[LONG-TERM RESULTS OF AIRBORNE POLLEN SURVEYS IN THE JAPANESE ARCHIPELAGO FROM THE PERSPECTIVE OF POLLEN ANTIGEN].

BACKGROUND: In 1986, the Ministry of Health and Welfare started an airborne pollen survey as part of measures against JC pollinosis. We reported the important tree pollen antigens in 2016. We have now estimated the longitudinal investigated results for successful prevention and treatment for allergic symptoms related to grass and weed pollen in Japan. METHOD: Since July 1986 we have monitored airborne pollen, year- round, using a gravitational pollen sampler (Durham's sampler), at more than 20 locations across Japan. Specimens were mailed to our facility, where they were stained with Calberla solution, counted under an optical microscope, and converted to the number of pollen per square centimeter. For convenience the number of collected pollen were compiled every six months, with the January to June samples classified as spring pollen and the July to December as autumn pollen even same family. RESULT: Total pollen counts at each location were extremely small compared to tree-pollen, averaging 73~650 pollen grains per year. The Sagamihara location had the greatest count. Unlike cedar and cypress there were no significant annual fluctuations, but grass and Ambrosia pollen counts are increasing in some regions. Spring grass pollen gave the largest count, at 30% of the total collected. CONCLUSION: This indicated we need to examine the rinoconjuctivitis and oral allergy syndrome related to herbaceous pollen carefully.The importance of airborne pollen surveys for the treatment of the patients with pollen allergies was suggested.

LONGITUDINAL MONITORING OF TREE AIRBORNE POLLEN IN JAPAN.

RATIONAL: In Japan patients with Japanese Cedar (JC) pollinosis have increased nation widely since the latter of 1970's. The Ministry of Health and Welfare of Japanese Governments has begun to take preventive measures against JC pollinosis and airborne pollen monitoring has begun to investigate as a causative agent since 1986. We have estimated the longitudinal investigation result for successful prevention and treatment against pollinosis in Japan. METHOD: We have monitored airborne pollen all year around since July 1986 by gravitational pollen sampler, Durham's sampler, at more than 20 locations in the Japanese Islands. Pollen samples were sent to our hospital and counted pollen number per cm2 after stained by Calberla solution and then classified main pollen grains as a causative agent of pollinosis. RESULT AND DISCUSSION: JC pollen number was the most of all, more than 40%, next cypress family, about 20%. They were occupied of more than 60% of all and they increased with the remarkable annual fluctuation as the allergen of JC pollinosis. Beech family pollen counting were also increasing and occupied about 10% of all pollen counts. In Hokkaido the prevalence of birch family pollen count was larger than that in other districts. There is cross-reactivity between beech and birch family which related with oral allergic syndrome.Perspective and Conclusion: In future new occurrences of oral allergy syndrome due to increasing allergic tree pollen grains would be appeared. The contentious pollen research should be important for patients with pollinosis in Japan.

Effects of antihistamine on up-regulation of histamine H1 receptor mRNA in the nasal mucosa of patients with pollinosis induced by controlled cedar pollen challenge in an environmental exposure unit.

In the present study, we examined the effects of antihistamine on the up-regulation of H1R mRNA in the nasal mucosa of patients with pollinosis induced by controlled exposure to pollen using an environmental exposure unit. Out of 20 patients, we designated 14 responders, whose levels of H1R mRNA in the nasal mucosa were increased after the first pollen exposure and excluded 6 non-responders. Accordingly, the first exposure to pollen without treatment significantly induced both nasal symptoms and the up-regulation of H1R mRNA in the nasal mucosa of the responders. Subsequently, prophylactic administration of antihistamine prior to the second pollen exposure significantly inhibited both of the above effects in the responders. Moreover, the nasal expression of H1R mRNA before the second pollen exposure in the responders pretreated with antihistamine was significantly decreased, as compared with that before the first pollen exposure without treatment. These findings suggest that antihistamines suppressed histamine-induced transcriptional activation of H1R gene in the nasal mucosa, in addition to their blocking effect against histamine on H1R, resulting in a decrease of nasal symptoms. These findings further suggest that by their inverse agonistic activity, antihistamines suppress the basal transcription of nasal H1R in the absence of histamine in responders.

