The Role of Histamine in the Pathophysiology of Asthma and the Clinical Efficacy of Antihistamines in Asthma Therapy

Mast cells play a critical role in the pathogenesis of allergic asthma. Histamine is a central mediator released from mast cells through allergic reactions. Histamine plays a role in airway obstruction via smooth muscle contraction, bronchial secretion, and airway mucosal edema. However, previous clinical trials of H1 receptor antagonists (H1RAs) as a treatment for asthma were not successful. In recent years, type 2 innate immunity has been demonstrated to be involved in allergic airway inflammation. Allergic asthma is defined by IgE antibody-mediated mast cell degranulation, while group 2 innate lymphoid cells (ILC2) induce eosinophilic inflammation in nonallergic asthma without allergen-specific IgE. Anti-IgE therapy has demonstrated prominent efficacy in the treatment of severe allergic asthmatics sensitized with specific perennial allergens. Furthermore, recent trials of specific cytokine antagonists indicated that these antagonists were effective in only some subtypes of asthma. Accordingly, H1RAs may show significant clinical efficacy for some subtypes of allergic asthma in which histamine is deeply associated with the pathophysiology.