Corticosteroids and theophylline have been used widely for the treatment of asthma. These two classes of drugs appear to reduce the tissue infiltration of eosinophils, predominant inflammatory cells in the airways of asthmatic patients. Corticosteroids inhibit the generation of both endothelial-activating Th2 cytokines (e.g. interleukin (IL)-4/IL-13) and eosinophil growth factors (e.g. IL-5/granulocyte-macrophage colony stimulating factor) and also attenuate the effects of eosinophil growth factors on the differentiation and prolonged survival of eosinophils. However, corticosteroids modulate directly neither eosinophil adhesiveness nor the expression of adhesion proteins on endothelial cells in vitro. Therefore, it is likely that the inhibitory effect of corticosteroids on the tissue infiltration of eosinophils is the consequence of indirect mechanisms, mainly via the inhibition of cytokines. Interestingly, theophylline, which is generally accepted as a bronchodilator, attenuates eosinophil adhesion to endothelial cells in vitro at a clinically therapeutic concentration. Furthermore, theophylline inhibits the expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 on endothelial cells that had been stimulated with IL-4 plus tumor necrosis factor-α. Thus, theophylline possibly exerts an inhibitory effect on both the adhesive property of eosinophils and the expression of adhesion molecules on endothelial cells. These findings possibly indicate that theophylline would be adequate to supplement the actions of corticosteroids in asthmatic airway inflammation, partly via its inhibitory effect on the interaction between blood eosinophils and endothelial cells.

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Rhinoviruses cause the majority of common colds, which often provoke wheezing in patients with asthma. The precise mechanisms responsible for the rhinovirus infection-induced exacerbations of bronchial asthma remain uncertain. However, several reports have demonstrated airway hyperresponsiveness, increases in chemical mediators in airway secretions, such as kinin and histamine, and airway inflammation in patients with bronchial asthma after rhinovirus infection. Rhinovirus infection induces the accumulation of inflammatory cells in airway mucosa and submucosa, including neutrophils, lymphocytes and eosinophils. Rhinovirus affects the barrier function of airway epithelial cells and activates airway epithelial cells and other cells in the lung to produce proinflammatory cytokines, including various types of interleukins, granulocyte-macrophage colony stimulating factor and RANTES, and histamine. Rhinovirus also stimulates the expression of intercellular adhesion molecule-1 (ICAM-1) and low-density lipoprotein receptors in the airway epithelium, receptors for major and minor rhinoviruses. Rhinovirus infection is inhibited by treatment with soluble ICAM-1 and by the reduction of ICAM-1 expression in airway epithelial cells after treatment with either glucocorticoid or erythromycin. Both soluble ICAM-1 and erythromycin have been reported to reduce the symptoms of common colds. Herein, we review the pathogenesis and management of rhinovirus infection-induced exacerbation of bronchial asthma and the relationship between rhinovirus infection and airway allergy.

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Asthma is a chronic inflammatory disorder of the airways superimposed upon structural changes that include an increase in smooth muscle and airway wall remodeling. In addition to a background of chronic mediator release, asthma is characterized by considerable variations in airway function brought about by important interactions with the environment, including allergen, pollutant and virus exposure. At least in mild-moderate disease, cytokines released from Th2 cells appear important in orchestrating the inflammation. The situation in more severe disease is complicated by the superimposition of a Th1 on top of a Th2 response. Until recently, the only controller treatment for chronic asthma has been corticosteroids. However, identification of specific effector molecules in asthma has led to targeting of specific pathways by using cytokines and cytokine inhibitors. Administration of a monoclonal blocking antibody against IgE has been shown to be highly efficacious in severe allergic asthma, but enhancement of Th1 responses or attempts to reduce eosinophils using anti-interleukin-5 monoclonal antibodies have no clinical benefit. In more severe asthma, blockade of tumor necrosis factor-α using the decoy etanercept has revealed efficacy in a small open study supporting the view that Th1, in addition to Th2, pathways are important as the disease adopts a more severe phenotype. Thus, like atopic dermatitis, it is likely that asthma is not a single disease, but a group of disorders that differ in the relative contribution of specific pathophysiological pathways.

