Complementary and alternative medicine for allergic rhinitis in Japan.

BACKGROUND: Complementary and alternative medicine (CAM) is extensively used in patients with allergic diseases worldwide. The purpose of this study was to investigate the actual situation of CAM practice in the treatment of allergic rhinitis. METHODS: We distributed questionnaires to otolaryngologists at 114 facilities in Japan. The subjects who participated in this study included children <16 years of age and adults ≥16 years of age diagnosed with allergic rhinitis by otolaryngologists. The survey was performed in the period from September 2007 to August 2009. Furthermore, we performed the same investigation out of the hospital setting, such as during general health examinations. All questionnaires were returned to Chiba University and analyzed. RESULTS: The proportions of patients who had ever experimented with CAM in the hospital survey were 7.1% (225/3170) and 19.2% (1416/7363) of children and adults, respectively. Approximately 36.2% of the adult patients thought that the treatments were effective. The main reasons for CAM use were safety, convenience and low price. However, the group who spent more than $1000 on CAM felt more dissatisfaction and anxiety related to treatment at the hospital. The situation of CAM practice was not consistent and was instead influenced by the backgrounds of the subjects. CONCLUSIONS: Many patients who receive CAM report feeling that the effects of treatment provided by hospitals are insufficient and have concerns about the side effects of such treatments. Information regarding standard treatments, as described in the guidelines, should become widely known and diffused, and strong communication with patients should be considered.

Characteristics of the Chiba environmental challenge chamber.

BACKGROUND: An 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. METHODS: The 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. RESULTS: The 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. CONCLUSIONS: The 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.

Comparison of nasal steroid with antihistamine in prophylactic treatment against pollinosis using an environmental challenge chamber.

Environmental challenge chambers (ECC) have been used to expose people to pollen allergens within a stable atmosphere and to examine the efficacy of treatment. Although pollinosis is one of the typical IgE-mediated type I allergic diseases, allergic inflammation is thought to contribute to the fundamental pathogenesis and prophylactic treatment may reduce exacerbations of pollinosis. The purpose of this study was to compare the efficacy of prophylactic treatment with nasal steroid (mometasone furoate nasal spray) or an antihistamine (fexofenadine) in the control of cedar pollinosis using the ECC. In a randomized, double-blind two-way crossover study, 48 patients received nasal steroid or antihistamine for 7 consecutive days (days 1-7). On day 8, patients were exposed to cedar pollen (8000 grains/m(3)) in the ECC for 3 hours. Nasal symptoms induced by pollen exposure were assessed. Total nasal symptom scores (TNSSs) during the exposure in the ECC were not significantly different between the antihistamine and the nasal steroid groups. Nasal symptoms induced by pollen exposure using the ECC persisted for up to 3 days. TNSSs after pollen exposure on days 8-11 were significantly lower in the nasal steroid group compared with the antihistamine group. Prophylactic treatment with nasal steroid is more effective than antihistamine against pollinosis, particularly in the late phase. Clinical trial registration JAPIC CTI 101182 (www.clinicaltrials.jp/user/ctiMain_e.jsp).

Immunological parameters associated with the development of allergic rhinitis: a preliminary prospective study.

BACKGROUND: Many subjects are sensitized to Japanese cedar pollen but do not develop allergic rhinitis (AR). The aim of this study was to examine the immunologic parameters related to the development of AR in sensitized subjects. METHODS: The subjects were 33 adults who were sensitized to Japanese cedar pollen, but had not developed as of 2007. Cedar pollen-specific IgE (sIgE) and total IgE (tIgE) in serum, cedar pollen antigen (Cry j 1) Cry j-specific memory Th2 cell clone size, and the Cry j-specific induced regulatory T cell (iTreg) level were examined before and after the season in 2008. RESULTS: Eight of the 33 subjects developed cedar pollinosis. The sIgE titers before the season in these eight subjects did not differ from those in the subjects who did not develop pollinosis, but the titers after the season were significantly higher in the group that developed pollinosis. The sIgE/tIgE ratio increased in almost all subjects, but the ratio was significantly higher before the season in the subjects who developed pollinosis. Cry j-specific Th2 cells were detected in all subjects, but the clone size only increased in those that developed pollinosis. The Cry j-specific iTreg population did not differ between the two groups. CONCLUSION: A high sIgE/tIgE ratio before the season may be predictive of development of pollinosis, and an increase in the allergen-specific Th2 clone size during the pollen season could be a biomarker for pollinosis. The role of allergen-specific iTreg cells in the development of pollinosis could not be clarified in this preliminary study.

