Oral allergy syndrome in patients with Japanese cedar pollinosis

Patients with pollinosis sometimes complain of oral symptoms (itching and tingling with or without edema of the lips, mouth and tongue) after eating fresh fruits and vegetables. This condition has been termed Oral Allergy Syndrome (OAS). Twenty-three patients with Japanese cedar pollinosis and OAS for fresh fruits and vegetables were included in this study. Their mean age was 31.3 years (range = 5 to 62). The fruits that caused OAS in these patients included melon, apple, peach, and kiwi fruit. Most patients with OAS exhibited hypersensitivity to more than two foods. Specific IgE antibodies to inhaled allergens of mite, Japanese cedar pollen, birch pollen, melon, apple, peach, and kiwi were evaluated using the Pharmacia CAP system. Eleven of the 16 subjects with specific IgE antibodies for birch pollen, did not suffer symptoms during the birch and alder pollen season. In subjects with specific IgE antibodies for fruits, 13 out of 20 patients showed specific IgE antibodies for apple, and 8 out of 9 patients with OAS for apples were also positive for specific IgE antibodies for apples. On the other hand, 17 patients had no specific IgE antibodies for melon, and only two patients and one patient showed specific IgE antibodies for kiwi fruit and peach, respectively. These results suggest that the evaluation of specific IgE antibodies to birch pollen and apple may be useful for diagnosing OAS in patients with Japanese cedar pollinosis.     

Approaches to immunotherapies for Japanese cedar pollinosis

Japanese cedar (Cryptomeria japonica; CJ) pollinosis is a typical type I allergy induced by CJ pollen and one of the most common allergic diseases in Japan. New immunotherapies have been developed for treatment of CJ pollinosis. We focus here on new immunotherapies for CJ pollinosis including sublingual immunotherapy with crude extract of CJ antigen, oral immunotherapy with transgenic rice expressing CJ allergens, a peptide vaccine using T cell epitopes of CJ allergens, DNA vaccines encoding either the CJ allergen gene or T cell epitope gene, and adjuvant-conjugated vaccines using CJ allergen conjugated with adjuvants such as CpG oligodeoxynucleotide or pullulan.     

Effect of Asian sand dust on Japanese cedar pollinosis

Objective

Asian sand dust (ASD), originating in the deserts of Mongolia and China, spreads over large areas and is associated with adverse effects on human health in East Asia, including asthma, heart disease, and some allergic diseases. However, the effect of ASD on patients with seasonal allergic rhinitis caused by Japanese cedar pollen (SAR-JCP), the most common form of allergic rhinitis, remains unclear. The aim of this study was to investigate the effect of ASD on SAR-JCP patients.

Methods

A total of 41 patients with SAR-JCP recorded nasal and ocular allergic symptom scores in a diary. We assessed the influence of ASD events on patients with SAR-JCP during the JCP season and before and after the JCP season.

Results

ASD events did not influence nasal and ocular allergy symptoms during the JCP season. Scores for sneezing and runny nose were significantly increased by ASD events in the pre-JCP season. Ocular symptom scores were significantly increased by ASD events in the post-JCP season.

Conclusion

Our results suggest that ASD may exacerbate allergy symptoms even before mass scattering of JCP, which usually does not cause allergic symptoms in patients with SAR-JCP. ASD also induced conjunctivitis symptoms after the JCP season. However, we did not observe any adverse effects of ASD on allergic symptoms during the JCP season.     

