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severe refractory asthma

Jillian M Cavallari, Tara S Jawaro, Nadia I Awad, Patrick J Bridgeman
Glucagon, a hormone secreted by pancreatic alpha cells, causes bronchial smooth muscle relaxation by activating the synthesis of cyclic adenosine monophosphate. It was studied in the 1980s and 1990s as a treatment option for the management of asthma but has since not been evaluated. Data to support its use are limited, but it may serve as a last-line agent for refractory asthma exacerbation. Here we describe 4 cases in which intravenous glucagon was used to manage severe, refractory asthma exacerbation in the emergency department...
September 30, 2016: American Journal of Emergency Medicine
P Chicharro, P Rodríguez, D de Argila
Omalizumab is a recombinant humanized monoclonal antibody that inhibits immunoglobulin E. It has been approved for the treatment of severe asthma and chronic spontaneous urticaria refractory to other treatments. Its use in the management of chronic inducible urticaria (a type triggered by certain stimuli) is still considered off-label, although this use has been discussed in some consensus papers. This review brings together case reports and case series describing the use of omalizumab to treat chronic inducible urticaria...
October 5, 2016: Actas Dermo-sifiliográficas
Brian A Neff, Stephen G Voss, Matthew L Carlson, Erin K O'Brien, Joseph H Butterfield
OBJECTIVE/HYPOTHESIS: Eosinophilic otitis media (EOM) is a variant of chronic otitis media that is characterized by the development of thick mucoid middle ear effusion, adult onset bronchial asthma, sinonasal polyposis, and aspirin sensitivity. EOM is typically refractory to corticosteroid therapy and surgical intervention. Pegylated interferon (PEG-IFN) has effectively treated hypereosinophilic syndrome in clinical trials; however, the efficacy of this medication for EOM treatment remains undefined...
September 26, 2016: Laryngoscope
M A Portelli, C Moseley, C E Stewart, D S Postma, P Howarth, J A Warner, J W Holloway, G H Koppelman, C Brightling, I Sayers
RATIONALE: Genetic polymorphisms in the asthma susceptibility gene, urokinase plasminogen activator receptor (uPAR/PLAUR) have been associated with lung function decline and uPAR blood levels in asthma subjects. Preliminary studies have identified uPAR elevation in asthma; however, a definitive study regarding which clinical features of asthma uPAR may be driving is currently lacking. OBJECTIVES: We aimed to comprehensively determine the uPAR expression profile in asthma and control subjects utilizing bronchial biopsies and serum, and to relate uPAR expression to asthma clinical features...
October 5, 2016: Allergy
Marina Pretolani, Anders Bergqvist, Gabriel Thabut, Marie-Christine Dombret, Dominique Knapp, Fatima Hamidi, Loubna Alavoine, Camille Taillé, Pascal Chanez, Jonas S Erjefält, Michel Aubier
BACKGROUND: The effectiveness of bronchial thermoplasty (BT) has been reported in severe asthma, yet its impact on the different bronchial structures remains unknown. OBJECTIVE: To examine the effect of BT on bronchial structures and to explore their association with clinical outcome in severe refractory asthmatics. METHODS: Bronchial biopsies (n = 300) were collected from 15 severe uncontrolled asthmatics before and 3 months after BT. Immunostained sections were assessed for airway smooth muscle (ASM) area, sub-epithelial basement membrane thickness, nerve fibers and epithelium neuroendocrine cells...
September 5, 2016: Journal of Allergy and Clinical Immunology
Rekha Chaudhuri, Charles McSharry, Liam G Heaney, Robert Niven, Christopher E Brightling, Andrew N Menzies-Gow, Christine Bucknall, Adel H Mansur, Waiting Lee, Malcolm Shepherd, Mark Spears, Douglas C Cowan, Holger Husi, Neil C Thomson
BACKGROUND: Asthma in the elderly as well as asthma of adult-onset has been associated with increased morbidity, but little is known specifically about the effects of age on clinical and inflammatory outcomes in severe refractory asthma. The aims of the study were to examine the effects of age [<65 versus ≥65 years] and age of onset of asthma [childhood-onset, <18 versus adult-onset, ≥18 years] on clinical and inflammatory variables in patients with severe asthma. METHODS: In 1042 subjects with refractory asthma recruited to the British Thoracic Society Severe Asthma Registry, we compared patient demographics, disease characteristics and biomarkers of inflammation in patients aged <65 years (n = 896) versus ≥65 years (n = 146) and onset at age <18 years (n = 430) versus ≥18 years (n = 526)...
