今日の臨床サポート 今日の臨床サポート

著者: 相良博典 昭和大学医学部 内科学講座 呼吸器・アレルギー内科学部門

監修: 長瀬隆英 東京大学名誉教授

著者校正/監修レビュー済:2023/05/24
患者向け説明資料

改訂のポイント:
  1. 本邦のAsanoらによって提唱された新たな診断基準を追加した。
  1. 血清中のアスペルギルスアレルゲンコンポーネント(Asp F 1)に対する特異的IgEの測定が、保険診療にて可能となった。

概要・推奨   

  1. 新たな浸潤影の出現に対して、プレドニゾロン(PSL) の投与を開始する事が推奨される。
  1. ステロイド薬への反応が悪い場合(ステロイド抵抗性)、ステロイドとイトラコナゾール(イトリゾール)の併用が推奨されている。

病態・疫学・診察 

疾患情報(疫学・病態)  
  1. アレルギー性気管支肺アスペルギルス症とは、アスペルギルスに対するアレルギー反応の結果生じる疾患で好酸球増多性肺浸潤症候群(PIE症候群:pulmonary infiltration with eosinophilia syndrome)の代表的疾患の1つと考えられている。
  1. 1952年にHinsonによって報告された疾患であり、吸入されたアスペルギルスの胞子が気道内で増殖し、その菌糸に感作されることによって起こり、アスペルギルスに対するⅠ、Ⅲ、Ⅳ型アレルギー反応が発症に関係している。
  1. ほとんどはAspergillus fumigatusによって発症するが、それ以外のアスペルギルス属や他の真菌でも発症が報告されている。
  1. 喘息あるいは嚢胞性線維症(cystic fibrosis)などの呼吸器の基礎疾患を持つ患者に発症するといわれ、特に喘息患者の1~2%に認められる。
問診・診察のポイント  
  1. 症状は喘鳴、末梢血好酸球の増加、胸部X線での移動する浸潤影、アスペルギルスを含む粘液栓がある。

これより先の閲覧には個人契約のトライアルまたはお申込みが必要です。

最新のエビデンスに基づいた二次文献データベース「今日の臨床サポート」。
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文献 

S C Donnelly, H McLaughlin, C P Bredin
Period prevalence of allergic bronchopulmonary mycosis in a regional hospital outpatient population in Ireland 1985-88.
Ir J Med Sci. 1991 Sep;160(9):288-90.
Abstract/Text The period of prevalence, 1988 inclusive, of Allergic Bronchopulmonary Aspergillosis (ABPA) and Allergic Bronchopulmonary Candiasis (ABPC), the two most frequently reported forms of allergic Bronchopulmonary Mycosis (ABPM), was investigated in an Irish regional hospital respiratory medicine outpatients, catchment area population 536,000. ABPM was defined by the presence of a majority of seven criteria: asthma, eosinophilia, elevated IgE, antibodies to Aspergillus Fumigatus or Candida Albicans, immediate skin test reaction to either fungus, culture of either fungus in sputum, and otherwise unexplained transient or permanent lung field x-ray abnormalities. New referrals were investigated for ABPM if they had asthma and eosinophilia, or asthma and lung field x-ray abnormalities. Fourteen patients with ABPM were identified from a total of 1390 new referrals, a period prevalence of just over one per cent. It is concluded that (1) ABPM is a relatively common disorder in an Irish regional hospital respiratory medicine outpatient population and (2) ABPC constitutes a higher proportion of this disorder than previously considered.

PMID 1769811
R Agarwal, A N Aggarwal, D Gupta, S K Jindal
Aspergillus hypersensitivity and allergic bronchopulmonary aspergillosis in patients with bronchial asthma: systematic review and meta-analysis.
Int J Tuberc Lung Dis. 2009 Aug;13(8):936-44.
Abstract/Text BACKGROUND: The prevalence of Aspergillus hypersensitivity (AH) and allergic bronchopulmonary aspergillosis (ABPA) in bronchial asthma is reported differently in various studies.
OBJECTIVE: To determine the prevalence of AH and ABPA in asthma using a systematic review.
METHODS: We searched the MEDLINE and EMBASE databases for studies published from 1965 to 2008 and included studies that report the prevalence of AH/ABPA in asthma. We calculated the proportions with 95% confidence interval (CI) to assess the prevalence of AH/ABPA in the individual studies and pooled the results using a random effects model.
RESULTS: Our search yielded 21 eligible studies. The prevalence of AH in bronchial asthma was 28% (95%CI 24-34), and was higher with an intradermal test vs. a prick test (28.7% vs. 24.8%, P = 0.002), but did not vary with the type of antigen used (indigenous or commercial). The prevalence of ABPA in bronchial asthma and Aspergillus-hypersensitive bronchial asthma was respectively 12.9% (95%CI 7.9-18.9) and 40% (95%CI 27-53). There was a wide variation in the criteria used for the diagnosis of ABPA. There was significant statistical heterogeneity assessed by the I(2) test and Cochran Q statistic in all the outcomes.
CONCLUSIONS: There is a high prevalence of AH and ABPA in patients with bronchial asthma. Careful screening should therefore be performed in all patients with bronchial asthma. Intradermal tests are more sensitive than prick tests for the diagnosis of AH. Finally, there is a need to adopt a uniform methodology and criteria for the diagnosis of AH/ABPA.

