Asthma is a complex disorder associated with the activation of T lymphocytes and with eosinophil infiltration within the airways. A substantial amount of current research involves the interaction among inflammatory cells as a result of the production of a wide array of T helper (h) 2 cytokines. Recent advances in the pathophysiologic mechanisms of asthma point to the importance of transcription factors of cytokines that underlie the development of Th2-type responses. The study of transcription factors has begun to reveal mechanisms of dysregulated gene regulation in asthmatic diathesis.

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Background: A study throughout 1999 of the airborne pollens of both Cryptomeria japonica and Cupressaceae (Chamaecyparis obtusa and Juniperus rigida in the present study) demonstrated unique patterns of pollen dispersal at three observation sites, namely Okayama and Nishinomiya cities in the Chugoku region and Sakura city in the Kanto region.
Methods/Results: In contrast with the Sakura site, where there was a low pollen count for Cupressaceae, high pollen counts were found at the two sites in Okayama and Hyogo Prefectures. There was a good correlation between results of pollen prick tests and the capsulated hydrophilic carrier polymer radioallergosorbent test (CAP-RAST) for C. japonica, C. obtusa and J. rigida. The fact that a positivity rate of 32.6% to the J. rigida pollen skin test was obtained in Sakura city in Chiba Prefecture, where no J. rigida pollen dispersal was observed, seems to demonstrate the existence of a common antigen epidemiologically. Daily pollen counts, symptom scores, medication scores and symptommedication scores of 25 patients with vernal pollinosis in Chiba Prefecture in whom the dose and use of internal and external medication was consistent with the severity of their symptoms, were all significantly related. The efficacy of pharmacotherapy seems to be inadequate when patients are exposed to pollen during a heavy pollen dispersal period without having taken any protection against it. Moreover, there seemed to be a certain critical point beyond which the symptoms rapidly worsened.
Conclusions: These results suggest that it is important to avoid exposure to pollen, based on the regional pollen information, as well as to administer appropriate medication.

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Background: Although interleukin (IL)-12, IL-10 and interferon (IFN)-γ are key cytokines that control the T helper (Th) 1/Th2 balance in human allergic disorders, details of their interactions in humans have not been clarified. Recently IL-10, one of the Th2 cytokines, has been shown to have an anti-inflammatory effect against allergic responses. To clarify the effect of IL-12 on the production of IFN-γ and IL-10, in the present study we examined responses of peripheral blood mononuclear cells (PBMC) from asthmatics to stimulation by Dermatophagoides farinae (Df) antigen in the presence of exogenous IL-12.
Methods: Peripheral blood mononuclear cells of Df-sensitized (n = 7) and non-sensitized (n = 5) asthmatics were stimulated by Df antigen after incubation with exogenous IL-12 (100 pg/mL). Interferon-γ and IL-10 produced in culture supernatants were measured by ELISA. The effect of IL-12 on lymphocyte proliferation was assayed by [³H]-thymidine incorporation in both groups.
Results: The production of IFN-γ by PBMC was significantly enhanced by incubation with IL-12 in both patient groups (P < 0.05), while IL-12 did not affect the production of IL-10 in either group. Lymphocyte proliferation induced by Df antigen was significantly higher in the Df-sensitized group (P < 0.01). This lymphocyte proliferation was significantly enhanced by exogenous IL-12 only in the Df-sensitized group (P < 0.05).
Conclusions: These observations indicate that IL-12 enhances Th1-shifted immune responses without affecting IL-10 production and suggest that IL-12 may effectively inhibit the Th2 dominant state of bronchial asthma by regulating the Th1/Th2 balance.

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Background: In the present study, we measured specific IgE radioallergosorbent test (RAST) levels for house dust, mites, Japanese cedar, kamogaya (Dactylis glomerata) and ragweed antigens in a group of atopic dermatitis (AD) patients and healthy volunteer subjects in our outpatient clinic. We also performed closed patch testing with patch test reagents using the aforementioned antigens prepared from commercially available skin reaction antigens.
Methods: The dermatologic symptom severity index, duration of disease, total serum IgE, lactate dehydrogenase (LDH) and eosinophil counts were assessed. The relationship between each of these parameters and the intensity of the response to the patch test was then evaluated.
Results: The patch test positivity rate increased in proportion with the duration of antigen application, with a maximum of 15.6% for mite antigen and a minimum of 4.7% for cedar antigen by 72 h. There were no antigens showing negative results in any patients. The positivity rate was lower for patch tests applied on highly keratinized areas of skin. The 72 h positive patch test responses were significantly correlated with total serum IgE, LDH, symptom severity index and specific IgE RAST levels. Most positive patch test responses were considered to be possible late phase reactions of the type I allergic response. However, a small number of patients had IgE RAST negative antigens but positive patch tests.
Conclusions: These findings suggest the presence of more than one mechanism by which a positive reaction is elicited.

