Novel anti-cholinergics in COPD

Prakash, Anoop; Babu, K. Suresh; Morjaria, Jaymin B.

doi:10.1016/j.drudis.2013.07.005

Cited by 14 publications

(14 citation statements)

References 50 publications

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“…Other risk factors are air pollution (both indoor and outdoor), occupation exposure to dust and chemicals, and frequent respiratory tract infections in childhood. There are available drugs for COPD based on anti-cholinergics, beta-2-agonist, phosphodiesterase-4-inhibitors and corticosteroids (Prakash et al, 2013 ). Despite intensive research all over the world, the biochemical, cellular, and molecular mechanisms underlying COPD pathobiology are not yet well understood.…”

Section: General Introduction and Pathologymentioning

confidence: 99%

Role of Proteases in Chronic Obstructive Pulmonary Disease

Pandey¹,

Mishra

2017

Front. Pharmacol.

113

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Chronic obstructive pulmonary disease (COPD) is generally associated with progressive destruction of airways and lung parenchyma. Various factors play an important role in the development and progression of COPD, like imbalance of proteases, environmental and genetic factors and oxidative stress. This review is specifically focused on the role of proteases and their imbalance in COPD. There are three classes (serine, mettalo, and cysteine) of proteases involved in COPD. In serine proteases, neutrophil elastase, cathepsin G, and proteinase-3 are involved in destruction of alveolar tissue. Matrix-mettaloproteinase-9, 12, 13, plays an influential role in severity of COPD. Among cysteine proteases, caspase-3, caspases-8 and caspase-9 play an important role in controlling apoptosis. These proteases activities can be regulated by inhibitors like α-1-antitrypsin, neutrophil elastase inhibitor, and leukocyte protease inhibitor. Studies suggest that neutrophil elastase may be a therapeutic target for COPD, and specific inhibitor against this enzyme has potential role to control the disease. Current study suggests that Dipeptidyl Peptidase IV is a potential marker for COPD. Since the expression of proteases and its inhibitors play an important role in COPD pathogenesis, therefore, it is worth investigating the role of proteases and their regulation. Understanding the biochemical basis of COPD pathogenesis using advanced tools in protease biochemistry and aiming toward translational research from bench-to-bedside will have great impact to deal with this health problem.

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Section: General Introduction and Pathologymentioning

confidence: 99%

Role of Proteases in Chronic Obstructive Pulmonary Disease

Pandey¹,

Mishra

2017

Front. Pharmacol.

113

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“…The airway hyperresponsiveness (AHR) is a state or phenotype of increased responsiveness of the airway to a variety of nonspecific triggers such as the cholinergic receptors agonist, acetylcholine (Ach) 1 ; 2 . Rather than the consequence of chronic obstructive pulmonary diseases (COPD), AHR may serve as a contributing mechanism to the development of this disease 3 .…”

Section: Introductionmentioning

confidence: 99%

“…The aggravated airway smooth muscle contraction, which is an important feature of AHR plays a vital role for COPD. The successful application of anti-cholinergic medications in COPD therapy highlights the significance of increased cholinergic activity in the pathogenesis 2 . Additionally, the mortality from COPD is correlated with the severity of AHR and the trend is more pronounced in smokers than non-smokers 5 .…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial Transplantation Attenuates Airway Hyperresponsiveness by Inhibition of Cholinergic Hyperactivity

Zhu

et al. 2016

Theranostics

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Increased cholinergic activity has been highlighted in the pathogenesis of airway hyperresponsiveness, and alternations of mitochondrial structure and function appear to be involved in many lung diseases including airway hyperresponsiveness. It is crucial to clarify the cause-effect association between mitochondrial dysfunction and cholinergic hyperactivity in the pathogenesis of airway hyperresponsiveness. Male SD rats and cultured airway epithelial cells were exposed to cigarette smoke plus lipopolysaccharide administration; mitochondria isolated from airway epithelium were delivered into epithelial cells in vitro and in vivo. Both the cigarette smoke plus lipopolysaccharide-induced cholinergic hyperactivity in vitro and the airway hyperresponsiveness to acetylcholine in vivo were reversed by the transplantation of exogenous mitochondria. The rescue effects of exogenous mitochondria were imitated by the elimination of excessive reactive oxygen species or blockage of muscarinic M3 receptor, but inhibited by M receptor enhancer. Mitochondrial transplantation effectively attenuates cigarette smoke plus lipopolysaccharide-stimulated airway hyperresponsiveness through the inhibition of ROS-enhanced epithelial cholinergic hyperactivity.

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“…In this perspective, the development of combination treatment such as UMEC/VI could be of great interest to the health community. With this concept in mind, a number of novel monotherapy LAMAs and LABAs, as well as combination bronchodilators, are in development, some in innovative delivery devices (Morjaria, unpublished data, 2014) 47. These would not only add to the armamentarium of therapies for this debilitating condition, but also provide patients much-needed therapeutic alternatives, which have been previously lacking.…”

Section: Clinical Perspectivesmentioning

confidence: 99%

Differential pharmacology and clinical utility of emerging combination treatments in the management of COPD – role of umeclidinium/vilanterol

Malerba¹,

Morjaria²,

Radaeli³

2014

COPD

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Chronic obstructive pulmonary disease (COPD) is a preventable and treatable disease characterized by airflow limitation that is not fully reversible. Bronchodilator therapy is the cornerstone in COPD treatment. Bronchodilation in COPD is mainly achieved via administration of long- and ultralong-acting β2-agonists and with long-acting muscarinic antagonists. New combinations of bronchodilators with dual-acting muscarinic antagonist and β2-agonist properties have been licensed, and others are currently being developed with the aim of achieving once-daily dosing, and therefore may improve the likelihood of treatment compliance. These combination bronchodilators include glycopyrronium bromide/indacaterol maleate, umeclidinium (UMEC) bromide/vilanterol trifenatate (VI), aclidinium bromide/formoterol and tiotropium bromide/olodaterol (Boehringer Ingelheim, Germany). This review will focus mainly on studies and clinical trials involving the novel fixed-dose combination of UMEC/VI at doses of 125/25 μg and 62.5/25 μg in patients with COPD. Data from large clinical trials involving more than 4,500 COPD patients indicate that UMEC/VI is an effective once-daily treatment in COPD with improved pulmonary function. Future studies assessing the impact of this combination on exacerbations, delay in disease progression, and health status in patients with COPD are warranted.

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Novel anti-cholinergics in COPD

Cited by 14 publications

References 50 publications

Role of Proteases in Chronic Obstructive Pulmonary Disease

Role of Proteases in Chronic Obstructive Pulmonary Disease

Mitochondrial Transplantation Attenuates Airway Hyperresponsiveness by Inhibition of Cholinergic Hyperactivity

Differential pharmacology and clinical utility of emerging combination treatments in the management of COPD – role of umeclidinium/vilanterol

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Novel anti-cholinergics in COPD

Cited by 14 publications

References 50 publications

Role of Proteases in Chronic Obstructive Pulmonary Disease

Role of Proteases in Chronic Obstructive Pulmonary Disease

Mitochondrial Transplantation Attenuates Airway Hyperresponsiveness by Inhibition of Cholinergic Hyperactivity

Differential pharmacology and clinical utility of emerging combination treatments in the management of COPD &ndash; role of umeclidinium/vilanterol

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Differential pharmacology and clinical utility of emerging combination treatments in the management of COPD – role of umeclidinium/vilanterol