Long-term sublingual immunotherapy provides better effects for patients with Japanese cedar pollinosis

ObjectiveJapanese cedar pollinosis is an endemic disease affecting a large proportion of Japan's population. Five seasons have passed since sublingual immunotherapy (SLIT) for Japanese cedar pollinosis was included in the public insurance coverage in Japan. In this study, we evaluated the clinical effects of long-term SLIT for Japanese cedar pollinosis on upper respiratory symptoms primarily represented by nasal symptoms and inflammation of the respiratory tract in the 2019 season, in which considerable amount of cedar pollen was dispersed.MethodsThis study involved 95 patients who were undergoing SLIT for Japanese cedar pollinosis after the initiation at some point between 2014 and 2018, and this group of patients was compared with a control group comprising 21 patients receiving preseasonal prophylactic treatment (with a second-generation antihistaminic drug). We evaluated the patients’ nasal/eye symptoms, total nasal symptom and medication score (TNSMS), and quality of life according to relevant guidelines. In addition, the levels of peripheral blood eosinophils, serum total IgE, Japanese cedar antigen-specific IgE, Cryj1-specific IgG4, and fractional exhaled nitric oxide (FENO) were measured as objective indices.ResultsFrom the fourth season (SLIT4), nasal discharge, sneezing, nasal obstruction symptoms, and TNSMS significantly decreased compared with those in the preseasonal prophylactic treatment and SLIT1 groups. In the patients suspected to have eosinophilic airway inflammation (with a baseline FENO ≥25 ppb), the interannual variability of FENO levels significantly reduced after 5 years of treatment.ConclusionThe efficacy of SLIT was noted from the first year of treatment, even in a year when pollen profusely dispersed. Thus, long-term continuous treatment with SLIT may alleviate nasal symptoms as well as eosinophilic airway inflammation.     

Epidemiology of Japanese cedar pollinosis: result of the survey in Mibu-machi

The prevalence rate of Japanese cedar pollinosis has increased since 1979. We conducted a survey of the residents of Mibu-mach, Tochigi, in 1988 and 1996 using a questionnaire to determine the prevalence rate of cedar pollinosis. Results showed its rate was 15.6% in 1988, and 25.6% in 1996. Age distribution analysis of patients with Japanese cedar pollinosis showed the highest prevalence in patients between the ages of 10 to 49 years in 1988, and between the ages of 10 to 59 years old in 1996. Within these age groups, the majority of the patients were females, but males were more prevalent than females in the age group under 19 years old. The prevalence rate of patients by age group revealed the same pattern as the age distribution of the patients. Age distribution of cedar pollinosis showed a peak in patients in their thirties both in 1988 and 1996. In conclusion, the numbers of patients with Japanese cedar pollinosis has been increasing remarkably in Mibu-mach. As climate or environmental conditions are varied in different geographical regions in Japan, further epidemiological studies in various regions of the country are required to clarify the actual prevalence rate of cedar pollinosis.     

Effectiveness of Nd: YAG laser therapy on Japanese cedar pollinosis

Many have reported on the effectiveness of laser surgery therapy for perennial allergic rhinitis. However, the suppressive effects of laser irradiation on allergic rhinitis and its symptoms have not been reported in patients with pollinosis. This is because therapeutic effects on pollinosis are difficult to evaluate. The amount of pollen in the air varies during the year, and from year to year. Also, allergic symptoms develop due to exposure to the amount of pollen which is markedly influenced by the weather. In this study, the severity of allergic symptoms in the pollen season was compared between patients treated with early medication, non-treated patients and patients treated with preseasonal contact Nd: YAG laser surgery. Results suggests that laser surgery was effective in reducing the severity of symptoms in patients with cedar pollinosis. Symptoms were milder in the laser group than in the medication group and non-treated group for 3-4 weeks after the start of seasonal pollinosis, although no differences were noted in the early weeks. This may be explained by the fact that laser irradiation reduces the lamina propria of the nasal mucosa, the site of allergic reactions. This also suggests that allergic pollen can't penetrate the mucosal surface which shows squamous epithelization after laser irradiation.     

