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https://www.readbyqxmd.com/read/29133975/severe-eosinophilic-asthma-from-the-pathogenic-role-of-interleukin-5-to-the-therapeutic-action-of-mepolizumab
#1
REVIEW
Corrado Pelaia, Alessandro Vatrella, Maria Teresa Busceti, Luca Gallelli, Rosa Terracciano, Rocco Savino, Girolamo Pelaia
Mepolizumab is an anti-interleukin-5 (IL-5) humanized monoclonal antibody that has been recently approved as an add-on biological treatment for severe eosinophilic asthma, by both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Moreover, mepolizumab is also currently included within the step 5 of the Global Initiative for Asthma guidelines, as an add-on therapy for severe uncontrolled asthma. The relevant therapeutic benefits detectable in patients with refractory eosinophilic asthma receiving mepolizumab depend on the pivotal pathogenic role played by IL-5 in these subjects...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29120588/association-between-serpinb2-gene-expression-by-real-time-pcr-in-respiratory-epithelial-cells-and-atopic-bronchial-asthma-severity
#2
Nissreen E ELBadawy, Randa S Abdel-Latif, Hoda A El-Hady
Atopic bronchial asthma is chronic respiratory diseases of high frequency and high morbidity and mortality especially in patients refractory to the ordinary medical management. This study aimed to investigate the association between Serpin family B Member 2 (SERPINB2) gene expression and bronchial asthma severity. A total of 127 adult patients with asthma were enrolled in this study. Allergic respiratory symptoms were assessed and patients were classified according to Global Initiative for Asthma (GINA) criteria...
January 2017: Egyptian Journal of Immunology
https://www.readbyqxmd.com/read/29033571/bronchial-thermoplasty-and-the-role-of-airway-smooth-muscle-are-we-on-the-right-direction
#3
REVIEW
Francesco Menzella, Mirco Lusuardi, Carla Galeone, Nicola Facciolongo
Asthma is characterized by inflammation of the airways that includes eosinophils, basal membrane thickening, epithelial sloughing, vascular changes, smooth muscle hypertrophy and hyperplasia, and mucous gland hyperplasia. Recently, there have been studies on the role of hypersensitivity and inflammation in asthma, but the role of bronchial smooth muscle remains unclear. Bronchial thermoplasty is an endoscopic procedure that is approved by the US Food and Drug Administration (FDA) for the treatment of severe refractory asthma, based on the local delivery of radio frequency at 65°C to the airways, with the aim of controlling bronchospasm through a reduction of airway smooth muscle (ASM)...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/29017221/-biologicals-in-the-treatment-of-bronchial-asthma
#4
I Haasler, C Taube
Biologicals are a therapeutic option for patients with severe asthma. Difficult asthma in patients with untreated comorbidities or persistent trigger factors is much more common than severe refractory asthma. Optimized medical treatment, adherence to medication, elimination of trigger factors and treatment of comorbidities are essential before escalating the therapy with a biological. A careful phenotyping of patient with severe asthma is necessary because all available biological are only effective in certain phenotypes of the disease...
October 2017: Pneumologie
https://www.readbyqxmd.com/read/28966754/comparison-of-interleukin-33-serum-levels-in-asthmatic-patients-with-a-control-group-and-relation-with-the-severity-of-the-disease
#5
Tooba Momen, Hamid Ahanchian, Mohsen Reisi, Seyedeh Azra Shamsdin, Armindokht Shahsanai, Majid Keivanfar
BACKGROUND: The relation between interleukin-33 (IL-33) and asthma is not precisely known yet. The present study set to compare the serum level of IL-33 in patients with asthma and controls and study the relation with the severity of disease. METHODS: The serum level of IL-33 and total IgE in 89 asthmatic patients and 57 controls were analyzed. The association of levels of IL-33 with the severity of disease, levels of total IgE, measures of spirometry (forced expiratory volume in 1 s [FEV1]), age, sex, presence or absence of other allergic diseases, and the disease duration was evaluated...
