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Biomedical subjects

Stephen T Holgate

Publications and source records attributed to Stephen T Holgate.

94 records · Page 6Linked to original sources

H1-antihistamines in asthma.

Histamine released from mast cells and basophils is an important mediator of airway inflammation in asthma, particularly in the development of the early allergic response. Although histamine has been shown to contribute significantly to the bronchoconstrictor response to allergen or exercise, leukotrienes are likely to play a more prominent role in these responses in asthma. The improved specificity, tolerability, and safety profile of the second-generation H1-antagonists associated with anti-inflammatory activities and bronchodilator activities, may contribute to relieve the symptoms of the upper and lower airways in patients with coexistent mild seasonal asthma and allergic rhinitis. Considering the global rise in the prevalence of allergy and asthma, the suggestion that H1-antagonists may delay the onset of asthma in infants is of considerable interest and merits further assessment. Although it is unlikely that monotherapy with most currently available H1-antagonists will provide significant clinical benefit in asthma, the potential of combined antihistamine and antileukotriene therapy may prove useful, particularly in subjects with poor compliance to inhaled corticosteroid therapy.

Asthma↗

Cytokine and anti-cytokine therapy for the treatment of asthma and allergic disease.

Until recently, the only controller treatment for chronic asthma has been corticosteroids. However, identification of specific effector molecules in asthma has led to targeting of specific pathways by using cytokines and cytokine inhibitors. Administration of a monoclonal blocking antibody against IgE has been shown to be highly efficacious in severe allergic asthma, but blockade of eosinophils using anti-IL-5 monoclonal antibodies has no clinical benefit. In more severe asthma, blockade of TNF-alpha using the decoy etanercept has revealed efficacy in a small open study suggesting that Th-1 in addition to Th-2 pathways are important as the disease adopts a more severe phenotype. It is likely that asthma is not a single disease but a group of disorders which differ in the relative contribution of specific pathophysiological pathways.

Asthma↗

Newer therapies for asthma: a focus on anti-IgE.

The prevalence of asthma and other allergic disorders has been on the increase not only in the western world but also in the developing countries. This increasing prevalence has lead research into the discovery and development of various new therapeutic strategies. The improved understanding about the pathophysiology of asthma has prompted the developments of novel molecules to tackle this problem. These include newer phosphodiesterase inhibitors, cytokine modulation strategies, allergen immunotherapy, and anti-IgE. Immunoglobulin E plays a major role in airway inflammation in asthma. Omalizumab, a novel humanised monoclonal antibody directed against the high affinity FcepsilonRI portion of the IgE has shown a lot of promise in the control of asthma symptoms and as a steroid sparing agent in the management of allergic asthma. This new molecule has an excellent safety profile and could play an important role in the management of patients with severe asthma. This review gives a brief overview of the newer therapies under investigation with special reference to omalizumab in the treatment of allergic asthma.

Anti-Allergic Agents↗