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https://www.readbyqxmd.com/read/28514613/kit-inhibition-by-imatinib-in-patients-with-severe-refractory-asthma
#1
RANDOMIZED CONTROLLED TRIAL
Katherine N Cahill, Howard R Katz, Jing Cui, Juying Lai, Shamsah Kazani, Allison Crosby-Thompson, Denise Garofalo, Mario Castro, Nizar Jarjour, Emily DiMango, Serpil Erzurum, Jennifer L Trevor, Kartik Shenoy, Vernon M Chinchilli, Michael E Wechsler, Tanya M Laidlaw, Joshua A Boyce, Elliot Israel
BACKGROUND: Mast cells are present in the airways of patients who have severe asthma despite glucocorticoid treatment; these cells are associated with disease characteristics including poor quality of life and inadequate asthma control. Stem cell factor and its receptor, KIT, are central to mast-cell homeostasis. We conducted a proof-of-principle trial to evaluate the effect of imatinib, a KIT inhibitor, on airway hyperresponsiveness, a physiological marker of severe asthma, as well as on airway mast-cell numbers and activation in patients with severe asthma...
May 18, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28464704/prospects-for-new-and-emerging-therapeutics-in-severe-asthma-the-role-of-biologics
#2
Seçil Kepil Özdemir, Sevim Bavbek
Asthma is a common and heterogeneous disease. While current conventional therapies are effective in the majority of the patients, a significant subgroup remain uncontrolled despite these treatments. Different biological agents are currently approved or undergoing development for treatment of asthma, including anti-IgE, anti-interleukin (IL)-5, anti-IL-13, anti-IL-4 and anti-thymic stromal lymphopoietin agents. This review will focus on the currently available evidence regarding the new and emerging biological agents in severe asthma...
May 10, 2017: Expert Review of Respiratory Medicine
https://www.readbyqxmd.com/read/28461761/managing-the-pediatric-patient-with-refractory-asthma-a-multidisciplinary-approach
#3
REVIEW
James Cook, Fran Beresford, Valentina Fainardi, Pippa Hall, Georgie Housley, Angela Jamalzadeh, Michelle Nightingale, David Winch, Andrew Bush, Louise Fleming, Sejal Saglani
Children with asthma that is refractory to high levels of prescribed treatment are described as having problematic severe asthma. Those in whom persistent symptoms result from a failure of basic asthma management are described as having "difficult asthma", while those who remain symptomatic despite these factors having been addressed are described as having "severe therapy-resistant asthma" (STRA). The majority of children have difficult asthma; asthma that is poorly controlled because of a failure to get the basics of asthma management right...
2017: Journal of Asthma and Allergy
https://www.readbyqxmd.com/read/28446972/thermal-ablation-for-asthma-current-status-and-technique
#4
REVIEW
William Krmisky, Michal J Sobieszczyk, Saiyad Sarkar
Bronchial thermoplasty (BT) is a novel technique used in the treatment of severe asthma. A catheter is advanced through the bronchoscope and directed radiofrequency waves are applied to the segmental bronchi to reduce airway smooth muscle mass. Several randomized clinical trials demonstrate improvement in quality of life and reduction in exacerbation rates after treatment. BT is a safe and cost effective treatment option for severe asthma which is refractory to medical treatment. Further studies are needed in order to better describe the mechanism of action and the asthma subphenotype that was best benefit from this treatment...
March 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28427296/predictors-of-response-to-therapy-with-omalizumab-in-patients-with-severe-allergic-asthma-a-real-life-study
#5
Maria Kallieri, Andriana I Papaioannou, Evgenia Papathanasiou, Polyxeni Ntontsi, Spyridon Papiris, Stelios Loukides
OBJECTIVES: Omalizumab is a recombinant humanized IgG1 monoclonal anti-IgE antibody, used for the treatment of severe refractory allergic asthma. However, not all patients with IgE levels within the limits of administration, respond to treatment. The aim of the present study, was to determine clinical and inflammatory characteristics that could predict response to omalizumab. METHODS: We studied retrospectively patients treated with omalizumab as per GINA guidelines in one asthma tertiary referral center...