Association of the MMP9 gene with childhood cedar pollen sensitization and pollinosis.

Matrix metalloproteinase 9 (MMP9) gene has been shown to be involved in the pathogenesis of allergic rhinitis (AR) and asthma. Previous studies suggested that single-nucleotide polymorphisms (SNPs) of the MMP9 gene conferred a risk for childhood asthma. However, whether the SNPs confer a risk for AR has not been previously investigated. The objective of this study was to investigate whether SNPs of the MMP9 gene are associated with risk of seasonal AR (pollinosis), perennial AR and allergen sensitization. A total of 670 school children were recruited in Japan and genotyped for functional polymorphism in the promoter (-1590C/T: rs3918242) and three amino-acid substitutions (R297Q: rs17576; P574R: rs2250889; R668Q: rs17577). Serum levels of total and specific IgE were determined. Disease status and other clinical characteristics of the subjects were investigated using a questionnaire. Associations between the MMP9 SNPs and both AR and serum IgE levels were evaluated. -1590C/T showed significant association with cedar pollinosis (corrected P (Pcor)=0.039). R668Q was in strong linkage disequilibrium (LD) with -1590C/T and showed significant association with cedar pollinosis (Pcor=0.023) and serum cedar pollen-specific IgE level (Pcor=0.022). A haplotype associated with -1590T and 668Q showed a significant association with cedar pollinosis, orchard grass pollinosis and cedar pollen-specific IgE (Pcor=0.0012, Pcor=0.0059 and Pcor=0.0041, respectively). R297Q and P574R were in weak LD with the rest of the SNPs and did not show significant association with disease. Compared with wild-type MMP9 protein (279R-574P-668R), a variant enzyme (279R-574P-668Q) that showed association with pollinosis had lower activity. However, lower enzyme activity was not associated with disease risk because another variant (279Q-574R-668R) showed lower enzyme activity but was not associated with pollinosis. The -1590T allele and its corresponding haplotype was associated with higher promoter activity and with pollen-specific IgE levels and pollinosis, suggesting that -1590C/T may have more impact on sensitization and disease development than R668Q. Our results suggest that the MMP9 gene confers susceptibility to cedar pollinosis in Japanese children. The MMP9 gene may be associated with pollinosis through sensitization processes.

Effects of aging on the natural history of seasonal allergic rhinitis in middle-aged subjects in South chiba, Japan.

BACKGROUND: The natural history of allergic rhinitis has been examined in a few longitudinal studies. The purpose of the study was to investigate the course, development and remission of seasonal allergic rhinitis (SAR) over 10 successive years in middle-aged subjects. METHODS: An annual questionnaire survey on allergic rhinitis symptoms combined with an examination of specific IgE has been undertaken in a rural town in south Chiba since 1995. The analyzed subjects were 703 residents who underwent every examination in 1995, 2004 and 2005. In the last 15 years, the annual pollen count in Chiba was highest in 2005. RESULTS: The sensitization rates to cedar pollen decreased with age in the same subject groups over 10 years, but the prevalence of SAR was higher in 2005 compared with 1995. Of the 52 subjects with SAR in 1995, the symptoms had disappeared in 10 subjects in 2005. Specific IgE had converted to negative or borderline in 4 of these patients, had decreased but was still positive in 4 and was increased or unchanged in 2. During the 10-year period, 22 subjects developed SAR, of whom 12 had increased specific IgE and 10 had similar or decreased specific IgE in 2005. CONCLUSION: SAR induced by cedar pollen takes a chronic course in the majority of middle-aged patients in south Chiba, Japan. The prevalence of SAR increased over 10 years due to a high level of pollen exposure. Changes in specific IgE were not directly associated with the development or remission of SAR.

