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Original article
Aspergillus and progression of lung disease in children with cystic fibrosis
  1. Sabariah Noor Harun1,2,
  2. Claire E Wainwright3,4,
  3. Keith Grimwood5,
  4. Stefanie Hennig2
  5. on behalf of the Australasian Cystic Fibrosis Bronchoalveolar Lavage (ACFBAL) study group
    1. 1School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia
    2. 2School of Pharmacy, University of Queensland, Brisbane, Queensland, Australia
    3. 3Respiratory and Sleep Medicine, Lady Cilento Children’s Hospital, South Brisbane, Queensland, Australia
    4. 4Child Health Research Centre, The University of Queensland, Brisbane, Queensland, Australia
    5. 5Menzies Health Institute Queensland, Griffith University and Gold Coast Health, Southport, Queensland, Australia
    1. Correspondence to Dr Sabariah Noor Harun, School of Pharmaceutical Sciences, Universiti Sains Malaysia, USM 11800, Malaysia; sabariahnoor{at}usm.my

    Abstract

    Background The impact of Aspergillus on lung disease in young children with cystic fibrosis is uncertain.

    Aims To determine if positive respiratory cultures of Aspergillus species are associated with: (1) increased structural lung injury at age 5 years; (2) accelerated lung function decline between ages 5 years and 14 years and (3) to identify explanatory variables.

    Methods A cross-sectional analysis of association between Aspergillus positive bronchoalveolar lavage (BAL) cultures and chest high-resolution CT (HRCT) scan findings at age 5 years in subjects from the Australasian Cystic Fibrosis Bronchoalveolar Lavage (ACFBAL) study was performed. A non-linear mixed-effects disease progression model was developed using FEV1% predicted measurements at age 5 years from the ACFBAL study and at ages 6–14 years for these subjects from the Australian Cystic Fibrosis Data Registry.

    Results Positive Aspergillus BAL cultures at age 5 years were significantly associated with increased HRCT scores for air trapping (OR 5.53, 95% CI 2.35 to 10.82). However, positive Aspergillus cultures were not associated with either FEV1% predicted at age 5 years or FEV1% predicted by age following adjustment for body mass index z-score and hospitalisation secondary to pulmonary exacerbations. Lung function demonstrated a non-linear decline in this population.

    Conclusion In children with cystic fibrosis, positive Aspergillus BAL cultures at age 5 years were associated contemporaneously with air trapping but not bronchiectasis. However, no association was observed between positive Aspergillus BAL cultures on FEV1% predicted at age 5 years or with lung function decline between ages 5 years and 14 years.

    • cystic fibrosis
    • paediatric lung disaese
    • respiratory infection

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    Footnotes

    • Contributors All authors meet the criteria of authorship. SNH was responsible for collecting and analysing the data and drafting the manuscript. CEW participated in concept development, supported data collection and reviewed and edited the manuscript. KG participated in concept development, reviewed and edited the manuscript. SH participated in concept development, reviewed and supported the analyses and reviewed and edited the manuscript.

    • Funding The original ACFBAL study was supported by the National Health and Medical Research Council (grants 9937868 and 351541) and the Children’s Hospital Foundation Queensland, Australia. The tobramycin inhalation solution and delivery system used throughout the ACFBAL study was supplied by Pathogenesis Corporation, Chiron Corporation and Novartis Pharmaceuticals Inc.

