Minoru Okuda

Epidemiology of Japanese cedar pollinosis throughout Japan

BACKGROUND Japanese cedar pollinosis (JCP) is a common disease posing a major public health problem in Japan. For health care policy planning and development of new treatment modalities, investigation of the accurate prevalence and current status of JCP nationwide is imperative. OBJECTIVE To ascertain the prevalence and the current status of JCP in Japan with use of a cross-sectional random sampling method. METHODS In a nationwide survey conducted shortly after the peak pollen season, self-evaluation questionnaire were mailed to 10,920 subjects from 390 of 3,370 places in 12 regions in Japan. RESULTS The response rate was 53.7%, and the usable response rate was 51.5%. The age-adjusted prevalence was 19.4%; the estimated prevalence was 13.1% after adjustment for misdiagnosis, incorrect answers, response rate, and case mix. JCP was most prevalent in the Kanto, Tokai, and Kinki areas and in working adults rather than in children or subjects ages 60 to 79 years. Total pollen count during the pollen season correlated well with the prevalence of JCP in individual regions. In subjects with JCP, nasal symptom were more severe than eye symptoms, 62.5% had severe or moderate interference with daily activities and consulted physicians, 54.1% took prescribed drugs, and 82% used some method to avoid pollen. CONCLUSIONS The age-adjusted prevalence of JCP was 19.4% of the Japanese population, and estimated prevalence after correction of possible biases was 13.1%. Prescribed drugs treated approximately 60% of subjects with JCP, and 80% of subjects tried self-care by avoiding pollen.

Changes in nasal metachromatic cells during allergen immunotherapy

We have investigated changes of nasal metachromatic cell number, nasal symptoms and nasal provocation at the third and sixth month during allergen immunotherapy. Twenty‐five subjects with perennial allergic rhinitis (house dust (23), Alternaria (2)) were divided into two groups: an immunotherapy‐treated group (n= 14) and a control group (n=11). At the first visit nasal symptom scores, nasal provocation reactions and the number of metachromatic cells in nasal mucosal epithelial scrapings were not significantly different between groups. At the third and sixth month after immunotherapy nasal symptom scores, nasal provocation and the metachromatic cells in epithelial scrapings were significantly reduced (P < 0.05) compared with the pretreatment values in the immunotherapy group, but unchanged in the control group. These results suggest that the reduction in metachromatic cell number at the nasal mucosal surface may be one of the mechanisms which could explain the improvement of nasal allergic symptoms by immunotherapy.

Fexofenadine improves the quality of life and work productivity in Japanese patients with seasonal allergic rhinitis during the peak cedar pollinosis season.

Background: Although currently in its infancy, quality of life (QOL) research in Japan is rapidly expanding and is expected to become a standard outcome measure in clinical trials. In Japan, QOL has not previously been assessed in patients with allergic rhinitis (AR); we report the first clinical study applying the recently validated Japanese translations of the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) and Work Productivity and Activity Impairment-Allergy Specific (WPAI-AS) Questionnaire to assess the effects of the oral antihistamine, fexofenadine, on QOL and work productivity due to cedar pollinosis. Patients and Methods: A randomized, double-blind, placebo-controlled, single-site study was conducted during the peak cedar pollinosis season in Japan. After a 7-day run-in period, subjects were randomized to receive fexofenadine HCl 60 mg twice daily (bid) or placebo for 2 weeks. Results: Overall, 206 Japanese subjects with AR were included in the intention-to- treat population (fexofenadine, n = 104, and placebo, n = 102). Fexofenadine statistically significantly improved overall QOL compared with placebo (p = 0.005) and improvements were reported in the RQLQ domains: activities (p = 0.047), practical problems (p = 0.003), nasal symptoms (p = 0.003) and eye symptoms (p ≤ 0.001). Clinically significant improvements in practical problems, eye symptoms and activity limitations, exceeding the 0.05 level, were observed with fexofenadine. These improvements in QOL were associated with significant symptom relief (p < 0.001 vs. placebo). Improvements in impairment at work were also reported with fexofenadine. Conclusion: In Japan, this is the first clinical study to show that fexofenadine HCl (60 mg b.i.d.) improves overall QOL and work productivity in patients with seasonal AR using validated Japanese instruments.

Histological and immunological studies on eosinophilic granuloma of soft tissue, so‐called Kimura's disease

Increase of serum IgE with frequent localization of IgE in the germinal centres, mast cell hyperplasia in lymph nodes and changes of specific granules in the infiltrated eosinophils, such as roughness of the matrix and appearance of tubular structures together with fusing and disappearance of the core, were demonstrated in eosinophilic granuloma of the soft tissue, so‐called Kimuras disease, in association with increase of anti‐Candida IgE antibody.

Basophilic cells in allergic nasal secretions.

SummaryEvidences on the important role of tissue mast cells in inducing allergy have accumulated. These cells are known to be present in nasal secretion but have not been well studied. In the present study basophilic cells containing granules which stained metachromatically appeared in the nasal secretion in various kinds of inhalant allergy. An increase in their number was observed after nasal provocation and during the pollinosis season and showed a decrease after a course of immunotherapy or during the off-season of pollinosis. They were well correlated in degree with nasal symptoms, nasal eosinophilia, and nasal provocative reactions. These results suggest that the appearance of the basophilic cell in nasal secretion is related to their specifity in nasal allergy. The possibility of onset of nasal allergy due to the release of chemical mediators from basophilic cells in nasal secretion was discussed.

Important factors in the nasal manifestation of allergy.

