86,582 research outputs found

    Innovative treatments for severe refractory asthma: how to choose the right option for the right patient?

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    Francesco Menzella,1 Carla Galeone,1 Francesca Bertolini,2 Claudia Castagnetti,1 Nicola Facciolongo1 1Department of Medical Specialties, Pneumology Unit, IRCCS- Arcispedale Santa Maria Nuova, Reggio Emilia, Italy; 2Department of Animal Science, Iowa State University, Ames, IA, USA Abstract: The increasing understanding of the molecular biology and the etiopathogenetic mechanisms of asthma helps in identification of numerous phenotypes and endotypes, particularly for severe refractory asthma. For a decade, the only available biologic therapy that met the unmet needs of a specific group of patients with severe uncontrolled allergic asthma has been omalizumab. Recently, new biologic therapies with different mechanisms of action and targets have been approved for marketing, such as mepolizumab. Other promising drugs will be available in the coming years, such as reslizumab, benralizumab, dupilumab and lebrikizumab. Moreover, since 2010, bronchial thermoplasty has been successfully introduced for a limited number of patients. This is a nonpharmacologic endoscopic procedure which is considered a promising therapy, even though several aspects still need to be clarified. Despite the increasing availability of new therapies, one of the major problems of each treatment is still the identification of the most suitable patients. This sudden abundance of therapeutic options, sometimes partially overlapping with each other, increases the importance to identify new biomarkers useful to guide the clinician in selecting the most appropriate patients and treatments, without forgetting the drug-economic aspects seen in elevated direct cost of new therapies. The aim of this review is, therefore, to update the clinician on the state of the art of therapies available for refractory asthma and, above all, to give useful directions that will help understand the different choices that sometimes partially overlap and to dispel the possible doubts that still exist. Keywords: severe asthma, phenotypes, monoclonal antibodies, IL-5, bronchial thermoplasty, biomarker

    Precision Medicine in Targeted Therapies for Severe Asthma: Is There Any Place for "omics" Technology?

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    According to the current guidelines, severe asthma still represents a controversial topic in terms of definition and management. The introduction of novel biological therapies as a treatment option for severe asthmatic patients paved the way to a personalized approach, which aims at matching the appropriate therapy with the different asthma phenotypes. Traditional asthma phenotypes have been decomposing by an increasing number of asthma subclasses based on functional and physiopathological mechanisms. This is possible thanks to the development and application of different omics technologies. The new asthma classification patterns, particularly concerning severe asthma, include an increasing number of endotypes that have been identified using new omics technologies. The identification of endotypes provides new opportunities for the management of asthma symptoms, but this implies that biological therapies which target inflammatory mediators in the frame of specific patterns of inflammation should be developed. However, the pathway leading to a precision approach in asthma treatment is still at its beginning. The aim of this review is providing a synthetic overview of the current asthma management, with a particular focus on severe asthma, in the light of phenotype and endotype approach, and summarizing the current knowledge about "omics" science and their therapeutic relevance in the field of bronchial asthma

    Towards precision medicine: The application of omics technologies in asthma management

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    Asthma is a chronic obstructive respiratory disease characterised by bronchial inflammation. Its biological and clinical features have been widely explored and a number of pharmacological treatments are currently available. Currently several aspects of asthma pathophysiological background remain unclear, and this is represent a limitation for the traditional asthma phenotype approach. In this scenario, the identification of new molecular and clinical biomarkers may be helpful in order to better understand the disease, define specific diagnostic tools and highlight relevant novel targets for pharmacological treatments. Omics technologies offer innovative research tools for addressing the above mentioned goals. However, there is still a lot to do both in the fields of basic research and in the clinical application. Recently, genome-wide association studies, microRNAs and proteomics are contributing to enrich the available data for the identification of new asthma biomarkers. A precise approach to the patient with asthma, particularly with severe uncontrolled asthma, requires new and specific therapeutic targets, but also proper tools able to drive the clinician in tailoring the treatment. On the other hand, there is a need of predictors to treatment's response, particularly in the field of biological drugs, whose sustainability implies a correct and precise selection of the patients. Translating acquired omics knowledge in clinical practice may address the unmet needs described above, but large-scale studies are required in order to confirm their relevance and effectiveness in daily practice. Thus in our opinion the application of omics is still lagging in the real-life setting

    Anti-il5 therapies for severe eosinophilic asthma: Literature review and practical insights