PMID 19723372
J N Allen, E R Pacht, J E Gadek, W B Davis
Acute eosinophilic pneumonia as a reversible cause of noninfectious respiratory failure.
N Engl J Med. 1989 Aug 31;321(9):569-74. doi: 10.1056/NEJM198908313210903.
Abstract/Text Although chronic eosinophilic pneumonia is a well-known disorder, acute eosinophilic pneumonia has not been as well characterized. We describe the clinical features, results of bronchoalveolar lavage, and follow-up studies of four patients with acute eosinophilic pneumonia. The patients presented with an acute febrile illness, severe hypoxemia (partial pressure of arterial oxygen less than 60 mm Hg), diffuse pulmonary infiltrates, an increased number of eosinophils (mean +/- SEM, 42 +/- 4.8 percent) in bronchoalveolar-lavage fluid, and an absence of infection and previous atopic illness. The illness resolved rapidly after treatment with erythromycin and corticosteroids. The patients received doses of oral prednisone that were tapered over 10 days to 12 weeks, and none have relapsed since the steroids were discontinued. After a minimum follow-up period of five months, clinical evaluation, chest radiography, and pulmonary-function tests have shown no residual abnormalities attributable to the acute eosinophilic pneumonia. Follow-up bronchoalveolar lavage has demonstrated less than or equal to 1 percent eosinophils in all patients. We believe that we are describing an acute form of eosinophilic lung disease distinct from previously described syndromes. It can be diagnosed by bronchoalveolar lavage and seems to respond to treatment with corticosteroids.

PMID 2761601
望月吉郎ほか:日呼吸会誌40:851, 2002.
日本医真菌学会 アスペルギルス症の診断・治療ガイドライン 2015.
N E Vlahakis, T R Aksamit
Diagnosis and treatment of allergic bronchopulmonary aspergillosis.
Mayo Clin Proc. 2001 Sep;76(9):930-8. doi: 10.4065/76.9.930.
Abstract/Text Allergic bronchopulmonary aspergillosis (ABPA) is an underdiagnosed pulmonary disorder in asthmatic patients and patients with cystic fibrosis. Its clinical and diagnostic manifestations arise from an allergic response to multiple antigens expressed by fungi, most commonly Aspergillus fumigatus, colonizing the bronchial mucus. The clinical course is one of recurrent exacerbations characterized by chest infiltrates evident on chest x-ray films and associated with cough, wheeze, and sputum production that usually respond to oral corticosteroid treatment. Specific immunologic and radiologic markers of disease include elevation of the total serum IgE levels, presence of aspergillus IgE antibodies, and the occurrence of central bronchiectasis. Long-term treatment with corticosteroids is often required for effective management. The adverse effects of chronic corticosteroid use have led to attempts at treatment with antifungal agents such as itraconazole. Itraconazole has been reported anecdotally to be effective, and evidence for its effectiveness in randomized trials is still accruing. Consideration should be given to its use as a corticosteroid-sparing agent or for treatment of patients in whom corticosteroid response is poor. The natural history and prognosis of ABPA are not well characterized but may be complicated by progression to bronchiectasis and pulmonary fibrosis. If ABPA is diagnosed and treated before the development of bronchiectasis and fibrosis, these complications may be prevented.

PMID 11560305
I Tillie-Leblond, A-B Tonnel
Allergic bronchopulmonary aspergillosis.
Allergy. 2005 Aug;60(8):1004-13. doi: 10.1111/j.1398-9995.2005.00887.x.
Abstract/Text Allergic bronchopulmonary aspergillosis (ABPA) occurs in nonimmunocompromised patients and belongs to the hypersensitivity disorders induced by Aspergillus. Genetic factors and activation of bronchial epithelial cells in asthma or cystic fibrosis are responsible for the development of a CD(4)+Th2 lymphocyte activation and IgE, IgG and IgA-AF antibodies production. The diagnosis of ABPA is based on the presence of a combination of clinical, biological and radiological criteria. The severity of the disease is related to corticosteroid-dependant asthma or/and diffuse bronchiectasis with fibrosis. The treatment is based on oral corticosteroids for 6-8 weeks at acute phase or exacerbation and itraconazole is now recommended and validated at a dose of 200 mg/day for a duration of 16 weeks.

