The prevalence and fatality rate of asthma have increased worldwide. Underdiagnosis and undertreatment of asthma are central to the occurrence of fatal asthma. Atopy is the principal risk factor associated with asthma. However, consideration of the epidemiologic, physiologic, pharmacologic, pathologic and clinical parameters of asthma assessment may provide valuable insight into death due to asthma. Psychologic and socioeconomic factors may further aggravate the asthma status. Ethnic minorities are at increased risk of asthma. The perception of dyspnea may be blunted in asthma sufferers. Slow-onset fatal asthma may be associated with submucosal eosinophilia, whereas sudden-onset may be associated with submucosal neutrophilia. Fatal asthma occurs in patients abusing regular β₂-agonist therapy. Peak flow assessment often provides insight into asthma deterioration prior to signs of respiratory distress. Markers of risk of death due to asthma further identify the fatality-prone asthma patient.

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The mechanisms of activation of mast cells have been studied in most detail in rat RBL-2H3 cells. These cells respond to antigen via the IgE receptor (FcεRl) through sequential activation of the tyrosine kinases, Lyn and Syk, and to adenosine analogs via the adenosine A₃ receptor (A₃R) and a pertussis toxin-sensitive G protein, most likely G_i-3. Other receptors, introduced through gene transfection, include the muscarinic m1 receptor (m1R) which acts via G_q/11. Stimulation of cells via FcεRl, A₃R or m1R leads to the activation of phospholipase (PL) C, PLD and mitogen-activated protein (MAP) kinase resulting in the generation of inositol phosphates and diglycerides, an increase of cytosolic Ca²⁺, the activation of protein kinase C (PKC) and the phosphorylation of various proteins by PKC and MAP kinase. The extent and time course of these events varies for each receptor. These variations, as well as the effects of pharmacologic probes, gene transfection and reconstitution of responses in washed permeabilized cells, indicate how these events relate to functional responses. A modest but sustained elevation of cytosolic Ca²⁺ through an influx of extracellular Ca²⁺ and activation of PKCβ and PKCδ are sufficient for optimal release of preformed secretory granules. Phosphorylation of a cytosolic PLA₂ by MAP kinase (p42^mapk) and a modest increase in cytosolic Ca²⁺ are necessary for the activation of PLA₂ and the binding of PLA₂ to membranes, respectively. Finally, both de novo generation and secretion via Golgi-derived vesicles of certain cytokines are dependent on Ca²⁺ and PKC as well as additional signals most probably phosphorylation of proteins by Syk and p42^mapk.

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The expired nitric oxide (NO) concentration is known to be higher in asthmatic subjects than in normal subjects. To elucidate the role of NO in asthma, we examined the expired NO concentrations in relation to the type (atopic, mixed, non-atopic), and severity (mild, moderate, severe) of asthmatics, as well as the influence of steroid treatment. Twenty-seven normal subjects, 48 asthmatics, 8 subjects with allergic rhinitis, and 13 subjects with pulmonary emphysema participated in the study. The expired NO concentration was significantly higher in asthmatics and patients with allergic rhinitis than in normal subjects (P<0.01). No significant difference was observed between the expired NO concentration in patients with pulmonary emphysema and that of normal subjects. The expired NO concentrations were significantly lower in non-atopic asthma than in atopic asthma. Nitric oxide levels were significantly lower in severe asthma than in mild asthma. High doses of steroid treatment are often used in severe asthma. The dose of inhaled beclomethasone and expired NO concentrations showed a negative correlation (r=-0.51587, P<0.004). Drip infusion of hydrocortisone tended to increase the exhaled NO concentration just after drip infusion, however, it decreased after 24h. These results suggest that steroid treatment decreases the expired NO concentrations in asthmatics, although it cannot be concluded that NO increases the severity of asthma. The measurement of expired NO concentrations is an easy, non-invasive test, which may be a useful tool for monitoring the condition of asthmatics.