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The airway wall of asthmatic patients is infiltrated with inflammatory cells, consisting chiefly of eosinophils and T lymphocytes. Among these T lymphocytes, Th2 cells are involved in the regulation of the IgE immune response and local allergic inflammation, which underlie allergic diseases. Various cytokines produced and released by Th2 cells play important roles in the development of many allergic diseases, including asthma, and the exacerbations of their disease states. Therefore, targeting of Th2 cell-derived cytokines is a rational therapeutic strategy for the treatment of asthma. Corticosteroids and immunosuppressive agents can potently inhibit Th2 cytokine-mediated responses, but have no selectivity for Th2 cells: they also exert pharmacological activity against cells other than inflammatory cells, thereby potentially causing adverse side-effects. However, suplatast tosilate is the only specific Th2 cytokine inhibitor that can be used clinically and it has been used widely in Japan as a maintenance drug in the treatment of asthma, atopic dermatitis and allergic rhinitis. There is considerable evidence of the effectiveness of suplatast tosilate in patients with mild asthma or moderate persistent asthma. Furthermore, an effect on cough variant asthma and a steroid-sparing effect have also been reported for suplatast tosilate.

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Allergy to common agents, such as plant pollens, dust mites and foods, is termed atopy. Atopy is the principal cause of the chronic inflammatory diseases of eczema (the skin), hayfever (the nose) and asthma (the lungs) in children and young adults. Atopy affects millions of individuals in Japan and other developed countries and is a major source of chronic ill health in childhood and of major health expenditure. Current treatments only control symptoms and there is an urgent need for a more fundamental understanding of the origins of atopy in order to plan more effective treatment and prevention. This may become a useful model for other common multifactorial disease.

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Long-acting β₂-adrenergic receptor agonists (LABA), a class of agents for the long-term management of childhood bronchial asthma, are recommended for use in combination with steroid inhalation for the treatment of the morning dip in severe childhood asthma. In the present review, salmeterol (SM), a LABA inhalant with a long-acting bronchodilator effect, was compared with the recently introduced tulobuterol patch (TBP) in terms of safety and efficacy, based on their respective clinical effects on childhood asthma. From a clinical perspective, both drugs had a preventive effect by suppressing the morning dip and exercise-induced asthma when used concomitantly with an inhaled corticosteroid, and both agents were associated with a lower incidence of adverse effects on the cardiovascular system than oral β₂-adrenergic receptor agonists. Based on these findings, both SM and TBP are concluded to be highly efficacious and safe bronchodilator agents that are appropriate for the long-term management of childhood asthma.

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Atopic disorders, such as asthma, eczema and rhinitis, develop due to the interactions between genetic and environmental factors. Atopy is characterized by enhanced IgE responses to environmental antigens. The production of IgE is upregulated by Th2 cytokines, in particular interleukin (IL)-4, and downregulated by Th1 cytokines, in particular interferon (IFN)-γ. In the present review, we present the genetic factors responsible for IgE production and genetic defects in the downregulation (brake) of IgE production, especially in terms of IL-12 and IL-18 signaling, mutations of the IL-12 receptor β2 chain gene and mutations of the IL-18 receptor α chain gene in atopy. Moreover, we newly present a genetic classification of atopy. There are four categories of genes that control the expression of allergic disorders, which include: (i) antigen recognition; (ii) IgE production (downregulation=brake; and upregulation); (iii) the production and release of mediators; and (iv) events on target organs. In the near future, this genetic classification will facilitate the development of tailor-made treatment.

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After completion of sequencing of the human genome, you will no longer be able to discover a new gene and may not be able to find a new molecule in the human body. Instead, you may find many new molecule networks. It will be possible to select information obtained from animal models just where orthologous genes are functioning similarly. Mouse disease models will not be used any longer where key orthologous genes are working differently than in humans. Analysis of cell type-selective transcripts from database searches is now available to minimize the efforts required for drug discovery. As such, it will soon be possible to use computational modeling to analyze integrative biological function and to test hypotheses without performing any in vivo or in vitro experimentation. However, before establishing a system simulating the human body, which consists of a variety of organs, which further consist of various types of cells, which then consist of various types of proteins, which consist of 20 types of amino acids, there are many steps that need to be understood.