September 2016: Respiratory Medicine
Paul M O'Byrne, Hristo Metev, Margareta Puu, Kai Richter, Christina Keen, Mohib Uddin, Bengt Larsson, Marie Cullberg, Parameswaran Nair
BACKGROUND: Airway neutrophilic inflammation is a pathological feature in some patients with severe asthma. Stimulation of the chemokine receptor CXCR2 mediates neutrophil migration into the airways. We investigated the safety and efficacy of AZD5069, a CXCR2 antagonist, as an add-on therapy in patients with uncontrolled severe asthma. METHODS: In this multicentre, randomised, double-blind, placebo-controlled, dose-finding trial, we enrolled patients aged 18 years or older with uncontrolled asthma despite combination therapy with long-acting β2 agonists and medium-dose or high-dose inhaled corticosteroids...
October 2016: Lancet Respiratory Medicine
B N B M Prasad
Bronchial asthma is an inflammatory disorder of airways characterized by hyper-responsiveness to a wide range of triggers and is associated with variable airflow obstruction that remits spontaneously or with the treatment. Several phenotype of asthma not responding to the currently acceptable standard therapy of high dose inhaled gluco-corticosteroids along with along acting β2 agonists come under the purview of refractory asthma. This condition is a heterogeneous and complex disease that requires a multi-disciplinary approach to identify accurately various sub-phenotypes to enable improved understanding of the pathogenesis and development of effective management strategies including use of novel methods and targeted therapy...
July 2016: Medical Journal, Armed Forces India
Ching-Hsiung Lin, Shih-Lung Cheng
Despite the expansion of the understanding in asthma pathophysiology and the continual advances in disease management, a small subgroup of patients remain partially controlled or refractory to standard treatments. Upon the identification of immunoglobulin E and other inflammatory mediators, investigations and developments of targeted agents have thrived. Omalizumab is a humanized monoclonal antibody that specifically targets the circulating immunoglobulin E, which in turn impedes and reduces subsequent releases of the proinflammatory mediators...
2016: Drug Design, Development and Therapy
Yue Liu, Marchel G Hill, Thomas Klose, Zhenguo Chen, Kelly Watters, Yury A Bochkov, Wen Jiang, Ann C Palmenberg, Michael G Rossmann
Isolates of rhinovirus C (RV-C), a recently identified Enterovirus (EV) species, are the causative agents of severe respiratory infections among children and are linked to childhood asthma exacerbations. The RV-C have been refractory to structure determination because they are difficult to propagate in vitro. Here, we report the cryo-EM atomic structures of the full virion and native empty particle (NEP) of RV-C15a. The virus has 60 "fingers" on the virus outer surface that probably function as dominant immunogens...
August 9, 2016: Proceedings of the National Academy of Sciences of the United States of America
Garry M Walsh
INTRODUCTION: The development of monoclonal antibody-based biologics targeted at inhibition of the Th2 cytokines IL-4, IL-5 and IL-13 represent potentially effective treatments for patients with the glucocorticoid refractory eosinophilic asthma phenotype. AREAS COVERED: Asthma exhibits marked heterogeneity both clinically and at the molecular phenotypic level, requiring specifically targeted treatments to block the key pathways of the disease. It is becoming apparent that significant clinical effects with anti-cytokine-based biologic therapies are more likely in carefully selected patient populations that take asthma phenotypes into account...
August 2, 2016: Expert Review of Clinical Immunology
Srinivas Bandaru, Pramod Tarigopula, Jyothy Akka, Vijaya Kumar Marri, Ramesh Kumar Kattamuri, Anuraj Nayarisseri, Madhavi Mangalarapu, Swetha Vinukonda, Hema Prasad Mundluru, Someswar Rao Sagurthi
BACKGROUND: Thr164Ile polymorphism in the ADRB2 gene encoding β2 adrenergic receptor (β2AR) has its functional consequence in declining ligand-receptor interactions and depressed coupling of β2AR to adenylcyclase. In the present study, we sought to evaluate the possible association of Thr164Ile polymorphism with asthma susceptibility, pharmacogenetic response to Salbutamol and varying degrees of severity. METHODS: Three hundred and ninety eight clinically diagnosed patients and four hundred and fifty six healthy controls were enrolled in the study...
October 30, 2016: Gene
Pierachille Santus, Dejan Radovanovic
INTRODUCTION: Asthma is a chronic inflammatory disease characterized by bronchial hyper-reactivity. Although many currently available treatment regimens are effective, poor symptom control and refractory severe disease still represent major unmet needs. In the last years, numerous molecular therapeutic targets that interfere with the innate inflammatory response in asthma have been identified. Promising preliminary results concern the signaling cascade promoted by prostaglandin D2 (PGD2) and its receptor antagonists...
