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.     

Identification of Cha o 3 homolog Cry j 4 from Cryptomeria japonica (Japanese cedar) pollen: Limitation of the present Japanese cedar–specific ASIT

Background

About one-third of the Japanese population suffers from Japanese cedar pollinosis, which is frequently accompanied by Japanese cypress pollinosis. Recently, a novel major Japanese cypress pollen allergen, Cha o 3, was discovered. However, whether a Cha o 3 homolog is present in Japanese cedar pollen remains to be determined.

The Relationship between Pollen Count Levels and Prevalence of Japanese Cedar Pollinosis in Northeast Japan

BackgroundThe prevalence of Japanese cedar (JC) pollinosis in Japanese children is increasing. However, few studies have reported the relationship between pollen count levels and the prevalence of pollinosis. To evaluate the relationship between JC pollen count levels and the prevalence of pollinosis in children, we investigated the sensitization and development of symptoms for JC pollen in two areas of Akita in northeast Japan with contrasting levels of exposure to JC pollen.MethodsThe study population consisted of 339 elementary school students (10–11 years of age) from the coastal and mountainous areas of Akita in 2005–2006. A questionnaire about symptoms of allergic rhinitis was filled out by the students’ parents. A blood sample was taken to determine specific IgE antibodies against five common aeroallergens.ResultsThe mean pollen count in the mountainous areas was two times higher than that in the coastal areas in 1996–2006. The prevalence rates of nasal allergy symptoms and sensitization for mites were almost the same in both areas. On the other hand, the rates of nasal allergy symptoms and sensitization for JC pollen were significantly higher in the mountainous areas than in the coastal areas. The rate of the development of symptoms among children sensitized for JC pollen was almost the same in both areas.ConclusionsThese results suggest that pollen count levels may correlate with the rate of sensitization for JC pollinosis, but may not affect the rate of onset among sensitized children in northeast Japan.     

日本柳杉花粉变应原致敏蛋白组分

日本柳杉花粉变应原致敏蛋白组分目前已分离纯化并鉴定的有Cry j 1、Cry j 2、Cry j 3、CJP-6、CJP-4、CJP-8及CPA9等,其中某些致敏蛋白组分还具有多种异构体,因此日本柳杉花粉变应原的成分构成十分复杂。Cry j 1和Cry j 2是目前公认的日本柳杉花粉的主要致敏蛋白组分,二者均为糖蛋白,分子结构中均包含B细胞表位和T细胞表位,也与柏科其他植物花粉致敏蛋白组分具有很高的交叉反应性。其中Cry j 1具有果胶裂解酶活性,Cry j 2则有聚甲基半乳糖醛酸酶活性。后续发现的日本柳杉致敏蛋白组分Cry j 3、CJP-6、CJP-4、CJP-8及CPA9等也均有与花粉症患者血清IgE有较高的结合能力,这些蛋白质特点各异,但都具有与其他植物来源变应原的交叉反应性。     

Effect of Cry-consensus peptide, a novel recombinant peptide for immunotherapy of Japanese cedar pollinosis, on an experimental allergic rhinitis model in B10.S mice.

BACKGROUND: We are developing an immunotherapeutic peptide, Cry-consensus peptide, for Japanese cedar pollinosis. Cry-consensus peptide is a recombinant polypeptide containing six major human T-cell epitopes derived from both Cry j 1 and Cry j 2, two major allergens of Japanese cedar pollen. We examined the effect of Cry-consensus peptide on an allergic rhinitis model in B10.S mice, which have one common T-cell epitope in the Cry-consensus peptide. METHODS: B10.S mice were sensitized with Cry j 1/alum, then the Cry-consensus peptide was administered subcutaneously once a week for 5 weeks from the last sensitization. Histamine was dropped in both nostrils (10 microL per nostril) of each mouse on the day before continuous intranasal instillation of Cry j 1. Soon after the final challenge with Cry j 1, the mice were observed for 5 minutes for the resulting number of sneezes. In addition, serum levels of Cry j 1-specific IgE and IgG2a antibody, eosinophil infiltration in nasal tissue, and Cry j 1-specific cytokine production from splenocytes were evaluated. RESULTS: Cry-consensus peptide markedly inhibited Cry j 1-induced sneezes, eosinophil infiltration, and eosinophil peroxidase (EPO) activity in nasal tissue. Cry-consensus peptide inhibited the production of anti-Cry j 1 IgE (Th2-mediated) and significantly enhanced anti-Cry j 1 IgG2a (Th1-mediated). In cytokine production from splenocytes, Cry-consensus peptide significantly decreased in IL-4/IFN-gamma and IL-5/IFN-gamma ratios. CONCLUSIONS: It was concluded that Cry-consensus peptide effectively controlled allergic responses, which results from shifting from a Th2-dominated to a Th1-dominated immune response.     

