Abstract
Little is known about early predictors of later cystic fibrosis (CF) structural lung disease. This study examined early predictors of progressive structural lung abnormalities in children who completed the Australasian CF Bronchoalveolar Lavage (ACFBAL) clinical trial at age 5-years and participated in an observational follow-up study (CF-FAB).
Eight Australian and New Zealand CF centres participated in CF-FAB and provided follow-up chest computed-tomography (CT) scans for children who had completed the ACFBAL study with baseline scans at age 5-years. CT scans were annotated using PRAGMA-CF scoring. Ordinal regression analysis and linear regression were used to investigate associations between PRAGMA-CF (Perth–Rotterdam Annotated Grid Morphometric Analysis for CF) outcomes at follow-up and variables measured during the ACFBAL study.
99 out of 157 ACFBAL children (mean±sd age 13±1.5 years) participated in the CF-FAB study. The probability of bronchiectasis at follow-up increased with airway disease severity on the baseline CT scan. In multiple regression (retaining factors at p<0.05) the extent of bronchiectasis at follow-up was associated with baseline atelectasis (OR 7.2, 95% CI 2.4–22; p≤ 0.001), bronchoalveolar lavage (BAL) log2 interleukin (IL)-8 (OR 1.2, 95% CI 1.05–1.5; p=0.010) and body mass index z-score (OR 0.49, 95% CI 0.24–1.00; p=0.05) at age 5 years. Percentage trapped air at follow-up was associated with BAL log2 IL-8 (coefficient 1.3, 95% CI 0.57–2.1; p<0.001) at age 5 years.
The extent of airway disease, atelectasis, airway inflammation and poor nutritional status in early childhood are risk factors for progressive structural lung disease in adolescence.
Abstract
In children with cystic fibrosis, airways disease severity on chest computed tomography at age 5 years increased the risk of bronchiectasis in adolescence and its extent was predicted by poorer nutrition, airway inflammation, and atelectasis http://bit.ly/2Nnk8LW
Footnotes
This article has supplementary material available from erj.ersjournals.com
This article has an editorial commentary: https://doi.org/10.1183/13993003.00105-2020
The following investigators constitute the ACFBAL Study Investigators Group: Claire E. Wainwright (Queensland Children's Hospital, Brisbane and The University of Queensland, Brisbane), Keith Grimwood (Griffith University and Gold Coast Health), Joyce Cheney (Queensland Children's Hospital, Brisbane), Narelle George (Pathology Queensland), John B. Carlin (Murdoch Children's Research Institute, Melbourne), Colin F. Robertson (Royal Children's Hospital, Melbourne), Suzanna Vidmar (Murdoch Children's Research Institute, 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 (Women's & Children's Hospital, Adelaide), Bruce Whitehead (John Hunter Children's Hospital, Newcastle), Catherine A. Byrnes (Starship Children's Hospital and The University of Auckland, Auckland), Harm A.W.M. Tiddens (Erasmus MC, Sophia Children's Hospital, Rotterdam, the Netherlands).
The following investigators constitute the CF FAB Study Investigators Group: Claire E. Wainwright (Queensland Children's Hospital, Brisbane and The University of Queensland, Brisbane), Keith Grimwood (Griffith University and Gold Coast Health), Peter D. Sly (The University of Queensland, Brisbane), Harm A.W.M. Tiddens (Erasmus MC, Sophia Children's Hospital, Rotterdam, the Netherlands), Geraint Rogers (SAHMRI and Flinders University School of Medicine, Adelaide), Richard (John) Massie (Royal Children's Hospital, Melbourne), Colin F. Robertson (Royal Children's Hospital, Melbourne), Peter J. Cooper (The Children's Hospital at Westmead, Sydney), Catherine A. Byrnes (Starship Children's Hospital and The University of Auckland, Auckland), Suzanna Vidmar (Murdoch Children's Research Institute, Melbourne), A. (James) Martin (Women's & Children's Hospital, Adelaide), Bruce Whitehead (John Hunter Children's Hospital, Newcastle), David Armstrong (Monash Medical Centre, Melbourne), John B. Carlin (Murdoch Children's Research Institute, Melbourne), Peter Wark (John Hunter Children's Hospital and University of Newcastle, Newcastle).
