Although there is wide variation in the prevalence of nasal allergies internationally, the extent to which this is due to variation in etiological factors is not known. The purpose of the present study was to define the relative importance of atopy and other risk factors for nasal allergies, including hayfever, among young adults in Melbourne. The subjects were participants in the second phase of the European Community Respiratory Health Survey; 876 adults between 20 and 45 years of age completed a detailed respiratory questionnaire, 745 had skin prick testing with common aeroallergens and 675 underwent methacholine challenge. Total and allergen-specific IgE levels were measured in 701 and 693 subjects by radioimmunoassay and RAST, respectively. Nasal allergies, including hayfever, were reported by 47.5% of randomly selected participants. Females, non-smokers, subjects with a family history of allergies, those with current asthma, a history of eczema and nasal symptoms induced by dust, pollen or food were significantly more likely to have nasal allergies. Oral antihistamines had been used by 45.7% of those reporting nasal allergies and 12.4% had received allergen immunotherapy. The risk of nasal allergies, including hayfever, was increased 6.1-fold by atopy, particularly by positive skin tests to outdoor allergens such as Birch, Timothy grass, plantain, olive, Cladosporium and Rye grass pollen. Total serum IgE was significantly higher in subjects reporting nasal allergies than in those who did not report such allergies. There were significant trends in the prevalence of nasal allergies with increasing titers of specific IgE directed against all allergens tested. In conclusion, the significant independent risk factors for nasal allergies, including hayfever, in young adults were atopy, particularly sensitization to Timothy grass, house dust mites and plantain, current asthma, not smoking, a history of eczema and female gender. Future research needs to distinguish between hayfever and perennial allergic rhinitis, which was not possible in the present study.

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Several risk factors for the development of allergic diseases are considered including, for example, the level of IgE in cord blood or in the peripheral blood of neonates and the antigenic effect of some foods that are ingested by both babies and mothers during pregnancy and during the lactation period. However, not all infants with atopic diathesis develop allergic diseases. To clarify the risk factors and the mechanism for developing allergic diseases, particularly bronchial asthma (BA), we prospectively investigated atopic diatheses and symptoms in children in a cohort using a questionnaire method. The factors correlated to development of allergic diseases, as a whole, at the age of 5-6 years were atopic family history and any allergic symptom at 4 months of age. However, not all subjects with atopic dermatitis developed BA later on. High levels of total IgE and positive IgE antibody against egg white were not risk factors for developing BA at the age of 5-6 years.

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We examined the chemotactic response of eosinophils to five eosinophil chemotactic factors (ECF; ECF-PI5, -PI6, -PI7, -PI8 and -PI9) from an established T cell line (STO2) in 31 patients with bronchial asthma (BA). The asthmatic patients were divided into three groups according to the ratio of the chemotactic response to ECF-PI5 and -PI9 (PI5/PI9). A type 1 response occurred when eosinophils responded to both ECF-PI5 and to ECF-PI9, a type 2 response occurred when eosinophils responded to ECF-PI5 only and a type 3 response occurred when eosinophils responded to ECF-PI9 only. Of 31 asthmatic patients, 21 exhibited a type 2 response, six exhibited a type 1 response and the remainder exhibited a type 3 response. In contrast, 23 of 25 healthy donors exhibited a type 1 response and none of them exhibited a type 2 response. This typing of asthmatic patients was apparently correlated with the clinical symptoms of the patients. All patients exhibiting a type 1 response were diagnosed with mild and episodic asthma and none of them had taken oral prednisolone. In contrast, many patients exhibiting a type 2 response were diagnosed with moderate, persistent and perennial asthma. Indeed, eight of these 21 patients had taken oral prednisolone. The patients exhibiting a type 3 response were diagnosed with mild to moderate and episodic asthma, but none of them had taken oral prednisolone. Furthermore, according to the total percentage migration to five STO2-derived ECF, asthmatic patients were further divided into two groups: high- and low-responding groups. Sixteen of 21 patients exhibiting a type 2 response belonged to the high-responding group, whereas all patients exhibiting a type 1 or type 3 response belonged to low-responding group. The present results indicate that such chemotactic heterogeneity of eosinophils to STO2-derived ECF is closely associated with the severity of BA, particularly with regard to the necessity of steroid therapy.

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The incidence of a positive family history with asthma and levels of serum IgE and IgE antibodies were examined in 136 patients with asthma in relation to age at onset of the disease. The frequency of subjects with a family history of asthma ranged from 37.9 to 75.0% in all groups classified by age at onset. The frequency of patients with a high serum IgE level (≥150IU/mL) was higher (51.7-63.2%) in all groups than the frequency of patients with a low serum level (<150IU/mL). The mean level of serum IgE was significantly higher in patients with a family history than in those without a family history, in subjects between the ages of 50 and 59 years at onset (mean age 63.4 years; P<0.02) and in those over the age of 60 years at onset (74.0 years; P<0.01). The number of patients with a positive RAST score either to house dust mite (HDM), cockroach, and Candida tended to decrease as the age at onset increased. However, the frequency of positive RAST to HDM was higher in patients with a family history and who were over the age of 50 years at onset compared with those patients between the ages of 40 and 49 years at onset, although the frequency was significantly higher in patients with family history than in those without family history (P<0.02). These results suggest that IgE-mediated allergic reactions are significant not only in those patients who are younger, but also in elderly patients with asthma.