Medical consultation dynamics in Japanese cedar pollinosis patients at an office building clinic in central Tokyo

To clarify medical consultation dynamics in Japanese cedar pollinosis patients visiting an office building clinic in an office block in central Tokyo, we surveyed number of patient at a private ENT clinic in Chiyoda-ku, Tokyo, during the Japanese cedar pollen season from 1990 to 1999. Based on questionnaires and CAP RAST tests in 1995, we studied the profiles of Japanese cedar pollinosis patients and determined positive rates of noncedar antigens. The gender ratio in 1995 was 674 men versus 501 women, most frequently men in their 40s and women in their 20s. Of these, 79.2% worked in Chiyoda-ku and Chuo-ku, but only 1.9% lived in these districts. Positive rates of noncedar antigens in 232 who received simultaneous CAP RAST tests were 64.7% for Japanese cypress, 38.3% for house dust, 35.3% for Dermatophagoides pteronyssinus, 34.4% for Epidermoptidae spp, 19.8% for mixed grasses, and 10.3% for mixed weeds (asteraceous plants). Patients positive for cedar alone were 19.0% and positive for both cedar and cypress but negative for other antigens were 23.3%; about 60% of these were suspected of multiple sensitization to antigens other than cedar and cypress. The number of pollens and patients were summarized weekly and compared. Those paying a first visit were peaked with an increase in pollen in the first week of March almost every year; second visits peaked 1 or 2 weeks later than the first visit. Little increase in first visit was noted even with increasing pollen dissemination from the latter half of March. The relationship between the number of pollen and patients each year from 1990 to 1999 correlated highly with the linear regression equation y = 0.1005x + 547.07 with R2 = 0.7562. The relationship between square roots of the number of pollen and patients each year for 5 year from 1995 to 1999 correlated very highly with the linear regression equation y = 11.167x + 376.72 with R2 = 0.9941. We concluded that the number of patients may be predicted with substantially higher accuracy based on the estimated amount of pollen in a given year.     

Preliminary study of a challenge test to the patients with Japanese cedar pollinosis using an environmental exposure unit

Objective

Although clinical studies on pollinosis have been performed employing placebo-controlled double-blind comparative and field techniques, accurate evaluation is difficult because the scattering pollen count and climatic conditions vary between years and regions, leading to a bias in the results. Thus, we prepared a pollen challenge test unit (allergen challenge chamber: ACC) which facilitates quantitative pollen challenge at any time, and, so, the acquisition of objective data.

Methods

The control of constant conditions and maintenance of specified pollen concentrations in ACC were investigated. In addition, the pollen distribution in ACC was measured while maintaining the level at 10,000 counts/m³. The pollen levels were measured employing the aspiration and Durham methods, and the measured values were compared. Furthermore, whether symptoms are adequately induced in the chamber during the non-cedar pollen-scattering season was investigated in 14 volunteers with cedar pollinosis.

Results

When the pollen level in ACC was set at 6000 counts/m³ or higher, the rate of variation was ±15%, within the adjustable range, and that of the pollen distribution in the chamber was within ±20%. When the volunteers with cedar pollinosis were exposed to cedar pollen in ACC, pollinosis symptoms were induced, and challenge for 2 consecutive days significantly induced symptoms.

Conclusions

The temporal and spatial variations of the pollen level in ACC were small, facilitating stable pollen challenge, and pollinosis symptoms were induced in the volunteers with cedar pollinosis. The challenge chamber may be useful to judge the effects of therapy against pollinosis.     

Seasonal variation of nasal surface basophilic cells and eosinophils in Japanese cedar pollinosis

Nasal pollinosis is caused by pollens of trees and grasses as allergen floating in the air during the seasons of blossom. In Japan, cedar pollinosis is the most prevalent of seasonal allergic rhinitis. We studied the seasonal variation of nasal mucosal basophilic cells (cells with basophilic and metachromatic granules) and eosinophils by nasal scraping of cedar pollinosis patients from June 1986 to May 1987, and found that during the season basophilic cells and eosinophils increased significantly, decreased but still remained for two or three monts after the season, and finally disappeared. The variation of eosinophils was more prominent than basophilic cells. The increase of both cells had close correlation with each other.     