Characteristics of the Chiba Environmental Challenge Chamber

BackgroundAn environmental challenge chamber (ECC), which we refer to as the α-chamber, was built at Chiba University in 2008. The aim of this study was to validate the functionality of the ECC.MethodsThe stability of the pollen distribution and concentration in the ECC and symptoms of patients with Japanese cedar pollinosis induced by cedar pollen exposure were examined. Carryover effects of symptoms induced by different exposure protocols and correlations between symptoms induced in the ECC and those in the natural cedar pollen season were also determined. All the studies using the α-chamber were conducted out of the cedar pollen season.ResultsThe severity of symptoms in the chamber reached a peak about 2 hours after the start of pollen exposure and plateaued thereafter. After subjects left the chamber, the symptoms persisted for several days. There was no significant difference between the severity of symptoms at exposure levels of 8000 and 12000 grains/m³. The symptoms were significantly increased by exposure for 3 consecutive days; however, there were no carryover effects in a study performed with a two-week interval. The total nasal symptom score (TNSS) in the natural pollen season showed a weak correlation with the mean TNSS on the day of exposure and the following 3 days. Symptoms in the ECC also had weak correlations with those in the early natural pollen season.ConclusionsThe ECC under well-controlled conditions is suitable for clinical studies and might accelerate development of treatment for seasonal allergic rhinitis. A complete evaluation requires inclusion of the persistent reaction after subjects leave the ECC.     

Long-term treatment of Japanese cedar pollinosis with Japanese cedar pollen SLIT drops and persistence of treatment effect: A post-marketing clinical trial

BackgroundThere have been no reports of treatment effect persistence after long-term sublingual immunotherapy (SLIT) in patients with Japanese cedar (JC) pollinosis. Therefore, we conducted a post-marketing clinical trial to investigate the efficacy, safety, and effect persistence of JC pollen SLIT drops after approximately 3 years of treatment.MethodsThis was an open-label trial of 233 patients with JC pollinosis who were treated with JC pollen SLIT drops for approximately 3 years (2015–2017) and followed-up for an additional 2 years (2018–2019). Efficacy and effect persistence were evaluated using nasal and ocular symptom scores, daily use of rescue medication, and Japanese Rhinoconjunctivitis Quality of Life Questionnaire scores recorded during the JC pollen dispersal season of each year. Safety was evaluated by monitoring adverse events and adverse drug reactions.ResultsThe mean combined total nasal symptom and medication score (range 0–18) during the peak symptom periods of 2015 through 2019 were 5.47 ± 3.38, 4.52 ± 3.13, 3.58 ± 2.63, 5.28 ± 4.01, and 6.83 ± 4.65, respectively. The percentage of patients who used no rescue medications during the same periods was 64.8%, 75.2%, 80.3%, 63.7%, and 50.3%, respectively. A total of 138 adverse drug reaction incidents were recorded in 73 of the 233 patients (31.3%), of which 134 incidents (97.1%) were mild in severity.ConclusionsJC pollen SLIT drops demonstrated treatment duration-dependent efficacy with effects that persisted for 2 years after cessation of treatment. The drug had a favorable safety profile over the 5-year study period.     

