Antifungal therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis

Antifungal therapies for allergic bronchopulmonary
aspergillosis in people with cystic fibrosis (Review)
Elphick H, Southern K
This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library2007, Issue 2 Antifungal therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis (Review)
Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
T A B L E O F C O N T E N T S
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
CRITERIA FOR CONSIDERING STUDIES FOR THIS REVIEW SEARCH METHODS FOR IDENTIFICATION OF STUDIES . . . . . . . . . . . . . . . . . . .
METHODS OF THE REVIEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
METHODOLOGICAL QUALITY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
NOTES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
POTENTIAL CONFLICT OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Antifungal therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis (Review)
Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
Antifungal therapies for allergic bronchopulmonary
aspergillosis in people with cystic fibrosis (Review)
Elphick H, Southern K
This record should be cited as:
Elphick H, Southern K. Antifungal therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. Cochrane
Database of Systematic Reviews 2000, Issue 4. Art. No.: CD002204. DOI: 10.1002/14651858.CD002204.
This version first published online: 23 October 2000 in Issue 4, 2000.
Date of most recent substantive amendment: 18 August 2000
A B S T R A C T
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 strategy
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: May 2006.
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
No completed randomised controlled trials were identified.
Main results
No completed randomised controlled trials were identified.
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. Trials with clear outcome measures are needed to properly evaluate this potentially useful treatment for cystic fibrosis.
Antifungal therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis (Review)
Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
P L A I N L A N G U A G E S U M M A R Y
Allergic bronchopulmonary aspergillosis (ABPA) contributes to progressive damage of the airways in about 10% of people with cysticfibrosis Standard therapy for ABPA is high dose corticosteroids, although these drugs have not been shown to prevent long-term deteriorationin lung function and chronic use is associated with serious side effects. An alternative treatment strategy for ABPA is reducing thefungus Aspergillus fumigatus using antifungal agents, which may reduce the need for high doses of steroids. This review aimed to identifyrandomised controlled trials (RCTs) evaluating the use of antifungal therapies for treatment of ABPA in cystic fibrosis. No completedtrials were identified. RCTs with clear outcome measures are needed to properly evaluate this potentially useful treatment for cysticfibrosis.
B A C K G R O U N D
An alternative strategy in the treatment of ABPA is to reduce orclear the lung of A. fumigatus colonisation by employing anti-fun-gal agents. A group of compounds, azoles, that can be taken orally, Cystic fibrosis (CF) is the most common life-limiting autosomal have activity against A. fumigatus. Of this group, itraconazole is recessive disorder affecting Caucasians (CF Foundation 2000).
the most active (Denning 1992). A separate compound with good Chronic, progressive lung disease is the major cause of morbidity activity against A. fumigatus is amphotericin B. However, this is and shortened survival. This lung disease is characterised by a not absorbed orally, and when given intravenously is frequently cycle of bacterial infection and lung damage (Hutchinson 1999).
associated with toxicity (Meunier 1991). Amphotericin has been With increasing age, Pseudomonas aeruginosa is the major cause of employed in a nebulised form to treat invasive infection with A. chronic infection. However, a proportion of people with CF are fumigatus but remains very expensive (Purcell 1995).
also affected by allergic bronchopulmonary aspergillosis (ABPA).
This is an allergic reaction to colonisation of the lungs with the Data from uncontrolled trials suggest itraconazole may be an ef- fungus Aspergillus fumigatus (A. fumigatus). ABPA is associated fective additional therapy to steroids (Denning 1991; Nepomu- with an accelerated decline in lung function in people with CF ceno 1999). The use of itraconazole for ABPA in people without (Simmonds 1990). ABPA is diagnosed by a collection of clinical CF is evaluated in a separate Cochrane Review (Wark 2004). A and laboratory criteria, including a consistent history; pulmonary randomised, double-blind trial of the use of itraconazole in ABPA infiltrates, which show as shadows on a chest X-ray (CXR); raised in people without CF (28 treated; 27 placebo) showed that those total serum immunoglobulin E (IgE) levels; skin test reaction to A. taking itraconazole responded better than those taking a dummy fumigatus antigen; and antibodies to A. fumigatus (Geller 1999).
treatment (placebo). This was defined by a reduction of at least As these criteria are not specific and vary with the course of disease, 50% in corticosteroid dose and 25% in serum IgE level, along a diagnosis of ABPA can be difficult to make.