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    Severe refractory asthma (SRA) still has a high economic and social impact, including a reduction in quality of life (QoL), productivity, a greater risk of exacerbations and emergency department (ED) visits. Another major issue is the need of oral corticosteroids (OCS), often due to a poor response to standard therapies or the lack of indication for currently available biological drugs. A thorough understanding of the immunological pathways and eosinophilopoietic processes allows a correct application of the new pharmacological strategies and leads to better clinical responses. For these unmet needs, several monoclonal antibody (mAb) drugs have been introduced over the past few years. These are mainly available for allergic and especially eosinophilic uncontrolled refractory asthma. As the number of therapeutic options increases, the choice of biological drugs can be made only after careful considerations of the particular asthma endotype, patients’ comorbidities and clinical data. The selection of the correct therapeutic option can therefore be guided after a careful evaluation of the particular endotype and phenotype, from the combined evaluation of inflammatory biomarkers, clinical picture and comorbidities. The careful evaluation of all these parameters can therefore help the physician in the optimal management of these complex patients, for whom it is often possible to achieve exceptional results by managing the available options in the best possible way. The aim of this review is to define the positioning of the biological drugs currently available for type 2 asthma, with a special focus on options for eosinophilic asthma in the context of the most recent knowledge of immunological pathways

    Effects of protein sources on performance, carcass composition, blood parameters and meat quality in Charolais heifers

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    The aim of the present study was to evaluate the effects of feeding faba bean and sweet lupin as alternative protein sources to soybean on productive performance, blood parameters, carcass composition, and chemical-physical characteristics of meat and its fatty acid (FA) profile in Charolais heifers. Twenty-four heifers were divided into three homogenous groups and fed with durum wheat straw and three iso-energetic and isonitrogenous pelleted complete diets containing 14% (on as-fed basis) soybean meal; 28% faba bean; and 20% sweet lupin seed. The animals were slaughtered after a 168 day feeding period, and the Longissimus lumborum muscle was sampled for meat quality measurements. The feed conversion index was better in the heifers fed faba bean compared with the soybean treatment group (6.71 versus 7.17). No differences were found among treatment groups in productive performance, slaughtering data and physical features. The concentration of linoleic acid in the meat of the soybean group differed significantly from that in the lupin group (2.38 versus 2.11%). Feeding lupin seed increased the concentrations of C20:3 n-6 (0.09%) and C20:4 n-6 (0.20%) in meat significantly, compared with the soya- and faba bean treatments (0.06-0.07% and 0.12-0.13%, respectively). No differences were found among groups for blood parameters, except for urea concentration, which was lower in the lupin group compared with the concentrations in the serum of heifers receiving the soya bean treatment (31.29 as opposed to 37.56 mg/dL). In conclusion, since faba bean and lupin seed did not affect any of the parameters negatively, these legume grains can be included successfully as alternative protein sources in beef cattle diet

    Effects of dietary extruded linseed (Linum usitatissimum L.) on performance and meat quality in Podolian young bulls

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    This study compared effects of a diet containing 3% extruded linseed (EL) (Linum usitatissimum L.) with a control diet (C) on growth, carcass traits, and meat quality in young Podolian bulls. After 208 days on feed, the bulls were slaughtered at 18 months of age. Samples of Longissimus lumborum (LI) were analysed to assess their physical and chemical parameters and intramuscular fatty acid composition. Average daily gain, feed intake and feed efficiency were not affected by treatments. Bulls fed EL (n = 6) had significantly greater final (612 kg versus 593 kg) and slaughter weights (583 kg versus 563 kg) than those fed C (n = 6). Compared with C, EL significantly increased percentages of lean from the pelvic limb (71.9% versus 69.3%) and of bone from the lumbar region (30.0 versus 27.1%). Meat pH recorded at slaughter was significantly greater for C than EL (6.7 versus 6.4). Diet did not affect meat colour, chemical composition and shear force of either the raw or cooked meat. Total amounts of saturated, monounsaturated and polyunsaturated fatty acids were not influenced by the diets. Concentrations of linoleic acid (C18:2 n-6) (3.30 versus 4.08) and total n-6 fatty acids (3.83 versus 4.73) were reduced by EL, while EL significantly enhanced linolenic acid (C18:3 n-3) (0.45 vs 0.20) and total n-3 fatty acids (1.64 versus 1.18) in the meat compared with C. Thus, dietary supplementation with 3% EL improved the amount of n-3 fatty acids in the meat from young Podolian bulls without affecting their performance
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