2017: International Journal of Preventive Medicine
https://www.readbyqxmd.com/read/28939412/th1-signatures-are-present-in-the-lower-airways-of-children-with-severe-asthma-regardless-of-allergic-status
#6
Julia A Wisniewski, Lyndsey M Muehling, Jacob D Eccles, Brian J Capaldo, Rachana Agrawal, Debbie-Ann Shirley, James T Patrie, Lisa J Workman, Alexander J Schuyler, Monica G Lawrence, W Gerald Teague, Judith A Woodfolk
BACKGROUND: The pathogenesis of severe asthma in childhood remains poorly understood. OBJECTIVE: To construct the immunological landscape in the airways of children with severe asthma. METHODS: Comprehensive analysis of multiple cell types and mediators was performed by flow cytometry and multiplex assay using bronchoalveolar lavage (BAL) specimens (n=68) from 52 highly characterized allergic and non-allergic children (0.5-17 years) with severe treatment-refractory asthma...
September 19, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28933516/anti-il5-therapies-for-asthma
#7
REVIEW
Hugo A Farne, Amanda Wilson, Colin Powell, Lynne Bax, Stephen J Milan
BACKGROUND: This review is the first update of a previously published review in The Cochrane Library (Issue 7, 2015). Interleukin-5 (IL-5) is the main cytokine involved in the activation of eosinophils, which cause airway inflammation and are a classic feature of asthma. Monoclonal antibodies targeting IL-5 or its receptor (IL-5R) have been developed, with recent studies suggesting that they reduce asthma exacerbations, improve health-related quality of life (HRQoL) and lung function...
September 21, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28933002/mepolizumab-for-treating-severe-eosinophilic-asthma-an-evidence-review-group-perspective-of-a-nice-single-technology-appraisal
#8
REVIEW
Iñigo Bermejo, Matt Stevenson, Katy Cooper, Sue Harnan, Jean Hamilton, Mark Clowes, Christopher Carroll, Tim Harrison, Shironjit Saha
As part of its single technology appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited the company (GlaxoSmithKline) that manufactures mepolizumab (Nucala(®)) to submit evidence on the clinical and cost effectiveness of mepolizumab for the treatment of severe eosinophilic asthma. The School of Health and Related Research Technology Appraisal Group (ScHARR-TAG) at the University of Sheffield was commissioned to act as the independent evidence review group (ERG). The ERG produced a review of the evidence for the clinical and cost effectiveness of mepolizumab as add-on to standard of care (SoC) compared with SoC and omalizumab, based upon the company's submission to NICE...
September 20, 2017: PharmacoEconomics
https://www.readbyqxmd.com/read/28919788/innovative-treatments-for-severe-refractory-asthma-how-to-choose-the-right-option-for-the-right-patient
#9
REVIEW
Francesco Menzella, Carla Galeone, Francesca Bertolini, Claudia Castagnetti, Nicola Facciolongo
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...
2017: Journal of Asthma and Allergy
https://www.readbyqxmd.com/read/28918658/the-role-of-upper-airway-pathology-as-a-co-morbidity-in-severe-asthma
#10
Amelia Licari, Ilaria Brambilla, Maria De Filippo, Dimitri Poddighe, Riccardo Castagnoli, Gian Luigi Marseglia
Severe asthma is a complex heterogeneous disease that is refractory to standard treatment and is complicated by multiple co-morbidities and risk factors. Several co-morbidities may contribute to worsen asthma control and complicate diagnostic and therapeutic management of severe asthmatic patients. Areas covered: A prevalent cluster of chronic upper airway co-morbid diseases is recognized in severe asthma. Evaluation for these disorders should always be considered in clinical practice. The aim of this review is to provide an updated overview of the prevalence, the pathogenetic mechanisms, the clinical impact and the therapeutic options for upper airway pathology in severe asthma, focusing on chronic rhinosinusitis and allergic rhinitis...
September 16, 2017: Expert Review of Respiratory Medicine
https://www.readbyqxmd.com/read/28910970/antibody-therapy-for-the-management-of-severe-asthma-with-eosinophilic-inflammation
#11
Ken Ohta, Hiroyuki Nagase, Maho Suzukawa, Shin Ohta
One of the characteristic features of asthma is chronic airway inflammation typically with eosinophil infiltration. Most asthmatics can be treated successfully with conventional treatment appropriate for their severity, but in some severe cases, asthma cannot be well controlled even with thorough treatment and this condition is known as 'refractory asthma'. To overcome severe refractory asthma, a new therapeutic strategy with biologics has been developed based on the knowledge of molecular mechanisms of airway inflammation in asthma, induced by the condition of high Th2-type responses and activation of eosinophils as well as allergic reactions...
