Indacaterol in chronic obstructive pulmonary disease: an update for clinicians

Yorgancıoğlu, Arzu

doi:10.1177/2040622311426204

Cited by 7 publications

(4 citation statements)

References 25 publications

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“…Indacaterol is a once-daily, inhaled, ultra-long-acting ADRB2 agonist recently approved by FDA for the management of patients with COPD ( Donohue et al, 2010 ). Furthermore, growing body of evidence indicates that indacaterol is statistically superior to twice-daily LABAs (salmeterol and formoterol) and once-daily anticholinergic tiotropium in COPD patients with dyspnea ( Yorgancioglu, 2012 ). While indacaterol is an important therapeutic agent for symptom relief in COPD patients, the molecular mechanism of its pharmacological action remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Indacaterol Inhibits Tumor Cell Invasiveness and MMP-9 Expression by Suppressing IKK/NF-κB Activation

Lee¹,

Ahn²,

Sung³

et al. 2014

Molecules and Cells

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The β2 adrenergic receptor (ADRB2) is a G protein-coupled transmembrane receptor expressed in the human respiratory tract and widely recognized as a pharmacological target for treatments of asthma and chronic obstructive pulmonary disorder (COPD). Although a number of ADRB2 agonists have been developed for use in asthma therapy, indacaterol is the only ultra-long-acting inhaled β2-agonist (LABA) approved by the FDA for relieving the symptoms in COPD patients.The precise molecular mechanism underlying the pharmacological effect of indacaterol, however, remains unclear. Here, we show that β-arrestin-2 mediates the internalization of ADRB2 following indacaterol treatment. Moreover, we demonstrate that indacaterol significantly inhibits tumor necrosis factor-α (TNF-α)-induced NF-κB activity by reducing levels of both phosphorylated-IKK and -IκBα, thereby decreasing NF-κB nuclear translocation and the expression of MMP-9, an NF-κB target gene. Subsequently, we show that indacaterol significantly inhibits TNF-α/NF-κB-induced cell invasiveness and migration in a human cancer cell line. In conclusion, we propose that indacaterol may inhibit NF-κB activity in a β-arrestin2-dependent manner, preventing further lung damage and improving lung function in COPD patients.

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Section: Discussionmentioning

confidence: 99%

Indacaterol Inhibits Tumor Cell Invasiveness and MMP-9 Expression by Suppressing IKK/NF-κB Activation

Lee¹,

Ahn²,

Sung³

et al. 2014

Molecules and Cells

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“…To further con rm the speci c β2AR effect and to compare the natural agonist to a medically used agonist, we used the β2 sympathomimetic indacaterol. Indacaterol is a LABA and it is proposed to dissociate slower from the membrane, to stay in close proximity to the β2AR and to continuously stimulate the receptor 56,57 . Like epinephrine, treatment with indacaterol signi cantly decreased LFA-1 activity, which was also reversible by propranolol (Fig.…”

Section: β2 Agonists Block Lfa-1 Activity and Cytotoxicity Of Nk Cellsmentioning

confidence: 99%

Chronic stimulation desensitizes β2 adrenergic receptor responses in Natural Killer cells

Watzl,

Jürgens,

Claus

et al. 2024

Preprint

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Psychosocial stress affects the function of the immune system via activation of the sympathetic nervous system and the release of the neurotransmitter epinephrine. Acute and chronic stress can have opposing effects on the immune system and chronic stress is correlated with higher incidences of infections and cancer. Here, we study the effect of epinephrine on the function of human Natural Killer (NK) cells as important innate lymphocytes for immune reactions against infections and cancer. Epinephrine-mediated stimulation of the β2 adrenergic receptor (β2AR) on NK cells inhibited early signaling events and blocked the function of the integrin LFA-1. This led to a reduced adhesion of NK cells to ICAM-1, explaining how NK cells are mobilized into the peripheral blood upon acute stress. Additionally, epinephrine stimulation transiently reduced NK cell degranulation, serial killing, cytokine production, and affected metabolic changes upon NK cell activation via the cAMP-PKA pathway. Repeated exposure to β2AR agonists resulted in the desensitization of the β2AR via a PKA feedback loop-initiated G-protein switch. Therefore, acute epinephrine stimulation of chronically β2AR stimulated NK cells no longer resulted in inhibited signaling and reduced LFA-1 activity, recapitulating the opposing effects of acute versus chronic stress. Sustained stimulation by long-acting β2 agonists (LABA) not only inhibited NK cell functions but also resulted in desensitization of the β2AR. However, peripheral NK cells from LABA-treated asthma patients still reacted unchanged to epinephrine stimulation, demonstrating that local LABA administration does not result in detectable systemic effects on NK cells.

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“…Several randomized studies performed in patients with moderate-to-severe COPD have shown that indacaterol improved the symptoms, lung function, and quality of life; reduced the use of rescue medications; and was well tolerated with an acceptable safety profile ( 9 - 13 ). The efficacy and safety of indacaterol have also been evaluated in Asian populations, including those in Japan ( 14 , 15 ).…”

Section: Introductionmentioning

confidence: 99%

Real-world Safety and Efficacy of Indacaterol Maleate in Patients with Chronic Obstructive Pulmonary Disease: Evidence from the Long-term Post-marketing Surveillance in Japan

et al. 2021

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Objective Evidence concerning the safety and efficacy of indacaterol maleate in a real-life setting is limited. The objective of this post-marketing surveillance was to evaluate the real-life safety and efficacy of indacaterol maleate in Japanese patients with chronic obstructive pulmonary disease (COPD). Methods This was a 52-week post-marketing surveillance conducted between April 2012 and December 2018. The safety endpoints included the incidence of adverse events (AEs), serious adverse events (SAEs), and adverse drug reactions (ADRs). The efficacy endpoints included the physician-reported global evaluation of treatment effectiveness (GETE), change from baseline in the COPD assessment test (CAT) results, forced vital capacity (FVC), forced expiratory volume in 1 second (FEV 1 ), and %FEV 1 following 4, 12, 26, and 52 weeks of indacaterol administration. Results Of the 1,846 enrolled patients, 1,726 were included in the safety and efficacy analyses. The mean age of the patients was 72.5 years old. Cough, pneumonia and COPD worsening were the most common AEs reported, while pneumonia (1.04%) was the most common SAE, and cough (1.68%) was the most common ADR. GETE showed that 69.70% of patients achieved an excellent/good/moderate response following indacaterol treatment. The CAT score decreased, and lung function parameters (FVC, FEV 1 and %FEV 1 ) improved across all the COPD stages following treatment with indacaterol. Conclusion Indacaterol showed a favorable safety and tolerability profile in Japanese patients with COPD without new safety signals observed in real-life settings. These findings demonstrated that indacaterol is an effective maintenance treatment in real-life practice for Japanese patients with COPD.

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Indacaterol in chronic obstructive pulmonary disease: an update for clinicians

Cited by 7 publications

References 25 publications

Indacaterol Inhibits Tumor Cell Invasiveness and MMP-9 Expression by Suppressing IKK/NF-κB Activation

Indacaterol Inhibits Tumor Cell Invasiveness and MMP-9 Expression by Suppressing IKK/NF-κB Activation

Chronic stimulation desensitizes β2 adrenergic receptor responses in Natural Killer cells

Real-world Safety and Efficacy of Indacaterol Maleate in Patients with Chronic Obstructive Pulmonary Disease: Evidence from the Long-term Post-marketing Surveillance in Japan

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