Allergic rhinitis is an increasingly prevalent disorder, affecting up to 40% of children and up to 30% of adults in the
The classification of allergic rhinitis has recently been revised and the disease is now categorised as either intermittent or persistent. The Allergic Rhinitis in Asthma (ARIA) guidelines drawn up under the auspices of the World Health Organization subdivide intermittent and persistent disease into mild and moderate–severe, depending on the impact on quality of life. When allergic rhinitis is sufficiently severe to disturb sleep, interfere with school or work performance, disturb everyday social and sporting abilities or if any symptom is particularly troublesome, it is classified as moderate–severe.
With the exception of moderate–severe persistent disease, for which intranasal corticosteroids are considered first-line therapy, oral or intranasal H1 antihistamines are a first choice for treatment of allergic rhinitis. According to the ARIA guidelines, H1 antihistamines can also be considered as a supplementary therapy in moderate–severe persistent disease.
H1 antihistamines have evolved substantially since the first molecules were synthesised in 1937, moving from poorly selective, centrally active molecules to selective, less sedating compounds. The so-called second-generation antihistamines have been developed further by the selection of active metabolites, which eliminated the problems of cytochrome P450-related drug interactions and cardiotoxicity of the parent compounds. An alternative approach has been to develop the active enantiomer of a parent compound to provide improved antihistaminic profiles. Although some of these molecules retain the potential to modify central nervous system function, this generally occurs with higher than standard doses and with considerably less frequency than with the first-generation antihistamines. In addition, these molecules are devoid of adverse effects on the heart, and therefore represent effective and well-tolerated treatments for modern day use.
Oral therapy has advantages over the intranasal route because the drug acts effectively at sites other than the nose, such as the eye, pharynx, palate and lower airways, which are commonly affected in seasonal allergic disease.
Of growing interest is the ability of second-generation H1 antihistamines to modify other histamine-dependent events that underlie symptom expression in allergic rhinitis. For example, histamine up-regulates expression of adhesion molecules on the vascular endothelium, such as selectins, which are involved in recruitment of leucocytes during the allergic inflammatory process. Expression of intercellular adhesion molecule (ICAM)-1 is also up-regulated in the airway epithelium. ICAM-1 is considered to be a major ligand for rhinovirus attachment and has led to the hypothesis that oral H1 antihistamines may be of benefit in childhood asthma to prevent exacerbations. A preventative role for these agents in the development and progression of allergic disease has also been explored, as histamine is known to be a key stimulus in the directed maturation of antigen presenting cells. Histamine can also activate macrophages to enhance their cytokine synthesis and can influence eosinophil behaviour.
Our growing awareness of the multiple effects of histamine means that, in the future, the role of second-generation H1 antihistamines is likely to extend beyond their present position in symptomatic therapy in allergic rhinitis.
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This Editorial has been written by the specialist opinion leader, Dr Peter Howarth,
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Last updated on: 27/08/2010 11:40:18