Relationship between airborne pollen count and treatment outcome in Japanese cedar pollinosis patients

In Japan, information on daily Japanese cedar pollen counts is made public during pollen season. If symptom severity and treatment outcome are predictable according to these pollen counts, management of seasonal allergic rhinitis may become more precise. The aims of the study were to evaluate the relationship between airborne pollen counts, symptom severity and treatment outcome in Japanese cedar pollinosis patients. In the randomized study, patients with moderate to most severe Japanese pollinosis were treated with fexofenadine (60 mg BD) or fexofenadine and nasal corticosteroids for 2 weeks. During the same period daily airborne pollen counts were measured. A total of 105 adult patients were enrolled. No difference of treatment efficacy was seen among groups. Detailed results of efficacy and safety were previously described elsewhere. In univariate analysis, the mean cumulative amount of airborne pollen exposure for 4 days prior to the study tended to affect symptom severity (P = 0.053) and the mean cumulative amount of airborne pollen during the treatment period tended to show difference among five treatment outcome categories (P = 0.066). In multivariate analysis, the mean cumulative amount of airborne pollen exposure for 4 days prior to the study was identified as the only significant factor of symptom severity (P = 0.0327) and cumulative amount of airborne pollen during the treatment period (P = 0.027) and allergic history (P = 0.027) were significant factors of treatment outcomes. No serious adverse effect was reported during the study. The amount of airborne pollen may be predictive of both symptom severity and treatment outcome.     

Exhaled and nasal nitric oxide in patients with Japanese cedar pollinosis and effects of nasal steroids

INTRODUCTION: Nitric oxide (NO) is produced by the action of NO synthase (NOS) using L-arginine as a substrate in various cells and found in air exhaled by humans. Previous studies suggest that almost all exhaled NO is derived from the upper airways and increases in patients with untreated asthma and allergic rhinitis. Exhaled NO is inhibited by treatment with inhalation of steroids that may be caused by inhibition of inducible nitric oxide synthase (iNOS). The purpose of this study is to determine whether exhaled and nasal NO increases in patients with Japanese cedar pollinosis compared with nonallergic healthy subjects, and whether it is affected by treatment with nasal steroids. Furthermore, we investigated its relation to nasal function and allergic rhinitis. SUBJECTS AND METHODS: 10 patients with Japanese cedar pollinosis and 5 healthy normal subjects were tested. All subjects had no history of respiratory infection for at least 2 weeks and did not smoke. Exhaled NO was collected in a sampling bag from oral and nasal breathing, and nasal NO was sampled directly from the nasal cavity. Both were measured by a chemiluminescence NO analyzer, ML9841, at a detection limit of 1 part per billion (ppb). Subjects used nasal steroids for 2 weeks and were measured similarly afterwards. RESULTS: NO concentrations in nasal air and air exhaled from the nose in patients with Japanese cedar pollinosis (277.9 +/- 59.5 ppb, 34.4 +/- 3.9 ppb, n = 10) were higher than the normal subjects (153.3 +/- 30.6 ppb, 19.9 +/- 3.4 ppb, n = 5) (p < 0.05). NO exhaled from the mouth was not significantly different between patients (20.5 +/- 4.9 ppb) and normal subjects (23.7 +/- 2.6 ppb). In patients with Japanese cedar pollinosis, the concentration of nasal NO and nasal exhaled NO were significantly decreased after treatment with nasal steroids (144.0 +/- 21.0 ppb, 26.1 +/- 3.0 ppb) (p < 0.01, p < 0.05), but there was no change in oral exhaled NO (17.2 +/- 3.3 ppb). In normal subjects, oral (22.5 +/- 5.3 ppb), nasal exhaled NO (19.1 +/- 2.3 ppb), and nasal NO (151.2 +/- 24.8 ppb) were not changed. CONCLUSION: In patients with Japanese cedar pollinosis, nasal NO was increased and decreased by nasal steroids. These results suggest that increased nasal NO in patients with allergic rhinitis is produced by induction of iNOS and that nasal NO produces the symptoms of nasal obstruction and rhinorrhea.     