PMID 15969680
Yasushi Hiramatsu, Yoshinobu Maeda, Nobuharu Fujii, Takashi Saito, Yuichiro Nawa, Masamichi Hara, Tomofumi Yano, Shoji Asakura, Kazutaka Sunami, Takayuki Tabayashi, Akira Miyata, Ken-ichi Matsuoka, Katsuji Shinagawa, Kazuma Ikeda, Keitaro Matsuo, Mitsune Tanimoto, West-Japan Hematology and Oncology Group
Use of micafungin versus fluconazole for antifungal prophylaxis in neutropenic patients receiving hematopoietic stem cell transplantation.
Int J Hematol. 2008 Dec;88(5):588-95. doi: 10.1007/s12185-008-0196-y. Epub 2008 Nov 29.
Abstract/Text A prospective randomized clinical trial assessed the efficacy and tolerance of micafungin compared with that of standard fluconazole treatment in patients undergoing hematopoietic stem cell transplantation (HSCT). Adult patients (n = 106) were randomly assigned to receive prophylaxis with either micafungin 150 mg (n = 52), or fluconazole 400 mg (n = 52). Success was defined as the absence of suspected, proven, or probable invasive fungal infection (IFI) through the end of therapy and the absence of proven or probable IFI through the end of the 4-week period following treatment. The overall efficacy of micafungin was comparable to that of fluconazole (94 vs. 88%; difference 6.0%; 95% confidence interval, -5.4 to +17.4%; P = 0.295). A total of 2 (4.0%) of 50 patients in the micafungin arm and 6 (12.0%) of 50 patients in the fluconazole arm received empirical antifungal therapy (P = 0.06). Micafungin treatment did not result in increasing adverse effects and had a safe profile as fluconazole in neutropenic patients. This randomized trial indicates that the efficacy and tolerance of micafungin 150 mg was comparable to that of fluconazole 400 mg, suggesting that micafungin at 150 mg daily represents a valuable new treatment option for antifungal prophylaxis in HSCT recipients.

PMID 19039629
John R Wingard, Shelly L Carter, Thomas J Walsh, Joanne Kurtzberg, Trudy N Small, Lindsey R Baden, Iris D Gersten, Adam M Mendizabal, Helen L Leather, Dennis L Confer, Richard T Maziarz, Edward A Stadtmauer, Javier Bolaños-Meade, Janice Brown, John F Dipersio, Michael Boeckh, Kieren A Marr, Blood and Marrow Transplant Clinical Trials Network
Randomized, double-blind trial of fluconazole versus voriconazole for prevention of invasive fungal infection after allogeneic hematopoietic cell transplantation.
Blood. 2010 Dec 9;116(24):5111-8. doi: 10.1182/blood-2010-02-268151. Epub 2010 Sep 8.
Abstract/Text Invasive fungal infection (IFI) is a serious threat after allogeneic hematopoietic cell transplant (HCT). This multicenter, randomized, double-blind trial compared fluconazole (N = 295) versus voriconazole (N = 305) for the prevention of IFI in the context of a structured fungal screening program. Patients undergoing myeloablative allogeneic HCT were randomized before HCT to receive study drugs for 100 days, or for 180 days in higher-risk patients. Serum galactomannan was assayed twice weekly for 60 days, then at least weekly until day 100. Positive galactomannan or suggestive signs triggered mandatory evaluation for IFI. The primary endpoint was freedom from IFI or death (fungal-free survival; FFS) at 180 days. Despite trends to fewer IFIs (7.3% vs 11.2%; P = .12), Aspergillus infections (9 vs 17; P = .09), and less frequent empiric antifungal therapy (24.1% vs 30.2%, P = .11) with voriconazole, FFS rates (75% vs 78%; P = .49) at 180 days were similar with fluconazole and voriconazole, respectively. Relapse-free and overall survival and the incidence of severe adverse events were also similar. This study demonstrates that in the context of intensive monitoring and structured empiric antifungal therapy, 6-month FFS and overall survival did not differ in allogeneic HCT recipients given prophylactic fluconazole or voriconazole. This trial was registered at www.clinicaltrials.gov as NCT00075803.