April 28, 2017: Postgraduate Medicine
https://www.readbyqxmd.com/read/28424691/increased-autophagy-related-5-gene-expression-is-associated-with-collagen-expression-in-the-airways-of-refractory-asthmatics
#6
Audrey H Poon, David F Choy, Fazila Chouiali, Rakhee K Ramakrishnan, Bassam Mahboub, Severine Audusseau, Andrea Mogas, Jeffrey M Harris, Joseph R Arron, Catherine Laprise, Qutayba Hamid
BACKGROUND: Fibrosis, particularly excessive collagen deposition, presents a challenge for treating asthmatic individuals. At present, no drugs can remove or reduce excessive collagen in asthmatic airways. Hence, the identification of pathways involved in collagen deposition would help to generate therapeutic targets to interfere with the airway remodeling process. Autophagy, a cellular degradation process, has been shown to be dysregulated in various fibrotic diseases, and genetic association studies in independent human populations have identified autophagy-related 5 (ATG5) to be associated with asthma pathogenesis...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28413387/successful-treatment-of-a-bullous-pemphigoid-patient-with-rituximab-who-was-refractory-to-corticosteroid-and-omalizumab-treatments
#7
Aslı Bilgiç Temel, Cumhur Ibrahim Bassorgun, Ayşe Akman-Karakaş, Erkan Alpsoy, Soner Uzun
Omalizumab is a humanized monoclonal antibody which is an FDA-approved treatment of severe allergic asthma and inhibits IgE binding to FcεRI. According to increasing evidence of IgE inhibition, omalizumab was suggested as a therapeutic approach for bullous pemphigoid (BP). Rituximab has been reported to be effective in various autoimmune diseases, including autoimmune bullous dermatoses. A specific protocol for the use of rituximab to treat BP patients is not yet available. There are only small case series and case reports about the efficacy and safety of rituximab in BP...
January 2017: Case Reports in Dermatology
https://www.readbyqxmd.com/read/28407269/clinical-functional-and-inflammatory-characteristics-in-patients-with-paucigranulocytic-stable-asthma-comparison-with-different-sputum-phenotypes
#8
P Ntontsi, S Loukides, P Bakakos, K Kostikas, G Papatheodorou, E Papathanassiou, G Hillas, N Koulouris, S Papiris, A I Papaioannou
BACKGROUND: According to induced sputum cell count, four different asthma phenotypes have been recognized (eosinophilic, neutrophilic, mixed and paucigranulocytic). The aim of this study was to detect functional and inflammatory characteristics of patients with paucigranulocytic asthma. METHODS: A total of 240 asthmatic patients were categorized into the four phenotypes according to cell counts in induced sputum. All patients underwent pulmonary function tests, and measurement of fraction of exhaled nitric oxide (FeNO)...
April 13, 2017: Allergy
https://www.readbyqxmd.com/read/28363401/neutrophilic-steroid-refractory-recurrent-wheeze-and-eosinophilic-steroid-refractory-asthma-in-children
#9
Tamazoust Guiddir, Philippe Saint-Pierre, Elsa Purenne-Denis, Nathalie Lambert, Yacine Laoudi, Rémy Couderc, Rahelé Gouvis-Echraghi, Flore Amat, Jocelyne Just
BACKGROUND: Little is known about inflammatory pathways of severe recurrent wheeze in preschool children and severe asthma in children. OBJECTIVES: The aim of the Severe Asthma Molecular Phenotype cohort was to characterize phenotypes of severe recurrent wheeze and severe asthma during childhood in terms of triggers (allergic or not), involved cells (eosinophil or neutrophil), and corticoid responsiveness. METHODS: Children with moderate-to-severe asthma and preschool children with moderate-to-severe recurrent wheeze were enrolled prospectively...
March 28, 2017: Journal of Allergy and Clinical Immunology in Practice
https://www.readbyqxmd.com/read/28348726/targeting-patients-with-asthma-for-omalizumab-therapy-choosing-the-right-patient-to-get-the-best-value-for-money
#10
REVIEW
Abir Al Said, Breda Cushen, Richard W Costello
The asthma syndrome has many manifestations, termed phenotypes, that arise by specific cellular and molecular mechanisms, termed endotypes. Understanding an individual's asthma phenotype helps clinicians make rational therapeutic decisions while the understanding of endotypes has led to the development of specific precision medications. Allergic asthma is an example of an asthma phenotype and omalizumab, a monoclonal antibody that neutralizes serum immunoglobulin (Ig)E, is a specific targeted treatment which was developed as a result of an understanding of the endotype of allergic asthma...