ZusammenfassungZur Klärung der Frage, ob Histamin durch Antigene von der Oberfläche der Nasenschleimhaut in ausreichender Menge produziert werden kann, um eine nasale Allergie zu manifestieren, und zur Feststellung, welcher der drei Faktoren: Zahl der basophilen Zellen der Oberfläche, Histaminfreisetzung dieser Zellen oder Histaminsensibilität der Schleimhaut für den Grad der nasalen Allergenprovokation der wichtigste ist, werden die allergeninduzierte Histaminfreisetzung, die Zahl der basophilen Zellen sowie die Histaminsensibilität der Schleimhaut bestimmt. Es zeigte sich, daß, in der genannten Reihenfolge die Histaminfreisetzung, die Zahl der basophilen Zellen und die Histaminempfindlichkeit der Schleimhaut entscheidend sind und eine nasale Provokationsreaktion hervorrufen.SummaryTo elucidate whether or not histamine can be released by antigen from the nasal surface layer in sufficient quantities to produce nasal manifestation of allergy and which among three factors, i.e., the number of surface basophilic cells, the histamine release from these cells, or the mucosal histamine sensitivity, is the most responsible for the degree of nasal allergen provocation, we determined the allergen-induced histamine release from specimens of the mucus-epithelial layer of patients with nasal allergy and also counted the number of basophilic cells in these specimens after staining by Hansels method. In addition, we evaluated the histamine sensitivity of the mucosa by the end-point test.The net histamine content released from the specimens of the nasal surface ranged from 25.5–310.7 μg/cm3, which was found to be sufficient to produce nasal manifestation of allergy. The correlation coefficients were calculated as the relationships between the degree of provocation reaction and the level of histamine released from the nasal surface, the basophilic cell number, histamine releasability and histamine reactivity. These values were 0.645, 0.440, 0.481, and 0.155, respectively, and, when they were analyzed statistically, the most significant correlations to the degree of provocation reaction were found to be those between the degree of provocation reaction and the histamine content released from the nasal surface, the basophilic cell number, or the histamine releasability and histamine reactivity (p<0.01), in that order.

Basic study of nasal provocative test first report: Side, site of the nose, size of site and allergen amount

SummaryThe methodology of the provocative nasal test has varied according to the investigators. In order to establish a standard method of this test quantification of the nasal challenge, including the amount of the allergen, nasal site, side and size of allergen deposition, was studied. From the results obtained it is preferable to use the end point test and to apply allergen to the anterior part of the inferior turbinate in a 7mm2 size of surface area, bilaterally. An alternative test is to use a fixed amount of allergen (500 μg house dust in house dust allergy).

Comparison of fluticasone furoate and fluticasone propionate for the treatment of Japanese cedar pollinosis.

Fluticasone furoate nasal spray (FFNS) is a novel, enhanced-affinity glucocorticoid administered in a unique side-actuated device for the treatment of allergic rhinitis. No previous clinical studies have compared the efficacy of FFNS with another intranasal steroid. The purpose of this study was to compare the efficacy and safety of FFNS, 110 microg/day, once daily with fluticasone propionate nasal spray (FPNS), 200 microg/day, twice daily in patients with Japanese cedar pollinosis to support the regulatory filing in Japan. In this multicenter, randomized, placebo-controlled, double-blind, parallel-group study, patients (>or=16 years old) were randomized to receive 2 weeks of treatment with FFNS (n = 151), FFNS placebo (n = 72), FPNS (n = 148), or FPNS placebo (n = 75). FFNS once daily was noninferior to FPNS twice daily in mean change from baseline in three total nasal symptom scores (3TNSS; sneezing, rhinorrhea, and nasal congestion; -1.23 +/- 0.140 and -1.06 +/- 0.142, respectively). Compared with placebo, FFNS was superior in reducing 3TNSS (p < 0.001). Both FFNS and FPNS showed similar mean changes from baseline in 4TNSS (3TNSS and nasal itching) and individual nasal symptom scores. The onset of action for FFNS was observed from the 1st day of treatment, whereas in the FPNS group it was observed on the 2nd day. There were similar improvements in rhinoscopy findings, activity of daily life interference, and patient-rated overall evaluation to therapy in the FFNS and FPNS groups. FFNS was well tolerated. Treatment with once-daily FFNS was effective and noninferior to twice-daily FPNS in reducing nasal symptoms. Faster onset of action for FFNS was observed.

Mast cells in allergic nasal epithelium and lamina propria before and after provocation. An electron microscopic study

A study of mast cells in subjects with nasal allergy was made by electron microscopy before and after provocation in three areas; the nasal epithelium, the subepithelial layer and the deep layer of the nasal lamina propria. The ration of degranulation of the mast cells in the nasal epithelium and subepithelial layer increased after provocation. The main features of exchanged granules of the mast cells in these areas were (1) swelling of lower electron density of the area enclosed by perigranular membrane, (2) lower electron density of the total area of granular substance with fibrillar and reticular changes, and (3) the disappearance of granular substance. It was, therefore, judged that the mast cells in the nasal epithelium and in the subepithelial layer play a more important part in the onset of a nasal allergic reaction than do those in the deep layer of the nasal lamina propria.

Electron microscope study of basophilic cells in allergic nasal secretions.

SummaryIn order to elucidate whether basophilic cells in nasal secretion belong to blood basophil or tissue mast cell, basophilic cells in the blood, nasal secretion, and nasal mucous membrane were electron microscopically observed in patients with house dust nasal allergy. The majority of basophilic cells in the nasal secretion was identical with the blood basophil in structure. The blood basophils pass through the vessels and emigrate in the mucous blanket in allergy.