Examination, diagnosis and classification for Japanese allergic rhinitis: Japanese guideline.

Many countries throughout the world have experienced an increase in the prevalence of allergic rhinitis (AR), which has come to be a major cause of morbidity in developed countries. The pathology underlying AR is regarded as IgE-mediated type I allergy characterized by mucosal inflammation that occurs in response to allergen exposure. In Japan, AR caused by Japanese cedar pollen, the most common allergic disease, has become a salient public health challenge. Almost all primary care physicians and otorhinolaryngologists have been consulted by AR patients between February and April. Although most such patients have received treatment, numerous patients with AR have not received proper examinations for AR. Clinical guidelines are systematically developed statements that are designed to help practitioners make decisions about appropriate and effective health care. Guidelines in many countries including Japan have been published for AR. Unfortunately, those guidelines have remained untested. Moreover, they might be difficult for non-specialists to use. In this review, we specifically examine the present standard examination for diagnosis of AR and optimal classification for AR in Japan. We hope that this review would be used not only for the support of daily practice but also for selection of AR patients for clinical trials.

Enhancement of anti-allergic effects mediated by the Kampo medicine Shoseiryuto (Xiao-Qing-Long-Tang in Chinese) with lysed Enterococcus faecalis FK-23 in mice.

Kampo is a traditional Japanese medicine originating from ancient Chinese medicine which included the administration of herbal prescription, lifestyle advice and acupuncture. Orally administered Kampo prescriptions are believed to be influenced by diet and intestinal microbiota. However, reports on the Kampo administration effects are still limited. Shoseiryuto (TJ-19), which has anti-allergic and anti-inflammatory properties, is a Kampo prescription used clinically for the treatment of allergic bronchial asthma. We examined whether Shoseiryuto administration is affected by a probiotic product, lysed Enterococcus faecalis FK-23 (LFK). BALB/c mice were sensitized with cedar pollen allergen, and the peritoneal accumulation of eosinophils was induced. During a sensitization period of 21 days, varying amounts of Shoseiryuto (and saline as a control) were administered to the mice. The accumulation of eosinophils was significantly reduced by 30 mg/day doses of Shoseiryuto but not by 3 or 9 mg/day doses. Similarly, 3 mg/day Shoseiryuto, 30 mg/day LFK, 3 mg/day of Shoseiryuto co-administered with 30 mg/day of LFK, and saline control were compared. A significant reduction in the accumulation of eosinophils was observed at 3 mg/day Shoseiryuto co-administered with 30 mg/day of LFK. These results suggest that Shoseiryuto-mediated anti-allergic effects are enhanced by the probiotic (LFK). Although not significant statistically, serum allergen-specific and total IgE levels in the treatment group exposed to the mixed agent (ie. Shoseiryuto and LFK) were generally lower than those receiving either one alone. The results indicate a synergistic effect of a Kampo medicine (Shoseiryuto, Xiao-Qing-Long-Tang in Chinese) and lysed Enterococcus faecalis FK-23 on allergic responses in mice.

[A case presenting anaphylaxis shock after intake of capsule packing cedar pollen].

The prevalence of Japanese cedar pollinosis is high to 26.5%, and it is properly remarked as "national disease" in Japan. General therapy strategies are composed of self-care by using mask or glasses to avoid antigen, and medical-care by using second-generation antihistamines or nasal corticosteroid spray. Meanwhile, there are other so-called self-medication patients who utilize health foods but do not consult to any physician. Papilla, commercial name of one kind of those health foods, is a capsular packed with cedar pollen. In February 2007, we experienced a 49-year-old female patient who presented anaphylaxis shock after intake of Papilla capsular. In this case, her special-IgE antibody and histamine release test were both positive to cedar pollen. Although Cry j 1, the major allergen in the Papilla capsular is a small amount, the cause of anaphylaxis can not be reasoned as anything except the pollen contents in this product. In conclusion, it is appropriate to consider it exercise induce anaphylaxis shock due to playing tennis after intake of the capsular.

Effects of Enterococcus sp. isolated from deep seawater on inhibition of allergic responses in mice.

