Allergology International
Online ISSN : 1440-1592
Print ISSN : 1323-8930
ISSN-L : 1323-8930
57 巻, 3 号
選択された号の論文の14件中1~14を表示しています
REVIEW ARTICLE
  • Hiroichi Nagai
    2008 年 57 巻 3 号 p. 187-196
    発行日: 2008年
    公開日: 2008/09/19
    ジャーナル フリー
    The purpose of this review is to summarize the role of prostaglandins (PGs) in allergic inflammation and to know the value of PGs, as a target molecule for an anti-allergic drug.
    PGD2 is the major PG produced by the cyclooxygenase pathway in mast cells. Our and others findings indicate that PGD2 is one of the potent allergic inflammatory mediators and must be a target molecule of anti-allergic agent. From our data, one of PGD2 receptor antagonists show clear inhibition of airway hypersensitivity caused by allergic reaction. Concerning the role of PGE2 in allergic inflammation, conflicting results have been reported. Many experimental data suggest an individual role of each PGE2 receptor, EP1, EP2, EP3 and EP4 in allergic reaction. Our results indicate the protective action of PGE2 on allergic reaction via EP3. In addition, one of EP3 agonists clearly inhibits the allergic airway inflammation. These findings indicate the value of EP3 agonists as an anti-allergic agent.
    In addition, some investigators including us reported that PGI2 plays an important role for the protection of the onset of allergic reaction. However, the efficacy of PGI2 analogue as an anti-allergic agent is not yet fully investigated.
    Finally, the role of thromboxane A2 (TxA2) in allergic reaction is discussed. Our experimental results suggest a different participation of TxA2 in allergic reaction of airway and skin. In this review, the role of PGs in allergic inflammation is summarized and the value of PGs as a target molecule for developing a new anti-allergic agent will be discussed.
  • Yoshimichi Okayama, Hirohisa Saito, Chisei Ra
    2008 年 57 巻 3 号 p. 197-203
    発行日: 2008年
    公開日: 2008/09/19
    ジャーナル フリー
    The G-protein-coupled receptors (GPCRs) are the largest known group of integral membrane receptor proteins and are the most common targets of pharmacotherapy. Mast cells (MCs) have been reported to play an important role in allergic diseases, such as urticaria and bronchial asthma. There is an increasing body of clinical evidence that MCs are recruited into allergic reactions by non-IgE-dependent mechanisms. Human MCs are activated and secrete histamine in response to neuropeptides, such as substance P and somatostatin, mediated by a GPCR, MRGX2. The microenvironment surrounding MCs in their resident tissues is likely to contain multiple factors that modify antigen-dependent MC activation. MCs express various GPCRs, and since the function of human MCs is modulated by various GPCR ligands, such as adenosine and sphingosine-1-phosphate, which are present in high levels in the bronchial alveolar lavage fluid of asthmatic patients, the GPCRs expressed on MCs may play an important role in human allergic diseases. The GPCRs expressed on MCs may serve as drug targets for the treatment of allergic diseases.
  • Kimihiro Okubo, Toshikazu Nagakura
    2008 年 57 巻 3 号 p. 205-209
    発行日: 2008年
    公開日: 2008/09/19
    ジャーナル フリー
    Seasonal allergic rhinitis (SAR) induced by Japanese cedar pollens is a substantial problem in Japan. Omalizumab, a novel humanized monoclonal anti-immunoglobulin E (IgE) antibody, has already been proven to reduce symptoms associated with SAR. To investigate the safety and efficacy of omalizumab in the treatment of patients with Japanese cedar pollen-induced SAR compared to placebo or anti-allergic drug, two randomized, double-blind studies were conducted in Japan. Omalizumab (150, 225, 300, or 375mg) or placebo was administered subcutaneously every 2 or 4 weeks based on serum total IgE and body weight at baseline. IPD was administered 300mg per day through the season. Primary and all secondary efficacy variable scores were significantly lower in the omalizumab group than in the placebo group (P <.01) and IPD, Th2 cytokine inhibitor group (P <.01). Omalizumab was effective and safe in the treatment of SAR induced by Japanese cedar pollens. And the methods of increasing effects by combining omalizumab with antibody-specific immunotherapy are being considered. These strategy is more effective than immune-therapy alone.