with evidence of clinical improvement with no increase in adverseevents (Stevens 2000). A second randomised controlled trial of The reported prevalence of ABPA in people with CF is around itraconazole in stable ABPA in people without CF showed a reduc- 10%, much higher than the non-CF population (Laufer 1984; tion in eosinophilic inflammation, serum IgE levels and exacerba- Mroueh 1994; Simmonds 1990). Many of the findings of ABPA tions, implying that itraconazole is a useful adjunctive treatment overlap with common manifestations of the lung disease in CF.
for ABPA (Wark 2003). Whilst encouraging, these data need to bereproduced in larger trials and the specific effects of itraconazole Corticosteroids, in high doses, are the main treatment for ABPA for ABPA in CF need to be evaluated. It cannot be assumed that because they are thought to treat the inflammatory and allergic therapies that have demonstrated efficacy in the non-CF popula- aspects of the condition. Whilst there is anecdotal evidence of im- tion will be equally efficacious and safe to use in people with CF.
pressive clinical and radiographic response to this therapy, there islittle support from randomised controlled trials (RCTs) (Capewell1989). There is evidence from uncontrolled trials for the use of O B J E C T I V E S
corticosteroids in ABPA in the non-CF population for acute treat-ment of exacerbations (Rosenberg 1978; Varkey 1998); and atdoses of prednisone of 7.5 mg/day they seem to inhibit the devel- The review aimed to test the hypotheses that antifungal interven- opment of infiltrates (Safirstein 1973). The long-term benefits of steroids on the course of the disease, particularly in people with (1) improve clinical status compared to placebo or standard ther- CF, are not clear and their many side effects are well-documented (2) do not have unacceptable adverse effects.
Antifungal therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis (Review)
Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
If benefit was demonstrated, we aimed to assess the optimal type, (b) reduction in peripheral eosinophil count duration and dose of antifungal therapy.
(c) reduction in total serum IgE(d) reduction in the frequency of isolation of A. fumigatus in res-piratory culture C R I T E R I A F O R C O N S I D E R I N G
S T U D I E S F O R T H I S R E V I E W
(3) Adverse events, in particular: liver function abnormalities; Types of studies
peripheral neuropathy (azoles); nephrotoxocity; and arrhythmias(amphotericin).
RCTs, published or unpublished. Quasi-randomised (e.g. alter- Outcomes were considered short-term if they were measured at the nate allocation and stratification) controlled trials (CCTs) would end of the treatment period, unless the treatment period was for have been included, if there was sufficient evidence that interven- six months or more, in which case outcomes were then considered tion and control groups were similar. Both short- and long-term long-term. Outcomes were also considered long-term if it was trials were to be included, where short-term trials include those more than three months between the end of the treatment and the that involve treatment for up to six months and long-term trials Outcome data were grouped into those measured at one, three, Types of participants
six, twelve months and annually thereafter. If the outcome data Children and adults with defined CF, diagnosed clinically and were recorded at other time periods, then consideration was given by sweat or genetic testing, including all ages and all degrees of severity, who also have ABPA diagnosed by clearly defined clinicaland laboratory criteria.
S E A R C H M E T H O D S F O R
Types of intervention
I D E N T I F I C A T I O N O F S T U D I E S
Antifungal treatments which have been compared to either placeboor no treatment, or where different doses of the same treatment See: Cochrane Cystic Fibrosis and Genetic Disorders Group have been used for treating ABPA in people with CF. Such tri- als would have been included if the only difference between thegroups was use of antifungal treatment or a comparison of differ- Relevant trials were identified from the Group’s Cystic Fibrosis Trials Register using the terms: azoles OR amphotericin ORitraconazole OR ambisone OR imidazole OR triazole OR The Cystic Fibrosis Trials Register is compiled from electronic searches of the Cochrane Central Register of Controlled Trials If any other antifungal interventions were studied, these would (Clinical Trials) (updated each new issue of The Cochrane Library), quarterly searches of MEDLINE, a search of EMBASEto 1995 and the prospective handsearching of two journals Types of outcome measures
- Pediatric Pulmonology and the Journal of Cystic Fibrosis.
