TNF-Alpha Antagonism in Severe Asthma?
Summary of "TNF-Alpha Antagonism in Severe Asthma?"
A small minority of patients with asthma have severe disease that is refractory or poorly responsive and remain persistently symptomatic despite maximal inhaled therapy. These patients represent an important unmet clinical need as they suffer considerable morbidity and mortality and consume a disproportionately large amount of health care resource. Tumour necrosis factor- alpha (TNF- alpha) is a pro-inflammatory cytokine that has been implicated in many aspects of the airway pathology in asthma. Evidence is emerging to suggest that it may play an important role in severe, refractory disease. The development of novel TNF-alpha antagonist has allowed us to test the role of this cytokine in vivo. Early studies demonstrated an improvement in asthma quality-of-life, lung function, airway hyperresponsiveness (AHR) and a reduction in exacerbation frequency, in patients treated with anti-TNF- alpha therapy. However, there is marked heterogeneity in response suggesting that benefit is likely to be reserved to a small sub-group. This view is supported by the lack of efficacy in later large clinical trials, although subgroups of responders were identified. Importantly, concerns have been raised about the safety of anti-TNF- alpha therapies in severe asthma. Therefore current evidence suggests that the risk of anti- TNF- alpha therapies outweighs benefit in severe asthma. In this review we will discuss the role of TNF- alpha biology and its role in severe asthma, the clinical trials conducted so far and summarize the patents related to TNF- alpha and the antagonist drug therapies.
Affiliation
Institute of Lung Health, University of Leicester, Department of Infection, Inflammation and Immunity, Leicester, LE3 9QP, UK. ceb17@le.ac.u.
Journal Details
This article was published in the following journal.
Name: Recent patents on inflammation & allergy drug discovery
ISSN: 1872-213X
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20807193
- DOI: http://dx.doi.org/
Medical and Biotech [MESH] Definitions
Synephrine
Sympathetic alpha-adrenergic agonist with actions like PHENYLEPHRINE. It is used as a vasoconstrictor in circulatory failure, asthma, nasal congestion, and glaucoma.
Prostaglandins F
(9 alpha,11 alpha,13E,15S)-9,11,15-Trihydroxyprost-13-en-1-oic acid (PGF(1 alpha)); (5Z,9 alpha,11,alpha,13E,15S)-9,11,15-trihydroxyprosta-5,13-dien-1-oic acid (PGF(2 alpha)); (5Z,9 alpha,11 alpha,13E,15S,17Z)-9,11,15-trihydroxyprosta-5,13,17-trien-1-oic acid (PGF(3 alpha)). A family of prostaglandins that includes three of the six naturally occurring prostaglandins. All naturally occurring PGF have an alpha configuration at the 9-carbon position. They stimulate uterine and bronchial smooth muscle and are often used as oxytocics.
Epinephrine
The active sympathomimetic hormone from the adrenal medulla. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics.
Ephedrine
A phenethylamine found in EPHEDRA SINICA. PSEUDOEPHEDRINE is an isomer. It is an alpha- and beta-adrenergic agonist that may also enhance release of norepinephrine. It has been used for asthma, heart failure, rhinitis, and urinary incontinence, and for its central nervous system stimulatory effects in the treatment of narcolepsy and depression. It has become less extensively used with the advent of more selective agonists.
Glycogen Debranching Enzyme System
1,4-alpha-D-Glucan-1,4-alpha-D-glucan 4-alpha-D-glucosyltransferase/dextrin 6 alpha-D-glucanohydrolase. An enzyme system having both 4-alpha-glucanotransferase (EC 2.4.1.25) and amylo-1,6-glucosidase (EC 3.2.1.33) activities. As a transferase it transfers a segment of a 1,4-alpha-D-glucan to a new 4-position in an acceptor, which may be glucose or another 1,4-alpha-D-glucan. As a glucosidase it catalyzes the endohydrolysis of 1,6-alpha-D-glucoside linkages at points of branching in chains of 1,4-linked alpha-D-glucose residues. Amylo-1,6-glucosidase activity is deficient in glycogen storage disease type III.
PubMed Articles
Emergency Treatment of Asthma.
To the Editor: In the article by Lazarus (Aug. 19 issue),(1) the author provides a comprehensive and balanced review of the emergency treatment of asthma but does not discuss the controversy around th...
Emergency Treatment of Asthma.
To the Editor: In the article by Lazarus (Aug. 19 issue),(1) the author provides a comprehensive and balanced review of the emergency treatment of asthma but does not discuss the controversy around th...
Emergency Treatment of Asthma.
To the Editor: In the article by Lazarus (Aug. 19 issue),(1) the author provides a comprehensive and balanced review of the emergency treatment of asthma but does not discuss the controversy around th...
Endobronchial Biopsy: A Guide for Asthma Therapy Selection in the Era of Bronchial Thermoplasty.
Objective. Bronchial thermoplasty (BT) reduces airway smooth muscle in patients with severe asthma. We developed a novel standardized histologic grading system assessing inflammation and structural re...
The Influence of Schizophyllum commune on Asthma Severity.
BACKGROUND: The sensitization and exposure to fungal allergens have been reported to be associated with asthma. The aim of this study was to clarify the impact of sensitization t...
Clinical Trials
TNF Alpha in Refractory Asthma
The purpose of this study was to investigate whether the administration of etanercept to patients with severe asthma improved their asthma related quality of life and a measure of the degr...
Inflammation and Corticosteroid Responsiveness in Severe Asthma
Some patients with mild asthma may develop severe asthma. It is not known what makes patients with mild asthma become severe, and we plan to find out why this happens. Patients with sever...
Dose Ranging Efficacy And Safety With Mepolizumab in Severe Asthma
The purpose of this study is to show whether mepolizumab given every 4 weeks intravenously (i.v.) can reduce the frequency of asthma exacerbations in subjects with severe asthma despite re...
The purpose is to determine if: 1) Escitalopram treatment will be associated with less oral corticosteroid use than placebo in outpatients with severe asthma and moderate or severe major d...
Redox Determinants in Severe Asthma
Hypotheses: 1) Airway pH regulation is abnormal in severe asthma; 2) In severe asthma, there is formation of cytotoxic nitrogen oxides and loss of beneficial nitrogen oxides in the airways