Effects of sublingual immunotherapy on nasal symptoms and sleep disturbance in patients with Japanese cedar pollinosis

ObjectiveJapanese cedar (JC) pollinosis is the most common seasonal allergic rhinitis (AR) in Japan. AR reduces the quality of life not only because of nasal symptoms but also because of sleep disturbance. In the present study, we investigated the effects of sublingual immunotherapy (SLIT) with a standardized JC pollen extract on nasal symptoms and AR-related sleep disturbance in patients with JC pollinosis.MethodsIn the present non-randomized controlled study, we assigned thirty-one patients with JC pollinosis who received SLIT into the SLIT group, and another thirty-eight patients with JC pollinosis who visited our hospital without treatment into the untreated group. We evaluated nasal symptoms and sleep disturbance using the classification of the severity of AR symptoms and the Athens Insomnia Scale, respectively.ResultsThe nasal symptom scores and the Athens Insomnia Scale scores of patients in the SLIT group were both significantly lower than those of patients in the untreated group. There was a significant correlation between total nasal symptom scores and the Athens Insomnia Scale scores.ConclusionsThese findings suggested that SLIT with JC pollen extract suppressed nasal symptoms in patients with JC pollinosis, leading to improvements in AR-related sleep disturbance and daytime troubles with daily life.     

Measurement of quality of life during different clinical phases of Japanese cedar pollinosis

OBJECTIVE: To assess Quality of Life (QOL) scores in patients with Japanese cedar (Cryptomeria japonica, CJ) pollinosis. METHODS: QOL was measured intraseasonally and extraseasonally in patients (n = 69) using the Medical Outcomes Study Short-Form Health Survey, and compared with healthy control subjects (n = 50). The differences in intraseasonal QOL scores between short and long disease duration groups were studied. The relation of intraseasonal QOL scores to nose symptoms was evaluated using Spearman's rank correlation. RESULTS: Significant decrease was observed in two of eight QOL items in intraseasonal measurements of patients. These QOL impairments improved extraseasonally. Scores for emotional problems in patients with long disease duration were less impaired than those with short disease duration. QOL scores in patients correlated poorly with the severity of nasal symptom. CONCLUSIONS: This is the first study to report QOL impairment in CJ pollinosis. Based on the findings long disease duration may improve emotional problems, and the correlation between disease severity and QOL is low.     

Costimulatory molecule expression on allergen-stimulated PBMC in cedar pollinosis subjects

B7-1 (CD80) and B7-2 (CD86) play important roles in the differentiation of Th1 and Th2 phenotypes. CD40-CD40L interaction supports the expression of CD80 and CD86 on antigen-presenting cells. Blocking studies suggest these molecules also play important roles in sensitization to a cedar pollen antigen by, but very few studies have concerned their effects on subsequent induction by antigens. We investigated the roles of CD80, CD86, and CD40 in the differentiation of Th1 and Th2 subsets after stimulation with the antigen in subjects with cedar pollinosis. Peripheral blood mononuclear cells (PBMC) were isolated from 12 subjects with pollinosis and 11 healthy controls and stimulated with cedar pollen extract. After in vitro stimulation, CD80, CD86, and CD40 expression on CD19+ cells were analyzed by flow cytometry. The production of type 1 and type 2 cytokines in culture supernatants was measured by FLISA. Proliferation studies were conducted in the presence or absence of anti-CD40 or CD86 mAbs. After in vitro stimulation, CD86 and CD40 were significantly up-regulated following stimulation in pollinosis subjects (p = 0.02 and p = 0.04). A significantly higher level of IL-5 (p = 0.02) was produced by PBMC of pollinosis subjects than by those of controls. Allergen-induced proliferation and IL-5 production of PBMC of pollinosis subjects were inhibited by anti-CD86 mAb but not CD40 mAb. These results indicate that the Th2 response predominated in pollinosis subjects and that CD86 rather than CD80 may be the costimulatory molecule involved in the allergen-induced activation of PBMC.     

