Volume 6, Issue 2 Reviews - February 2009
Medical Journal Reviews
Gary Hellerman, PhD, in collaboration with Richard Lockey, MD, WAO Web Chief Editor, conducted these reviews of premier medical journal articles for practicing allergists. Read their top three picks here, and link to the remaining reviews from the list below.
1. Predicting worsening asthma control following the common cold. The effects of rhinovirus infection on asthmatics vary, but upper respiratory infections commonly worsen asthma and lead to exacerbations. In this multicenter study, 413 adult asthmatics were followed for over a year to determine if the severity of a cold could predict loss of asthma control. To quantify the loss of asthma control, subjects completed the mini-Asthma Control Questionnaire (mini-ACQ) and to measure cold severity, the Wisconsin Upper Respiratory Symptom Survey-21 (WURSS-21). The questionnaires were done about every 8 weeks, and upon the onset of a cold, the WURSS-21 was completed daily for the duration of the cold and the mini-ACQ was done at 7 and 14 days after its onset. Significant loss of asthma control occurred in 134 subjects and the WURSS-21 scores on the second day were predictive of subsequent worsening of asthma. Editor's comment: Documentation of cold symptoms by asthmatics may help reduce the post-cold loss of asthma control. Walter MJ et al., Eur Respir J, 2008; 32: 1548-1554.
感冒後に喘息が悪化することはよく知られているが、この研究では、２日目の感冒症状の重症度を Wisconsin Upper Respiratory Symptom Survey-21 (WURSS-21) により定量化し、その後の喘息症状 mini-Asthma Control Questionnaire (mini-ACQ) との相関をみた。その結果、この両者には相関関係が認められた。感冒症状の重症度を把握することにより、その後の喘息症状を予測できる可能性が示された。
2. Azathioprine or methotrexate maintenance for ANCA-associated vasculitis. Patients with Wegener's granulomatosis (WG) or microscopic polyangiitis (MP) can be induced into remission by a course of i.v. corticosteroids and cyclophosphamide. Either methotrexate (Mtx) or azathioprine (Aza) can then be given as an immunosuppressant for post-treatment maintenance. This study compares the efficacy and safety of Mtx vs Aza administered to 126 WG or MP patients in remission. One group of 63 randomized patients received 2.0 mg/kg Aza per day while the other was given 0.3 mg/kg Mtx per week, increased to 25 mg per week, for 12 months. Adverse events (AEs) requiring discontinuation of the drug or causing death were the primary endpoints recorded over a mean period of 29±13 months. During maintenance therapy, 29 Aza patients (46%) and 35 Mtx patients (56%) had one or more AEs and among these individuals, 7 in the Aza group and 12 in the Mtx group had AEs severe enough to cause discontinuation or death. The relapse-free survival rates were 71.8% for Aza compared to 74.5% for Mtx, and the hazard ratio for risk of relapse with Mtx vs Aza was 0.92. The conclusion is that the safety and efficacy of Mtx and Aza are not statistically different. Editor's comment: Given the equivalency of the two medications, the decision of which one to use for maintenance control of ANCA-associated vasculitis can be made based on the individual's tolerance. Pagnoux C, et al. N Engl J Med 2008; 359:2790-2803.
ウェゲナー肉芽腫症、チャーグ・ストラウス症候群、顕微鏡的多発血管炎などの抗好中球細胞質抗体 ANCA 陽性血管炎に対する治療として免疫抑制薬アザチオプリンとメトトレキセートそれぞれの効果を検討した。その結果、両者とも同等に有効（再発なしの寛解率 70% 以上）であり、同程度の副作用（ 50% 前後）がみられた。
3. A syndrome with congenital neutropenia and mutations in G6PC3. Mutations in several different genes are linked to severe congenital neutropenia (SCN) with susceptibility to bacterial infection, lack of mature neutrophils, heart and urogenital defects and increased risk of leukemia. A genome-wide linkage analysis of two consanguineous families of children with SCN resulted in the identification of a homozygous mutation in the gene for glucose-6-phosphatase, G6PC3, that abolished G6P activity. The parents were heterozygous for the mutation. An additional seven unrelated SCN patients were found to have biallelic G6PC3 mutations. None had hypoglycemia commonly seen in glycogen storage disorders also associated with neutropenia. The defect in glucose-6-phosphatase caused loss of mature neutrophils through apoptosis and was associated with increased susceptibility to infection, heart defects, superficial vein prominence and urogenital abnormalities. Mutant G6PC3 activity measured by in vitro glucose production was at background levels compared to the wild type enzyme. Neutrophils, hematopoietic progenitor cells and other cells such as fibroblasts from SCN patients showed an increased rate of spontaneous and induced apoptosis. The tendency to apoptosis in myeloid progenitor cells was reversed by transfection with a plasmid expressing wild type G6PC3. Enzymatic analysis of neutrophils from SCN patients revealed a decrease in the anti-apoptotic protein Mcl-1 which may account for the increased apoptosis. Editor's comment: This paper should be read as a model for excellence in experimental design, data analysis and presentation. Boztug K et al. New Engl J Med 2009; 360:32-43. (also see the editorial by Dale and Link, pp 3-5
重症好中球減少症の家系についてゲノムワイドな遺伝子解析を行い、グルコース 6 リン酸代謝酵素 G6P3C の変異が原因であることをつきとめた。両親は G6P3C のヘテロ変異、患者はホモ変異をもっていた。患者はアポトーシスに起因する成熟好中球減少の他に、泌尿生殖器、心臓、上大静脈に奇形を認めることがあった。
All 10 reviews are posted here.
WAO の公式機関誌 WAO Journal の紹介です。非ステロイド系抗炎症剤過敏症の新しい疾患群に関する報告などが掲載されています。アクセスするためにパスワードが設定されています (www.WorldAllergy.org) が、日本アレルギー学会の会員 (WAO の会員 ) であれば誰でも簡単に無料で閲覧できます。
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