Yoko Osawa

Association of serum interleukin‐33 level and the interleukin‐33 genetic variant with Japanese cedar pollinosis

Background IL‐33, an IL‐1‐like cytokine, is a ligand for IL1RL1, which is an important effector molecule of type 2 T helper responses. Although IL‐33/IL1RL1 interaction has been suggested to be important in induction of allergic airway inflammation, serum levels of IL‐33 and the genetic influences of the polymorphisms of IL‐33 in human allergic diseases are unclear.

Prevalence of Allergic Rhinitis and Sensitization to Common Aeroallergens in a Japanese Population

Background: Allergic rhinitis (AR) is recognized as a major health problem worldwide, and its prevalence depends on the age range of the subjects. The aims of this study were to determine the current prevalence of AR, effects of age on the prevalence of IgE sensitization to inhalant allergens, and serum total IgE levels in Japanese subjects. Methods: We conducted a survey of 1,540 subjects between 20 and 49 years of age in 2006 and 2007 and examined the prevalence of AR and sensitization to 7 common aeroallergens. We measured serum total IgE and specific IgE to 7 aeroallergens. AR was determined based on symptoms, predominantly in the nose and eyes, caused by aeroallergens as mentioned in a questionnaire and sensitization to any of the 7 aeroallergens as assessed by measurement of serum specific IgE. Results: The prevalence of AR was 44.2% (681 of the 1,540 subjects) and there was no difference among age decades. Of the 1,540 subjects, 1,073 (69.7%) were sensitized to at least 1 of the 7 aeroallergens. The most common allergen in AR was Japanese cedar pollen (89.6%, 610 of the 681 with AR) in all the age decades examined. The sensitization rate to mites was significantly higher in the younger subjects. Conclusion: Our data suggest that the prevalence of AR between 20 and 49 years of age has increased by nearly 10% during the last 10 years. Cedar pollen and mites were predominant allergen sources among the 7 aeroallergens in the Japanese population.

Efficacy of oral olopatadine hydrochloride for the treatment of seasonal allergic rhinitis: A randomized, double-blind, placebo-controlled study.

Adequate treatment is critical for maintaining a good level of quality of life (QOL) during the pollen season in patients suffering from seasonal allergic rhinitis (SAR). Olopatadine, a histamine H(1)-receptor antagonist, has been approved in the United States and Europe for the treatment of AR and allergic conjunctivitis as a nasal spray and an ophthalmic solution, respectively. We conducted a randomized, double-blind, placebo-controlled study to determine whether orally administered olopatadine for prophylactic purposes might also be effective for the control of nasal allergy symptoms, especially nasal congestion, in patients with SAR due to Japanese cedar pollen (SAR-JP). A total of 110 patients with SAR caused by JP were randomized to the treatment. The subjects recorded their nasal and ocular allergic symptom scores in a diary, and their QOL was assessed by the Japanese version of the Rhinoconjunctivity Quality of Life Questionnaire. Treatment with oral olopatadine significantly suppressed sneezing (p < 0.001), rhinorrhea (p < 0.001), and nasal congestion (p < 0.05). The total QOL score during the peak JP season was superior in the olopatadine group than in the placebo group (p < 0.05). However, orally administered olopatadine did not exert any significant effect against eye itching and watering of the eyes, unlike olopatadine nasal spray. Treatment with olopatadine tablets yielded superior QOL scores in the domains of usual daily activities and outdoor activities when compared with placebo. No serious adverse effects of the treatment were reported during the study period. These results suggest that oral olopatadine treatment may be a useful alternative treatment strategy for AR.

Factors associated with the development and remission of allergic diseases in an epidemiological survey of high school students in Japan.

Background Allergic diseases are an important health problem for children and adults. It is important to know how allergic diseases develop and remit from infancy to adolescence. Early intervention is effective in treating allergic diseases. Objective We performed a large-scale questionnaire survey of high school students in Fukui Prefecture, Japan, and analyzed the factors associated with the development and remission of allergic diseases. Methods A total of 21,802 students participated in the epidemiologic survey, and the valid response rate was 89.3% (19,461). We applied an inverse probability weighting method with propensity scores. Results The present prevalence rate of allergic rhinitis (AR) was 19.2%. The remission rate of AR was 15.3%. Only children and firstborns had a significantly higher risk of developing symptoms of allergic diseases [only child: AR, 1.37; bronchial asthma (BA), 1.30; food allergy (FA), 1.33 and firstborn: AR, 1.38; BA, 1.10]. Constipation was an associated factor for development of atopic dermatitis (AD) (1.17) and AR (1.17), regular intake of lactic acid bacteria was not an associated factor for development of allergic diseases but was a factor for remission of AD (1.22). Hypohidrosis was an associated factor for development of AD (1.25). High academic performance was an associated factor for development of AR (1.20) but was a negative factor for development of BA (0.89). The values in parentheses are significant adjusted odds ratios. Conclusion This epidemiologic survey showed that the hygiene hypothesis and intestinal bacterial flora might influence the development of symptoms and remission of allergic diseases.