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The Ig-like receptors provide positive and negative regulation of immune cells upon recognition of various ligands, thus enabling those cells to respond adequately to extrinsic stimuli. Murine paired Ig-like receptor (PIR)-A and PIR-B, a typical receptor pair of the Ig-like receptor family, are expressed on a wide range of cells in the immune system, such as B cells, mast cells, macrophages and dendritic cells, mostly in a pair-wise fashion. The PIR-A requires the homodimeric Fc receptor common γ chain for its efficient cell-surface expression and for the delivery of activation signaling. In contrast, PIR-B inhibits receptor-mediated activation signaling in vitro upon engagement with other activating-type receptors, such as the antigen receptor on B cells and the high-affinity Fc receptor for IgE on mast cells. Although the ligands for PIR-A and PIR-B remain unknown, recent studies on PIR-B-deficient mice have provided us with valuable insight into the physiological significance of PIR-B, particularly in its regulatory role in balancing the humoral immune response.

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Cyclic nucleotides are powerful signaling molecules and their sole means of removal is through the action of cyclic nucleotide phosphodiesterases (PDEs). Elevating levels of cAMP is beneficial in many diseases, including neurological conditions, cancers, viral infections and most inflammatory disorders. There are 11 known PDE families, with PDE4 being the most highly expressed. Evidence of the clinical usefulness of PDE4 inhibition has come from the use of specific chemical inhibitors and the generation of knock-out mice models. There exists an extensive range of PDE4 family members, because there are four subfamilies, each encoded by their own gene and each capable of generating multiple isoforms. Several members of the PDE4 family are found to be expressed in every cell and tissue studied and evidence is now being uncovered indicating unique functions for each. Their actions are controlled by their expression patterns, subcellular location and interaction with other signaling pathways. The first generation of PDE4 inhibitors, although potent anti-inflammatory agents, failed as pharmaceuticals owing to their emetic and gastric side-effects. A new generation of chemical inhibitors is now nearing the market, which display greatly reduced side-effects. In the future lies the generation of more specific inhibitors that will focus upon particular diseases. This will be achieved by targeting specific PDE4 family members. Because the current target of chemical inhibition (the catalytic site) is virtually identical between isoforms, this specificity is likely to be achieved by blocking the enzyme's interaction with other signaling cascades.

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It is now widely accepted that aspirin, along with other non-steroidal anti-inflammatory drugs (NSAIDs), may precipitate asthma attacks in a minority of susceptible individuals. The syndrome is part of a mucosal inflammatory disease that typically affects the nasal, as well as the bronchial, mucosa and sometimes the gut and skin also. Although the mucosal cellular infiltrate in aspirin-sensitive asthma and rhinitis resembles that of asthma and rhinitis in general, there is evidence of increased expression of asthma-relevant cytokines, such as interleukin-5 and granulocyte-macrophage colony stimulating factor, and a more intense infiltrate of mast cells and eosinophils. One key feature of aspirin-sensitive asthma is thought to be the overproduction of cysteinyl leukotrienes, principally by these local mast cells and eosinophils, but whether this represents a fundamental abnormality or is simply a consequence of greater numbers and activation of inflammatory cells is unclear. Genetic polymorphisms of the leukotriene C₄ synthase gene, which result in elevated expression of this enzyme, may also play a role. In addition, overexpression of cysteinyl leukotriene receptors, particularly CysLT₁, may contribute to an enhanced response of local inflammatory and structural cells to cysteinyl leukotrienes. Aspirin challenge in these patients is accompanied by acute further elevation of the already elevated baseline cysteinyl leukotriene synthesis, a phenomenon that is most closely related to the ability of aspirin and related NSAIDs to inhibit the cyclooxygenase enzyme COX-1. The reason for this is unknown, although it has been suggested that the COX-1 product prostaglandin E₂ (PGE₂) serves as a 'brake' to leukotriene synthesis and that somehow this mechanism is deficient in aspirin-sensitive asthmatics. A better understanding of the pathogenesis of aspirin-sensitive asthma will undoubtedly lead to better approaches to treatment. Aside from the use of drugs that inhibit cysteinyl leukotriene synthesis or block the action of cysteinyl leukotrienes on their receptors, recent data suggest that PGE₂, and possibly lipoxin analogs, may also prove effective in the treatment of aspirin-sensitive asthma.

