The role of nonsedating antihistamines in asthma therapy.
There is well-established evidence that histamine plays a significant role as a chemical mediator in asthma. However, although antihistamines are commonly used for the treatment of allergic rhinitis, their use in asthma has been somewhat controversial. Mechanistically, their application for asthma appears logical. In addition to their effects at the histamine receptor, antihistamines, in a dose-dependent fashion, inhibit the release of preformed mediators such as histamine and mediators synthesized de novo including the metabolities of arachidonic acid from mast cells and basophils. Antihistamines also show, in a concentration-dependent manner, anti-inflammatory and immunomodulatory activity through their effects on epithelial cells, endothelial cells, macrophages, eosinophils, and T lymphocytes. Clinically, there appears to be a link between allergic rhinitis and asthma such that treatment of the upper airway has been shown to benefit lower airway disease. Of interest is that although antihistamines have been shown to reduce asthma symptoms and improve quality of life, generally, they have not, at doses sufficient to control rhinitis, improved objective measures of lung function. This could potentially be achieved, in a fashion similar to that observed in concentration-dependent in vitro studies, by using higher medication levels. However, most antihistamines, both first- and second-generation, cannot be used above recommended doses without causing unacceptable side effects including sedation and psychomotor function impairment. As newer antihistamines with improved therapeutic indices have been developed, asthma studies can and must be conducted to evaluate high-dose therapy with the potential of reaping the anti-inflammatory and immunomodulatory effects of these drugs.
Zitt
Myron J
MJ
Department of Medicine, Division of Allergy and Immunology, State University of New York at Stony Brook, Stony Brook, New York, USA.
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects; D004804:Eosinophils / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects; D006632:Histamine / Q000378:metabolism; D017442:Histamine Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D006993:Hypnotics and Sedatives / Q000009:adverse effects; D016676:Macrophages, Alveolar / Q000187:drug effects; D008407:Mast Cells / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D017442:Histamine Agonists; D006993:Hypnotics and Sedatives; D006632:Histamine