ORIGINAL ARTICLE
  • Johsuke Hara, Masaki Fujimura, Shigeharu Myou, Toshiyuki Kita, Miki Ab ...
    2008 年 57 巻 3 号 p. 211-217
    発行日: 2008年
    公開日: 2008/09/19
    ジャーナル フリー
    Background: 30-80% of outgrown asthma subjects develop symptoms again later in life. We investigated inflammation and function of lower airway in adolescents with former asthma.
    Methods: 326 never-smoking young adults (mean age 24.0 years) were interviewed with special emphasis on history of asthma. Diagnosis of asthma was based on GINA guidelines. Former asthma subjects consisted of ones with a history of physician-diagnosed childhood asthma, who had been free of asthma symptoms without the use of medication for at least 10 years prior to the study. Provocative concentration of methacholine causing a 20% fall in forced expiratory volume in 1 second (FEV1)(PC20) and eosinophil percentage in induced sputum were measured.
    Results: 31 subjects were former asthma subjects (FBA), 11 subjects were current asthma subjects (CBA) and 284 subjects had no history of asthma (non-BA). PC20 and FEV1/FVC ratio were significantly lower in the FBA group than in the non-BA group (P < 0.01). Maximal mid-expiratory flow (MMF) was significantly lower in the FBA group than in the non-BA group (P < 0.05). Sputum eosinophil percentage was significantly increased in the FBA group compared with the non-BA group (P < 0.01). PC20 was significantly lower in the CBA group than in the FBA and non-BA groups (P < 0.01). FEV1, FEV1/FVC ratio and MMF were significantly lower in the CBA group than in the FBA group (P < 0.05, P < 0.05 and P < 0.05, respectively) and the non-BA group (P < 0.01, P < 0.01 and P < 0.05, respectively). Sputum eosinophils were significantly higher in the CBA group than in the FBA and non-BA groups (P < 0.01).
    Conclusions: This study shows that subjects with long-term outgrown asthma continue to have airway eosinophilic inflammation, airway hyperresponsiveness and airway narrowing.
  • Takehiro Higashi, Masatoshi Wakui, Kazuhisa Nakano, Kumiko Hashimoto, ...
    2008 年 57 巻 3 号 p. 219-222
    発行日: 2008年
    公開日: 2008/09/19
    ジャーナル フリー
    Background: Immunomodulators such as lipopolysaccharides (LPS) and forskolin change the nature of dendritic cells (DCs) to induce Th1 and Th2 cells, respectively, thereby designated Th1 or Th2 adjuvants. Our previous study showed that such activities can be qualitatively evaluated by expression patterns of Notch ligand isoforms, using human monocyte-derived DCs and some leukemic cell lines, such as THP-1 or KG-1. However, quantitative evaluation of the adjuvant activities was not fully established.
    Methods: PMA-treated human monocytic cell line THP-1 was used as a target. Cells were stimulated with various adjuvants, and the intracellular levels of cAMP were determined.
    Results: Th2 adjuvant forskolin was qualitatively evaluated by an increased expression of Delta1 in PMA-treated THP-1 cells, as reported in our previous study. In PMA-treated THP-1 cells, intracellular cAMP levels increased after stimulation with forskolin, in a dose-dependent manner. On the other hand, LPS, one of the known Th1 adjuvants, suppressed the increased cAMP level in a dose-dependent manner.
    Conclusions: Th2- and Th1-adjuvant activities can be quantitatively evaluated by using PMA-treated THP-1 cells and PMA-treated/forskolin-stimulated THP-1 cells, respectively.
  • Takahiro Tsuburai, Naomi Tsurikisawa, Sonoko Morita, Hideki Hasunuma, ...
    2008 年 57 巻 3 号 p. 223-229
    発行日: 2008年
    公開日: 2008/09/19
    ジャーナル フリー
    Background: Exhaled nitric oxide (eNO) is a useful marker of eosinophilic airway inflammation in asthmatics. There have been no studies to show the relationship between eNO measured by offline methods and the degree of bronchial hyperresponsiveness in asthmatic patients treated with inhaled corticosteroids.
    Methods: The study population comprised asthmatics at our outpatient clinic. We measured eNO levels by two methods ("eNOs" was measured with a Sievers kit; and "eNOc" was measured with a kit from the Center for Environmental Information Science, Japan). We also used spirometry to test bronchial hyperresponsiveness to acetylcholine (PC20Ach).