July 1, 2017: International Immunology
https://www.readbyqxmd.com/read/28840844/increased-serum-il-17a-and-th2-cytokine-levels-in-patients-with-severe-uncontrolled-asthma
#12
Takehiro Hasegawa, Hitoshi Uga, Akio Mori, Hirokazu Kurata
Asthma is a syndrome of chronic bronchial inflammation and airway remodelling. Initially, asthma has been categorized into atopic and nonatopic types, based on antigen-specific IgE levels. Moreover, recently, asthma has been classified into different endotypes based on its pathophysiology, leading to the selection of the most optimal and effective therapies. Although T helper cell type 2 (Th2) cytokines were proven to play critical roles in atopic asthma, IL-17A has been reported to be involved in severe refractory asthma...
March 1, 2017: European Cytokine Network
https://www.readbyqxmd.com/read/28803775/pulmonary-function-in-patients-with-eosinophilic-chronic-rhinosinusitis
#13
Kensuke Uraguchi, Shin Kariya, Seiichiro Makihara, Mitsuhiro Okano, Takenori Haruna, Aiko Oka, Rumi Fujiwara, Yohei Noda, Kazunori Nishizaki
OBJECTIVE: There is a close relationship between upper and lower respiratory tract diseases. Chronic rhinosinusitis patients frequently have lung diseases including asthma and chronic obstructive pulmonary disease. Eosinophilic chronic rhinosinusitis is considered a refractory and intractable subtype of chronic rhinosinusitis. However, there has been no report on pulmonary function in patients with eosinophilic chronic rhinosinusitis. The purpose of this study is to examine the pulmonary function in eosinophilic chronic rhinosinusitis patients and non-eosinophilic chronic rhinosinusitis patients, and evaluate clinical factors associated with the pulmonary function of these patients...
August 10, 2017: Auris, Nasus, Larynx
https://www.readbyqxmd.com/read/28783702/natural-killer-cell-mediated-inflammation-resolution-is-disabled-in-severe-asthma
#14
Melody G Duvall, Cindy Barnig, Manuela Cernadas, Isabell Ricklefs, Nandini Krishnamoorthy, Nicole L Grossman, Nirav R Bhakta, John V Fahy, Eugene R Bleecker, Mario Castro, Serpil C Erzurum, Benjamin M Gaston, Nizar N Jarjour, David T Mauger, Sally E Wenzel, Suzy A Comhair, Andrea M Coverstone, Merritt L Fajt, Annette T Hastie, Mats W Johansson, Michael C Peters, Brenda R Phillips, Elliot Israel, Bruce D Levy
Severe asthma is typically characterized by chronic airway inflammation that is refractory to corticosteroids and associated with excess morbidity. Patients were recruited into the National Heart, Lung, and Blood Institute-sponsored Severe Asthma Research Program and comprehensively phenotyped by bronchoscopy. Bronchoalveolar lavage (BAL) cells were analyzed by flow cytometry. Compared with healthy individuals (n = 21), patients with asthma (n = 53) had fewer BAL natural killer (NK) cells. Patients with severe asthma (n = 29) had a marked increase in the ratios of CD4(+) T cells to NK cells and neutrophils to NK cells...
March 10, 2017: Science Immunology
https://www.readbyqxmd.com/read/28762062/sequential-rituximab-and-omalizumab-for-the-treatment-of-eosinophilic-granulomatosis-with-polyangiitis-churg-strauss-syndrome
#15
REVIEW
David Aguirre-Valencia, Iván Posso-Osorio, Juan-Carlos Bravo, Fabio Bonilla-Abadía, Gabriel J Tobón, Carlos A Cañas
Eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as Churg-Strauss syndrome (CSS), is a small vessel vasculitis associated with eosinophilia and asthma. Clinical manifestations commonly seen in patients presenting with EGPA range from upper airway and lung involvement to neurological, cardiac, cutaneous, and renal manifestations. Treatment for severe presentations includes steroids, cyclophosphamide, plasmapheresis, and recently, rituximab. Rituximab is associated with a good response in the treatment of vasculitis, but a variable response for the control of allergic symptoms...