The objective of the present study was to assess the effects of Enterococcus sp. strain TN-3 isolated from deep seawater on inhibition of eosinophil accumulation, IgE production and active cutaneous anaphylaxis (ACA). We investigated the effects of viable and non-viable TN-3 on allergen-induced peritoneal eosinophil accumulation in mice. Viable (5.4 x 1010 colony-forming units per 60 mg) or non-viable TN-3 (60 mg) was orally administered to BALB/c mice that had been sensitised with the cedar pollen (Cryptomeria japonica) allergen. Oral administration of non-viable TN-3 was effective in suppressing eosinophil accumulation while viable TN-3 was ineffective. We also examined the dose-response relationship for non-viable TN-3 in regard to eosinophil accumulation, IgE production and ACA in allergen-primed mice. Non-viable TN-3 was orally administered at doses of 15 mg (low dose), 30 mg (medium dose) and 60 mg (high dose) to BALB/c mice that had been sensitised with cedar pollen allergen. The anti-allergic effects expressed as inhibition of eosinophil accumulation, IgE production and ACA were found at the low and high doses, but not at the medium dose. These results suggest that non-viable TN-3 exhibited anti-allergic effects at doses of 15 and 60 mg.

Effects of lysed Enterococcus faecalis FK-23 on allergen-induced peritoneal accumulation of eosinophils and serum total IgE concentration in inbred mice.

Recent clinical trials have shown the possibility of probiotics in prevention and treatment of allergic diseases. The purpose of this experimental study was to assess the influence of lysed Enterococcus faecalis FK-23 (LFK) on allergic responses in different mouse strains. We performed a comparative study on the effects of LFK for allergen-induced peritoneal accumulation of eosinophils and serum total IgE concentration by using BALB/c, C57BL/6, C3H/HeN and C3H/HeJ mice. There was no significant difference in total number of peritoneal accumulated cells induced by cedar pollen allergen between the control and LFK groups in any strain of mice (p > 0.05); however, the ratio of eosinophils to total accumulated cells was significantly decreased in LFK-treated mice of BALB/c (p = 0.016), C3H/HeN (p = 0.010) and C3H/HeJ (p = 0.004), but not C57BL/6 (p > 0.05). No significant difference in serum total IgE concentration was found between the control and LFK groups of different mouse strains (p > 0.05). These results reveal a different effect of LFK on suppressing allergen-induced local eosinophila in inbred strains of mice, suggesting the effectiveness of probiotics on limiting allergy might be under the influence of individual genetic background.

Clinical effects of a hop water extract on Japanese cedar pollinosis during the pollen season: a double-blind, placebo-controlled trial.

The clinical effects of an oral administration of a hop water extract (HWE) on the improvement of Japanese cedar pollinosis (JCPsis) symptoms were investigated. In a double-blind, placebo-controlled trial, 39 subjects took a drink containing either 100 mg of HWE or a placebo for 12 weeks during the pollen season. Nasal symptoms (sneezing attacks, nasal discharge, and nasal obstruction) were assessed from the subjects' diaries. A clinical examination and blood sampling were carried out before and 4, 8 and 12 weeks after the initiation of treatment. As a result, a significant difference was observed in the symptom score and in the symptom-medication score 10 weeks after the intervention in comparison with the placebo group. Improvements were observed in nasal swelling, nasal color, amount of nasal discharge, and characteristics of nasal discharge in the intervention group 12 weeks after the treatment. No significant eosinophil infiltration into the nasal discharge was apparent in the intervention group throughout the study period, although it was observed in the placebo group. These findings indicate that an oral administration of HWE may be effective in alleviating the allergic symptoms related to JCPsis.

Changes in plasma TARC levels during Japanese cedar pollen season and relationships with symptom development.

