Treatment with long acting muscarinic antagonists stimulates serum levels of irisin in patients with COPD.

Abstract

Long acting muscarinic antagonists (LAMA) are currently considered the therapeutic mainstay for patients with COPD and have been shown to improve clinical outcomes including symptoms, exercise capacity and airflow limitation. Irisin, is a newly discovered hormone-like myokine generated by skeletal muscle cells in response to exercise and it is suggested to regulate energy expenditure and exercise capacity. The aim of the present study was to investigate if treatment with LAMA alters serum irisin levels in patients with COPD. Irisin was assessed by ELISA in the serum of 506 patients with COPD, GOLD II-IV, with a smoking history >10 PY, who were included in the PROMISE-COPD cohort. The effect of inhaled LAMA on serum irisin levels was evaluated in a proof-of-concept cohort of 40 COPD patients. Univariate linear regression analysis revealed that there was a significant negative association of irisin with age-adjusted Charlson score (p = 0.003) and a positive association of irisin with 6-min walking distance (6MWD) (p = 0.018) and treatment with LAMA (p = 0.004) but not with LABA or ICS. Multivariate analysis revealed that the association of irisin with LAMA treatment remains significant after adjustment for age-adjusted score and 6MWD. In the proof-of-concept cohort a single inhalation of LAMA stimulated serum irisin levels after 4 h. These findings imply that treatment of COPD patients with LAMA increase circulating irisin, thus explaining some of the beneficial extra-pulmonary effects of these drugs when used in the treatment of COPD.

• Authors: Jyotshna Mandal, Michael Roth, Eleni Papakonstantinou, Qingzhu Sun, Luigi Costa, Lucas Boeck, Andreas Scherr, Janko Rakic, Renaud Louis, Branislava Milenkovic, Wim Boersma, Konstantinos Kostikas, Francesco Blasi, Joachim Aerts, Gernot Rohde, Alicia Lacoma, Antoni Torres, Tobias Welte, Michael Tamm, Daiana Stolz
• Journal: Pulmonary pharmacology & therapeutics (Pulm Pharmacol Ther) Vol. 48 Pg. 111-116 (02 2018) ISSN: 1522-9629 [Electronic] England
• PMID: 29066215 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017. Published by Elsevier Ltd.

Chemical References

• Delayed-Action Preparations
• FNDC5 protein, human
• Fibronectins
• Muscarinic Antagonists

Topics

• Age Factors
• Aged
• Cohort Studies
• Delayed-Action Preparations
• Enzyme-Linked Immunosorbent Assay
• Exercise Test (methods)
• Female
• Fibronectins (blood)
• Follow-Up Studies
• Humans
• Linear Models
• Male
• Middle Aged
• Multivariate Analysis
• Muscarinic Antagonists (administration & dosage, pharmacology)
• Proof of Concept Study
• Pulmonary Disease, Chronic Obstructive (drug therapy, physiopathology)