Clinical & Experimental Allergy Reviews最新文献

Patients with allergic rhinitis (AR) report ocular symptoms 40–70% of the time. These symptoms can be burdensome and have a major impact on patients' quality of life. Most clinicians believe that ocular symptoms result from direct contact of allergen with the conjunctiva, although other explanations such as a nasal-ocular reflex, blockage of the nasal lacrimal duct, and systemic effects of cytokines released from the nasal mucosa can explain the association. However, if direct contact by an allergen is the sole explanation, how do we explain the efficacy of intranasal steroids on the eye symptoms of AR, especially because most intranasal steroids have <0.5% systemic bioavailability? This paper highlights a potential mechanism for the development of ocular symptoms after nasal exposure to antigen, the nasal-ocular reflex, and speculates how intranasal steroids can affect this reflex and eye symptoms. Two nasal-challenge studies assessing the nasal-ocular reflex are presented. The first shows the presence of a nasal-ocular reflex in response to localized nasal-antigen challenge, which is initiated by the release of histamine and blocked by a topical, intranasal antihistamine. The second study shows that the nasal-ocular reflex is augmented with repeated nasal antigen challenge, a response that is inhibited by pretreatment with an intranasal steroid. These studies provide an explanation for the way in which treatment with intranasal steroids can work locally in the nose to reduce ocular symptoms in patients with AR. This explanation, however, would only be valid if the majority of eye symptoms in patients with AR were caused by the nasal-ocular reflex and not by direct contact of antigen with the conjunctiva – an assumption supported by clinical studies.

Pollen immunotherapy exerts greater efficacy in the pollen season when the pollen count is not high than when it is high. Every pollen season, around half or more patients who have received pollen immunotherapy for >5 years are judged as good responders; those who have received immunotherapy for <5 years generally do less well. Therefore, the clinical response seems to depend on natural pollen counts and the duration of immunotherapy. In this study, peripheral blood mononuclear cells (PBMCs) were sampled before and during the pollen season to examine IL-4, IL-5, and IFN-γ levels. It was revealed that pollen immunotherapy could decrease IL-4 and -5 expression by pollen antigen-stimulated PBMCs. When patients under immunotherapy were divided into good and poor response groups, clinical effectiveness was related to the depressed level of IL-5 synthesis, but not to that of IL-4 synthesis. Our study suggests that a decrease of IL-5 expression during the pollen season is a key working mechanism of immunotherapy related to clinical effectiveness. In our patients, the incidence of systemic reactions was 5.8%/patient and <0.1%/injection. A higher incidence of systemic reactions was observed in patients with the presence or a past history of asthma, the presence but not a past history of atopic dermatitis, and higher levels of total IgE (>1000 U/mL). The incidence of systemic reactions in patients with 1 risk factor such as asthma, atopic dermatitis, and high IgE was 16.9%/patient and 0.1%/injection, whereas that in those without risk factors was 1.6%/patient and <0.1/injection.

Although Vidian neurectomy is very effective as a means of alleviating symptoms of chronic rhinitis (allergic rhinitis and vasomotor rhinitis), it is presently seldom used because of a high incidence of complications such as disturbed lacrimal secretion and sensory disorders of the cheek and gum. In 1997, Kikawada succeeded in endoscopically cutting the posterior nasal nerve (a ramus of the Vidian nerve) at the level of the sphenopalatine foramen under clear vision. This technique has since been improved into one that allows safe and rapid completion of the operation using a bipolar device. This new technique of endoscopic posterior nasal neurectomy with a bipolar device will be presented in this paper.

Glucocorticoids are lipid substances synthesized by the adrenal cortex that are essential for life and regulate myriad physiological processes ubiquitously in organs and tissues as mediated by intracellular glucocorticoid receptors (GRs). From the clinical standpoint, although glucocorticoids have potent anti-inflammatory and immunosuppressive effects, their adverse effects profiles and so-called glucocorticoid resistance are barriers to their widespread use. GRβ, a splice variant isoform of GRα, the predominant isoform of the receptor, and co-activators and co-repressors are believed to be important for GR-mediated actions. The mechanism of action of GRα and its co-activators and co-repressors and the mechanism of resistance to glucocorticoid treatment were investigated by confocal microscopic imaging of GRα and GRβ and by assessing protein–protein interaction of GRα and nuclear factor-κB and of GRα and activator protein-1 (AP-1). The possibility of new drug development of selective GR modulators, which reduce GR-related adverse effects such as steroid-induced osteoporosis, steroid-induced diabetes mellitus, and infection yet confer beneficial anti-inflammatory effects and immunosuppressive action is discussed.

