Asthma therapy in the new millennium.
Bronchial asthma is one of the most common chronic diseases in modern society and yet, despite the availability of highly effective drugs, there is increasing evidence to suggest that its incidence is increasing. It is a general health problem in several industrialised countries and will remain one for the next decades. With regard to asthma pathogenesis, our understanding has increased tremendously over the last two decades. Therefore, the potential for specific targeted and constructed therapies has become evident. Monoclonal antibodies to IgE, soluble receptors or antibodies to certain cytokines such as IL-4 and IL-5 are being investigated as possible treatments for asthma. Besides the already known receptor antagonists, new compounds directed to novel receptor types (e.g. cytokine, adenosine, adhesion molecules, etc.) are now under development. New targets in the cytosol will come into focus. Preliminary studies of selective phosphodiesterase (PDE) inhibitors in asthmatic patients have been encouraging. It is also very likely that the use of glucocorticoids cannot be excluded from therapy. However, we should generate new glucocorticoids with less side-effects, probably by using the so-called retrometabolic drug design. The first representative of this new steroid class, loteprednol is already approved for the therapy of certain allergic disorders. Because asthma is a disease of many different gene polymorphisms, gene therapy seems to be of low success at present. Alternatively, antisense oligonucleotides could be used. Future developments may also include strategies targeting the remodeling of structural elements of the airways. Today's intensive search for new treatments should ensure a greater diversity of therapeutic possibilities for the management of asthma in the next millennium.
Pahl
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Department of Experimental and Clinical Pharmacology and Toxicology, Friedrich-Alexander-University of Erlangen, Germany. pahl@pharmakologie.uni-erlangen.de
Szelenyi
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D001249:Asthma / Q000628:therapy*; D002462:Cell Membrane / Q000187:drug effects; D016207:Cytokines / Q000037:antagonists & inhibitors; D015316:Genetic Therapy; D006801:Humans; D007073:Immunoglobulin E / Q000502:physiology; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects
D016207:Cytokines; D016328:NF-kappa B; D016376:Oligonucleotides, Antisense; D007073:Immunoglobulin E