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.