Cysteinyl leukotrienes, a group of compounds with potent bioactivity to constrict bronchial smooth muscle cells and recruit eosinophils and other inflammatory cells into the airways, act as key modulators of the pathophysiology of allergic rhinitis and asthma. Drugs targeting leukotriene-related molecules such as leukotriene synthase inhibitors and CysLT₁-receptor antagonists are widely used as safe and effective agents for the treatment of these diseases. The main limitation of anti-leukotriene drugs, however, is that there is a substantial proportion of patients who do not respond to these drugs. Therefore, identification of genetic and non-genetic factors that determine the pharmacologic response should further increase the usefulness of anti-leukotriene drugs. We undertook a multidirectional approach based on the assumption that the pharmacologic response to anti-leukotriene drugs is determined by factors related to pharmacokinetics such as drug metabolism, and pharmacodynamics such as the expression and function of leukotriene synthases and receptors. Among patients with asthma, we identified two genetic variations (polymorphisms) in the promoter of arachidonate 5-lipoxygenase and leukotriene C₄ synthase as possible factors to distinguish responders from non-responders to anti-leukotriene drugs. This pharmacogenetic approach might be useful to establish the basis of individualized treatment for patients with asthma as well as those with allergic rhinitis.

Allergic rhinitis (AR) is a common manifestation of allergic diseases, affecting 10–25% of the world's population. In the tropics, the majority of AR is persistent. The year-round warm, humid climate is conducive for the proliferation of dust mites and moulds, two of the most common aeroallergens implicated in persistent allergic rhinitis (PAR). The management of AR includes patient education, allergen avoidance, pharmacological treatment, and specific immunotherapy. Patient education, especially regarding dust and mould exposure reduction, can be effective but is often under-utilized. Second generation, non-sedating H₁-antihistamines rapidly relieve most nasal symptoms because they effectively block the histamine H₁-receptors that trigger plasma exudation and oedema. Congestion is most effectively controlled by intranasal glucocorticosteroids (INSs), which are currently the most potent AR drug treatment. The beneficial effects of steroids depend on their long-term, multi-pathway anti-inflammatory effects, unlike H₁-antihistamines, which directly block neural and vascular H₁ receptors. However, especially in PAR, patients' compliance with INS therapy has a significant impact on treatment efficacy, because year-round treatment is required. Subcutaneous inhalant allergen immunotherapy (SCIT) is effective against a broad range of AR symptoms, and may be able to alter the natural course of allergy and prevent asthma onset. SCIT can significantly reduce the severity of allergic disease, including nasal obstruction, and decrease the need for anti-allergic drugs. Immunotherapy (IT) can also be given as sublingual drops (SLIT). Recent studies have shown the SLIT to be effective in reducing AR symptoms and medication use. Both types of IT require long-term patient compliance for successful treatment. Drug and IT interventions may not be economically feasible in certain patients. In conclusion, the type of AR most prevalent in the tropics is PAR, which must be treated year round. Improvement of educational programmes for the public and physicians alike seems to be the most effective treatment strategy.

Glucocorticosteroids are the most effective drugs for controlling inflammation of allergic rhinitis (AR). Because of their strong pharmacological action, which can be a so-called ‘double-edged sword’, glucocorticosteroids are usually taken intranasally so as to reduce their potential for eliciting adverse effects. Accumulating evidence suggests that intranasal glucocorticosteroids control not only nasal symptoms but also ocular symptoms. In contrast to sedating H₁-receptor antagonists, intranasal glucocorticosteroids can improve impaired performance such as daytime sleepiness associated with AR. In Japanese cedar pollinosis, treatment begun immediately after initiation of pollen release or onset of initial symptoms, known as prophylactic (initial) treatment, is recommended. The current version of the practical guideline for management of allergic rhinitis in Japan recommends the use of chemical mediator release inhibitors, second-generation H₁-receptor antagonists, or leukotriene receptor antagonists for prophylactic treatment. However, recent evidence suggests that intranasal glucocorticosteroids might also be useful as first-line drugs for prophylactic treatment. The molecular mechanism of anti-inflammatory action of glucocorticosteroids supports this contention. Moreover, a meta-analysis of studies of intranasal glucocorticosteroids given as monotherapy has revealed that these agents are superior to oral H₁-receptor antagonists and leukotriene antagonists for controlling major symptoms of AR. These findings suggest that glucocorticosteroids, especially intranasal glucocorticosteroids, might be positioned as first-line drugs for the treatment of both perennial and seasonal AR.