February 2017: Therapeutic Advances in Chronic Disease
https://www.readbyqxmd.com/read/28263381/obesity-promotes-prolonged-ovalbumin-induced-airway-inflammation-modulating-t-helper-type-1-th1-th2-and-th17-immune-responses-in-balb-c-mice
#11
F M C Silva, E E Oliveira, A C C Gouveia, A S S Brugiolo, C C Alves, J O A Correa, J Gameiro, J Mattes, H C Teixeira, A P Ferreira
Clinical and epidemiological studies indicate that obesity affects the development and phenotype of asthma by inducing inflammatory mechanisms in addition to eosinophilic inflammation. The aim of this study was to assess the effect of obesity on allergic airway inflammation and T helper type 2 (Th2) immune responses using an experimental model of asthma in BALB/c mice. Mice fed a high-fat diet (HFD) for 10 weeks were sensitized and challenged with ovalbumin (OVA), and analyses were performed at 24 and 48 h after the last OVA challenge...
March 6, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28260352/extra-esophageal-presentation-of-gerd-new-understanding-in-a-new-era
#12
Irene Martinucci, Eleonora Albano, Santino Marchi, Corrado Blandizzi
Associations of gastroesophageal reflux disease (GERD) with extraesophageal manifestations, such as chronic cough, asthma, and laryngitis, are reported frequently, and there is a strong evidence of biological plausibility in support of this relationship. On the other hand, extraesophageal reflux disease (EERD) is usually multifactorial in nature with reflux being just one of the several potential contributing cofactors. Moreover, the accuracy of currently available diagnostic tests for EERD is suboptimal, and therefore the causal relationship between GERD and EERD remains far from being conclusively proven...
March 3, 2017: Minerva Gastroenterologica e Dietologica
https://www.readbyqxmd.com/read/28208047/targeted-therapy-for-chronic-respiratory-disease-a-new-paradigm
#13
REVIEW
Peter G Gibson, Matthew J Peters, Claire E Wainwright
Targeted therapy has emerged as a highly effective treatment approach for chronic respiratory diseases. Many of these conditions have dismal outcomes; however, targeted therapy shows great results for the subgroup who respond. This represents a new way to approach these conditions and offers great promise as a future treatment direction. In severe eosinophilic asthma, therapy that targets the interleukin-5 pathway with monoclonal antibodies leads to a 50% reduction in asthma exacerbations in previously refractory disease...
February 20, 2017: Medical Journal of Australia
https://www.readbyqxmd.com/read/28197221/factors-leading-to-refractory-asthma-in-patients-from-saudi-arabia
#14
Amal M Al-Moamary, Mohamed S Al-Hajjaj, Mohamed S Al Moamary
AIM: The aim of this study was to study the clinical characteristic of patient with refractory asthma (RA) from Saudi Arabia. METHODS: This paper prospectively studied in a university hospital factors leading to RA in a cohort of patients who have inadequately controlled asthma or with frequent exacerbations despite optimum controller therapy. It also studied patients with asthma that requires extended periods of oral steroids to control. RESULTS: The mean age was 45...
January 2017: Annals of Thoracic Medicine
https://www.readbyqxmd.com/read/28187115/clinical-course-of-enterovirus-d68-in-hospitalized-children
#15
Jennifer E Schuster, Rangaraj Selvarangan, Ferdaus Hassan, Kayla B Briggs, Lindsay Hays, Jenna O Miller, Barbara Pahud, Henry T Puls, Mary Ann Queen, Marita T Thompson, Gina Weddle, Mary Anne Jackson
BACKGROUND: Enterovirus D68 (EV-D68) has been sporadically reported as a cause of respiratory tract infections. In 2014, an international outbreak of EV-D68 occurred and caused severe respiratory disease in the pediatric population. METHODS: A retrospective chart review was performed of children admitted to Children's Mercy Hospital from August 1, 2014, to September 15, 2014, with positive multiplex polymerase chain reaction testing for EV/rhinovirus (RV). Specimens were subsequently tested for EV-D68, and clinical data were obtained from the medical records...
