1,721,024 research outputs found

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

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    Mario Malerba,1 Jaymin Bhagwanji Morjaria,2 Alessandro Radaeli3 1Department of Internal Medicine, University of Brescia, Brescia, Italy; 2Department of Academic Respiratory Medicine, Hull York Medical School, University of Hull, Castle Hill Hospital, Cottingham, United Kingdom; 3Department of Emergency, Spedali Civili di Brescia, Brescia, Italy Abstract: 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. Keywords: COPD treatment, umeclidinium, vilanterol, bronchodilators combination, long acting beta2-agonists, long acting muscarinic receptor antagonist

    Therapeutic potential for novel ultra long-acting beta(2)-agonists in the management of COPD: biological and pharmacological aspects

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    Chronic obstructive pulmonary disease (COPD) is characterised by progressive airflow limitation. In moderate-to-severe COPD, long-acting bronchodilators are the basis of therapy. Inhaled long-acting β 2-agonists (LABAs) are used for the treatment of COPD. LABAs have been in use since the 1990s enabling persistent bronchodilation for 12 hours; however, sustained bronchodilation is desirable. Compared with twice-daily LABAs, new LABAs with ultra-long duration (ultra-LABAs) could provide improvements in efficacy and compliance with fast onset of action, 24-hour bronchodilation and a good safety profile. Several novel ultra-LABAs showing once-daily delivery profiles are in development. In this article, we discuss these novel agents' properties and clinical trials of their efficacy and safety, including the only licensed ultra-LABA, indacaterol.Chronic obstructive pulmonary disease (COPD) is characterised by progressive airflow limitation. In moderate-to-severe COPD, long-acting bronchodilators are the basis of therapy. Inhaled long-acting beta(2)-agonists (LABAs) are used for the treatment of COPD. LABAs have been in use since the 1990s enabling persistent bronchodilation for 12 hours; however, sustained bronchodilation is desirable. Compared with twice-daily LABAs, new LABAs with ultra-long duration (ultra-LABAs) could provide improvements in efficacy and compliance with fast onset of action, 24-hour bronchodilation and a good safety profile. Several novel ultra-LABAs showing once-daily delivery profiles are in development. In this article, we discuss these novel agents' properties and clinical trials of their efficacy and safety, including the only licensed ultra-LABA, indacaterol

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

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    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

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

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    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

    THE POTENTIAL THERAPEUTIC ROLE OF POTASSIUM CHANNEL MODULATORS IN ASTHMA AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE

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    The involvement of a number of potassium channels has been reported in respiratory conditions such as asthma and chronic obstructive pulmonary disease (COPD), supporting the idea that potassium channel modulating agents may help control it. Experimental evidence and preclinical models suggest that ATP-dependent K(+) (K(ATP)) channel openers, big-conductance K(+) (BK(CA)) channel openers, and intermediate-conductance K(+) (IK(CA)) channel blockers may be the most effective agents for treating asthma and COPD. Modulation of potassium channels by these agents may produce beneficial effects such as bronchodilation, a reduction in airways hyperresponsiveness (AHR), a reduction in cough and mucus production and an inhibition in airway inflammation and remodelling. The aim of this paper is to investigate the role of K(+) channel modulation in the pathogenesis, progression and exacerbation of asthma and COPD, and to review the evidence suggesting that K(+) channel modulators may be a valuable treatment option for these respiratory diseases

    Airway hyperresponsiveness in a large group of subjects with alpha(1)-antitrypsin deficiency: a cross-sectional controlled study

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    Background. It has been suggested that subjects with alpha(1) -antitrypsin (AAT) deficiency, lacking a major antiprotease defence against airway inflammation, might be more susceptible of development of airway hyperresponsiveness (AHR). Moreover, lower AAT blood levels might also be able to influence the severity of AHR. Objectives. This study was aimed to investigate the prevalence of AHR in a large group of subjects with AAT deficiency included in the Italian Registry and to evaluate the relationship between AAT blood levels and the severity of AHR in this population. Design. Cross-sectional controlled study. Setting. Regional Reference Centre for AAT deficiency in Brescia, Italy. Methods. A total of 114 subjects with AAT deficiency underwent pulmonary function tests. Eighty-six were eligible to perform a bronchial provocation test with methacholine (MCh) (baseline FEV1 > 60% predicted) to assess the provocative dose producing a 20% fall of FEV1 (PD20 FEV1 ). Similar measurements were performed in a control group of 27 age-matched normal subjects. Results. The prevalence of AHR (PD20 FEV1 < 2000 mug MCh) was not different between AAT deficiency subjects and controls (16.3% and 11.1%, respectively; P = 0.66), and also amongst two subgroups of AAT deficiency subjects divided according to different protease inhibitor (Pi) phenotypes (PiMZ-MS, PiSZ-ZZ). Hyperresponsive subjects with AAT deficiency, however, showed a positive correlation between AAT blood levels and PD20 FEV1 values (r = 0.71, P < 0.01). Conclusions. These findings indicate that AAT deficiency subjects did not exhibit a greater prevalence of airway hyperresponsiveness as compared with control subjects, but suggest that, in the subset of AAT deficiency subjects hyperresponsive to MCh, lower levels of AAT are associated with a higher severity of AHR

    Determinants of smoking status in a sample of outpatients afferent to a tertiary referral hospital

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    The identification of determinants of attempts to quit smoking and quitting smoking success is crucial for effective smoking prevention and/or cessation programs. Thus, here we have conducted a survey to determine the sociodemographic characteristics of tobacco use and the potential determinants of quitting smoking among a population of 140 subjects—101 smokers and 39 ex-smokers—referred to our clinic for respiratory diseases. Subject characteristics included demographic data, employment and education status, respiratory disease family history, smoking habits, life habits, diet, alcohol intake, and physical activity. In comparison with former smokers, active smokers were younger, lived with at least one smoking family member, and were more frequently exposed to passive smoke. They also displayed a higher coffee consumption, a higher frequency of in-between-meal snacks, and a lower chronic obstructive pulmonary disease (COPD) prevalence. In comparison with subjects who had never attempted to quit smoking, individuals who had attempted to quit smoking were younger, had a lower pack-year median, consumed a higher amount of coffee and alcohol, and conducted regular physical activity. Determinants of successful smoking cessation were older age, lower passive smoking exposure and daily coffee intake, and COPD diagnosis. Overall, our findings underscore the importance of health education in fostering successful smoking cessation in respiratory disease patients

    Vilanterol trifenatate for the treatment of COPD.

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    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
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