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

Platelet activation and cardiovascular co-morbidities in patients with chronic obstructive pulmonary disease.

Objective: Platelet activation in COPD patients is associated with an increased risk of cardiovascular events. Aim of the study: to assess the mean platelet volume (MPV), as an index of platelet activation, in patients with COPD both when stable or during exacerbation. Research design and methods: 478 patients with COPD (75 with exacerbation) and 72 age-matched healthy controls were enrolled. Medical history, co-morbidities, medications, pulmonary function tests, MPV and blood cell count, erythrocyte sedimentation rate (ERS) and C reactive protein (CRP) were recorded. Results: MPV was higher in COPD patients than in controls (8.7 \ub1 1.1 fL and 8.4 \ub1 0.8 fL respectively, p = 0.025) and increased across the severity of the diseases as assessed by the GOLD post bronchodilator FEV1 categorized I to IV (p>0.05). MPV was higher in COPD patients during acute exacerbation as compared with stable condition (8.7 \ub1 1.0 fL and 8.9 \ub1 1.0 fL, p = 0.021). MPV 65 10.5 fL correlated with the presence of at least one co-existing cardiovascular disease (p = 0.008) . No correlation was observed between MPV and CRP or ERS in patients or in controls. An inverse significant correlation was found between platelets count and MPV in COPD patients. Conclusions: Elevated MPV is associated with lower platelet count and with cardiovascular co-morbidity in COPD patients. MPV value is higher in more severe COPD and during acute exacerbation. Present findings warrant future studies to confirm a possible clinically relevant role for platelet activation and cardiovascular risk in the population of COPD

Bronchoalveolar lavage, sputum and exhaled clinically relevant inflammatory markers: values in healthy adults.

11noBronchoalveolar lavage (BAL), induced sputum and exhaled breath markers (exhaled nitric oxide and exhaled breath condensate) can each provide biological insights into the pathogenesis of respiratory disorders. Some of their biomarkers are also employed in the clinical management of patients with various respiratory diseases. In the clinical context, however, defining normal values and cut-off points is crucial. The aim of the present review is to investigate to what extent the issue of defining normal values in healthy adults has been pursued for the biomarkers with clinical value. The current authors reviewed data from literature that specifically addressed the issue of normal values from healthy adults for the four methodologies. Most studies have been performed for BAL (n = 9), sputum (n = 3) and nitric oxide (n = 3). There are no published studies for breath condensate, none of whose markers yet has clinical value. In healthy adult nonsmokers the cut-off points (mean+2sd) for biomarkers with clinical value were as follows. BAL: 16.7% lymphocytes, 2.3% neutrophils and 1.9% eosinophils; sputum: 7.7 x 10(6).mL(-1) total cell count and 2.2% eosinophils; nitric oxide: 20.2 ppb. The methodologies differ concerning the quantity and characteristics of available reference data. Studies focusing on obtaining reference values from healthy individuals are still required, more evidently for the new, noninvasive methodologies.nonemixedBALBI B; PIGNATTI P; CORRADI M; BAIARDI P; BIANCHI L; BRUNETTI G; RADAELI A; MOSCATO G; MUTTI A; SPANEVELLO A; MALERBA MBalbi, B; Pignatti, P; Corradi, M; Baiardi, P; Bianchi, L; Brunetti, G; Radaeli, A; Moscato, G; Mutti, A; Spanevello, Antonio; Malerba, M

Exhaled nitric oxide in patients with PiZZ Phenotype-related α 1-anti-trypsin deficiency

