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Corticosteroid treatment is associated with increased filamentous fungal burden in allergic fungal disease - 04/08/18

Doi : 10.1016/j.jaci.2017.09.039 
Marcin G. Fraczek, PhD a, b, d, Livingstone Chishimba, PhD b, , Rob M. Niven, MD b, Mike Bromley, PhD a, Angela Simpson, MD, PhD b, Lucy Smyth, PhD e, David W. Denning, FRCP a, b, c, Paul Bowyer, PhD a, b,
a Manchester Fungal Infection Group, Division of Infection Immunity and Respiratory Medicine, School of Biological Sciences, University of Manchester, Manchester, United Kingdom 
b Manchester Academic Health Science Centre, Manchester University NHS Foundation Trust (Wythenshawe), Manchester, United Kingdom 
c National Aspergillosis Centre, Manchester University NHS Foundation Trust (Wythenshawe), Manchester, United Kingdom 
d School of Biological Sciences, Manchester Institute of Biotechnology, University of Manchester, Manchester, United Kingdom 
e School of Environment and Life Sciences, University of Salford, Salford, United Kingdom 

Corresponding author: Paul Bowyer, PhD, The University of Manchester, Manchester Fungal Infection Group, Institute of Inflammation and Repair, Core Technology Facility, Manchester, UK.The University of ManchesterManchester Fungal Infection GroupInstitute of Inflammation and RepairCore Technology FacilityManchesterUK

Abstract

Background

Allergic diseases caused by fungi are common. The best understood conditions are allergic bronchopulmonary aspergillosis and severe asthma with fungal sensitization. Our knowledge of the fungal microbiome (mycobiome) is limited to a few studies involving healthy individuals, asthmatics, and smokers. No study has yet examined the mycobiome in fungal lung disease.

Objectives

The main aim of this study was to determine the mycobiome in lungs of individuals with well-characterized fungal disease. A secondary objective was to determine possible effects of treatment on the mycobiome.

Methods

After bronchoscopy, ribosomal internal transcribed spacer region 1 DNA was amplified and sequenced and fungal load determined by real-time PCR. Clinical and treatment variables were correlated with the main species identified. Bronchopulmonary aspergillosis (n = 16), severe asthma with fungal sensitization (n = 16), severe asthma not sensitized to fungi (n = 9), mild asthma patients (n = 7), and 10 healthy control subjects were studied.

Results

The mycobiome was highly varied with severe asthmatics carrying higher loads of fungus. Healthy individuals had low fungal loads, mostly poorly characterized Malasezziales. The most common fungus in asthmatics was Aspergillus fumigatus complex and this taxon accounted for the increased burden of fungus in the high-level samples. Corticosteroid treatment was significantly associated with increased fungal load (P < .01).

Conclusions

The mycobiome is highly variable. Highest loads of fungus are observed in severe asthmatics and the most common fungus is Aspergillus fumigatus complex. Individuals receiving steroid therapy had significantly higher levels of Aspergillus and total fungus in their bronchoalveolar lavage.

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Key words : Lung mycobiome, Aspergillus, steroid, antifungal, allergic bronchopulmonary aspergillosis, asthma

Abbreviations used : ABPA, BAL, ICS, ITS, OCS, RT-PCR, SA, SAFS


Plan


 M.B. and P.B. receive support from Medical Research Council (MRC) grant MR/M02010X/1. M.F., M.B., and P.B. were funded by EU Framework 7 (FP7-2007-2013) under grant agreement HEALTH-F2-2010-260338 “ALLFUN.”
 Disclosure of potential conflict of interest: L. Chishimba has received grants from the University of Manchester, National Aspergillosis Centre, and Novartis; has received travel support from AstraZeneca and GlaxoSmithKline; and has received payment for lectures from Novartis and AstraZeneca. R. M. Niven has consultant arrangements with AstraZeneca, Boehringer, Boston, Chiesi, Novartis, Roche, TEVA Pharmaceutical Industries, and Vectura; has received payment for lectures from AstraZeneca, Boehringer, Boston, Chiesi, GlaxoSmithKline, Napp, Novartis, Roche, and TEVA; and has received travel support from Boehringer, Chiesi, Napp, Novartis, and TEVA. M. Bromley has a board membership with Syngenics Limited; has consultant arrangements with Synergy Health PLC (also known as Genon Laboratories Limited); is employed by the University of Manchester and Lariat Consulting LLP; and has received grants from the Biotechnology and Biological Sciences Research Council, Wellcome Trust, the Medical Research Council, the European Union, Innovate UK, DuPont, Hans Knoll Institute, and F2G Limited. L. Smyth is employed by University of Salford and has received a grant from Kidscan. D. W. Denning has received grants from Pfizer, Gilead, Merck Sharp Dohme, and Astellas; has received personal fees from Pfizer, Gilead, Merck Sharp Dohme, Basilea, Pulmocide, Dynamiker, Cidara, Syncexis, Astellas, Biosergen, Quintilles, Pulmatrix, and Pulmocide; and has a patent for assays for fungal infection. P. Bowyer has received a grant from the Medical Research Council (MR/M02010X/1) and has received payment for lectures from Gilead Ltd. The rest of the authors declare that they have no relevant conflicts of interest.


© 2017  Publié par Elsevier Masson SAS.
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Vol 142 - N° 2

P. 407-414 - août 2018 Retour au numéro
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