Prevalence of inhaled antigen sensitization and nasal eosinophils in Japanese children under two years old

OBJECTIVE The increasingly younger age of onset of allergic rhinitis (AR) has recently become a problem. This study examined the prevalence of inhaled antigen sensitization and nasal eosinophils in children younger than two years old, with measurement of the serum concentrations of aeroallergen-specific IgE antibodies to house dust mites, cat fur, and Japanese cedar pollen, measurement of nasal eosinophil counts, and a questionnaire administered to the childrens parents. METHODS The subjects were a group of healthy children undergoing 18-month infant health checks provided by the local government, and sick children younger than two years old at the pediatric hospital. RESULTS Among 408 healthy infants, 44 (10.7%) had antigen-specific IgE antibodies, 29 (7.1%) had nasal eosinophils, and eight (2.0%) had both specific IgE antibodies and nasal eosinophils. Nasal assessment revealed that 125 children had rhinorrhea. Of the infants who showed both sensitization to antigens and nasal eosinophils, six (1.5%) had confirmed rhinorrhea. Among 186 sick children younger than two years old at the pediatric hospital, aeroallergen-specific IgE antibodies were detected in five (2.6%). The presence of nasal eosinophils was confirmed in six children (3.2%), which percentage was smaller than that of the healthy group. No infant had either sensitization to antigens or nasal eosinophils. CONCLUSION The findings described above indicate that the minimum prevalence of AR might be 1.5% in 18-month-old children and that around 10% of affected children have aeroallergen-specific IgE antibodies in Japan. The incidence of AR in young children might increase further.

Cytosine–phosphate–guanosine-DNA induces CD274 expression in human B cells and suppresses T helper type 2 cytokine production in pollen antigen-stimulated CD4-positive cells

Co‐stimulatory molecules are important for regulating T cell activation and immune response. CD274 [programmed death ligand 1 (PD‐L1), B7‐H1] has emerged as an important immune modulator that can block T cell receptor signalling. We have investigated whether PD‐L1 and other co‐stimulatory ligands could be expressed in human B cells stimulated by cytosine–phosphate–guanosine (CpG)‐DNA. CpG‐DNA strongly induced the co‐inhibitory molecule ligand, PD‐L1, of human B cells. Results show that nuclear factor‐kappa B (NF‐κB) signalling is involved directly in CpG‐DNA‐induced PD‐L1 expression in human B cells. We sought to determine the effect of CpG‐DNA‐treated B cells on T helper type 2 (Th2) cytokine production in Cry j 1 (Japanese pollen antigen)‐stimulated human CD4‐positive cells from patients with seasonal allergic rhinitis caused by Japanese cedar pollen. CpG‐DNA‐treated B cells reduced Cry j 1‐induced interleukin (IL)‐5 and IL‐13 production in CD4‐positive cells. When the binding of PD‐1 to PD‐L1 was inhibited by PD‐1‐immunoglobulin (Ig), this chimera molecule reversed the previously described reductions in IL‐5 and IL‐13 production. In contrast, the CpG B‐treated B cells increased both interferon (IFN)‐γ and IL‐12 production in the presence of Cry j 1‐stimulated CD4‐positive cells. CpG‐DNA simultaneously reduced the expression of B7RP‐1 [also known as inducible co‐stimulator ligand (ICOSL), B7‐H2] and the ligand of CD30 (CD30L). These results indicate that CpG‐DNA induces co‐inhibitory molecule ligand PD‐L1 expression in human B cells and PD‐L1 can suppress Th2 cytokine production in Cry j 1‐stimulated CD4‐positive cells, while CpG‐DNA increased Th1 cytokine production and reduced the expression of co‐stimulatory molecule ligands that can promote Th2 inflammatory responses.

Long-term sublingual immunotherapy for Japanese cedar pollinosis and the levels of IL-17A and complement components 3a and 5a

Allergen-specific immunotherapy is the only treatment that can alter the natural course of allergic disease. We performed long-term sublingual immunotherapy (SLIT) for patients with seasonal allergic rhinitis caused by Japanese cedar pollen (SAR-JCP), screened molecules as candidate biomarkers, and investigated serum IL-17A and complement components 3a (C3a) and C5a in order to evaluate whether these molecules show changes correlated to symptom scores. In this study, we found that the long-term SLIT reduced the serum levels of IL-17A and C3a and C5a. The levels of C3a in the patients significantly decreased from year 1 compared with those at the baseline, and their levels of IL-17A significantly decreased from year 2 compared with those at baseline. The levels of IL-17A, C3a, and C5a at year 4 of SLIT were significantly lower than not only those at baseline, but also those at year 1. A significant positive correlation was found between the symptom medication scores and the levels of IL-17A at year 4. The symptom medication scores in the group in which IL-17A levels decreased at year 4 were significantly lower than those in the group without such a decrease. The serum level of IL-17A might prove useful as a biological parameter to ascertain the effectiveness of SLIT for patients with SAR-JCP. It is necessary to produce new therapeutics for non-responders in whom serum IL-17A levels are still higher against long-term SLIT.

Allied health – 3007. The biomarker of sublingual immune therapy.

Background Allergic rhinitis (AR) is recognized as a major health problem worldwide. Allergen-specific immunotherapy (SIT) is the only available treatment that can alter the natural course of allergic disease. Recent findings in experimental models of allergic rhinitis suggest that complement 3a and 5a regulate the development of maladaptive Th2 and Th17 immunity. We investigated the changes of C3a, C5a, IL-17a in the serum of patients treated by Sublingual immune therapy (SLIT).

The Advantage of Ketamine Anesthesia for Insertion of Ear Tubes in Infants

When a tympanic membrane tube is inserted in an infant with otitis media with effusion, the procedure is often performed under general anesthesia. In such cases, hospitalization for a few days is generally required. The health expenditure increases with general anesthesia and hospitalization. Recently a one-day operation has been widely performed and demonstrates merits such as reduction of health expenditures and patient burden. Therefore, we attempted intravenous anesthesia using ketamine hydrochloride for one-day procedure. With respect to 41 cases of infant exudative otitis media, profitability was compared in the hospitalization under general anesthesia group and the one-day procedure with ketamine hydrochloride group. Tube insertion was completed in a very short time under ketamine anesthesia. In the ketamine group, there were no major complications and the health expenditure was limited. Ketamine is a very suitable anesthesia for tympanic membrane tube insertion in an infant.