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Background: Because microflora has been reported to have an important effect on the development of allergic disorders, we measured intestinal microflora levels in 4-month-old infants and studied the development of allergic disorders.
Methods: Blood samples from 18 4-month-old infants and 15 1-year-old infants were examined for total serum IgE and specific IgE antibodies. Stool samples from 18 4-month-old infants were examined for the presence of microflora.
Results: A positive correlation was observed between the ratio of breast-feeding at 1 month and the percentage of bifidobacteria in the intestine at 4 months (correlation ratio=0.54; P=0.022). Atopic dermatitis was observed in 12 of 18 infants at 4 months and in five of 15 infants at 1 year. Egg white-specific IgE was positive (≥ 0.70U_A/mL) in six infants at 4 months and in seven infants at 1 year. No relationship was observed between the percentage of bifidobacteria, lactobacilli or clostridia in the intestinal tract at 4 months and the development of allergy. However, all five infants who exhibited a percentage of bacteroides (compared with the total intestinal microflora level) of more than 10% at 4 months had positive egg white-specific IgE and higher levels of total IgE (>25IU/mL) at 1 year; these relationships were statistically significant (P=0.01).
Conclusions: Colonization with bacteroides at 4 months of age is suggested to be related to the allergic state at 1 year of age.

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Background: Cysteinyl leukotrienes (CysLTs) and thromboxane (TX) A₂ have been implicated in the pathogenesis of bronchial asthma. Urinary leukotriene E₄ (LTE₄) and 11-dehydro-TXB₂ (11DTXB₂) levels are often used to assess the production of CysLTs and TXA₂. However, few studies have examined the products of these two mediators in the same asthmatic patients. To define the potential roles of CysLTs and TXA₂ in the pathogenesis of bronchial asthma in children, their urinary levels were measured in the present study.
Methods: Urinary LTE₄ and 11DTXB₂ levels were measured by enzyme immunoassay (EIA) and radioimmunoassay (RIA), respectively. Urine samples from asthmatic children were measured during the stable condition and during an acute attack.
Results: Urinary LTE₄ levels during an acute attack (median 476 pg/mg creatinine; range 191-1100 pg/mg creatinine) and during the stable condition (median 332 pg/mg creatinine; range 128-965 pg/mg creatinine) were significantly higher (P<0.05) than those of controls (median 233 pg/mg creatinine; range 103-389 pg/mg creatinine). Urinary 11DTXB₂ levels during an acute attack and during the stable condition (median 1666 (range 110-5105) and 1009 (range 46-6070) pg/mg creatinine, respectively) were significantly higher (P<0.05) than those of controls (median 252 pg/mg creatinine; range 41-716 pg/mg creatinine). Comparing different stages of asthma, LTE₄ levels during an acute attack were significantly higher (P<0.05) than during the stable condition; however, there was no difference in urinary TXB₂ levels.
Conclusions: The present findings suggest that high levels of CysLTs and TXA₂ are associated with the pathogenesis of bronchial asthma. The measurement of urinary LTE₄ and 11DTXB₂ would be useful in understanding the individual pathogenesis of asthmatic children.