    Results: We recruited 192 stable asthmatics. There was a significant relationship between eNOs and eNOc (r = 0.919, p < 0.001). LogPC20Ach levels were negatively correlated with eNOs or eNOc levels (eNOs, r = -0.31, p < 0.001; eNOc, r = -0.23, p = 0.0013). We classified the subjects into two groups based on eNOs levels ((A) the subjects with high eNOs levels (n = 92) and (B) the subjects with normal eNOs levels (n = 100)) ; logPC20Ach was significantly correlated with eNOs (r = -0.34, p = 0.001) or eNOc (r = -0.28, p = 0.0075) but not correlated with %FEV1 in (A), whereas logPC20Ach was not significantly correlated with eNO but significantly correlated with %FEV1 (r = 0.33, p = 0.002) in (B).
    Conclusions: Levels of eNOs and eNOc were correlated with the degree of bronchial hyperresponsiveness to acetylcholine in adult asthmatics treated with inhaled corticosteroids. Our findings suggest that offline monitoring of eNO will facilitate the management of bronchial asthma in patients treated with these drugs.
  • Hiroyuki Ohbayashi, Mitsuru Adachi
    2008 年 57 巻 3 号 p. 231-239
    発行日: 2008年
    公開日: 2008/09/19
    ジャーナル フリー
    Background: To evaluate whether hydrofluoroalkane-beclomethasone dipropionate (HFA-BDP) controls eosinophilic inflammation, including that in the distal airways, more effectively than fluticasone propionate (FP) Diskus®.
    Methods: Fifty patients with well-controlled mild to moderate persistent asthma using FP for more than 6 months were randomly assigned to FP and HFA-BDP groups, and the treatment regimens of the two groups were switched twice between FP and HFA-BDP in a double cross-over manner at 3-month intervals after 2-week washout periods. Evidence of eosinophilic inflammation in blood and induced sputum samples was assessed, together with pulmonary function testing and an Asthma-related Quality of Life Questionnaire (AQLQ) survey after each treatment period.
    Results: The peripheral blood differential eosinophil count and sputum levels of eosinophil cationic protein (ECP) showed reciprocal changes during the study periods in both groups. The blood differential eosinophil count was significantly lower during the HFA-BDP than during the FP treatment period in both the FP (p = 0.004) and the HFA-BDP (p = 0.020) group. The late-phase induced sputum ECP level was significantly decreased during the HFA-BDP treatment period in both the FP (p = 0.016) and the HFA-BDP group (p = 0.023). The significant elevation of surfactant protein D values in the late-phase sputum observed in both groups indicated that late-phase sputum was obtained mainly from proximal peripheral airways. Both symptom and activity limitation domains of the AQLQ in the HFA-BDP group significantly increased after switching from FP to HFA-BDP. There were no significant changes in pulmonary function indices in either group at any time during the study.
    Conclusions: HFA-BDP improved residual eosinophilic inflammation in asthmatic airways, including distal airways, more effectively than FP.
  • Atsuki Fukushima, Tamaki Sumi, Waka Ishida, Ayako Ojima, Minako Kajisa ...
    2008 年 57 巻 3 号 p. 241-246
    発行日: 2008年
    公開日: 2008/09/19
    ジャーナル フリー
    Background: We showed previously that α-galactosylceramide (α-GalCer) treatment elevated splenic CD4+CD25+Foxp3+ T-cell numbers and suppressed the development of experimental allergic conjunctivitis (EC). Here, we investigated whether CD4+CD25+Foxp3+ T cells mediate the suppressive effects of α-GalCer treatment on EC.
    Methods: To deplete CD4+CD25+Foxp3+ T cells, neonatal mice were thymectomized and intraperitoneally injected with anti-CD25 Ab. At 6 weeks of age, these mice were immunized with ragweed (RW) in aluminum hydroxide. Ten days later, the mice were challenged with RW in eye drops and 24 hours later, the conjunctivas and spleens were harvested for histological and flow cytometric analyses, respectively. α-GalCer or vehicle was injected 2 hours prior to RW challenge. In addition, α-GalCer was injected into thymus-intact EC-developing mice that had not been treated with anti-CD25 Ab.