BACKGROUND: Japanese cedar pollinosis (JCPsis) is an immunoglobulin E-mediated type I allergy caused by exposure to Japanese cedar pollen (JCP). Blood thymus and activation-regulated chemokine (TARC) levels are well known as an objective parameter for disease severity for several allergic disorders. The present study aims to evaluate the relationship between TARC levels and disease symptoms during the pollen season. METHODS: Analysis was performed of results of symptom scores and blood parameters obtained from 42 JCPsis patients who participated in a probiotic (Bifidobacterium longum BB536) intake trial in the JCP season of 2005 (January to April), using a randomized, double-blind, placebo-controlled design. RESULTS: Significant increases in plasma TARC levels were observed in subjects receiving placebo (p < 0.05 in February and p < 0.01 in March), but not in subjects receiving BB536. Increased plasma TARC levels were markedly greater in subjects who experienced severe symptoms and were thus excluded early from the intervention (placebo group: n = 8; BB536 group: n = 2). Significant differences were found in changes from baseline TARC levels in February and March between the subjects where treatment was terminated early and the remaining ones. Among the remaining subjects, significant positive correlations were found as regards changed values of TARC compared to baseline in March and April with symptom scores recorded in the pollen season. CONCLUSION: Changed values of blood TARC in the pollen season may offer promising parameters for assessing disease severity and monitoring treatment.

An evaluation of the clinical efficacy of tomato extract for perennial allergic rhinitis.

BACKGROUND: Recently, some common foods in daily life have been found to have anti-allergic effects. We have reported that tomato extract (TE) could possibly inhibit histamine release and mouse ear-swelling responses. Moreover, it is reported that TE could relieve the symptoms for Japanese cedar pollinosis. METHODS: To evaluate the anti-allergic effect of TE, we performed a randomized, double-blind, placebo-controlled study in 33 patients with perennial allergic rhinitis (PAR) using oral administration of TE (360 mg per day) or placebo for 8 weeks. RESULTS: We found that the sneezing score significantly decreased in the TE group at the end of the trial compared to the beginning (P < 0.05). There were decreasing tendencies of rhinorrhea and nasal obstruction in the TE group. The patients' quality of life was significantly improved in the TE group after 8 weeks of treatment (P < 0.05), but not in placebo group. A significant improvement in total symptom scores, combining sneezing, rhinorrhea and nasal obstruction, was observed after oral administration of TE for 8 weeks (P < 0.01). The safety of TE treatment was confirmed by laboratory tests and inspection of general conditions. CONCLUSIONS: TE can be expected to safely improve the nasal symptoms of PAR.

Clinical efficacy of probiotic Bifidobacterium longum for the treatment of symptoms of Japanese cedar pollen allergy in subjects evaluated in an environmental exposure unit.

BACKGROUND: Japanese cedar pollinosis (JCPsis) affects nearly one in six Japanese. Oral administration of Bifidobacterium longum BB536 has been shown to be effective in relieving JCPsis symptoms during the pollen season. METHODS: This double- two-way crossover study was designed to evaluate the efficacy of BB536 on reducing symptoms in JCPsis patients exposed to Japanese cedar pollen (JCP) in an environmental exposure unit (EEU) outside of the normal JCP season. After a 1-week run-in period, subjects (n=24) were randomly allocated to receive BB536 powder (approximately 5x1010) or placebo twice a day for 4 weeks. After a 2-week washout period, subjects were crossed over to another 4 weeks of intake. At the end of each intake period, subjects received controlled JCP exposure for 4 hours in the EEU. Symptoms were self-rated 30 minutes before and every 30 minutes during the exposures. From the first day of exposure through the next 5 successive days, participants self-rated their delayed symptoms and medication uses. Blood samples were taken before the exposures. The mean JCP levels for exposures were 6500 to 7000 grains/m3 air. RESULTS: In comparison with placebo, BB536 intake significantly reduced the ocular symptom scores during JCP exposures. Evaluating delayed symptoms after exposures indicated that scores for disruption of normal activities were significantly lower in the BB536 group compared with the placebo group. Prevalence of medication use was markedly reduced by BB536 intake. CONCLUSIONS: These results suggest the potential beneficial effect of BB536 in relieving symptoms of JCP allergy.

Effect of antihistamine eye drops on the conjunctival provocation test with Japanese cedar pollen allergen.