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Background: The role of Th2 type cytokines in the persistence of chronic rhinosinusitis, especially that induced by non-infectious inflammatory causes, has been noted. However, the original cause of sinus eosinophilia remains unclear and whether the presence of allergic rhinitis (AR) may be a risk factor has been an issue of debate. In the present study, we examined cytokine expression and the distribution of CD4-positive cell subsets in the paranasal sinus mucosa of patients with chronic sinusitis.
Methods: total of 133 sinusitis patients was examined. Patients were subdivided into four groups based on the presence of AR and the degree of local eosinophil infiltration. The expression of granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin (IL)-5, IL-8, IL-16, eotaxin and interferon (IFN)-γ mRNA was detected by reverse transcription-polymerase chain reaction. Immunohistochemical localization of CD4-, CXCR3- and CCR4-positive cells in the same specimens was quantitatively analyzed using a laser scanning confocal microscope.
Results: The group of non-AR patients with low eosinophilia (the AR(-)Eo(-) group) only showed an increase in IFN-γ mRNA expression. In contrast, the other three groups showed similar cytokine profiles, with high expression levels for GM-CSF, IL-5 and eotaxin mRNA. The total number of CD4⁺ cells was also increased in these three groups. The density of CCR4-positive CD4⁺ cells was significantly higher in groups with high eosinophilia, irrespective of the presence of AR. As a result, the CXCR3⁺/CCR4⁺ cell ratio in the AR(-)Eo(-) group was significantly increased compared with the other three groups.
Conclusions: hese results indicate that high expression of Th2-type cytokines concomitant with the infiltration of a predominant number of CD4⁺ cells and their Th2 subsets play a role in the pathogenesis of eosinophil inflammation in sinus mucosa. In addition, the finding that some of the non-atopic patients also shared Th-2 type immune responses provides support for the concept of chronic sinusitis as a Th2-mediated disease process.

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Background: It is very important to use anti-inflammatory agents, including inhaled corticosteroids, in the management of asthma because bronchial inflammation is a fundamental component of bronchial asthma. Although management according to this strategy is recommended in several countries, the actual situation of asthmatic patients in Japan is poorly understood. To clarify the actual management of asthma in Japan, the present study was undertaken.
Methods: In 1998, for 8 weeks from September through to October, questionnaires on asthma control and satisfaction in daily life were given to asthmatic patients. In addition, questionnaires regarding patient profiles and medication were given to the patients' physicians. The same questionnaires were repeated in 1999 and 2000. The information obtained from the same patients and their physicians who responded in each of the three years was used for analysis.
Results: We analyzed 840 cases. During this period, over 80% of patients used oral theophylline, although the percentage of patients using inhaled steroids and leukotriene receptor antagonists increased from 67.0 and 29.8% in 1998 to 75.1 and 34.2%, respectively, in 2000. Asthma control (including the presence of attacks and self-evaluation by each patient), asthma-related symptoms and sleep disturbance improved significantly. However, there was no improvement in satisfaction in daily life of asthmatic patients surveyed. Multiple-regression analysis revealed that self-evaluation of asthma control by each patient was significantly related to improvement in satisfaction in daily life.
Conclusions: These results indicate that anti-inflammatory agents, including inhaled corticosteroids and leukotriene receptor antagonists, contributed to improved asthma control, whereas oral theophylline is characteristically used in Niigata Prefecture, Japan. However, not all asthma-related problems, such as satisfaction in daily life, improved and self-evaluation of asthma control by patients may play a key role in improving their satisfaction in daily life.

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Background: Multiple chemical sensitivity (MCS) is characterized by chemically induced symptoms from multiple organs. These symptoms occur in response to demonstrable exposure to chemically unrelated compounds at doses far below those known to cause harmful effects in the general population. Although the mechanism of this action remains unclear and no acceptable and well-documented treatment for MCS has yet been established, regarding neurogenic inflammation, it has been hypothesized that an increased density of C-fiber neurons is found in symptomatic tissues.
Methods: Using capsaicin, we examined the sensitivity of the cough reflex in patients with MCS and chronic cough (CC) and compared the findings with those in control subjects. Fifteen patients (four males, 11 females; mean (± SD) age 38.3 ± 16.3 years) suffering from MCS and 29 patients (10 males, 19 females; mean age 46.4 ± 15.9 years) who had cough symptoms lasting 4 weeks or longer and normal chest radiograph findings (CC) were enrolled in the present study. Twenty-nine healthy subjects (14 males, 15 females; mean age 37.9 ± 9.5 years) who had no history of coughing during the previous 6 months and no chronic respiratory diseases were enrolled as controls. Subjects inhaled stepwise incremental concentrations of capsaicin (0.122-62.5 µmol/L) for 15 s. Inhalation was performed at 45 s intervals and the number of coughs per minute was counted. The provocation was terminated when the subject coughed five or more times. Ventilatory functions (forced vital capacity (FVC), forced expiratory volume in 1 s and the expiratory flow rate at 50 and 75% FVC (V₅₀ and V₂₅, respectively)) were also measured.
Results: No significant differences were observed in ventilatory function test findings between the three groups. The log concentration of capsaicin causing five or more coughs (C5) was 0.150 ± 0.630, 0.611 ± 0.691 and 1.120 ± 0.612µmol/L in MCS, CC and control subjects, respectively. The log C5 in MCS subjects was significantly lower than that in CC and control subjects.
Conclusions: Capsaicin is a cough-inducing agent in humans that possibly acts on non-myelinated C-fiber endings. The findings of the present study indicate that the mechanisms underlying MCS may originate in the sensory nervous system.