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Background: A number of recent studies has demonstrated a critical role for mast cells and mast cell-derived cytokines, especially tumour necrosis factor (TNF), in the control of host defense mechanisms during inflammation. In the presesnt study, we investigated whether TNF-deficient (TNF^-/-) and granulocytemacrophage colony stimulating factor (GM-CSF)-deficient (GM-CSF^-/-) mice expressed defects in normal mast cell function.
Methods: Because the first step in the passive cutaneous anaphylactic (PCA) reaction is fixation of the antibody to mast cells, we tried to obtain a PCA in TNF^-/- and GM-CSF^-/- mice.
Results: While an anti-dinitrophenyl IgE monoclonal antibody induced a strong PCA reaction in wild-type mice, it was not possible to obtain a PCA reaction in either TNF^-/- or GM-CSF^-/- mice. We next examined whether mast cells were present in these mice and if so, did they have functional FcεRI receptors on their surface. The number of mast cells in smears from the peritoneal fluid of the TNF^-/- and GM-CSF^-/- mice was similar to that seen in wild-type mice. However, the expression of FcεRI on mast cells from the peritoneal fluid of TNF^-/- and GM-CSF^-/- mice, measured by either rosetting assay or FACScan analysis, was compromised compared with wild-type mice. Previous studies have established that defects in FCεRI expression often have found that IgE production was com- promised in both TNF^-/- and GM-CSF^-/- mice.
Conclusions: The observed defects may partially explain the immunodeficiency of these cytokine-deficient animals during infection.

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Background: Airborne Cryptomeria japonica pollen has been detected from July to September, after the main pollen dispersal season (during florescence), in Toyama and Niigata prefectures, Japan.
Methods: To identify the source of the pollen, two possible pathways were investigated: (i) secondary pollen dispersal from the ground; and (ii) release from male flowers remaining on the tree crown in C. japonica forests.
Results: Secondary pollen dispersal from the ground ceased just after the main pollen dispersal season ended. However, male flowers remained on the crown until the end of September and released significant amounts of pollen, which contained as much allergenic Cry j 1 as normal pollen dispersed during the spring. There is a significant positive correlation between airborne pollen counts in the spring (FebruaryMay) and summer (JuneSeptember).
Conclusions: These results indicate that the main sources of airborne pollen grains during the summer are male flowers remaining on the tree crown after their florescence.

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Background: Exercise-induced broncho-obstruction (EIB) is common among asthmatic children with a prevalence rate of 40-90. It is one of the leading causes of the deterioration of the general condition of asthmatics and the limitation of physical activity. Therefore, early recognition and provision of adequate therapy is necessary. However, it is not possible to achieve this without first having information about the features of the bronchial response. The aim of the present study was to determine the bronchial response to exercise and to establish a connection between bronchial response and the clinical features of the disease in asthmatic children.
Methods: One hundred and three clinically stable children with different clinical severities of asthma were studied with a standardized step-up exercise test. The airway response to exercise was investigated by peak flowmetry to measure the peak expiratory flow rate (PEFR). Bronchial permeability was determined before and after exercise at 0, 5, 10, 15, 30 and 60 min and then hourly for the next 11 h. These determinations were repeated at the same time points on a non-exercise (control) day.
Results: The test resulted in four types of response to exercise: (i) non-obstructive; (ii) isolated early airway response (EAR); (iii) dual-waved; and (iv) prolonged EAR. The frequency of these responses in the study population was 33.0, 39.81, 26.21 and 0.97%, respectively. No significant difference in clinical features, such as severity and duration of disease, baseline values for PEFR, atopic status, age and gender, was observed with different forms of response to exercise. However, children with moderate and severe asthma had significantly more frequent EIB-positive type responses than children with a mild form of asthma.
Conclusions: Responses to exercise in asthmatic children are heterogeneous and, quite possibly, are particular to each individual patient.

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