Primary outcomes
Unpublished work is identified by searching the abstract books of three major cystic fibrosis conferences: the International Cystic Fibrosis Conference; the European Cystic Fibrosis Conference and the North American Cystic Fibrosis Conference. For full (b) improvement in chest X-ray (CXR) scores details of all searching activities for the register, please see the (c) improvement in spirometric lung function e.g. forced expira- relevant sections of the Cystic Fibrosis and Genetic Disorders (d) nutritional status, e.g. weight gain, body mass index (this out- In addition, principal investigators known to work in the field come measure may be complicated by the confounding influence and previous authors were contacted for unpublished or follow- (3) Time to next exacerbation or acute ABPA episode Pharmaceutical companies who manufacture antifungal agents,were also approached.
Secondary outcomes
(1) Laboratory evidence of improvement in ABPA
Date of the most recent search of the Group’s Cystic Fibrosis (a) reduction in serum IgE and IgG to A. fumigatus Antifungal therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis (Review)
Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
M E T H O D S O F T H E R E V I E W
M E T H O D O L O G I C A L Q U A L I T Y
No trials were identified for this review.
The two authors (HEE and KWS) planned to independentlyselect the trials to be included in the review. Each author wasto assess the methodological quality of each trial based on a method described by Schulz (Schulz 1995). In particular, authorswould examine details of the randomisation method, allocation No trials were identified for this review.
concealment, whether the trial was blinded, whether intention-to-treat analysis was possible from the available data and if thenumber of participants lost to follow up or subsequently excluded D I S C U S S I O N
from the trial was recorded. Each author planned to independentlyextract data using standard data acquisition forms. If disagreement Allergic bronchopulmonary aspergillosis is an important compli- arose on the suitability of a trial for inclusion in the review or on cation of CF, contributing to worsened morbidity and leading to its quality, the authors planned to reach a consensus by discussion.
progressive deterioration in lung function. Most of the findingsof ABPA overlap with common manifestations of the lung disease For continuous outcomes, the authors planned to record either the in CF, which makes the diagnosis complicated. Whilst there is mean change from baseline for each group or mean post treatment/ anecdotal evidence of response to corticosteroid therapy, there is intervention values and the standard deviation or standard error no support from RCTs in CF. The long-term benefits of steroids for each group. For binary outcome measures we plan to calculate on the course of the disease, particularly in people with CF, are a pooled estimate of the treatment effect for each outcome not clear and their many side effects are well-documented. Con- across trials, (the odds of an outcome among treatment allocated sequently, treatment with antifungal agents may be advantageous participants to the corresponding odds among controls).
over treatment with corticosteroids alone, and may lead to theability to reduce the doses of steroid therapy. Two RCTs of itra- In order to allow an intention-to-treat analysis, authors will seek conazole in ABPA in people without CF have shown a reduc- data on the number of participants by allocated treatment group, tion in corticosteroid dose and eosinophilic inflammation, along irrespective of compliance and whether or not the participant was with clinical and serological evidence of improvement with no later thought to be ineligible or otherwise excluded from treatment increase in adverse events. A number of uncontrolled trials and or follow up. The authors aimed to test for heterogeneity between case reports have also documented that the use of itraconazole in trial results using a standard chi-squared test. They planned to ABPA is advantageous. However, a recent report of suppression of perform a sensitivity analysis based on the methodological quality adrenal glucocorticoid synthesis observed a potential adverse ef- fect in 11 out of 25 people with CF treated with both itraconazole Where trials included participants with ABPA, both with and and budesonide. The likely pathogenesis is that an itraconazole without CF, the authors intended to attempt a separate analysis caused an increase in systemic budesonide concentration due to for those with CF and ABPA. Where this could not be done, the inhibited metabolism, leading to suppressed adrenocorticotrophic results would not be included in the meta-analysis, but would be hormone (ACTH) secretion (Skov 2002). The presence of adrenal described. The impact of these trials would then be assessed by insufficiency would be an important adverse effect to identify as sensitivity analysis. People with non-CF ABPA are the subject of an outcome measure in future trials.
another Cochrane Review (Wark 2004), where they will be dealt At present, there are no RCTs to evaluate the use of antifungal therapies for the treatment of ABPA in people with CF. Trialswith clear outcome measures are needed to properly evaluate this The authors planned to make an overall analysis with and without potentially useful treatment for CF.
quasi-randomised trials, to ensure that these did not bias thefinal result. The authors planned to analyse different antifungaltreatments separately, e.g. oral azoles separately from nebulised A U T H O R S ’ C O N C L U S I O N S
Implications for practice
There are no published data available to recommend the use of D E S C R I P T I O N O F S T U D I E S
antifungal therapies for ABPA in people with CF. Use of thesedrugs in people with CF remains experimental and RCTs evalu- No trials were identified for this review.
ating both efficacy and safety are needed.