Reduction of Cedar Pollen Adhesion by Lecithin Polymer Coating

BackgroundAvoidance of allergens is one of the most effective treatments of allergenic diseases, including pollinosis. Although various masks and goggles for pollinosis sufferers are commercially available, little work has been done on preventing adhesion of pollen to the human body and clothes. We have examined the effect of polymer coating on adhesion of cedar pollen to skin, hair and fabrics, and found that a lecithin polymer (LP), containing both cationic and anionic sites, is highly effective in reducing adhesion levels.MethodsWe evaluated the changes in electrostatic charge and frictional coefficient of sample surfaces after coating with an anionic polymer (AP), a cationic polymer (CP), a nonionic polymer (NIP), or LP (each applied by spraying 0.10% polymer solution in ethanol/water). Pollen adhesion level was evaluated by observation of the number of cedar pollen particles on video microscope (VMS) images and by quantification of cedar pollen antigen Cry j1 with a sandwich ELISA system. Adhesion of pollen to human skin or hair was also examined by VMS observation.ResultsLP-coated samples showed a significant reduction in electrostatic charge level and frictional coefficient. We presumed that these properties are closely related to the significant reduction in the adhesion level of cedar pollen or Cry j1 compared with CP, AP or NIP-coated samples. A similar effect was seen on LP-treated skin, and LP-treated waxed hair.ConclusionsOur results suggest that coating with LP could help in the management of pollinosis by reducing the contact level of patients with cedar pollen antigens.     

Absence of Nasal Blockage in a Japanese Cedar Pollen-Induced Allergic Rhinitis Model Mouse

BackgroundJapanese cedar pollen-induced allergic rhinitis in a guinea pig model clearly induced not only sneezing but also biphasic nasal blockage. To date, there have only been a few reports on models of murine allergic rhinitis which clearly show nasal blockage. Therefore, in order to try and develop such a model, we administered multiple dosages of intranasal pollen or purified antigen protein Cry j 1.MethodsB10.S mice were sensitized by intranasal instillations of either pollen extract or Cry j 1 twice a day for 7 days, which was adsorbed on Al(OH)₃. Subsequently, once a week, the mice were given multiple intranasal instillation challenges of either the pollen suspension or Cry j 1 and the frequency of sneezing was observed after respective challenges were made. Specific airway resistance (sRaw) was measured as an indicator for nasal blockage. Cry j 1-specific IgE levels were measured using an enzyme-linked immunosorbent assay.ResultsThe serum Cry j 1-specific IgE level showed clear elevation only in the group sensitized by Cry j 1 + Al(OH)₃ and then challenged by Cry j 1. No elevations were seen in the groups sensitized by pollen extract + Al (OH)₃ followed by a pollen suspension challenge. There was an immediate increase in sneezing after challenges in all of the sensitized-challenged groups. Nevertheless, no increases in sRaw in any of the groups were detected at any of the time points during the 8 hours following the challenges.ConclusionsCry j 1 may be more effective than crude antigens for efficient sensitization/challenge in mice. No increase in sRaw occurred, even in mice that possessed high amounts of Cry j 1-specific IgE and that exhibited sneezing.     

Prevalence of Artemisia species pollinosis in western Poland: impact of climate change on aerobiological trends, 1995-2004.

BACKGROUND: Artemisia species pollen represents a major cause of allergy in Central Europe. Variations in the pollen season, the influence of climate variables and the prevalence of pollinosis to it were analyzed in Poznan, in western Poland between 1995 and 2004. METHODS: A Hirst volumetric spore trap was used for atmospheric sampling. Pollination date trend analysis and Spearman correlation tests were performed. Skin prick tests (SPT) and allergen specific immunoglobulin (lg)E antibody measurements were performed in 676 and 524 patients, respectively. RESULTS: The Artemisia species pollen season grew longer due to a clear advance in the starting day and only a slightly earlier end point; the peak day also came slightly earlier. Rainfall in the first fortnight of July highly influenced pollen season severity. Temperature was directly correlated with daily Artemisia species pollen levels; relative humidity was inversely correlated. Twelve percent of patients had a positive SPT reaction to Artemisia species. Their symptoms were rhinitis and conjunctivitis (15%), atopic dermatitis (15%), chronic urticaria (14.3%), bronchial asthma (2.4%), and facial and disseminated dermatitis (1.3%). Elevated specific IgE concentrations were detected in the sera of 10.1% of patients. CONCLUSIONS: Artemisia species pollen is an important cause of pollinosis in western Poland. Pollen season intensity is highly influenced by rainfall in the previous weeks. Trends towards earlier season starts and longer duration, possibly caused by climate change, may have an impact on the allergic population.     

