Inhaled corticosteroid therapy remains the basis for the treatment of chronic asthma. Recent understanding of its use includes the benefits of early introduction, and of its plateaued dose-benefit effects. Additional beneficial effects on asthma control and prevention of asthma exacerbations can be obtained by combining middle-to high-dose inhaled corticosteroid with long-acting β-agonists and slow-release theophylline. Leukotriene inhibitors, particularly leukotriene receptor antagonists, are novel treatments that may also be combined with inhaled steroid therapy. Although current asthma treatments are very effective, a subgroup of asthma patients (difficult or therapy-resistant asthma) do not respond adequately to these treatments and need maintained oral corticosteroid therapy. New asthma treatments are particularly needed for this group. New treatments for asthma include more potent topical corticosteroids which have less potential for side-effects, inhibition of eosinophil chemotaxis and activation such as anti-IL-5, anti-eotaxin, eotaxin receptor antagonist, anti-VL-A₄, anti-IgE therapy, restoring Th-1/Th-2 balance either by increasing Th-1 or reducing Th-2 T-cell activity, anti-inflammatory cytokines such as IL-10, and specific inhibitors of PDE₄. These treatments may be considered as either controllers, remitters (inducing remission of disease), or preventors according to their modes of action and their clinical effects. Currently, there does not appear to be any prospect of a cure for asthma.

View full abstract

Stinging insect allergy is a relatively common medical problem, responsible for an estimated 40 fatalities per year in the USA and considerable anxiety and lifestyle modification. There are no criteria to identify people at risk of initial venom anaphylaxis. Reactions may occur at any age and are unrelated to the time interval of prior venom exposure. There is an approximate 60% re-sting reaction rate in people who have had sting anaphylaxis and have positive venom skin tests. Re-sting reactions are more likely to occur in adults than in children and in people who have had more severe anaphylactic symptoms. Positive venom intradermal skin tests confirm the diagnosis of potential stinging insect allergy in people who have had sting reactions. Venom immunotherapy provides almost 100% protection from further sting reactions. It is recommended for all people who have had venom anaphylaxis and have positive skin tests, except for children who have dermal reactions only. Details of venom dosing are well established. The adequate duration of venom immunotherapy is still an unresolved issue. Conversion to a negative skin test appears to be an absolute criterion to discontinue treatment. In the presence of a persistent positive skin test, 3-5 years of immunotherapy is generally sufficient. People who have had severe reactions, such as loss of consciousenss, may require indefinite therapy.

View full abstract

Several mechanisms of immunologic tolerance have been proposed, including deletion, anergy and active suppression. Deletion and anergy have been reported based on data from both in vivo and in vitro experiments, but evidence to support the involvement of active suppression in tolerance has been elusive, principally because of the difficulty in defining regulatory T (Tr) cells with immunosuppressive activity. However, data characterizing the function of Tr cells has recently begun to emerge both from experiments in the field of oral tolerance and from others utilizing transgenic (Tg) mice. One such model which we described uses Tg mice expressing a foreign physiological soluble antigen, beef insulin (BI), while another uses T cell receptor (α/β) Tg mice, whose T cell receptors (TCR) are specific for ovalbumin (OVA). Using such models, adoptive transfer of the Tr clones specific for myelin basic protein (MBP) from orally tolerant mice into naive mice was shown to protect the animals from experimental autoimmune encephalomyelitis (EAE). Transforming growth factor-beta (TGF-β) has been shown to be responsible for the immunosuppression. Tr clones functioning in self-tolerance have also been obtained from mice expressing TCR or BI transgenes. T cell cultures from OVA specific TCR expressing Tg mice were stimulated in the presence of interleukin-10 (IL-10) and OVA peptide to produce Tr clones. The Tr clones secreted IL-10 and TGF-β as immunosuppressive factors. Tr clones with a different characteristic have been obtained from BI Tg mice. Adoptive transfer of the Tr clones into normal mice suppressed the BI specific antibody response. These Tr clones have type II Th cytokine profile and produced TGF-β as an inhibitory cytokine. TGF-β production also led to functional bystander suppression in the BI Tg mice. These three different types of Tr clones show considerable heterogeneity in the cytokine profiles. Further investigation of Tr cells will be important for our understanding of autoimmunity and the development of tactics for the therapy of autoimmune disease.