Antifungal therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis (Review)
Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
Implications for research
This systematic review has identified the need for a well-designed, A search of the Group’s trials register found no new trials eligible adequately-powered, multicentre, randomised controlled trial to assess the efficacy and possible adverse effects of antifungal ther-apies for ABPA in people with CF. Outcome measures, such as -------------------------------------------- pulmonary function, should be clearly stated and multicentre tri- als should be co-ordinated so that maximum power is available A search of the Group’s trials register found no new trials eligible to achieve a clear result. Trials should look at the effects on both acute exacerbations and chronic outcome measures and therefore -------------------------------------------- cross-over trials would not be suitable. The adjuvant role of anti- fungals with corticosteroids should be investigated, including the A search of the Group’s trials register found no new trials eligible effects on reduction of corticosteroid dose and the potential for serious adverse effects, including adrenal suppression. It cannotbe assumed that therapies that have demonstrated efficacy in thenon-CF population will be equally efficacious and safe to use in P O T E N T I A L C O N F L I C T O F
people with CF and therefore these two groups should be studied I N T E R E S T
A C K N O W L E D G E M E N T S
The authors would like to thank the referees, particularly Dr P Wark P, Wilson AJ, Gibson PG. Azoles for allergic bronchopul- Wark, for their useful comments and suggestions.
monary aspergillosis (Cochrane Review). In: The Cochrane Li-brary, Issue 4, 2002. Oxford: Update Software Ltd.
--------------------------------------------- S O U R C E S O F S U P P O R T
External sources of support
A search of the Group’s Cystic Fibrosis Trials Register found no new trials eligible for inclusion in this review.
Internal sources of support
--------------------------------------------- R E F E R E N C E S
Additional references
and new agents. Diagnostic Microbiology and Infectious Disease 1992; Capewell 1989
15(1):21–34.
Capewell S, Chapman BJ, Alexander F, Greening AP, Crompton GK.
Geller 1999
Corticosteroid treatment and prognosis in pulmonary eosinophilia.
Geller DE, Kaplowitz H, Light MJ, Colin AA. Allergic bronchopul- Thorax 1989;44(11):925–9.
monary aspergillosis in cystic fibrosis: reported prevalence, regional CF Foundation 2000
distribution, and patient characteristics. Chest 1999;116(3):639–46.
Cystic Fibrosis Foundation. National Patient Registry. Annual Data Hutchinson 1999
Hutchison ML, Govan JR. Pathogenicity of microbes associated with Denning 1991
cystic fibrosis. Microbes and Infection 1999;1(12):1005–14. [Med-
Denning DW, Van Wye JE, Lewiston NJ, Stevens DA. Adjunctive therapy of allergic bronchopulmonary aspergillosis with itraconazole.
Chest 1991;100(3):819.
Lai HC, FitzSimmons SC, Allen DB, Kosorok MR, Rosenstein BJ, Denning 1992
Campbell PW, et al. Risk of persistent growth impairment after al- Denning DW, Hanson LH, Perlman AM, Stevens DA. In vitro sus- ternate-day prednisone treatment in children with cystic fibrosis. The ceptibility and synergy studies of Aspergillus species to conventional Lancet 2000;342(12):851–9.
Antifungal therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis (Review)
Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
Laufer 1984
Schulz 1995
Laufer P, Fink JN, Burns WT, Singer GF, Kalbfleisch JH, Greenberger Schulz KF, Chalmers I, Hayes RJ, Altman DG. Empirical evidence of PA. Allergic bronchopulmonary aspergillosis in cystic fibrosis. Journal bias. Dimensions of methodological quality associated with estimates of Allergy and Clinical Immunology 1984;73(1 Pt 1):44–8.
of treatment effects in controlled trials. JAMA 1995;273(5):408–12.