    Results: α-GalCer treatment significantly suppressed EC in the thymus-intact mice that had not been treated with anti-CD25 Ab. In contrast, α-GalCer treatment of thymectomized and anti-CD25 Ab-treated mice did not affect the severity of EC or splenic CD4+CD25+Foxp3+ T-cell numbers. However, α-GalCer treatment did significantly increase splenic CD4+CD25+Foxp3+ T-cell numbers in thymectomized mice that had not received anti-CD25 Ab.
    Conclusions: α-GalCer treatment during the effector phase of EC increased CD4+CD25+Foxp3+ T-cell numbers, which in turn suppressed the development of EC.
  • Kimihiro Okubo, Kohtaro Baba
    2008 年 57 巻 3 号 p. 247-255
    発行日: 2008年
    公開日: 2008/09/19
    ジャーナル フリー
    Background: Secretion of nasal discharge was enhanced and airway-resistance in the nasal cavity was augmented, resulting in nasal congestion, when leukotrienes were administered to the nasal mucosa. These results indicate that leukotrienes play an important role in the pathogenesis of allergic rhinitis.
    Methods: A double-blind clinical study was carried out to evaluate the efficacy and the safety of montelukast, a cysteinyl leukotriene receptor 1 antagonist, 5mg, 10mg or placebo orally administered once daily at bedtime for 2 weeks, to Japanese patients with seasonal allergic rhinitis. The composite nasal symptom scores (average over the 2-week treatment period) were compared among the montelukast 5mg and 10mg groups with the placebo group.
    Results: The composite nasal symptom score significantly improved in the montelukast 5mg and 10mg groups compared with the placebo group. The administration of montelukast 5mg or 10mg once daily was well tolerated and the safety profiles were similar to those of the placebo. There were no significant differences in the incidences of adverse experience or drug-related adverse experience among the montelukast 5mg, 10mg groups and the placebo group.
    Conclusions: Both montelukast 5mg and 10mg doses show clinically meaningful efficacy for the treatment of patients with seasonal allergic rhinitis and the safety profiles of those are comparable to that of the placebo.
  • Norimasa Izumi, Hiroyuki Mizuguchi, Hayato Umehara, Satoshi Ogino, Hir ...
    2008 年 57 巻 3 号 p. 257-263
    発行日: 2008年
    公開日: 2008/09/19
    ジャーナル フリー
    Background: H1 antihistamines are widely used as therapeutics for allergic diseases. Sedation is a well-known side effect of H1 antihistamines and sometimes it is life-threatening for patients. Thus it is important to evaluate the sedative properties of H1 antihistamines to avoid side effects. For this purpose, histamine H1 receptor (H1R) occupancy and proportional impairment ratios (PIR) are now being used. However, it is not easy to obtain these parameters. Here, we sought to evaluate the sedative properties of H1 antihistamines by means of a large-scale surveillance at health insurance pharmacies.
    Methods: The survey was conducted at 37 health insurance pharmacies. The therapeutic efficacy and the degree of sleepiness were quantified through a questionnaire using the visual analog scale (VAS) directly from 1742 patients who received H1 antihistamines.
    Results: The degree of sleepiness caused by the first-generation antihistamines was significantly higher than that of the second-generation antihistamines. The high VAS score in case of efficacy was found in d-chlorpheniramine, olopatadine, and ebastine. Among the mean values of efficacy, all second-generation antihistamines except for loratadine, bepotastine, and mequitazine were significantly higher than that of clemastine. Regarding the degree of sleepiness, clemastine scored the highest VAS score, and significantly lower scores were obtained in all second-generation antihistamines.
    Conclusions: The sedative properties of the H1 antihistamines obtained from VAS analysis were very similar to those of H1R occupancy from positron emission tomography (PET) studies and PIR from meta-analysis. Our results indicate that large-scale surveillance using VAS might be useful to evaluate the profiles of H1 antihistamines.
  • Kimihiro Okubo, Minoru Gotoh, Shigeharu Fujieda, Mitsuhiro Okano, Hiro ...
    2008 年 57 巻 3 号 p. 265-275
    発行日: 2008年
    公開日: 2008/09/19
    ジャーナル フリー
    Background: Seasonal allergic rhinitis (SAR) induced by Japanese cedar pollen is a substantial problem in Japan. Sublingual immuno-therapy (SLIT) is safer than conventional antigen-specific immunotherapy, the only treatment modality by which complete cure of the disease can be expected. We investigated the safety and efficacy of SLIT in the treatment of cedar pollinosis patients compared to placebo.