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The aim of the present study was to analyze in situ expression of cytokines (i.e. interleukin (IL)-4, IL-5, IL-6 and interferon (IFN)-γ in the gut after oral challenge with ovalbumin (OVA) in mice intraperitoneally sensitized with OVA and aluminum). High anti-OVA IgE production was elicited after sensitization. We confirmed the anaphylactic response in the gut after oral challenge by evaluation of the edema of villi and marked eosinophil infiltration in the lamina propria. Immunohistochemical studies demonstrated the presence of IL-4-, IL-5-and IL-6-producing cells (PC) and a lack of IFN-γ-PC in Peyer's patch. The kinetics of IL-5-PC and eosinophil infiltration showed a good synchronization. The predominance of the type 2 helper T cell (Th2) cytokine may lead to the anaphylactic response and marked eosinophil infiltration in the gut in our system. It is possible that our system mimics the immunological events that occur in the gut in food allergy.

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Ovalbumin coupled with liposomes (OVA-liposome) induced selective unresponsiveness of anti-OVA IgE antibody production in BALB/c mice, whereas OVA adsorbed with aluminum hydroxide (OVA-alum) induced a substantial amount of anti-OVA IgE antibody production. Ovalbumin-liposome and OVA-alum predominantly induced IgG_2a and IgG₁ anti-OVA production, respectively. These results suggest that OVA-liposome and OVA-alum induce type 1 and type 2 T helper (Th) immune responses, respectively. To further investigate this issue, we examined the cytokine production induced by these two distinct adjuvants. Spleen cells taken from mice immunized with either OVA-liposome or OVA-alum were cultured in vitro with OVA and the cytokine production from each culture was analyzed. It was demonstrated that spleen cells from mice immunized with OVA-liposome produced more interferon (IFN)-γ than those immunized with OVA-alum and, furthermore, interleukin (IL)-4 was produced only by spleen cells from mice immunized with OVA-alum. These results favor the notion that OVA-liposome and OVA-alum induce Th1 and Th2 cytokines, respectively. Interestingly, the production of IL-2, a Th1 cytokine, was higher in the OVA-alum-immunized group and the production of IL-10, a Th2 cytokine, remained at low levels in both groups after primary immunization; levels of IL-10 increased in the OVA-liposome-immunized group after secondary immunization. These results do not agree with the above notion and, thus, suggest that it may be important to consider the balance between IFN-γ-producing cells and IL-4-producing cells rather than that between Th1 and Th2 cells for the regulation of IgE antibody production.

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The influence of azelastine (AZ) on murine mast cell induction was examined by in vitro cell culture techniques. Splenocytes from normal BALB/c mice suspended in RPMI-1640 medium supplemented with interleukin-3 were cultured in the presence or absence of AZ. The number of mast cells increased gradually with culture time and reached a peak on the 16th day when cells were cultured without AZ. The addition of 1.0μg/mL AZ to the culture medium resulted in complete suppression of mast cell growth, but a lower concentration of AZ (0.5μg/mL) had no demonstrable effects on the growth of mast cells. Azelastine induced apoptotic cell death in mast cells when cells were cultured in the presence of 1.0μg/mL AZ for more than 24h. However, this apoptosis-inducing activity of AZ was not observed in either eosinophils or neutrophils that were obtained from mouse peritoneal cavity.

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The majority of cases of allergic asthma in experimental animals have been provoked by inhalation with mist antigen. Because of the inherent inability of some species to breathe through the mouth, including guinea pigs, mice and rats, an upper airway response may be substantially involved in experimental asthma induced by antigen inhalation. With this in mind, we evaluated three types of nebulizers (a hand-made glassware pressure nebulizer (GPN), a DeVilbiss nebulizer (DN) and an ultrasonic nebulizer (UN)) with respect to their ability to adequately sensitize/challenge guinea pigs by antigen inhalation in bronchial asthma. Several solutions and suspensions, including antigen and Al(OH)₃, were atomized with these three nebulizers. The results obtained were as follows: irrespective of the type of solution or suspension used, of the three nebulizers, GPN generated mists with the smallest diameter. The rank order of median diameter of the mists generated was GPN (1.6-2.1μm)<DN (2.2-3.5μm)<UN (4.3-4.7μm). When Evans blue mists produced by the GPN were presented to guinea pigs, 79% of the mist trapped in the whole airway was found in the lung, while 49 and 79% of mists produced by DN and UN, respectively, were already deposited in the upper airway. These results strongly suggest that GPN is more useful for inhalation challenge in experimental asthma in animals.

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