View full abstract

In a large number of allergic individuals, inhalant allergens are important causative and triggering agents in respiratory allergies. It is essential to survey the pollen and mold around the patient's environment for the diagnosis and treatment of airborne allergy. Rotorod samplers were installed at well-ventilated places in seven collecting stations in Seoul, the capital of Korea, which has a population of 12 million. Airborne particles carrying allergens were collected daily from each station for 2 years (1 October 1995 to 30 September 1997). After being stained with Calberla's fuchsin, they were identified, counted and recorded. The weather in Seoul was also recorded. Pollen was found from the middle of February through to the end of December. The peak date for pollen was 12 May (peak mean daily count: 701 grains/m³/day) and for mold it was 23 June (peak mean daily count: 936 spores/m³/day). Alder, birch, pine, oak, maple, elm, juniper, willow, and gingko trees were prevalent during the tree season, lasting from the middle of February to late July. Then sagebrush, ragweed, Japanese hop, and pigweed followed during the weed season, which lasts from the middle of July to the end of December. In skin prick test results, house dust mite was the most common positive allergen in Seoul, followed by cockroach. Among the pollens, mugwort was the most common positive, followed by ragweed mix, alder, birch, and grasses mix. Among the molds, there were high counts of Cladosporium and Alternaria during the year, excluding January. Ascospore of Leptospheria was highest during the monsoon season.

View full abstract

Monocytes/macrophages have recently been shown to play a significant role in the pathogenesis of allergic diseases. As the level of soluble CD14 (sCD14) in serum is considered a marker of monocyte/macrophage activation, we measured the levels of sCD14 in allergic asthma and atopic dermatitis (AD), along with acute infectious and inflammatory diseases, to see its clinical relevance. Serum samples were taken from patients with acute infectious and inflammatory diseases, allergic asthma, and atopic dermatitis. sCD14 was measured with our own ELISA system and its level in each disease was compared with normal controls as well as its disease severity. sCD14 was elevated and correlated with C-reactive protein in infectious and inflammatory diseases (n = 26), confirming that it reflects inflammation. sCD14 was also significantly increased both in asthma (n = 94) and adult chronic AD (n = 22). In asthmatic patients, those with higher sCD14 tended to have more severe symptoms, but there was no statistical correlation between sCD14 and severity. In adult chronic AD patients, a correlation between sCD14 and disease severity was observed. However, sCD14 was not elevated in infant AD patients (n = 18) irrespective of severity, suggesting differences in the degree of monocyte/macrophage involvement in the pathogenesis between adult chronic and infant AD. The levels of sCD14 were shown to be upregulated in allergic diseases and might be useful as a marker of monocyte/macrophage involvement in allergic inflammation.

View full abstract

Saiboku-to (TJ-96), a traditional Kampo herbal formation, has been used in the treatment of bronchial asthma in Japan as an anti-allergy herbal medicine. We investigated the effect of TJ-96 on leukotriene (LT)C₄ release from eosinophils and basophils isolated from healthy volunteers. Pre-incubation of eosinophils with TJ-96 inhibited ionophore- or formyl-methionyl-leucyl-phenylalanine (FMLP)-induced LTC₄ generation by eosinophils in a dose-dependent fashion. The TJ-96 was more potent in the release by ionophore (IC₅₀ = 60 mg/mL) than the release induced by FMLP (IC₅₀ = 300 mg/mL). Maximal inhibition was observed when eosinophils were pretreated with TJ-96 for 5 min. Although TJ-96 at high concentrations inhibited IgE-mediated histamine release from human basophils, inhibition of IgE-mediated LTC₄ release was not statistically significant. The potent inhibitory activity was found in the extract of Glycyrrhiza root, one of the herbal components of TJ-96, but the inhibitory effects were not due to either glycyrrhizin or liquiritin, the main elements of the Glycyrrhiza root. These results raise the possibility that the clinical efficacy of TJ-96 is derived, at least in part, from its potent inhibitory effect on LTC₄ release from eosinophils.