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Background: Respiratory viral infections are known to be a risk factor for the exacerbation of asthma. In a model of asthma with influenza A virus infection, dendritic cells play an important role during antigen sensitization and antigen challenge. However, the role of T cells in the asthma-influenza A model was unclear. The aim of the present study was to assess the roles of T cells during antigen sensitization and antigen challenge in the asthmatic model.
Methods: C57BL/6 mice were infected with influenza A virus and were sensitized with inhaled antigen during the acute phase of the virus infection. Anti-CD4 or anti-CD8 monoclonal antibodies were administered during antigen sensitization or antigen challenge to evaluate the role of CD4⁺ or CD8⁺ T cells in this murine model of asthma. The onset of asthma was determined by eosinophil recruitment into the lung.
Results: During antigen sensitization, depletion of either CD4⁺ or CD8⁺ T cells resulted in an absence of eosinophil infiltration into the lung after antigen challenge. However, during antigen challenge, depletion of CD4⁺ T cells did cause such an absence of eosinophil infiltration.
Conclusions: During antigen sensitization, both CD4⁺ and CD8⁺ T cells were required in C57BL/6 mice for exacerbation of asthma. During antigen challenge, CD4⁺ T cells were important for the onset of asthma, whereas CD8⁺ T cells do not affect eosinophil recruitment into the lung.

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Background: Neuropeptides are considered to be factors that trigger, exacerbate or modulate allergic diseases and inflammatory skin reactions. In addition, it has been indicated that allergic diseases are highly correlated with stress.
Methods: 2,4,6-Trinitrochlorbenzene (TNCB) and crowding stress were applied to mouse atopic dermatitis (AD) models for the purpose of provoking chronic dermatitis. In addition, TNCB-sensitized mice were given olopatadine hydrochloride (10 or 3mg/kg), an anti-allergic agent, orally. The neuropeptide content in the skin tissues and serum IgE levels were measured in these mice.
Results: Repeated local application of TNCB solution induced itching skin lesions, together with an increase in levels of substance P, a decrease in calcitonin gene-related peptide levels and early augmentation of IgE production. Treatment with crowding stress brought about a transient increase in substance P. Furthermore, we observed significant decreases in substance P and serum IgE levels when the administration of olopatadine hydrochloride was started before the elicitation of chronic dermatitis caused by repeated application of TNCB solution. These changes were more definite in the group administered a higher dose of the drug (10mg/kg).
Conclusions: It is suggested that repeated contact allergic dermatitis or mental stress may promote the development and exacerbation of AD and that substance P has a role in this response. In addition, it seems that an anti-allergic drug, such as olopatadine hydrochloride, possibly downregulates substance P, thereby suppressing the development of AD. In the future, the development and clinical application of a drug that strongly influences the release of neuropeptides, such as substance P, and the expression of neuropeptide receptors would be expected for the treatment of AD.