鼻用糖皮质激素治疗儿童上气道咳嗽综合征疗效观察

目的分析丙酸氟替卡松鼻喷剂在儿童上气道咳嗽综合征治疗中的疗效。方法121例诊断为上气道咳嗽综合征（upperairwaycoughsyndrome,UACS）的患儿随机分为治疗组（63例）和对照组（58例）,所有患者根据原发病因采用抗炎、抗过敏等对症治疗,同时避免接触变应原。治疗组加用丙酸氟替卡松鼻喷剂喷鼻,对照组伴鼻塞患者加用呋麻滴鼻液。疗程结束后采用视觉模拟量表判断咳嗽缓解情况。结果随访4周,两组患者慢性咳嗽、鼻后滴流等症状均有不同程度改善,治疗组有效率（93．65％）明显高于对照组（74．14％）,差异具有统计学意义（P〈0．05）。结论鼻用糖皮质激素治疗以慢性咳嗽为主要表现的儿童上气道咳嗽综合征安全有效,值得临床推广应用。     

武汉城区柳杉花粉症发病的初步研究

目的：调查武汉城区柳杉花粉症的发病情况。方法：采用问卷调查、鼻腔检查和变应原皮肤试验等方法对湖北医科大学３０９例医学生进行柳杉花粉症的有关调查;并用皮肤划痕试验及鼻粘膜激发试验对２０５例变应性鼻炎患者行柳杉花粉症的临床调查。结果：①３０９例医学生中柳杉花粉变应原皮试阳性２４例（７．８％）;②２０５例变应性鼻炎患者中柳杉花粉变应原皮试阳性５９例（２８．８％）。结论：柳杉花粉症在武汉城区是一种常见的花     

The kinetics of CD80 and CD86 expression on antigen-presenting cells in cedar pollinosis subjects

CD80 and CD86, which are costimulatory molecules in T-cell activation, play important roles in the differentiation of Th1- or Th2-phenotypes. The results of blocking studies using neutralizing antibodies have suggested that CD80 and CD86 also play important roles in sensitization to cedar pollen antigen, but very few studies have examined the kinetics of CD80 and CD86 expression on antigen-presenting cells (APC). We studied the kinetics of CD80 and CD86 expression on APC after allergen-stimulation in cedar pollinosis subjects. A skin-prick test was performed in nine subjects with pollinosis and seven control subjects. Peripheral blood mononuclear cells (PBMC) were isolated and stimulated with Japanese cedar pollen extract. Zero to 8 days following in vitro stimulation, the expression of CD80 and CD86 in either CD14+ or CD19+ cells was analyzed by two-color flow cytometry. The expression of CD28, CTLA-4 and CD40L on CD4+ cells was analyzed by two-color flow cytometry after eliminating either CD14+ or CD19+ cells. After in vitro stimulation, the expression of both CD80 and CD86 was significantly upregulated in pollinosis subjects compared to control subjects. However, the difference was observed in the kinetics of CD80 and CD86 expression following allergen stimulation. The expression of CD86 was upregulated earlier than that of CD80 after in vitro stimulation. In the absence of CD19+ cells, the expression of CD28, CTLA-4, and CD40L in CD4+ cells was significantly lower than that in the absence of CD14+ cells. These results indicate that CD19+ cells of pollinosis subjects expressed higher CD80 and CD86 than that of control subjects, and that the kinetics of CD80 and CD86 expression following stimulation differed. In pollinosis subjects, CD19+ cells may thus function as APC in allergen-induced activation of PBMC.