View full abstract

We evaluated the incidence of the association of HLA class II phenotype and specific IgE responsiveness against house dust mite (HDM) and/or Japanese cedar pollen (Jc) in 176 patients with allergic rhinitis, with or without bronchial asthma, and 107 nonallergic subjects. Specific IgE antibody titration against the purified allergens Der f1 and Der f2 from HDM, and against Cry J1 and Cry J2 from Jc, was performed by using enzyme-linked immunosorbent assay (ELISA) and radio-immunoassay (RIA) in sera from all subjects. HLA class II oligotyping was performed by the polymerase chain reaction sequence specific oligonucleotide (PCR-SSO) method on the DRB1^*, DQA1^*, DQB1^* and DPB1^* alleles using peripheral blood cells. The high IgE responders ≥ class 4 to the purified allergens were identified by using the IgE antibody reference concentration obtained by ELISA, RIA and routine IgE CAP RAST. Compared to the controls, the patients with both rhinitis and asthma showed significantly higher frequencies of DRB1^* 0901, DQB1^* 0303, and DPB1^* 0401 alleles. High IgE responsiveness to HDM was associated with DRB1^* 1101, 0901, DQB1^* 0303, and DPB1^*0401 alleles. The patients with anti-Der f1 IgE antibody concentration exceeding 72.2 ng/mL showed significantly elevated frequencies for DQB1^*0401 and DPB1^*0401 alleles, and those with anti Der f2 IgE antibody concentration exceeding 46.2 ng/mL showed significantly elevated frequencies for DPB1^*0401 and 0901 alleles. High IgE responsiveness to Jc with Cry j1 and Cry j2 was associated with the DRB1^* 1201 alleles.

View full abstract

Although patients with a history of hymenoptera venom anaphylaxis showed significantly reduced plasma levels of angiotensin-I and angiotensin-II compared to controls, there is no study in the literature to investigate the renin angiotensin aldosterone system (RAAS) in patients with anaphylactic reaction induced by immunotherapy. The purpose of this study is to determine the role of the renin angiotensin aldosterone system in patients who had an anaphylactic reaction induced by allergen immunotherapy with pollen, house-dust and mold extracts. Plasma levels of angiotensin-I, angiotensin-II, angiotensin converting enzyme and aldosterone were measured in 20 patients who experienced anaphylaxis during allergen immunotherapy. The control group consisted of 15 immunotherapy patients without any history of anaphylaxis. The Mann-Whitney U-test was performed for comparison of the two groups, and a P value less than 0.05 was considered statistically significant. Angiotensin-I, angiotensin-II, angiotensin converting enzyme and aldosterone levels were similar in both the study and control groups and no statistical significance was found between the two groups (P > 0.05). The RAAS does not appear to play a role in the pathogenesis of anaphylactic reactions due to allergen immunotherapy with pollen, house-dust and mold extracts.

View full abstract

Prediction of yearly atmospheric pollen counts is a very important component in the prevention of allergenic symptoms. We investigated the relationship between atomspheric pollen counts and the formation of male flowers of Cryptomeria japonica D. Don (C. japonica). An atmospheric pollen survey of C. japonica was conducted from 1983 to 1996 using a Durham's sampler. A regression analysis was performed between the total pollen count and July temperature in previous years. The atmospheric pollen counts of C. japonica had a high positive correlation with the mean temperature in July of the previous year. However, the predicted using average mean July temperature records of the previous year were insufficient, especially in years following high pollen count. In experimental conditions, using 60 C. japonica trees in pots, the formation of male flowers was shown to increase with a rise in incubation temperature. In a forest of C. japonica, our results showed that the length and weight of new needle growth from old needles, which produced many flowers in the previous year, were shorter and lighter, respectively. These aerobiological and plant physiological studies provide evidence that a smaller number of pollen counts are a common result in a year following one in which many male flowers are produced, even if the mean July temperature of that year was high.

View full abstract