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The effects of TYB-2285 and its metabolites (TC-286 and TC-326) on the adhesion of eosinophils and neutrophils to cultured human umbilical vein endothelial cells (HUVEC) stimulated with tumour necrosis factor α (TNF-α) were investigated. The treatment of HUVEC with TNF-α enhanced eosinophil adhesion in a dose-dependent manner (1-100U/mL). The adhesion of eosinophils to TNF-α (100U/mL)-stimulated HUVEC was inhibited by TYB-2285 and its metabolites in a dose-dependent manner (10^-8-10^-5mol/L). These compounds showed stronger inhibitory effects than any other anti-allergic drugs, such as disodium cromoglycat (DSCG), ketotifen and tranilast. TYB-2285, TC-286 and TC-326 did not inhibit the adhesion of neutrophils at the same range (10^-8-10^-5mol/L).
In our adhesion assay system, eosinophil adhesion to TNF-α-stimulated HUVEC was blocked by monoclonal antibody against VLA-4 (anti-VLA-4) but not by that against Mac-1 (anti-Mac-1). In contrast, neutrophil adhesion was blocked by anti-Mac-1, but not by anti-VLA-4.
The results of the present study demonstrate that TYB-2285 and its metabolites selectively inhibit the adhesion of eosinophils to HUVECs stimulated with TNF-α and also suggest that TYB-2285, TC-286 and TC-326 might block the VLA-4/VCAM-1 pathway selectively.

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Damage of bronchial epithelium is a feature of airway viral infection and airway inflammatory disease, such as bronchial asthma. Adhesion molecules, which are expressed on bronchial epithelium, play an important role in the pathogenesis of epithelial damage and airway inflammation. We analysed ICAM-1 and VCAM-1 expression on human bronchial epithelial cell line, NCI-H292, after influenza virus A infection. ICAM-1 was expressed on control cells constitutively. Influenza virus A infection caused a three-fold increase in ICAM-1 expression on NCI-H292 cells. Supernatant of virus-infected cells was analysed for the concentration of IL-1β and TNF-α but these cytokines were not detected. VCAM-1 was not expressed on control cells and did not change after cytokine stimulation or virus infection. These findings suggest that influenza virus infection may induce ICAM-1 expression on bronchial epithelium without intervention of leukocytes, and ICAM-1 expressed on epithelium plays a major part in the pathophysiology of airway inflammatory disease caused by viral infection.

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The dispersion of latex allergen bound on glove powder has been shown to be of clinical importance to latex-sensitized medical staff and patients. To investigate whether latex aeroallergen is associated with the development of latex allergic reactions in health care workers, air samples were collected in 33 hospital rooms and two physicians' offices. Concentrations of latex allergens in the samples were determined by a competitive inhibition immunoassay and related to reported hypersensitivity reactions and to specific IgE results of 111 staff members engaged in these rooms. Latex aeroallergen (up to 205ng/m³) could be detected in all rooms where powdered latex gloves were used and ventilation systems were not installed. Conjunctivitis (n=10), rhinitis (n=12) and dyspnea (n=4) were reported exclusively by employees working in such contaminated rooms. Also workers with latex-specific IgE antibodies (n=17) were found only in these rooms. Urticaria in personnel (n=26) was reported in rooms with and without detectable allergen load. All symptoms were significantly associated with latex-specific IgE antibodies. Our results demonstrate that immediate-type sensitization and allergic symptoms are associated with detectable latex aeroallergen.

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A questionnaire on asthma management was sent to 586 physicians, consisting of specialists authorized by the Japanese Society of Allergology and councillors of the Society, who were treating patients with bronchial asthma. Of the total of 306 (52%) respondents in November 1993, 241 replied to questions relating to adult asthma and 129 to questions relating to childhood asthma (including duplicate replies).
Responses to the questionnaire on the diagnosis, patient education and management of asthma indicated that a reduced number of patients with severe asthma were seen in 1993 in both Pediatric and Internal Medicine Departments compared with 5 years before, despite the increase in total number of asthma patients in Japan. Specifiic IgE radioallergosorbent test (RAST) measurements were frequently performed instead of skin testing for diagnosis, and eosinophil count and bronchodilator response served as an adjunct to the diagnosis. Patients were frequently asked detailed questions about aspirin-induced asthma, which accounted for 8.8, 2.2 and 1.5% of patients with asthma in the adult, schoolchildren (6-16 years) and infant (≤5 years) groups, respectively. In achieving ‘control of asthma’, first priority was given to coping with the symptoms in children aged 5 years or less and to enabling routine daily life activities in patients 6 years of age or older. Usefulness of peak flow measurements was widely recognized and a detailed plan for allergen avoidance (house dust) was often given to patients.

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