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.     

Japanese cedar and cypress pollinosis updated: New allergens,cross-reactivity,and treatment

Pollen from many tree species in the Cupressaceae family is a well-known cause of seasonal allergic diseases worldwide. Japanese cedar pollinosis and Japanese cypress pollinosis, which are caused by pollen from Japanese cedar (Cryptomeria japonica) and Japanese cypress (Chamaecyparis obtusa), respectively, are the most prevalent seasonal allergic diseases in Japan. Recently, the novel major Japanese cypress allergen Cha o 3 and the homologous Japanese cedar allergen Cry j cellulase were identified, and it was shown, for the first time, that cellulase in plants is allergenic. Although the allergenic components of pollen from both species exhibit high amino acid sequence identity, their pollinosis responded differently to allergen-specific immunotherapy (ASIT) using a standardized extract of Japanese cedar pollen. Pharmacotherapy and ASIT for Japanese cedar and cypress pollinosis have advanced considerably in recent years. In particular, Japanese cedar ASIT has entered a new phase, primarily in response to the generation of updated efficacy data and the development of new formulations. In this review, we focus on both Japanese cypress and cedar pollinosis, and discuss the latest findings, newly identified causative allergens, and new treatments. To manage pollinosis symptoms during spring effectively, ASIT for both Japanese cedar and Japanese cypress pollen is considered necessary.     

Treatment duration-dependent efficacy of Japanese cedar pollen sublingual immunotherapy: Evaluation of a phase II/III trial over three pollen dispersal seasons

BackgroundWe conducted a randomized, placebo-controlled, double-blind clinical trial to investigate the optimal dose and long-term efficacy and safety of Japanese cedar (JC) pollen tablets for SLIT (JapicCTI-142579). Here, we report details of the effects of the JC pollen SLIT tablet on rhinitis and conjunctivitis symptoms over three pollen dispersal seasons.MethodsA total of 1042 JC pollinosis patients (aged 5–64 years) were randomized to receive tablets containing placebo (P), 2000, 5000, or 10,000 Japanese allergy units (JAU) of JC pollen for 15 months to identify an optimal dose. Patients receiving P (n = 240) and the optimal dose (5000 JAU; A, n = 236) were then randomized to receive P or A for an additional 18 months (AA, AP, PA, and PP groups, allocation ratio 2:1:1:2). Nasal and ocular symptoms, rescue medication use, and quality of life (QOL) were assessed on quantitative scales.ResultsIn the second and third seasons, the AA, AP, and PA groups exhibited significantly better improvements in nasal, ocular, and medication scores compared with the PP group in the order AA > AP > PA > PP during the second season and AA > PA > AP > PP during the third season. Rescue medication use and QOL scores were also significantly better in the AA, AP, and PA groups compared with the PP group.ConclusionsThe JC pollen SLIT tablet relieved nasal and ocular symptoms and medication use and improved QOL in a treatment duration-dependent manner. Continuous dosing regimens appear to enhance the efficacy of the drug.     