    Methods: A randomized, placebo-controlled, double-blind study was conducted in 61 cedar pollinosis patients. Increasing doses of standardized Japanese cedar extract or placebo were administered sublingually in intervals ranging from daily to once a week after six weeks. The primary efficacy variable was the mean of the daily total symptom scores (TSS) during the pollen dispersing period. Secondary efficacy variables included the QOL scores and related variables.
    Results: Primary efficacy variable scores were significantly lower for some days in the SLIT group than in the placebo group (P <.01 or P <.05). Secondary efficacy for the QOL score in SLIT group was almost of half of placebo group. There was no significant difference in the overall incidence of side effects between the SLIT group and the placebo group.
    Conclusions: SLIT was effective and safe in the treatment of cedar pollinosis.
CASE REPORT
  • Nobuyuki Katayama, Masaki Fujimura, Masahide Yasui, Haruhiko Ogawa, Sh ...
    2008 年 57 巻 3 号 p. 277-280
    発行日: 2008年
    公開日: 2008/09/19
    ジャーナル フリー
    We report a case of hypersensitivity pneumonitis and asthma attacks caused by environmental fungi in a 75-year-old man. The diagnosis was established by inhalation challenge with Bjerkandera adusta and Aspergillus fumigatus. The patient was admitted for treatment of fever, wheezing, and dyspnea. Chest computed tomography showed small nodular shadows with diffuse, partially patchy, ground-glass opacities. The findings of bronchoalveolar lavage fluid were compatible with hypersensitivity pneumonitis. His symptoms and objective findings, including chest radiographs, worsened after returning home, suggesting the existence of causative antigens in his house. B. adusta and A. fumigatus were isolated from the living room and bedroom. Based on the results of antigen inhalation bronchoprovocation test, he was given a diagnosis of hypersensitivity pneumonitis caused by B. adusta and bronchial asthma attacks caused by B. adusta and A. fumigatus. After cleaning the entire house, the patient has had no recurrence of the symptoms on returning home.
  • Amanda Lam, Inderpal Randhawa, William Klaustermeyer
    2008 年 57 巻 3 号 p. 281-284
    発行日: 2008年
    公開日: 2008/09/19
    ジャーナル フリー
    Background: Drug hypersensitivity is classically divided into IgE mediated and non-IgE mediated disease. We report a rare case of consequent IgE mediated and non-IgE mediated reactions within the beta lactam class of antibiotics.
    Case Summary: An 84-year-old man developed toxic epidermal necrolysis (TEN) due to ceftriaxone, a third generation cephalosporin, involving 72% of the body surface area. The patient recovered but within weeks subsequently developed an acute IgE mediated allergic reaction to piperacillin/tazobactam, an extended spectrum penicillin. Further IgE RAST revealed positive results to penicillin major determinant.
    Discussion: This case demonstrates the complexity of drug hypersensitivity reactions. While it is accepted that IgE mediated penicillin allergy is a predisposition to cephalosporin allergy, this case displays an unusual correlation between drug hypersensitivity and drug class. There have been few studies that evaluate the cross reactivity with penicillin or other beta-lactams in subjects with primary hypersensitivity to cephalosporins. This clinical scenario emphasizes the need of more studies on cephalosporin allergy in particular as shown by this case of sequential non-IgE mediated cephalosporin induced TEN reaction pursuant by an IgE mediated penicillin allergy.
  • Satoshi Fukushima, Masato Kidou, Hironobu Ihn
    2008 年 57 巻 3 号 p. 285-287
    発行日: 2008年
    公開日: 2008/09/19
    ジャーナル フリー
    Background: The diagnosis of fixed 'drug' eruption is not difficult for dermatologists, but it is difficult to identify the causative agent when the patient denies ingestion of any drugs. There have been some reported cases of fixed 'food' eruption.
    Case Summary: A 71-year-old woman experienced repeated erythema and tense bulla with a burning sensation and pruritus on the right ankle. The eruption remitted leaving pigmentation. The patient denied previous ingestion of any drug. We suspected cashew nut as the causative agent. Oral challenge and patch tests with cashew nut were positive.
    Discussion: A fixed eruption without any antecedent drug ingestion should alert us to think of food as a causative agent.
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