Simmonds 1990
Meunier 1991
Simmonds EJ, Littlewood JM, Evans EG. Cystic fibrosis and aller- Meunier F, Prentice HG, Ringden O. Liposomal amphotericin B: gic bronchopulmonary aspergillosis. Archives of Disease in Childhood safety data from a phase 2/3 clinical trial. Journal of Antimicrobial 1990;65(5):507–11.
Chemotherapy 1991;28(Suppl B):83–91.
Skov 2002
Mroueh 1994
Skov M, Main KM, Sillesen IB, Muller J, Koch C, Lanng S. Iatro- Mroueh S, Spock A. Allergic bronchopulmonary aspergillosis in pa- genic adrenal insufficiency as a side-effect of combined treatment of tients with cystic fibrosis. Chest 1994;105(1):32–6.
itraconazole and budesonide. European Respiratory Journal 2002;20
(1):127–33.
Nepomuceno 1999
Stevens 2000
Nepomuceno IB, Esrig S, Moss RB. Allergic bronchopulmonary as- Stevens DA, Schwartz HJ, Lee JY, Moskovitz BL, Jerome DC, Catan- pergillosis in cystic fibrosis: role of atopy and response to itracona- zaro A, et al. A randomised trial of itraconazole in allergic bron- zole. Chest 1999;115(2):364–70.
chopulmonary aspergillosis. New England Journal of Medicine 2000; Purcell 1995
342(11):756–62.
Purcell IF, Corris PA. Use of nebulised liposomal amphotericin B Varkey 1998
in the treatmenof Aspergillus fumigatus empyema. Thorax 1995;50
Varkey B. Allergic bronchopulmonary aspergillosis: clinical perspec- tives. Immunology and allergy clinics of North America 1998;18(3):
479–501.
Rosenberg 1978
Wark 2003
Rosenberg M, Patterson R, Roberts M, Wang J. The assessment of Wark PA, Hensley MJ, Saltos N, Boyle MJ, Toneguzzi RC, Epid GD, immunologic and clinical changes occuring during corticosteroid et al. Anti-inflammatory effect of itraconazole in stable allergic bron- therapy for allergic bronchopulmonary aspergillosis. American Jour- chopulmonary aspergillosis: A randomised controlled trial. Journal nal of Medicine 1978;64(4):599–606.
of Allergy and Clinical Immunology 2003;111(5):952–7.
Safirstein 1973
Wark 2004
Safirstein BH, D’Souza MF, Simon G, Tai E, Pepys J. Five year follow- Wark P, Wilson AJ, Gibson PG. Azoles for allergic bronchopul- up of allergic bronchopulmonary aspergillosis. American Review of monary aspergillosis (Cochrane Review). In: The Cochrane Library, Respiratory Disease 1973;108(4):450–9.
2, 2004. Oxford, UK: Update Software, Ltd.
G R A P H S A N D O T H E R T A B L E S
I N D E X T E R M S
Medical Subject Headings (MeSH)
Antifungal Agents [∗therapeutic use]; Aspergillosis, Allergic Bronchopulmonary [∗drug therapy]; Cystic Fibrosis [∗complications];Randomized Controlled Trials MeSH check words
C O V E R S H E E T
Antifungal therapies for allergic bronchopulmonary aspergillosis in people with cystic fi-brosis Contribution of author(s)
Dr Southern conceived the review and contributed towards the writing of the protocol andreview.
Antifungal therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis (Review)
Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
Dr Elphick drafted the protocol and review. Dr Elphick completed the updates of the reviewand acts as guarantor of the review.
Issue protocol first published
Review first published
Date of most recent amendment
Date of most recent
SUBSTANTIVE amendment
What’s New
Review update: August 2006A search of the Group’s Cystic Fibrosis Trials Register found no new trials eligible forinclusion in this review.
Date new studies sought but
none found
Date new studies found but not
yet included/excluded
Date new studies found and
included/excluded
Date authors’ conclusions
section amended
Contact address
Dr Heather ElphickAction LabSheffield Children’s HospitalWestern BankSheffieldS10 2THUKE-mail: [email protected]: +44 114 271 7369 Cochrane Library number
Editorial group
Cochrane Cystic Fibrosis and Genetic Disorders Group Editorial group code
Antifungal therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis (Review)
Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

Source: http://fungalsinusitisgroup.org/UserFiles/ABPACHOCRANE.pdf