Additional contributions: We are indebted to all current and former clinical and research staff from Queensland Children's Hospital, Brisbane: Nicholas Gailer, Natalie Smith, Careana Moss, Katrina Jess, Peta Yarrow; The Children's Hospital at Westmead, Sydney: Merilyn McArthur, Sam Forbes, Hiran Selvadurai; Royal Children's Hospital, Melbourne: Sarath Ranganathan, Phil Robinson, Natalie Zajakovski; Starship Children's Hospital, Auckland, Jan Tate, Rochelle Moss; Erasmus MC, Sophia Children's Hospital, Rotterdam, the Netherlands: Els Van Der Wiel.
Author contributions: Study conception and planning: C.E. Wainwright, S. Vidmar, K. Grimwood, P.D. Sly, C.A. Byrnes, J.B. Carlin, P.J. Cooper, C.F. Robertson, R.J. Massie, M.P.C. Kemner van de Corput, J. Cheney and H.A.W.M. Tiddens. Data collection: C.A. Byrnes, P.J. Cooper, C.F. Robertson, R.J. Massie, JC and C.E. Wainwright. Imaging analysis: N.E. Wijker, M.P.C. Kemner van de Corput and H.A.W.M. Tiddens. Data analysis: statistical analysis led by S. Vidmar with advice from JC. N.E. Wijker, C.E. Wainwright, H.A.W.M. Tiddens and K. Grimwood contributed to planning of statistical analysis. All authors were involved in data interpretation, and preparation, review and approval of the final manuscript.
Support statement: This study was supported by grants from the Australian National Health and Medical Research Council (9937868, 351541and 1044829). C.E. Wainwright was supported through Practitioner Fellowship through The Children's Hospital Foundation Brisbane (RG0692016).
Conflict of interest: N.E. Wijker reports grants from Australian National Health and Medical Research Council, during the conduct of the study.
Conflict of interest: S. Vidmar reports grants from Australian National Health and Medical Research Council, during the conduct of the study.
Conflict of interest: K. Grimwood reports grants from the Australian National Health and Medical Research Council, during the conduct of the study.
Conflict of interest: P.D. Sly reports grants from Australian National Health and Medical Research Council, during the conduct of the study.
Conflict of interest: C.A. Byrnes reports grants from Australian National Health and Medical Research Council and Faculty Research Development Fund, University of Auckland, New Zealand, during the conduct of the study.
Conflict of interest: J.B. Carlin reports grants from Australian National Health and Medical Research Council, during the conduct of the study.
Conflict of interest: P.J. Cooper reports grants from Australian National Health and Medical Research Council, during the conduct of the study.
Conflict of interest: C.F. Robertson reports grants from Australian National Health and Medical Research Council, during the conduct of the study.
Conflict of interest: R.J. Massie reports grants from Australian National Health and Medical Research Council, during the conduct of the study.
Conflict of interest: M.P.C. Kemner van de Corput reports grants from Australian National Health and Medical Research Council, during the conduct of the study.
Conflict of interest: J. Cheney reports grants from Australian National Health and Medical Research Council, during the conduct of the study.
Conflict of interest: H.A.W.M. Tiddens reports grants from Australian National Health and Medical Research Council, during the conduct of the study; has provided lectures to Roche and Novartis; grants from CFF, Vertex, Chiesi and Vectura; fees for lectures and advisory board work from Gilead, outside the submitted work; in addition, has a patent PRAGMA-CF scoring system with royalties paid and is heading the Erasmus MC-Sophia Children's Hospital core laboratory lung analysis. FLUIDDA has developed computational fluid dynamic modelling based on chest CTs obtained from Erasmus MC-Sophia for which royalties are received by Sophia Research BV.
Conflict of interest: C.E. Wainwright reports grants from Australian National Health and Medical Research Council, during the conduct of the study; and research grants from Vertex Pharmaceuticals Inc., Boehringer Ingelheim and Novo Nordisk Pharmaceuticals; fees for lectures and to attend meetings from Vertex Pharmaceuticals, DKBMed, Novartis Pharmaceuticals, University of Miami, Gilead Sciences Ltd and In Vivo Academy Limited; fees for consultancy, steering committee and advisory board work from Vertex Pharmaceuticals; fees for editorial board work from Thorax; fees for reviewing from BMJ and DKBMed; fees for transport and accommodation from Vertex Pharmaceuticals; and currently holds board positions on the International Advisory Board Vertex Pharmaceuticals P/L, and Associate Editor, Thorax and Respirology.
- Received August 26, 2019.
- Accepted December 30, 2019.
- Copyright ©ERS 2020
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