000448
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001082
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002345
Pays : United States
Organisme : NHLBI NIH HHS
ID : U10 HL098098
Pays : United States
Organisme : NHLBI NIH HHS
ID : U10 HL064313
Pays : United States
Organisme : NHLBI NIH HHS
ID : U10 HL098107
Pays : United States
Organisme : NIEHS NIH HHS
ID : P42 ES030990
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000150
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002548
Pays : United States
Organisme : NHLBI NIH HHS
ID : U10 HL098096
Pays : United States
Organisme : NIAID NIH HHS
ID : K23 AI125785
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007118
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000050
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000454
Pays : United States
Organisme : NHLBI NIH HHS
ID : U10 HL098103
Pays : United States
Organisme : NHLBI NIH HHS
ID : U10 HL098090
Pays : United States
Organisme : NHLBI NIH HHS
ID : U10 HL098112
Pays : United States

Commentaires et corrections

Type : CommentIn
Type : CommentIn

Informations de copyright

Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

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Auteurs

Juan Carlos Cardet (JC)

Department of Medicine, Brigham and Women's Hospital, Boston, Mass.

Xiaofeng Jiang (X)

Departments of Environmental Health, Genetics & Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, Mass.

Quan Lu (Q)

Departments of Environmental Health, Genetics & Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, Mass.

Norma Gerard (N)

Department of Pediatrics, Boston Children's Hospital, Boston, Mass.

Kristen McIntire (K)

Department of Medicine, Brigham and Women's Hospital, Boston, Mass.

Homer A Boushey (HA)

Department of Medicine, University of California San Francisco, San Francisco, Calif.

Mario Castro (M)

Department of Medicine, Washington University, St Louis, Mo.

Vernon M Chinchilli (VM)

Department of Public Health Sciences, Penn State College of Medicine, Hershey, Pa.

Christopher D Codispoti (CD)

Department of Medicine, Rush University Medical Center and Department of Pediatrics, Stroger Hospital of Cook County, Chicago, Ill.

Anne-Marie Dyer (AM)

Department of Public Health Sciences, Penn State College of Medicine, Hershey, Pa.

Fernando Holguin (F)

Department of Medicine, Pittsburgh University, Pittsburgh, Pa.

Monica Kraft (M)

Department of Medicine, University of Arizona, Tucson, Ariz.

Stephen Lazarus (S)

Department of Medicine, University of California San Francisco, San Francisco, Calif.

Robert F Lemanske (RF)

Departments of Medicine and Pharmacy Practice, University of Wisconsin, Madison, Wis.

Njira Lugogo (N)

Department of Medicine, Duke University, Durham, NC.

Dave Mauger (D)

Department of Public Health Sciences, Penn State College of Medicine, Hershey, Pa.

Wendy C Moore (WC)

Department of Internal Medicine, Wake Forest University, Winston-Salem, NC.

James Moy (J)

Department of Medicine, Rush University Medical Center and Department of Pediatrics, Stroger Hospital of Cook County, Chicago, Ill.

Victor E Ortega (VE)

Department of Internal Medicine, Wake Forest University, Winston-Salem, NC.

Stephen P Peters (SP)

Department of Internal Medicine, Wake Forest University, Winston-Salem, NC.

Lewis J Smith (LJ)

Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill.

Julian Solway (J)

Department of Medicine, University of Chicago, Chicago, Ill.

Christine A Sorkness (CA)

Departments of Medicine and Pharmacy Practice, University of Wisconsin, Madison, Wis.

Kaharu Sumino (K)

Department of Medicine, Washington University, St Louis, Mo.

Michael E Wechsler (ME)

Department of Medicine, National Jewish University, Denver, Colo.

Sally Wenzel (S)

Department of Medicine, Pittsburgh University, Pittsburgh, Pa.

Elliot Israel (E)

Department of Medicine, Brigham and Women's Hospital, Boston, Mass. Electronic address: eisrael@bwh.harvard.edu.

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Classifications MeSH

questionsmedicales.fr › Thérapeutique › Traitement médicamenteux › Voies d'administration de substances chimiques et des médicaments › Administration par inhalation › Loss of bronchoprotection with ICS plus LABA...
questionsmedicales.fr › Hormones corticosurrénaliennes › Loss of bronchoprotection with ICS plus LABA...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Loss of bronchoprotection with ICS plus LABA...
questionsmedicales.fr › Composés chimiques organiques › Composés organiques du phosphore › Phosphonates › Diphosphonates › Alendronate › Loss of bronchoprotection with ICS plus LABA...
questionsmedicales.fr › Maladies du système immunitaire › Hypersensibilité › Hypersensibilité immédiate › Hypersensibilité respiratoire › Asthme › Loss of bronchoprotection with ICS plus LABA...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Méthodologie en recherche épidémiologique › Méthode en double aveugle › Loss of bronchoprotection with ICS plus LABA...
questionsmedicales.fr › Composés polycycliques › Composés à cycles fusionnés › Stéroïdes › Androstanes › Androstènes › Androstadiènes › Fluticasone › Loss of bronchoprotection with ICS plus LABA...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Loss of bronchoprotection with ICS plus LABA...
questionsmedicales.fr › Disciplines des sciences naturelles › Science › Recherche › Étude de validation de principe › Loss of bronchoprotection with ICS plus LABA...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs aux neuromédiateurs › Récepteurs catécholaminergiques › Récepteurs adrénergiques › Récepteurs bêta-adrénergiques › Récepteurs bêta-2 adrénergiques › Loss of bronchoprotection with ICS plus LABA...
questionsmedicales.fr › Composés chimiques organiques › Amines › Éthylamines › Phénéthylamines › Salbutamol › Xinafoate de salmétérol › Loss of bronchoprotection with ICS plus LABA...