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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
Jeremy D Waldram, Ronald A Simon
Aspirin-exacerbated respiratory disease (AERD) is characterized by chronic rhinosinusitis with nasal polyps, asthma, and reactions to cyclooxygenase-1-inhibiting drugs. This condition is often refractory to standard medical treatments and results in aggressive nasal polyposis that often requires multiple sinus surgeries. Aspirin desensitization followed by daily aspirin therapy is an important treatment option, and its efficacy has been validated in multiple research studies. Aspirin desensitization is not without risk, but specific protocols and recommendations exist to mitigate the risk...
November 2016: Immunology and Allergy Clinics of North America
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
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
R Gonçalves, C Valente, E Ferreira, J E Serra, J Saraiva da Cunha
Cytomegalovirus is a double stranded DNA virus that can be present in nearly all organs and body fluids. The primary infection is usually asymptomatic in the immunocompetent host and it is common among adolescents and young adults. The symptomatic form appears, in the majority of cases, as a mononucleosis syndrome with full recovery without specific treatment. We report a case of a 25 years old woman who presented with hepatitis due to CMV infection and history of omalizumab administration one month earlier...
2016: IDCases
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
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
M Soledad Cabrera-Ramírez, M Sandra Domínguez-Sosa, Silvia Andrea Borkoski-Barreiro, Juan Carlos Falcón-González, Ángel Ramos-Macías
INTRODUCTION AND OBJECTIVES: Endoscopic sinus surgery is currently the surgical procedure chosen in cases of sinonasal polyposis refractory to medical treatment. The aim of this study was to show our experience in managing such patients operated using endoscopic sinus surgery. METHOD: A retrospective study of 246 patients with chronic rhinosinusitis and nasal polyps who were operated by endoscopic surgery. We studied the characteristics of the population, symptoms, grade of affectation, complications and recurrences...
August 8, 2016: Acta Otorrinolaringológica Española
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
Edward Noon, Claire Hopkins
Chronic rhinosinusitis has a significant impact on health-related and generic quality-of-life, has a high cost burden to both society and patients, and may be associated with absenteeism, loss of productivity and poor respiratory function. Though there is a paucity of level 1 evidence, endoscopic sinus surgery may be considered in medically refractory patients and a variety of objective and subjective outcome measures exist to assess the effectiveness of intervention. We outline the outcome measurements available and review in-depth the published outcomes to date...
2016: BMC Ear, Nose, and Throat Disorders
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)
S Nair, R S Bhadauria, S Sharma
BACKGROUND: Rhinosinusitis is a significant health problem which results in large financial burden on society. The study evaluated the prevalence and severity of individual symptoms of chronic rhinosinusitis (CRS) and the impact of endoscopic sinus surgery (ESS) on the symptoms and medication used in patients with CRS. METHODS: Patients with refractory CRS were assessed prospectively with ESS intervention. We studied the symptoms, change in medical therapy, complications of surgery and effect of other factors like smoking, polyposis and asthma on endoscopy and computed tomography scan scores...
January 2010: Medical Journal, Armed Forces India
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
Hideaki Shirasaki, Etsuko Kanaizumi, Tetsuo Himi
OBJECTIVE: The cysteinyl leukotrienes (CysLTs) are lipid mediators that have been implicated in the pathogenesis of allergic rhinitis. Pharmacological studies of CysLTs indicate that two classes of receptors, CysLT1R and CysLT2R exist. CysLT1R is a high affinity LTD4 receptor with lower affinity for LTC4, and a CysLT1R antagonist is currently used to treat asthma and allergic rhinitis. CysLT2R binds to LTC4 and LTD4 with equal affinity. GPR99 (also called GPR80), previously described as an oxoglutarate receptor (OXGR1), has recently emerged as a potential novel receptor with LTE4...
June 17, 2016: Auris, Nasus, Larynx
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