Increase of regulatory T cells and the ratio of specific IgE to total IgE are candidates for response monitoring or prognostic biomarkers in 2-year sublingual immunotherapy (SLIT) for Japanese cedar pollinosis.

The aims of this study were to examine the therapeutic effects of sublingual immunotherapy (SLIT) and to identify potential biomarkers that would predict the therapeutic response in a randomized, double-blind, placebo-controlled clinical trial. The trial was carried out over two pollinosis seasons in 2007 and 2008. Carry-over therapeutic effects were analyzed in 2009. SLIT significantly ameliorated the symptoms of pollinosis during the 2008 and 2009 pollen seasons. Cry j 1-specific cytokine production in a subgroup of patients with mild disease in the SLIT group was significantly attenuated. The ratio of specific IgE to total IgE before treatment correlated with the symptom-medication score in the SLIT group in 2008. Patients with increased Cry j 1-iTreg in the SLIT group had significantly improved QOL and QOL-symptom scores. In summary, the specific IgE to total IgE ratio and upregulation of Cry j 1-iTreg are candidates for biomarker of the clinical response to SLIT.

A randomized, double-blind, placebo-controlled study of ten-cha (Rubus suavissimus) on house dust mite allergic rhinitis.

OBJECTIVE: Self-care with ten-cha is the most common complementary alternative medicine for allergic rhinitis in Japan, but evidence for an actual therapeutic effect is lacking. The purpose of the study was to investigate the effect of ten-cha (Rubus suavissimus) on house dust mite allergic rhinitis. METHODS: The study was performed in the otolaryngology departments of 5 facilities (Chiba University, Kagoshima University, Fukui University, Okayama University, and Nippon Medical School) from July to December 2009. A randomized double-blind study was performed with central enrollment and allocation. The subjects ingested 400mg of ten-cha extract or placebo (3 capsules/day) daily for 4 weeks as a food intervention. The number of subjects was chosen with anticipation of an effect equivalent to that of mast cell-stabilizing drugs. A nasal allergy diary-based symptom score and a QOL score were used for evaluation. RESULTS: The ten-cha and placebo groups included 47 and 42 subjects, respectively. The improvement rates for sneeze, nasal discharge, nasal obstruction, and symptom scores were greater in the ten-cha group than in the placebo group throughout the intervention period, and the effect tended to increase with time in the ten-cha group. However, the differences between the groups were not significant. QOL was not significantly improved in either group. CONCLUSION: Ingestion of ten-cha had an effect on allergic rhinitis, but the effect of Ten-Cha was limited and did not differ significantly from placebo. These results suggest that ten-cha does not exhibit an effect equivalent to mast cell-stabilizing drugs at the dose used in this study.

Reevaluation of pollen quantitation by an automatic pollen counter.

Accurate and detailed pollen monitoring is useful for selection of medication and for allergen avoidance in patients with allergic rhinitis. Burkard and Durham pollen samplers are commonly used, but are labor and time intensive. In contrast, automatic pollen counters allow simple real-time pollen counting; however, these instruments have difficulty in distinguishing pollen from small nonpollen airborne particles. Misidentification and underestimation rates for an automatic pollen counter were examined to improve the accuracy of the pollen count. The characteristics of the automatic pollen counter were determined in a chamber study with exposure to cedar pollens or soil grains. The cedar pollen counts were monitored in 2006 and 2007, and compared with those from a Durham sampler. The pollen counts from the automatic counter showed a good correlation (r > 0.7) with those from the Durham sampler when pollen dispersal was high, but a poor correlation (r < 0.5) when pollen dispersal was low. The new correction method, which took into account the misidentification and underestimation, improved this correlation to r > 0.7 during the pollen season. The accuracy of automatic pollen counting can be improved using a correction to include rates of underestimation and misidentification in a particular geographical area.

Cedar and cypress pollinosis and allergic rhinitis: quality of life effects of early intervention with leukotriene receptor antagonists.