July 31, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28751262/do-individuals-with-asthma-experience-airway-hyper-responsiveness-after-exposure-to-nitrogen-dioxide
#16
Julie E Goodman, Erin M Kennedy, Mara Seeley
The current 100 ppb short-term National Ambient Air Quality Standard for NO2, and EPA's determination of a causal association for respiratory effects, are based in part on controlled human exposure studies evaluating airway hyper-responsiveness (AHR). A meta-analysis by Goodman et al. (2009) found increased AHR at 100 ppb NO2 but no clear concentration-response relationship up to 600 ppb, and an overall lack of an AHR effect for studies involving exercise or exposure to allergens. Several factors have been suggested to explain why effects on AHR are observed while people are at rest, but not during exercise or after exposure to allergens...
July 25, 2017: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/28668237/point-of-care-blood-eosinophil-count-in-a-severe-asthma-clinic-setting
#17
Enrico Heffler, Giovanni Terranova, Carlo Chessari, Valentina Frazzetto, Claudia Crimi, Silvia Fichera, Giuseppe Picardi, Giuliana Nicolosi, Morena Porto, Rossella Intravaia, Nunzio Crimi
BACKGROUND: One of the main severe asthma phenotypes is severe eosinophilic or eosinophilic refractory asthma for which novel biologic agents are emerging as therapeutic options. In this context, blood eosinophil counts are one of the most reliable biomarkers. OBJECTIVE: To evaluate the performance of a point-of-care peripheral blood counter in a patients with severe asthma. METHODS: The blood eosinophil counts of 76 patients with severe asthma were evaluated by point-of-care and standard analyzers...
July 2017: Annals of Allergy, Asthma & Immunology
https://www.readbyqxmd.com/read/28658551/spectrum-of-t-lymphocyte-activities-regulating-allergic-lung-inflammation
#18
REVIEW
Erwin W Gelfand, Anthony Joetham, Meiqin Wang, Katsuyuki Takeda, Michaela Schedel
Despite advances in the treatment of asthma, optimization of symptom control remains an unmet need in many patients. These patients, labeled severe asthma, are responsible for a substantial fraction of the disease burden. In these patients, research is needed to define the cellular and molecular pathways contributing to disease which in large part are refractory to corticosteroid treatment. The causes of steroid-resistant asthma are multifactorial and result from complex interactions of genetics, environmental factors, and innate and adaptive immunity...
July 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28638418/the-expression-of-stat3-and-stat5a-genes-in-severe-refractory-asthma
#19
Kayvan Saeedfar, Mehrdad Behmanesh, Esmaeil Mortaz, Mohammad Reza Masjedi
BACKGROUND: Despite being a high burden disorder, the pathogenesis of severe refractory asthma (SRA) is poorly understood. There are some evidences for the involvement of members of the signal transducer and activator of transcription (STAT) family, including STAT3 and STAT5a. Our study aimed to evaluate the gene expression of STAT3 and STAT5a in asthma and SRA to establish if there is an association. MATERIALS AND METHODS: Using quantitative real-time polymerase chain reactions (qRT-PCR), the transcript levels of STAT3 and STAT5a were evaluated in peripheral blood mononuclear lymphocytes (PBML) isolated from 13 patients with SRA, 14 with mild asthma, and 30 healthy volunteers...
2017: Tanaffos
https://www.readbyqxmd.com/read/28619778/in-patients-with-severe-uncontrolled-asthma-does-knowledge-of-adherence-and-inhaler-technique-using-electronic-monitoring-improve-clinical-decision-making-a-protocol-for-a-randomised-controlled-trial
#20
Matshediso C Mokoka, Lorna Lombard, Elaine M MacHale, Joanne Walsh, Breda Cushen, Imran Sulaiman, Damien Mc Carthy, Fiona Boland, Frank Doyle, Eoin Hunt, Desmond M Murphy, John Faul, Marcus Butler, Kathy Hetherington, J Mark FitzGerald, Job Fm van Boven, Liam G Heaney, Richard B Reilly, Richard W Costello
INTRODUCTION: Many patients with asthma remain poorly controlled despite the use of inhaled corticosteroids and long-acting beta agonists. Poor control may arise from inadequate adherence, incorrect inhaler technique or because the condition is refractory. Without having an objective assessment of adherence, clinicians may inadvertently add extra medication instead of addressing adherence. This study aims to assess if incorporating objectively recorded adherence from the Inhaler Compliance Assessment (INCA) device and lung function into clinical decision making provides more cost-effective prescribing and improves outcomes...
June 15, 2017: BMJ Open
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