Article

Emerging Therapeutic Options for the Management of COPD

Department of Pharmacy Practice, School of Pharmacy, Northeastern University, Boston, MA, USA.
Clinical Medicine Insights: Circulatory, Respiratory and Pulmonary Medicine 04/2013; 7(1):7-15. DOI: 10.4137/CCRPM.S8140
Source: PubMed

ABSTRACT

Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death worldwide and is projected to be the third by 2020. COPD is characterized by chronic airflow limitation caused by airway inflammation and parenchymal destruction that is usually progressive. Inhaled bronchodilators continue to be the mainstay of the current management of COPD. Safety and efficacy data of the recently approved medications including aclidinium, glycopyrronium, roflumilast, and indacaterol are reviewed here.

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    • "(LAMA). Clinical data indicates that the combination of both drug classes achieves a better effect on symptom control [6] [7]. In airway smooth muscle cells (ASMC) the muscarinic receptor 3 (M3) is the main mediator of bronchoconstriction, and therefore its blockade relaxes airway muscles and eases breathing [8]. "
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    ABSTRACT: Combined muscarinic receptor antagonists and long acting β2-agonists improve symptom control in chronic obstructive pulmonary disease (COPD) significantly. In clinical studies aclidinium bromide achieved better beneficial effects than other bronchodilators; however, the underlying molecular mechanisms are unknown. This study assessed the effect of aclidinium bromide combined with formoterol on COPD lung (n=20) and non-COPD lung (n=10) derived epithelial cells stimulated with TGF-β1+carbachol on: (i) the generation of mesenchymal cells in relation to epithelial cells, (II) extracellular matrix (ECM) deposition, and (iii) the interaction of ECM on the generation of epithelial and mesenchymal cells. TGF-β1+carbachol enhanced the generation of mesenchymal cells, which was significantly reduced by aclidinium bromide or formoterol. The effect of combined drugs was additive. Inhibition of p38 MAP kinase and Smad by specific inhibitors or aclidinium bromide reduced the generation of mesenchymal cells. In mesenchymal cells, TGF-β1+carbachol induced the deposition of collagen-I and fibronectin which was prevented by both drugs dose-dependently. Formoterol alone reduced collagen-I deposition via cAMP, this however, was overruled by TGF-β1+carbachol and rescued by aclidinium bromide. Inhibition of fibronectin was cAMP independent, but involved p38 MAP kinase and Smad. Seeding epithelial cells on ECM collagen-I and fibronectin induced mesenchymal cell generation, which was reduced by aclidinium bromide and formoterol. Our results suggest that the beneficial effect of aclidinium bromide and formoterol involves cAMP affecting both, the accumulation of mesenchymal cells and ECM remodeling, which may explain the beneficial effect of the drugs on lung function in COPD.
    Full-text · Article · Nov 2015 · Pharmacological Research
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    • "However, use of the muscarinic receptor antagonists as therapeutics in COPD is not novel, but the previously available drugs had unwanted side effects, especially on the cardiovascular system.3,4 Thus, novel long-acting muscarinic receptor antagonists have been developed in recent years, and have been proven to effectively reduce symptoms in COPD patients with less severe side effects in the cardiovascular system.5,6 Here we provide a summary of the most recent clinical safety studies on the action of aclidinium bromide. "
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    ABSTRACT: Chronic obstructive pulmonary disease (COPD) is increasing worldwide and is predicted to become the third most frequent cause of death by 2030. Muscarinic receptor antagonists, alone or in combination with long-acting β2-agonists, are frequently used for COPD therapy. Aclidinium bromide is a novel muscarinic receptor antagonist, and clinical studies indicate that its metabolism is more rapid than that of other muscarinic receptor inhibitors, so systemic side effects are expected to occur less frequently. Aclidinium bromide is well tolerated, and when compared with other muscarinic receptor antagonists, the drug achieves better control of lung function, especially night-time symptoms in COPD patients. This review summarizes the safety profile and side effects reported by recent clinical studies using aclidinium bromide alone.
    Full-text · Article · Jun 2014 · Therapeutics and Clinical Risk Management