    • Competing interests CW reports grants from Australian National Health and Medical Research Council and non-financial support from Pathogenesis, then Chiron, and then Novartis during the conduct of the ACFBAL study, reports income on a per-patient basis derived from Pharmaceutical Studies – Vertex Pharmaceuticals Inc, Boehringer-Ingelheim and Ablynx NV. Epidemiological research support from GlaxoSmithKline – Analysis of Bronchoalveolar lavage (BAL) fluid from children with respiratory disorders; 2010–2012 Research Grant from Novo Nordisk Pharmaceuticals P/L- CF-IDEA Study; 2012–2013 Other Reimbursement: Vertex Pharmaceuticals Inc. – Consultant on the Vertex Physician Pediatric CF Advisory Board and the Vertex Innovation Awards (VIA) Grants Committee Gilead Sciences, Inc. – AZLI Advisory Board Honorarium 2010 Medscape – Consultation interview regarding CF Studies 2012 Vertex Pharmaceuticals 2013 San Francisco return flight and accommodation as Investigator in Lumacaftor study (104) Vertex Pharmaceuticals 2014 return flight and accommodation + honorarium as invited speaker at European CF Conference, Gothenburg, Sweden Vertex Pharmaceuticals (Australia) 2015 honorarium as speaker at a Vertex sponsored educational meeting series Vertex Pharmaceuticals 2015 Chicago return flight and accommodation as Investigator in Lumacaftor study (109) Vertex Pharmaceuticals (Australia) 2015 honorarium for attendance at Advisory Board meeting at Australasian CF Conference held in Sydney in August; Vertex Pharmaceuticals P/L honorarium to attend the Vertex Steering Committee Meetings re VX15-770-123 Study and to attend the Global Medical Advisory Board Meeting in March 2016. Novartis Pharmaceuticals 2013 return travel and accommodation to give a symposium at European CF Conference in Lisbon Novartis Pharmaceuticals Australia P/L 2013 honorarium to present symposium at Australasian CF Conference in Auckland Novartis Pharmaceuticals 2014 return flight and accommodation + honorarium as invited speaker at National Pediatric Congress in Lebanon Novartis Pharmaceuticals Australia P/L 2015 honorarium to present symposium at Australasian CF Conference in Sydney in August; The University of Miami honorarium for meeting attendance. Thorax honorarium for associate editor duties Q3/Q4 2015 and BMJ honorarium for consulting work in April 2016. Current Board Positions – Thoracic Society Australia and New Zealand; and International Advisory Board Vertex Pharmaceuticals P/L. (N.B. Payments for all items listed above have been made into an institutional consultancy fund account). KG reports grants from Australian National Health and Medical Research Council and non-financial support from Pathogenesis, then Chiron, and then Novartis during the conduct of the ACFBAL study.

    • Patient consent Obtained.

    • Ethics approval Ethics committees at each of the eight study sites approved the ACFBAL study, and ethics committees in Australia (HREC/12/QRCH/171/AM01) and New Zealand (13/NTB/102) approved the CF FAB study.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data sharing statement The Australasian Cystic Fibrosis Bronchoalveolar Lavage research group—listed in the authorship—potentially have access to the ACFBAL data. Any decisions regarding the use of the data or publications within the group and/or access to the data from outside the group must be discussed and agreed by a core panel designated by the ACFBAL researchers.

    • Collaborators The following investigators constitute the ACFBAL Study Investigators Group: Claire E Wainwright, Lady Cilento Children’s Hospital, Brisbane and The University of Queensland , Brisbane; Keith Grimwood, Griffith University; Joyce Cheney, Lady Cilento Children’s Hospital, Brisbane; Narelle George, Pathology Queensland; Colin F Robertson, Royal Children’s Hospital, Melbourne; Rosemary Carzino, Murdoch Children’s Research Institute, Melbourne; Marj Moodie, Deakin University, Melbourne; David S Armstrong, Monash Medical Centre, Melbourne; Peter J Cooper, The Children’s Hospital at Westmead, Sydney; A (James) Martin, Womens & Children’s Hospital,Adelaide; Bruce Whitehead, John Hunter Children’s Hospital, Newcastle; Catherine A Byrnes, Starship Children’s Hospital and University of Auckland, Auckland; Harm A Tiddens, Erasmus MC, Sophia Children’s Hospital, Rotterdam, The Netherlands; Nicholas Gailer, B Creative Industries; Katrina Jess, Lady Cilento Children’s Hospital ,Brisbane; Peta Yarrow, Lady Cilento Children’s Hospital ,Brisbane; Merilyn McArthur, The Children’s Hospital at Westmead, Sydney; Sam Forbes, The Children’s Hospital at Westmead, Sydney; Hiran Selvadurai, The Children’s Hospital at Westmead, Sydney; John Massie, Royal Children’s Hospital, Melbourne; Sarath Ranganathan, Royal Children’s Hospital, Melbourne; Phil Robinson, Royal Children’s Hospital, Melbourne; Jan Tate, Starship Children’s Hospital, Auckland; Els Van Der Wiel, Erasmus MC, Sophia Children’s Hospital, Rotterdam, the Netherlands.

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