BACKGROUND: Allergic rhinitis involves inflammation of the nasal passages. The use of nasal steroids is generally very effective in providing significant symptom relief. However, compliance for their use is sometimes poor. METHODS: To examine the efficacy of early intervention (before pollen dispersal) with oral cysteinyl leukotriene receptor antagonists (LTRA) on pollinosis in patients with allergy to cedar and Japanese cypress pollens, groups of subjects were treated with LTRA or a placebo for 4 weeks at the beginning of the cedar pollen dispersal season. Subsequently, all patients received nasal steroid therapy concomitantly with LTRA throughout the remaining period of the pollen dispersal season. The effects of such early treatment with LTRA on pollinosis were investigated using symptom scores from an allergy diary and quality of life (QOL) scores. RESULTS: Sneezing and nasal congestion scores were significantly lower in the LTRA-pretreated subjects than observed in the placebo-pretreated patients between weeks 4 and 6 and weeks 3 and 5, respectively. QOL scores improved significantly in all domains after concomitant therapy with nasal steroids. The percent improvement in the nasal congestion score after the concomitant therapy was significantly higher in the LTRA group (69%) than in the placebo group (41%). CONCLUSION: Significant differences observed in symptoms and in QOL effects between LTRA- and placebo-pretreated patients and the absence of major adverse effects noted in these studies suggest that early intervention with LTRA is beneficial and safe and should be considered in the management of pollinosis-associated allergic rhinitis.

[Lowered effectiveness of immunotherapy for cypress pollinosis by using Japanese cedar pollen extract].

BACKGROUND: Japanese cedar and cypress pollen share a common antigen. The cedar pollen season is followed by the cypress pollen season. However, both the clinical significance and involvement of cypress pollinosis in the treatment of the cedar pollinosis have not yet been clarified. METHODS: The clinical efficacy of sublingual immunotherapy with cedar pollen extract for cedar pollinosis was evaluated during the cypress pollen dispersal season in Japan. In addition, the change in cypress pollen specific IgE antibodies of the patients with cedar pollinosis was examined before and after the pollen season. RESULTS: Sublingual immunotherapy with cedar pollen extract did not improve the clinical symptoms of the cedar pollinosis patients combined with cypress pollinosis in the cypress pollen season. The cypress pollen specific IgE antibodies were found to demonstrate significant seasonal changes. CONCLUSION: The presence of cypress pollinosis should therefore be taken into consideration when planning the optimal treatment for cedar pollinosis. Sublingual immunotherapy with cedar pollen extract may not be effective for cypress pollinosis.

A randomized controlled trial of sublingual immunotherapy for Japanese cedar pollinosis.

BACKGROUND: Japanese cedar pollen represents an important and unique allergen. Sublingual immunotherapy (SLIT) has been suggested to be a highly effective route of desensitization against a variety of allergens. However, little information is available about its use in cedar pollen allergy. METHODS: A blinded randomized, placebo-controlled trial employing SLIT for cedar pollinosis was conducted over a period of 6 months. Sixty-seven subjects were enrolled and the symptom scores during the pollen season were evaluated by a symptom diary, measurement of cedar-specific IgE and IgG4, and determination of Cry j-specific Th2 clones before SLIT and before and after the pollen season. RESULTS: No major adverse effects were observed in either group. The serum-specific IgG4 activity increased significantly after SLIT in the active group. The active group also exhibited significantly lower symptom scores compared to the placebo. The specific Th2 clone sizes were not significantly different between the groups before the pollen season. However, an increase in the clone size was observed after the pollen season in the placebo group, but not in the active group. CONCLUSION: Use of SLIT for Japanese cedar pollinosis was found to be safe and associated with an increase in cedar-specific IgG4 levels. Such therapy inhibited the increase in Cry j-specific Th2 clone size induced by pollen exposure. Finally, use of SLIT resulted in significant improvement of the clinical symptoms of cedar pollinosis in this patient population. These observations suggest that SLIT may offer another safe approach to the management of cedar pollinosis.