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Azoles for allergic bronchopulmonary aspergillosis associated with asthma

  • Review
  • Intervention




Allergic bronchopulmonary aspergillosis is hypersensitivity to the fungus Aspergillus fumigatus that complicates patients with asthma and cystic fibrosis. The mainstay of treatment for allergic bronchopulmonary aspergillosis remains oral corticosteroids, though this does not completely prevent exacerbations and may not prevent the decline in lung function.


The purpose of this review was to determine the efficacy of azoles in the treatment of allergic bronchopulmonary aspergillosis.

Search methods

We searched the Cochrane Airways Group Asthma trials register, CENTRAL, MEDLINE and EMBASE. Searches are current as of May 2008.

Selection criteria

All controlled trials that assessed the effect of azole antifungal agents compared to placebo or other standard therapy for allergic bronchopulmonary aspergillosis were reviewed. Patients with cystic fibrosis were not included.

Data collection and analysis

Two reviewers independently assessed trial quality and extracted data. Study authors were contacted for additional information. Adverse effects information was collected from the trials.

Main results

Twelve trials were identified, but only three were prospective, randomised and controlled. A total of 94 participants were included. One demonstrated a reduction in immunological markers of disease activity and symptom scores using ketoconazole 400 mg daily for 12 months. There was no significant improvement in lung function. The other two examined the use of itraconazole for 16 weeks. In one there was a reduction in sputum eosinophils by 35% compared to 19% with placebo (p < 0.01). In the same trial, the number of exacerbations requiring oral corticosteroids was 0.4 per patient with itraconazole compared with 1.3 per patient with placebo (p < 0.03). Meta-analysis of data from both trials showed that itraconazole treated patients were more likely to have decline in serum IgE over 25% or more (Peto OR 3.30; 95% confidence intervals 1.30 to 8.15).

Authors' conclusions

Itraconazole modifies the immunologic activation associated with allergic bronchopulmonary aspergillosis and improves clinical outcome, at least over the period of 16 weeks. Adrenal suppression with inhaled corticosteroids and itraconazole is a potential concern.








Cochrane Airways Group Asthma trials register、CENTRAL、MEDLINEおよびEMBASEを検索した。2008年5月現在、検索中である。






試験12件を同定したが、前向きランダム化比較試験は3件のみであった。参加者計94名が選択さらた。試験1件から、400mgケトコナゾールを12ヶ月間連日投与した結果、疾患活動性の免疫学的マーカーおよび症状スコアの低下が認められた。肺機能に有意な改善はみられなかった。その他の試験2件では、16週間のイトラコナゾールの使用について評価されていた。うち1件では、痰中好酸球がプラセボで19%低下していたのに対してイトラコナゾールでは35%低下した(p<0.01)。同試験で、経口ステロイド薬を必要とする悪化の回数は、イトラコナゾール治療患者では一人あたり0.4回であったのに対し、プラセボ治療患者では1.3回であった(p<0.03)。両試験で得られたデータのメタアナリシスから、イトラコナゾール治療患者の方が、血清中IgE値が25%以上低下する可能性が高いことが明らかにされた(Peto OR 3.30;95%信頼区間(CI)1.30~8.15)。




監  訳: 林 啓一,2009.2.20

実施組織: 厚生労働省委託事業によりMindsが実施した。

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Plain language summary

Antifungal drugs (azoles) for allergic bronchopulmonary aspergillosis associated with asthma

Allergic bronchopulmonary aspergillosis is a condition that complicates some people with chronic asthma. Standard treatment for this condition is high doses of oral steroids. The azole antifungal drugs attack the fungus that causes this condition and short term studies suggest that they may have some benefit when added to standard therapy.

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