BACKGROUND: Approximately 16.2% of the Japanese population suffer from cedar pollinosis, with various manifestations such as ophthalmic, laryngo-pharyngeal and skin symptoms in addition to nasal symptoms. Thus, the annual pollen season is an agonizing period for patients. No study has reported symptoms and their clinical courses after conjunctival provocation with purified cedar pollen allergen Cry j1 as well as suppression of these allergen-induced ocular symptoms by antihistamine eye drops. METHODS: Nine patients with Japanese cedar pollinosis who had no nasal or ocular symptoms were included in the present study, after obtaining informed consent in writing. 1) Purified cedar pollen allergen Cry j1 was instilled in the left eye and phosphate-buffered saline (PBS) in the right eye as a control. 2) Levocabastine hydrochloride ophthalmic suspension and ketotifen fumarate ophthalmic solution were respectively instilled in the left and right eyes, which were then challenged with the allergen. Ocular symptoms after provocation with the allergen were recorded through the clinical course. RESULTS: Pollen allergen-induced ocular symptoms were itching and hyperemia of the palpebral conjunctiva, and itching lasted for more than 5 hours. Moreover, preadministration of antihistamine eye drops suppressed the increases in the ocular symptom scores, eliminating itching within 1 hour. Allergen provoked not only ocular symptoms but also nasal symptoms in 77.8% of patients. CONCLUSIONS: Preadministration of antihistamine eye drops suppressed the symptoms induced by the allergen, which suggests that this is an effective early therapy for Japanese cedar pollinosis, if it is started before the pollen season. However, self-protection by patients using a mask may not be effective enough to suppress nasal symptoms during the pollen season, requiring them to additionally wear glasses to avoid exposure to the allergen.

Lack of association between the IL13 variant Arg110Gln and susceptibility to cedar pollinosis in a Japanese population.

BACKGROUND: Interleukin (IL)-13 has come to be appreciated as a molecule critically involved in allergic inflammatory responses. Recent studies revealed that a common variant in the coding region of the IL13 gene, Arg110Gln, has been implicated in the development of asthma and atopy. METHODS: To assess whether the IL13 variant Arg110Gln is associated with cedar pollinosis, one of the most common atopic diseases in the Japanese population, we examined the Arg110Gln variant using PCR-RFLP to compare the genotype and allele frequencies between 95 patients with cedar pollinosis and 95 healthy control subjects. Relationships between the Arg110Gln variant and the pollinosis-related traits, e.g. rhinitis severity, eosinophil counts in nasal secretion and serum total and allergen-specific IgE levels, were also investigated. RESULTS: The frequencies of the minor allele Gln110 were 25.8% in patients with cedar pollinosis and 30.9% in healthy control subjects (p > 0.05). There was also no significant difference in the genotype frequencies between cases and controls (p > 0.05). In addition, we found no significant association of the Arg110Gln variant with any of the pollinosis-related phenotypes (p > 0.05). CONCLUSIONS: Our data suggest lack of evidence for identifying the variant Arg110Glnat the IL13 locus as a genetic risk factor involved in the development of Japanese cedar pollinosis.

[Impact of allergic rhinitis on work productivity: a pilot study].

BACKGROUND: Allergic rhinitis can interfere with cognitive function, can impair work productivity, and may cause work absences. In this study, we evaluated the impact of Japanese cedar pollinosis (JCP) on work productivity. METHODS: The study was conducted between February 24 and March 8, 2003 (peak pollen season), and 512 workers with JCP were enrolled. Study outcomes included self-reported work productivity (absenteeism and presenteeism) and quality of life (the Medical Outcomes Study Short Form-36). RESULTS: Most patients (91%) did not lose their work time due to JCP during the past 7 days. Approximately half of patients reported a 25% reduction in productivity compared with non pollination season. In multiple logistic regression analysis, the following factors were selected as independent risk factors for lost work time: duration of disease (adjusted odds ratio (aOR) = 0.658) and itching eyes (aOR = 1.552). Likewise, SF-36 PCS (aOR = 0.946), MCS (aOR = 0.927) and using pollinosis relief products (aOR = 2.020) were predictors of lost productivity. CONCLUSION: This study shows that we should pay more attention to ocular symptoms as well as nasal symptoms and improve patients' quality of life as soon as possible in order to reduce productivity losses.

[A comparative study between real time monitor KH-3000 and conventional Durham sampler measuring airborne pollen].