March 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/28187065/clinical-course-of-enterovirus-d68-in-hospitalized-children
#16
Jennifer E Schuster, Rangaraj Selvarangan, Ferdaus Hassan, Kayla B Briggs, Lindsay Hays, Jenna O Miller, Barbara Pahud, Henry T Puls, Mary Ann Queen, Marita T Thompson, Gina Weddle, Mary Anne Jackson
BACKGROUND: Enterovirus D68 (EV-D68) has been sporadically reported as a cause of respiratory tract infections. In 2014, an international outbreak of EV-D68 occurred and caused severe respiratory disease in the pediatric population. METHODS: A retrospective chart review was performed of children admitted to Children's Mercy Hospital from August 1-September 15, 2014 with positive multiplex PCR testing for enterovirus/rhinovirus (EV/RV). Specimens were subsequently tested for EV-D68, and clinical data were obtained from the medical records...
December 13, 2016: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/28145942/clinical-pathologic-correlation-of-sarcoidosis-associated-multifocal-chorioretinitis-in-an-elderly-patient
#17
Mohamed G A Saleh, John L OʼDonnell, Ronald P Davis, David Wilson, Phoebe Lin
BACKGROUND/PURPOSE: To describe a case of histopathologic clinical correlation of sarcoidosis-related multifocal chorioretinitis in an elderly individual. METHODS: This is a single case report and review of the pertinent literature. A 72-year-old white woman with a history of asthma was referred with bilateral asymmetric low-grade chronic panuveitis with advancing peripheral punched-out chorioretinal lesions despite systemic corticosteroid treatment. RESULTS: Coalescent chorioretinal punched-out lesions on fundus examination in the more severely affected right eye did not respond to corticosteroid treatment, and the refractory nature resulted in a suspicion of intraocular lymphoma despite a previous inconclusive diagnostic vitrectomy result...
January 31, 2017: Retinal Cases & Brief Reports
https://www.readbyqxmd.com/read/28143691/changing-paradigms-in-the-treatment-of-severe-asthma-the-role-of-biologic-therapies
#18
Rohit K Katial, Greg W Bensch, William W Busse, Bradley E Chipps, Joshua L Denson, Anthony N Gerber, Joshua S Jacobs, Monica Kraft, Richard J Martin, Parameswaran Nair, Michael E Wechsler
Cytokine antagonists are monoclonal antibodies that offer new treatment options for refractory asthma but will also increase complexity because they are effective only for patients with certain asthma subtypes that remain to be more clearly defined. The clinical and inflammatory heterogeneity within refractory asthma makes it difficult to manage the disease and to determine which, if any, biologic therapy is suitable for a specific patient. The purpose of this article is to provide a data-driven discussion to clarify the use of biologic therapies in patients with refractory asthma...
March 2017: Journal of Allergy and Clinical Immunology in Practice
https://www.readbyqxmd.com/read/28137226/management-of-status-asthmaticus-in-children
#19
Kam-Lun E Hon, Alexander K C Leung
BACKGROUND: Status asthmaticus is an acute exacerbation of asthma that is persistent and intractable and remains unresponsive to initial treatment with bronchodilators and systemic corticosteroids and that can result in hypoxemia, hypercarbia, and secondary respiratory failure. METHOD: We reviewed treatment and recent patents on management of status asthmaticus. CONCLUSIONS: Supplemental oxygen should be given to maintain an oxygen saturation of ≥92% in room air...
January 30, 2017: Recent Patents on Inflammation & Allergy Drug Discovery
https://www.readbyqxmd.com/read/28127050/hmscs-suppress-neutrophil-dominant-airway-inflammation-in-a-murine-model-of-asthma
#20
Gyong Hwa Hong, Hyouk-Soo Kwon, Kyoung Young Lee, Eun Hee Ha, Keun-Ai Moon, Seong Who Kim, Wonil Oh, Tae-Bum Kim, Hee-Bom Moon, You Sook Cho
Although chronic eosinophilic inflammation is a common feature in patients with asthma, some patients have neutrophil-dominant inflammation, which is known to be associated with severe asthma.Human mesenchymal stem cells (hMSCs) have shown promise in treating various refractory immunological diseases. Thus, hMSCs may represent an alternative therapeutic option for asthma patients with neutrophil-dominant inflammation, in whom current treatments are ineffective. BALB/c mice exposed to ovalbumin and polyinosinic:polycytidylic acid (Poly I:C) to induce neutrophilic airway inflammation were systemically treated with hMSCs to examine whether the hMSCs can modulate neutrophilic airway inflammation...
January 27, 2017: Experimental & Molecular Medicine
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