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Antifungal therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis

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Abstract

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Background

Allergic bronchopulmonary aspergillosis (ABPA) is an allergic reaction to colonisation of the lungs with the fungus Aspergillus fumigatus and affects around 10% of people with cystic fibrosis. ABPA is associated with an accelerated decline in lung function. High doses of corticosteroids are the main treatment for ABPA; although the long‐term benefits are not clear, their many side effects are well‐documented. A group of compounds, the azoles, have activity against Aspergillus fumigatus and have been proposed as an alternative treatment for ABPA. Of this group, itraconazole is the most active. A separate antifungal compound, amphotericin B, has been employed in aerosolised form to treat invasive infection with Aspergillus fumigatus, and may have potential for the treatment of ABPA. Antifungal therapy for ABPA in cystic fibrosis needs to be evaluated.

Objectives

The review aimed to test the hypotheses that antifungal interventions for the treatment of ABPA in cystic fibrosis:
1. improve clinical status compared to placebo or standard therapy (no placebo);
2. do not have unacceptable adverse effects.

If benefit was demonstrated, we aimed to assess the optimal type, duration and dose of antifungal therapy.

Search methods

We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings.

In addition, pharmaceutical companies were approached.

Date of the most recent search of the Group's Trials Register: 17 March 2014.

Selection criteria

Published or unpublished randomised controlled trials, where antifungal treatments have been compared to either placebo or no treatment, or where different doses of the same treatment have been used in the treatment of ABPA in people with cystic fibrosis.

Data collection and analysis

Four trials were identified by the searches; none of which was judged eligible for inclusion in the review.

Main results

No completed randomised controlled trials were included.

Authors' conclusions

At present, there are no randomised controlled trials to evaluate the use of antifungal therapies for the treatment of ABPA in people with cystic fibrosis, although trials in people who do not have cystic fibrosis have shown clinical and serological evidence of improvement and a reduction in the use of corticosteroids with no increase in adverse effects. Trials with clear outcome measures are needed to properly evaluate this potentially useful treatment for cystic fibrosis.

PICOs

Population
Intervention
Comparison
Outcome

The PICO model is widely used and taught in evidence-based health care as a strategy for formulating questions and search strategies and for characterizing clinical studies or meta-analyses. PICO stands for four different potential components of a clinical question: Patient, Population or Problem; Intervention; Comparison; Outcome.

See more on using PICO in the Cochrane Handbook.

Plain language summary

Treatments to fight fungal infections which cause allergic bronchopulmonary aspergillosis in people with cystic fibrosis

Review question

We planned to review evidence about the effect of treatments to fight fungal infections which cause allergic bronchopulmonary aspergillosis in people with cystic fibrosis.

Background

Allergic bronchopulmonary aspergillosis (ABPA) is an allergic lung reaction to a type of fungus (usually Aspergillus fumigatus) in some people with cystic fibrosis. It causes cough and wheezing and sometimes fever. If left untreated ABPA can lead to chronic lung damage. It is usually treated with a high dose of corticosteroids (also known as steroids). However, it has not been proven that corticosteroids can prevent lung function deteriorating in the long term. Also, long‐term use of steroids is linked to some serious side effects. Treating the fungus which causes ABPA may be an alternative to using high doses of steroids to combat the allergic reaction.

Search date

The evidence is current to: March 2014.

Study characteristics

No trials were found which we could include in the review.

Key results

There are some trials in people who don't have cystic fibrosis which have shown that if treatment is given to reduce the fungus, the steroid dose can be reduced with no adverse effects. However, in one cystic fibrosis centre, researchers observed that when people were given an anti‐fungal treatment in addition to steroids, several of them became unable to produce enough cortisol (a hormone) in their adrenal glands in response to stress. There is not enough evidence for us to recommend the use of antifungal treatment in people with cystic fibrosis and ABPA. There should be a trial of these drugs to assess their effects in the long and the short term.