AbstractThere is no report of exhaled NO (eNO) in subjects with different phenotypes ofα1 -anti-trypsin (AAT) deficiency.Exhaled nitric oxide was evaluated by means of single-breath chemiluminescence analysis (fractional exhaled concentration at the plateau level [plFENO]) in 40 patients with AAT deficiency. Patients were divided according to the protease inhibitor (Pi) phenotype: PiMZ/MS, n=25; PiSZ n=6; PiZZ, n=9. Nineteen healthy subjects served as controls. Levels of eNO in PiZZ patients were also compared with those of subjects, without AAT deficiency (PiMM), matched for diagnosis, sex, age, smoking habit and forced expiratory volume in 1 sec (FEV1). In AAT deficiency subjects airway hyper-responsiveness to methacholine (PD20FEV1) was also assessed.plFENOwas significantly lower in the PiZZ group (4·5±1·4 ppb) than in matched PiMM subjects (8·2±3·8 ppb), in healthy controls (9·3±2·8 ppb) and in patients of other phenotypes. Dynamic lung volumes and DLCOwere significantly lower in PiZZ than in other AAT-deficient patients. Bronchial hyper-responsiveness was not different among AAT phenotypes.These results suggest that eNO may be significantly reduced in PiZZ as compared to healthy control subjects and to AAT subjects with other phenotypes, independent of the level of airway obstruction. Whether, at least potentially, eNO may be considered as an early marker of lung involvement in AAT deficiency must be confirmed with studies on larger number of subjects

Polarization Dependence of Anomalous X-ray Scattering in Orbital Ordered Manganites

In order to determine types of the orbital ordering in manganites, we study theoretically the polarization dependence of the anomalous X-ray scattering which is caused by the anisotropy of the scattering factor. The general formulae of the scattering intensity in the experimental optical system is derived and the atomic scattering factor is calculated in the microscopic electronic model. By using the results, the X-ray scattering intensity in several types of the orbital ordering is numerically calculated as a function of azimuthal and analyzer angles.Comment: 9 pages, 7 figure

Exhaled nitric oxide levels in alpha-1-antitrypsin PiMZ subjects

Although the likelihood of intermediate alpha-1-antitrypsin deficiency (PiMZ) patients developing chronic obstructive pulmonary disease (COPD) remains uncertain, several investigators have suggested that a lack of antiprotease inhibitor activity may favour the development of airway inflammation with subsequent pulmonary tissue damage. The levels of exhaled nitric oxide (FeNO) in PiMZ subjects are unknown and polymorphisms in nitric oxide synthase have been linked to lung disease susceptibility in subjects with alpha-1-antitrypsin (AAT) deficiency. This study was aimed at assessing FeNO levels in a group of PiMZ subjects and comparing it with the concentrations found amongst groups of COPD and control patients. A group of 31 PiMZ subjects, 31 COPD patients and 30 controls underwent pulmonary function tests, AAT assay and phenotyping, and FeNO measurement in an ambulatory setting. FeNO values observed in the group of PiMZ subjects (21.6 +/- 8.9 ppb) showed a significant increase compared with COPD (14.5 +/- 8.7 ppb; P < 0.01) and the control groups (9.1 +/- 2.9 ppb; P < 0.01). Within the PiMZ population, a significant, negative correlation was observed between plasma AAT levels and FeNO readings. Not only did PiMZ subjects show increased FeNO levels compared with COPD patients and controls; FeNO levels proved to be related to the reduced concentration of plasma AAT. Such findings seem to suggest the importance of FeNO measurements on PiMZ subjects for monitoring a possible progression of airway inflammation to obstructive lung disease as observed in some of these patients

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

UPPER EXTREMITY DEEP VEIN THROMBOSIS AS AN UNCOMMON COMPLICATION OF PACEMAKER IMPLANTATION: A CASE REPORT

Venous complications of pacemaker implantation rarely cause immediate clinical problems. An 89-year-old man, without thrombophilia, 4 weeks after a pacemaker implantation experienced functional impotence of the left arm that appeared warm, reddened, oedematous and painful. Color Doppler Ultrasonography revealed a thrombosis of the axillary vein extended to the proximal third of the ulnar vein. In our opinion, upper extremity deep vein thrombosis (UEDVT) represents an important complication of post-surgical pacemaker implantation that should be suspected early, even without specific symptoms and thrombophilia