Evaluating the effects of testing period on pollinosis symptoms using an allergen challenge chamber

BackgroundWe previously built a pollen challenge test unit (allergen challenge chamber: ACC) to collect objective data about Japanese cedar pollinosis. In this study, we investigated adequate conditions for pollen challenge using the ACC.MethodsThe study consisted of two parts. The first part was conducted in November, which is not in pollen season. Subjects were exposed to Japanese cedar pollen at a concentration of 50,000 grains/m³ in the chamber for 120 min each day over the course of three consecutive days. The second part was conducted in April, which is just after pollen season. Subjects were exposed to Japanese cedar pollen at the same concentration (50,000 grains/m³) in the chamber for 90 min on a single day. Subjects recorded nasal and ocular symptoms before challenge and every 15 min after challenge initiation. The minimum cross-sectional area in the nasal cavity was measured using acoustic rhinometry before and after challenge as an indicator of nasal obstruction. Inflammatory markers in nasal lavage fluid and serum were also measured before and after challenge.ResultsNasal and ocular symptoms were significantly exacerbated after challenge on all days of the single and 3-consecutive-day challenge tests, particularly on the third day of the consecutive challenge test. Nasal and ocular symptoms were also quickly induced with challenge immediately after the end of pollen season. No significant changes in inflammatory markers were seen.ConclusionsCare is needed with regard to pollen challenge conditions in the ACC, including timing of the challenge, to induce pollinosis symptoms that accurately reflect chronic inflammation.     

Observations of airborne Cryptomeria japonica pollen in the summer

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 (February-May) and summer (June-September).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.     

Analysis of Helper T Cell Responses to Cry j 1-Derived Peptides in Patients with Nasal Allergy: Candidate for Peptide-Based Immunotherapy of Japanese Cedar Pollinosis

BackgroundAllergen specific immunotherapy is highly effective, but adverse events may occur during treatment. Peptide-based immunotherapy has been proposed as one of new strategies for reduction of allergic adverse reactions. We examined the possibility of candidate peptides for the development of peptide-based immunotherapy for Japanese cedar pollinosis.MethodsTwelve Cry j 1-specific T-cell lines were established from peripheral blood mononuclear cells (PBMC) of 12 patients with Japanese cedar pollinosis. Using these T-cell lines, 37 Cry j 1-derived overlapping peptides were assessed for their proliferative responses and cytokine production.ResultsFour peptides corresponding to the Cry j 1 sequence were able to induce proliferative responses to more than one T-cell line: p61-80 (3/12; 25.0%); p115–132 (2/12; 16.6%); p206–225 (4/12; 33.3%); and p337–353 (5/12; 41.7%). Furthermore, T-cell lines generated from 11 of 12 donors (91.7%) responded to at least one of these four peptides. On the other hand, the pattern of cytokine production from Cry j 1-specific T-cell lines varied. Moreover, cytokine production patterns by stimulation with Cry j 1 peptide did not reflect those by stimulation with Cry j 1 protein.ConclusionsOur results suggest four Cry j 1-derived peptides (p61–80, p115–132, p206–225 and p337–353) may be considered to be the immunodominant T-cell epitopes of the Cry j 1 molecule, and can be useful for the design of peptide-based immunotherapy for the management of Japanese cedar pollinosis.     

Two Thirds of Forest Walkers with Japanese Cedar Pollinosis Visit Forests even During the Pollen Season

BackgroundThe most common type of pollinosis in Japan is Japanese cedar pollinosis (JCP). While forest walking is a common form of recreation for Japanese people, it has been unclear whether forest walkers with JCP still choose to visit forested areas during the pollen season or whether they avoid those areas, and as such, the aim of this study was to investigate this question.MethodsThe study participants were all healthy men and women volunteers aged 20 years or over who visited the Tokyo University Forest in Chiba during 4 different days. The survey was conducted using self-administered questionnaires.ResultsThe number of available responses was 498. Of these, 112 participants who experienced JCP were included in the analysis. Seventy-three participants (65.2%) responded that they visit forests even during the pollen season. The association between forest walking choices during the pollen season and self-rated levels of pollinosis symptoms was not statistically significant (Cramer’s V = 0.13, p = 0.47). As many as 60% of the participants who reported serious symptom levels responded that they visit forested areas even during the pollen season.ConclusionsThese results revealed that two thirds of forest walkers who had experienced JCP visited forests even during the pollen season. This indicates the further need for public service announcements informing people with JCP that the risk of pollen exposure and subsequent JCP reaction is increased by visiting forested areas during the pollen season.     

