Vilanterol trifenatate for the treatment of COPD

Introduction: Currently the treatment of chronic obstructive pulmonary disease (COPD) has limited effectiveness and there is a need to develop new drugs. International guidelines recommend the use of long-acting bronchodilators (β2 agonists and anti-cholinergics/muscarinics), inhaled steroids and associations between these drugs in the maintenance treatment of moderate-to-severe COPD. Area covered: Vilanterol trifenate is a new once-daily highly selective β2-agonist available in USA and Europe in association with umeclidinium bromide (a long-acting anti-muscarnic agent) and fluticasone furoate (an inhaled corticosteroid) for the once-daily maintenance treatment of COPD. Vilanterol combined in fixed-dose treatments has been tested in numerous clinical trials involving thousands of patients. Expert commentary: These new once-daily formulations have the potential to improve compliance to long-term inhaled therapy. This paper will review the clinical and experimental data regarding vilanterol use in the regular treatment of COPD as well as provide a critical discussion of possible future treatment settings

Evaluation of the anti-inflammatory effects of synthesised tanshinone I and isotanshinone I analogues in zebrafish

During inflammation, dysregulated neutrophil behaviour can play a major role in a range of chronic inflammatory diseases, for many of which current treatments are generally ineffective. Recently, specific naturally occurring tanshinones have shown promising anti-inflammatory effects by targeting neutrophils in vivo, yet such tanshinones, and moreover, their isomeric isotanshinone counterparts, are still a largely underexplored class of compounds, both in terms of synthesis and biological effects. To explore the anti-inflammatory effects of isotanshinones, and the tanshinones more generally, a series of substituted tanshinone and isotanshinone analogues was synthesised, alongside other structurally similar molecules. Evaluation of these using a transgenic zebrafish model of neutrophilic inflammation revealed differential anti-inflammatory profiles in vivo, with a number of compounds exhibiting promising effects. Several compounds reduce initial neutrophil recruitment and/or promote resolution of neutrophilic inflammation, of which two also result in increased apoptosis of human neutrophils. In particular, the methoxy-substituted tanshinone 39 specifically accelerates resolution of inflammation without affecting the recruitment of neutrophils to inflammatory sites, making this a particularly attractive candidate for potential pro-resolution therapeutics, as well as a possible lead for future development of functionalised tanshinones as molecular tools and/or chemical probes. The structurally related β-lapachones promote neutrophil recruitment but do not affect resolution. We also observed notable differences in toxicity profiles between compound classes. Overall, we provide new insights into the in vivo anti-inflammatory activities of several novel tanshinones, isotanshinones, and structurally related compounds

Profile of inhaled glycopyrronium bromide as monotherapy and in fixed-dose combination with indacaterol maleate for the treatment of COPD

Anoop Prakash,1 K Suresh Babu,2 Jaymin B Morjaria1,31Department of Respiratory Medicine, Castle Hill Hospital, Cottingham, 2Department of Respiratory Medicine, Queen Alexandra Hospital, Cosham, Portsmouth, 3Department of Academic Respiratory Medicine, Hull York Medical School, University of Hull, Castle Hill Hospital, Cottingham, UKAbstract: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality. The cornerstone of pharmacological treatment for COPD is bronchodilation. Inhaled glycopyrronium bromide is a long-acting muscarinic antagonist developed as a maintenance treatment for patients with COPD. Phase III trials have shown that glycopyrronium produces rapid and sustained bronchodilation with an efficacy similar to tiotropium and is well tolerated, with a low incidence of muscarinic side effects in patients with moderate to severe COPD. A combination of glycopyrronium bromide with indacaterol maleate (QVA149) has recently been approved as a once-daily maintenance therapy in adult patients with COPD. Phase III trials (the IGNITE program) with QVA149 have demonstrated significant improvements in lung function versus placebo, glycopyrronium, and tiotropium in patients with moderate to severe COPD, with no safety concerns of note. Hence QVA149 is a safe treatment option for moderate to severe COPD patients in whom long-acting muscarinic antagonist monotherapy is inadequate.Keywords: chronic obstructive pulmonary disease, glycopyrronium bromide, indacaterol maleate, umeclidinium, QVA149, long-acting muscarinic antagonis

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

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 \u3b22-agonists and with long-acting muscarinic antagonists. New combinations of bronchodilators with dual-acting muscarinic antagonist and \u3b22-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 \u3bcg and 62.5/25 \u3bcg 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.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 beta(2)-agonists and with long-acting muscarinic antagonists. New combinations of bronchodilators with dual-acting muscarinic antagonist and beta(2)-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 mu g and 62.5/25 mu g 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

Health effects in COPD smokers who switch to electronic cigarettes: a retrospective-prospective 3-year follow-up