September 2016: Expert Opinion on Investigational Drugs
Neha M Dunn, Rohit K Katial
Patients with severe asthma and concomitant chronic rhinosinusitis often have severe, refractory upper and lower airway inflammation. This inflammation has been proposed to be similar throughout the upper and lower airways leading to the unified airways concept. This article reviews chronic rhinosinusitis with and without nasal polyps, and the subgroup with aspirin-exacerbated respiratory disease, while focusing on the relationship with asthma. Additionally, diagnosis and treatment with current and newer therapies are discussed...
August 2016: Immunology and Allergy Clinics of North America
Kuang-Yu Wei, Shan-Yueh Chang, Sheng-Huei Wang, Her-Young Su, Chen-Liang Tsai
Life-threatening refractory metabolic acidosis due to starvation ketoacidosis is rarely reported, even among nondiabetic pregnant women, and may be overlooked. Furthermore, stressful situations may increase the acidosis severity.In the present case, a nondiabetic multiparous woman was admitted for a near-fatal asthma attack and vomiting during the third trimester of pregnancy. She was intubated and rapidly developed high anion gap metabolic acidosis. We diagnosed the patient with starvation ketoacidosis based on vomiting with concomitant periods of stress during pregnancy and the absence of other causes of high anion gap metabolic acidosis...
June 2016: Medicine (Baltimore)
Peter J Barnes
Multiple kinases play a critical role in orchestrating the chronic inflammation and structural changes in the respiratory tract of patients with asthma and chronic obstructive pulmonary disease (COPD). Kinases activate signaling pathways that lead to contraction of airway smooth muscle and release of inflammatory mediators (such as cytokines, chemokines, growth factors) as well as cell migration, activation, and proliferation. For this reason there has been great interest in the development of kinase inhibitors as anti-inflammatory therapies, particular where corticosteroids are less effective, as in severe asthma and COPD...
July 2016: Pharmacological Reviews
Renata Rubinsztajn, Ryszarda Chazan
Asthma is a heterogeneous inflammatory disease. Most patients respond to current standard of care, i.e., bronchodilators, inhaled glucocorticosteroids and other anti-inflammatory drugs, but in some adequate asthma control cannot be achieved with standard treatments. These difficult-to-treat patients would be the target population for new biological therapies. At present, omalizumab is the only biological agent approved for the treatment of early-onset, severe IgE-dependent asthma. It is safe, effective, and well tolerated...
2016: Advances in Experimental Medicine and Biology
Xianglan Yao, Elizabeth M Gordon, Amisha V Barochia, Alan T Remaley, Stewart J Levine
New treatments are needed for patients with asthma who are refractory to standard therapies, such as individuals with a phenotype of "type 2-low" inflammation. This important clinical problem could potentially be addressed by the development of apolipoprotein A-I (apoA-I) mimetic peptides. ApoA-I interacts with its cellular receptor, the ATP-binding cassette subfamily A, member 1 (ABCA1), to facilitate cholesterol efflux out of cells to form nascent high-density lipoprotein particles. The ability of the apoA-I/ABCA1 pathway to promote cholesterol efflux from cells that mediate adaptive immunity, such as antigen-presenting cells, can attenuate their function...
August 2016: Chest
Kojiro Honda, Hiroo Wada, Masuo Nakamura, Keitaro Nakamoto, Toshiya Inui, Mitsuru Sada, Takashi Koide, Saori Takata, Takuma Yokoyama, Takeshi Saraya, Daisuke Kurai, Haruyuki Ishii, Hajime Goto, Hajime Takizawa
BACKGROUND: Recent reports have suggested an involvement of neutrophilic inflammation driven by interleukin (IL)-17 from Th17 cells, especially in severe, refractory asthma. It remains unknown about the possible interactions of this cytokine and other proinflammatory cytokines to direct neutrophilic airway inflammation. MATERIALS AND METHODS: We evaluated the effects of IL-17A, IL-17E, and IL-17F in combination with other stimuli such as tumor necrosis factor (TNF) -α on the production and expression of IL-8 in human bronchial epithelial cells...
May 2016: Experimental Lung Research
Katie Baker, Kristof Raemdonck, Bilel Dekkak, Robert J Snelgrove, John Ford, Fisnik Shala, Maria G Belvisi, Mark A Birrell
BACKGROUND: Asthma prevalence has increased world-wide especially in children; thus there is a need to develop new therapies that are safe and effective especially for patients with severe/refractory asthma. CD4(+) T cells are thought to play a central role in disease pathogenesis and associated symptoms. Recently, TRPV1 has been demonstrated to regulate the activation and inflammatory properties of CD4(+) cells. The aim of these experiments was to demonstrate the importance of CD4(+) T cells and the role of TRPV1 in an asthma model using a clinically ready TRPV1 inhibitor (XEN-D0501) and genetically modified (GM) animals...
2016: Respiratory Research
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