Association of Japanese cedar pollinosis and sensitization with HLA-DPB1 in the Japanese adolescent

Background

Allergic rhinitis (AR) is a heterogeneous disorder that significantly affects daily activity, work productivity, sleep, learning, and quality of life in all generations. Japanese cedar (JC) pollen is the most common allergen responsible for the development of AR in Japan. AR caused by JC pollen is considered to be a multifactorial inheritance disease that is caused by both environmental and genetic factors. The aim of this study was to investigate whether Human Leukocyte Antigen-DPB1 (HLA-DPB1) is associated with JC sensitization/pollinosis.

A randomized control trail of stepwise treatment with fluticasone propionate nasal spray and fexofenadine hydrochloride tablet for seasonal allergic rhinitis

Background: In Japan, oral antihistamines are frequently used as the initial treatment for seasonal allergic rhinitis (SAR), and intranasal steroids are added when nasal symptoms worsen. This study aimed to evaluate whether starting treatment with fluticasone propionate nasal spray (FP) from the beginning of pollinosis symptoms and adding fexofenadine hydrochloride tablet (FEX) when SAR is aggravated could achieve improved amelioration of nasal symptoms throughout the pollen season in comparison with a treatment that involves starting with FEX and later adding FP.Methods: In this pragmatic, randomized, open-label, parallel-group trial, 51 Japanese cedar pollinosis patients (age, 16–85 years) were randomly divided and administered FP 100 mcg twice daily as an initial drug with FEX 60 mg twice daily as an additional drug and the same treatment in the reverse order. Nasal symptoms were evaluated in a daily dairy using a 4-point scale. The primary outcome was area under curve of the line representing the daily total nasal symptom score in the pollen season on a graph.Results: Initial treatment with FP was significantly (P = 0.0015) more effective than initial treatment with FEX in improving the primary outcome. The average daily total nasal symptom score in the initial treatment with FP group was better than that in the initial treatment with FEX group throughout the pollen season.Conclusions: Initiating treatment with FP and adding FEX might lead to improved outcomes for nasal symptoms in comparison with the same drugs administered in the reverse order.     

The Efficacy of Early Treatment of Seasonal Allergic Rhinitis with Benifuuki Green Tea Containing O-methylated Catechin before Pollen Exposure: An Open Randomized Study

BackgroundWe previously reported that 'benifuuki' green tea containing O-methylated catechin significantly relieved the symptoms of perennial or seasonal rhinitis compared with a placebo green tea that did not contain O-methylated catechin in randomized double-blind clinical trials. In this study we assessed the effects of 'benifuuki' green tea on clinical symptoms of seasonal allergic rhinitis.MethodsAn open-label, single-dose, randomized, parallel-group study was performed on 38 subjects with Japanese cedar pollinosis. The subjects were randomly assigned to long-term (December 27, 2006 – April 8, 2007, 1.5 months before pollen exposure) or short-term (February 15, 2007: after cedar pollen dispersal – April 8, 2007) drinking of a 'benifuuki' tea drink containing 34 mg O-methylated catechin per day. Each subject recorded their daily symptom scores in a diary. The primary efficacy variable was the mean weekly nasal symptom medication score during the study period.ResultsThe nasal symptom medication score in the long-term intake group was significantly lower than that of the short-term intake group at the peak of pollen dispersal. The symptom scores for throat pain, nose-blowing, tears, and hindrance to activities of daily living were significantly better in the long-term group than the short-term group. In particular, the differences in the symptom scores for throat pain and nose-blowing between the 2 groups were marked.ConclusionsWe conclude that drinking 'benifuuki' tea for 1.5 months prior to the cedar pollen season is effective in reducing symptom scores for Japanese cedar pollinosis.