PMID 20826719
D A Stevens, H J Schwartz, J Y Lee, B L Moskovitz, D C Jerome, A Catanzaro, D M Bamberger, A J Weinmann, C U Tuazon, M A Judson, T A Platts-Mills, A C DeGraff
A randomized trial of itraconazole in allergic bronchopulmonary aspergillosis.
N Engl J Med. 2000 Mar 16;342(11):756-62. doi: 10.1056/NEJM200003163421102.
Abstract/Text BACKGROUND: Allergic bronchopulmonary aspergillosis is a hypersensitivity disorder that can progress from an acute phase to chronic disease. The main treatment is systemic corticosteroids, but data from uncontrolled studies suggest that itraconazole, an orally administered antifungal agent, may be an effective adjunctive therapy.
METHODS: We conducted a randomized, double-blind trial of treatment with either 200 mg of itraconazole twice daily or placebo for 16 weeks in patients who met immunologic and pulmonary-function criteria for corticosteroid-dependent allergic bronchopulmonary aspergillosis. A response was defined as a reduction of at least 50 percent in the corticosteroid dose, a decrease of at least 25 percent in the serum IgE concentration, and one of the following: an improvement of at least 25 percent in exercise tolerance or pulmonary-function tests or resolution or absence of pulmonary infiltrates. In a second, open-label part of the trial, all the patients received 200 mg of itraconazole per day for 16 weeks.
RESULTS: There were responses in 13 of 28 patients in the itraconazole group (46 percent), as compared with 5 of 27 patients in the placebo group (19 percent, P=0.04). The rate of adverse events was similar in the two groups. In the subsequent open-label phase, 12 of the 33 patients who had not had a response during the double-blind phase (36 percent) had responses, and none of the patients who had a response in the double-blind phase of the trial had a relapse.
CONCLUSIONS: For patients with corticosteroid-dependent allergic bronchopulmonary aspergillosis, the addition of itraconazole can lead to improvement in the condition without added toxicity.

PMID 10717010
Peter Alexander Blanch Wark, Michael John Hensley, Nicholas Saltos, Michael James Boyle, Ruth Christine Toneguzzi, Grad Dip Clin Epid, Jodie Louise Simpson, Patrick McElduff, Peter Gerard Gibson
Anti-inflammatory effect of itraconazole in stable allergic bronchopulmonary aspergillosis: a randomized controlled trial.
J Allergy Clin Immunol. 2003 May;111(5):952-7.
Abstract/Text BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) complicates chronic asthma and results from hypersensitivity to the fungus Aspergillus fumigatu s, causing an intense systemic immune response and progressive lung damage.
OBJECTIVE: We sought to determine whether treatment with the antifungal agent itraconazole reduced eosinophilic airway inflammation in subjects with ABPA.
METHODS: A randomized, double-blind, placebo-controlled trial was performed in stable subjects with ABPA (n = 29). Subjects received 400 mg of itraconazole per day (n = 15) or placebo (n = 14) for 16 weeks. All subjects were reviewed monthly with history, spirometry, and sputum induction to measure airway inflammation, serum total IgE and IgG levels to A fumigatu s, and blood eosinophil counts.
RESULTS: By using regression analysis in a random-effects model, subjects receiving itraconazole had a decrease in sputum eosinophils of 35% per week, with no decrease seen in the placebo arm (P <.01). Sputum eosinophil cationic protein levels decreased with itraconazole treatment by 42% per week compared with 23% in the placebo group (P <.01). Itraconazole reduced systemic immune activation, leading to a decrease in serum IgE levels (310 IU/mL) compared with levels seen in the placebo group (increase of 18 IU/mL, P <.01) and a decrease in IgG levels to A fumigatu s (15.4 IU/mL) compared with levels seen in the placebo group (increase of 3.7 IU/mL, P =.03). There were fewer exacerbations requiring oral cortico-steroids in those treated with itraconazole compared with in the placebo group (P =.03).
CONCLUSION: Itraconazole treatment of subjects with stable ABPA reduces eosinophilic airway inflammation, systemic immune activation, and exacerbations. These results imply that itraconazole is a potential adjunctive treatment for ABPA.

PMID 12743557
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、渡邉裕次、井ノ口岳洋、梅田将光および日本医科大学多摩永山病院 副薬剤部長 林太祐による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、 著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※同効薬・小児・妊娠および授乳中の注意事項等は、海外の情報も掲載しており、日本の医療事情に適応しない場合があります。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適応の査定において保険適応及び保険適応外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適応の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
相良博典 : 特に申告事項無し[2024年]
監修:長瀬隆英 : 特に申告事項無し[2025年]

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