Riccardo Polosa,1–3,* Jaymin Bhagwanji Morjaria,4,5,* Umberto Prosperini,6 Cristina Russo,7 Alfio Pennisi,8 Rosario Puleo,1–3 Massimo Caruso,1,2 Pasquale Caponnetto1,2 1Department of Clinical & Experimental Medicine, University of Catania, Catania, Italy; 2Centre for the Prevention and Treatment of Tobacco Addiction (CPCT), Teaching Hospital “Policlinico – V. Emanuele”, University of Catania, Catania, Italy; 3Institute of Internal and Emergency Medicine, Teaching Hospital “Policlinico – V. emanuele”, University of Catania, Catania, Italy; 4Department of Respiratory Medicine, Royal Brompton & Harefield Hospital Foundation Trust, Harefield Hospital, Harefield, UK; 5Imperial College, Harefield, UK; 6Hospital “San Vincenzo”, Taormina, Italy; 7Emergency Department, Hospital “Arnas Garibaldi”, Catania, Italy; 8Department of Respiratory Medicine, Private clinics “Musumeci-Gecas”, Catania, Italy *These authors contributed equally to this work Background: Health effects of electronic cigarette (EC) use in patients with chronic obstructive pulmonary disease (COPD) are largely unexplored.Aim: We present findings from a long-term prospective assessment of respiratory parameters in a cohort of COPD patients who ceased or substantially reduced conventional cigarette use with ECs.Methods: We prospectively re-evaluated COPD exacerbations, spirometric indices, subjective assessments (using the COPD Assessment Tool [CAT] scores), physical activity (measured by the 6-minute walk distance [6MWD]), and conventional cigarette use in EC users with COPD who were retrospectively assessed previously. Baseline measurements prior to switching to EC use were compared to follow-up visits at 12, 24, and 36 months. Age- and sex-matched regularly smoking COPD patients who were not using ECs were included as reference (control) group.Results: Complete data were available from 44 patients. Compared to baseline in the EC-user group, there was a marked decline in the use of conventional cigarettes. Although there was no change in lung function, significant improvements in COPD exacerbation rates, CAT scores, and 6MWD were observed consistently in the EC user group over the 3-year period (p<0.01). Similar findings were noted in COPD EC users who also smoked conventional cigarettes (“dual users”).Conclusion: The present study suggests that EC use may ameliorate objective and subjective COPD outcomes and that the benefits gained may persist long-term. EC use may reverse some of the harm resulting from tobacco smoking in COPD patients. Keywords: smoking cessation, electronic cigarette, COPD, tobacco harm reductio

Effect of acute exacerbations on circulating endothelial, clotting and fibrinolytic markers in COPD patients.

Patients with chronic obstructive pulmonary disease (COPD) are prone to clinical exacerbations that are associated with increased airway inflammation, a potent pro-thrombotic stimulus. Limited information is available on the mechanisms underlying the putative alterations of the endothelial-coagulative system during acute exacerbations. The aim was to investigate whether the activation of the endothelial-coagulative system occurs in association with the acute inflammatory response of COPD exacerbation. We monitored the blood levels of surrogate markers of inflammation: interleukin-6 (IL-6); endothelium damage: von Willebrand's factor (vWF); clotting activation: D-dimer (D-D), and prothrombin fragment 1+2 (F1+2); fibrinolytic response: plasminogen activator inhibitor 1 (PAI-1), in COPD subjects, during hospital admission and after clinical resolution. In 30 COPD subjects, IL-6, vWF, D-D and F1+2 levels were elevated during exacerbation and decreased significantly at clinical stability (IL-6, p = 0.005; vWF, p < 0.001; D-D, p < 0.001; F1+2, p < 0.001). PAI-1 levels did not change at exacerbation compared to clinically stable situations. Positive correlations were observed between several of the markers measured. Elevation of IL-6, vWF, D-D and F1+2 levels during COPD exacerbations implies a strict association between acute inflammation, endothelial activation and clotting initiation. This was not associated with a change in PAI-1, implying an increase in the fibrinolytic response to inflammation. The pro-thrombotic nature of COPD exacerbations sustained by enhanced clotting activation appears to be mitigated by excessive fibrinolysis

Implications of incidental findings from lung screening for primary care: data from a UK pilot

Regional lung cancer screening (LCS) is underway in England, involving a “lung health check” (LHC) and low-dose CT scan for those at high risk of cancer. Incidental findings from LHCs or CTs are usually referred to primary care. We describe the proportion of participants referred from the West London LCS pilot to primary care, the indications for referral, the number of general practitioner (GP) attendances and consequent changes to patient management, and provide an estimated cost-burden analysis for primary care. A small proportion (163/1542, 10.6%) of LHC attendees were referred to primary care, primarily for suspected undiagnosed chronic obstructive pulmonary disease (55/163, 33.7%) or for QRISK® (63/163, 38.7%) assessment. Ninety one of 159 (57.2%) participants consenting to follow-up attended GP appointments; costs incurred by primary care were estimated at £5.69/LHC participant. Patient management changes occurred in only 36/159 (22.6%) referred participants. LHCs result in a small increase to primary care workload provided a strict referral protocol is adhered to. Changes to patient management arising from incidental findings referrals are infrequent