Real time monitoring of airborne pollen has gradually increased because monitoring is laborsaving and provides better real-time information. A problem arose, however, due to differences between the KH3000 (Yamato Co. Ltd) monitor and the conventional Durham sampler pointed out in results of airborne pollen monitoring in Wakayama in 2004. We compared the two monitors for airborne pollen in Wakayama in 2004, which less dispersed than usual. The peak monitored by the KH-3000 monitor was not consistent with the prime period of Japanese cedar and cypress pollen dispersion, especially in February and April, although they correlated highly in March. The inconsistency in February is thought to be caused by snow, and that in April by falsely monitoring beech-tree airborne pollen-which is similar in size-in addition to Japanese cedar and cypress pollen. This report points out the need to take these conditions (snow and other plants pollen) into account when a real time monitor is used for collecting pollen information.

[Regional comparison of patient-reported outcomes in Japanese cedar pollinosis].

BACKGROUND: There is little information about the relationship between local pollen counts and pollinosis symptoms of the local patients. In this study, we compared patient-reported outcomes (PROs) of Japanese cedar pollinosis (JCP) according to regions. METHODS: The study was conducted between February 24 and March 8, 2003 (peak pollen season), and 1200 patients were recruited from 15 ENT clinical sites in 4 regions : central Osaka (n = 576), southern Osaka (n = 195), northern Wakayama (n = 234), and southern Wakayama (n = 195). PROs consisted of nasal symptoms, ocular symptom, learning and work impairment, and QOL (SF-36). RESULTS: In non-treatment group, there were significant differences in ocular symptom and learning and work impairment among regions. On the other hand, patients with longer duration of treatment had better symptom relief regardless of pollen level in early treatment group. As to QOL, SF-36 summary scores did not differ among regions in both groups. CONCLUSION: This study shows that patients without early treatment seemed to be affected by pollen level on their ocular symptom and its related outcomes. In patients with early treatment, however, the treatment duration had bigger impact on PROs than the local pollen counts.

[Effects of drug adherence on patient outcomes to early treatment for Japanese cedar pollinosis].

Drug adherence is one of the important aspects in caring for patients with allergic rhinitis. To improve clinical efficacy of early treatment for Japanese cedar pollinosis (JCP), we evaluated the effect of drug adherence on patients' outcomes. Patients were randomly selected from 16 ENT clinical sites in Osaka and Wakayama between February 24 and March 8, 2003 (peak pollen season). Efficacy was assessed using patients' ratings of nasal and ocular symptoms and overall assessment in their condition compared with previous season ones. Costs include direct costs of the drugs used for treatment to JCP from January to February. Five hundred one patients taking early treatment were enrolled. Compared to low adherence patients, those who reported higher level of adherence significantly improved overall health condition, and achieved better symptom relief of rhinorrhea and nasal congestion. In multiple logistic regression analysis, the following factors were independent risk factors for low adherence: student (p=0.002), using OTC medications (p=0.006), and short-duration of medication (p=0.001). Low costs were also risk factor for low adherence. We conclude that taking medications for JCP for 22-28 days is the best way to enhance patients' outcomes.

[Willingness to pay for Japanese cedar pollinosis: comparison between pollination and non-pollination seasons].

Allergic rhinitis is not fatal illness, but its high prevalence and several symptoms result in substantial medical cost. There is increasing interest in the use of economic evaluations in healthcare; therefore, we investigated patients' willingness to pay (WTP) for prevention and cure from Japanese cedar pollinosis (JCP), and compared WTP values assessed in non-pollination season (June 1998) and pollination season (February-March 2003). Japanese economic woes got worse in 2003 than in 1998. Patients were randomly selected from ENT clinical sites in Osaka, 175 and 645 patients completed WTP questionnaire in 1998 and 2003, respectively. WTP value was lower in 2003 than in 1998, which related to part-time employees and housewives' reducing WTP. Declining WTP value did not associated with the differences in patient characteristics between 1998 and 2003 including age, duration of disease, nasal symptom severity and comorbid condition. These results show that we have to take employment status into account in economic evaluations. Decline in WTP for JCP in 2003 was strongly affected by Japanese sluggish economy, and the WTP seemed to be stable value in individual patients.