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Background: Recently, a second prostaglandin D₂ (PGD₂) receptor, chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2), was identified. Because PGD₂ was reported to have chemotactic activity on eosinophils, CRTH2 expressed on eosinophils attracted interest as a receptor associated with eosinophil migration to, and accumulation at, inflammatory sites. To elucidate the mechanism regulating the expression of CRTH2 on eosinophils, the effects of PGD₂, interleukin (IL)-4, IL-5 and interferon (IFN)-γ on CRTH2 expression were investigated.
Methods: Blood eosinophils were purified using Percoll and anti-CD16 antibody coated magnetic beads. Eosinophils were incubated with PGD₂ and/or IL-4, IL-5 and IFN-γ. The expression of CRTH2 on eosinophils was measured using a FACScan cytometer (Becton Dickinson Immunocytometry Systems, San Jose, CA, USA).
Results: Prostaglandin D₂ and IL-5, but not IL-4 and IFN-γ, downregulated the expression of CRTH2 on eosinophils. Furthermore, PGD₂- and IL-5-induced downregulation of CRTH2 on human eosinophils was inhibited by phenylarsine oxide, a receptor internalization inhibitor.
Conclusions: These results suggest that PGD₂ and IL-5 regulate CRTH2 expression on eosinophils through CRTH2 internalization. The decreased expression of CRTH2 on tissue eosinophils may make these cells remain at the site of allergic inflammation.

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Background: Adhesion molecules participate in an important part of inflammatory process in relation to the accumulation of inflammatory cells, such as eosinophils. The expression of adhesion molecules differs depending upon the cells and tissue. In the present study, to elucidate these differences, a comparative study was performed on the prolongation of eosinophil survival via adhesion molecules.
Methods: Blood eosinophils were purified using Percoll and anti-CD16 antibody coated magnetic beads. Eosinophils were incubated with or without the various concentrations of adhesion molecules for 18 or 36 h. Eosinophil survival was analyzed by a flow cytometer with staining by annexin V (AV) and propidium iodide (PI).
Results: Intercellular adhesion molecule (ICAM)-1, fibronectin (FN) and cellular fibronectin (cFN), but not vascular cell adhesion molecule (VCAM)-1, significantly prolonged eosinophil survival compared with control. The present comparative study for eosinophil survival showed the following tendency: cFN=FN > ICAM-1 > VCAM-1. Moreover, enhancement of prolonged eosinophil survival by connecting segment-1 was greater than that by FN and cFN.
Conclusions: The regulation of adhesion molecules, by not only preventing eosinophil adhesion but also eosinophil activation, may be a potential target in the treatment of allergic inflammatory disorders.

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We report the detailed clinical course of a 47-year-old woman with aspirin-induced asthma in which non-steroidal anti-inflammatory drug (NSAID) intolerance developed over a 3 year period. The patient had mild asthma and was admitted with a femoral fracture in August 1996. Although she was given NSAIDs, including rectal diclofenac and oral loxoprofen, there was no worsening of asthma. After discharge, she was followed as having NSAID-tolerant asthma. When she developed perennial rhinitis and anosmia subsequent to an upper respiratory tract infection, asthma control was well maintained. Later, she experienced three episodes of severe asthmatic attacks after intake of aspirin or ketoprofen. Thus, we investigated her NSAID tolerability in September 1999. Sodium tolmetin inhalation challenge demonstrated a positive reaction, leading to the diagnosis of aspirin-induced asthma. Open challenges with loxoprofen and diclofenac also provoked positive reactions. The present case illustrates the potential variability of aspirin-induced asthma. Aspirin or NSAIDs challenge tests should be performed when nasal symptoms, particularly anosmia, develop or worsen.

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We report herein two cases of atopic cough in which Basidiomycetes was detected from pharyngeal swabs and in which gargling with amphotericin B was efficacious. One case is a 38-year-old woman and the other is a 54-year-old woman. Both patients visited Ishikawa-ken Saiseikai Kanazawa Hospital for the diagnosis and treatment of isolated severe non-productive cough. They did not have bronchial hyperresponsiveness to methacholine or heightened bronchomotor tone. Bronchodilator therapy was not effective for their coughing. Basidiomycetes was isolated from pharyngeal swabs in both cases. Oral cleansing with amphotericin B at 300mg/day for approximately 2 weeks was effective in treating the severe coughs. This is the first report concerning the effectiveness of oral cleansing with amphotericin B for atopic cough, in which Basidiomycetes was detected from pharyngeal swabs.

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