Thorax 68:643-651 doi:10.1136/thoraxjnl-2012-202342
  • Cystic fibrosis
  • Original article

Prospective evaluation of respiratory exacerbations in children with cystic fibrosis from newborn screening to 5 years of age

Open Access
  1. 1Department of Paediatrics, University of Auckland, Auckland, New Zealand
  2. 2Department of Paediatric Respiratory Medicine, Starship Children's Health, Auckland, New Zealand
  3. 3Clinical Epidemiology and Biostatistics Unit, Murdoch Children's Research Institute, Melbourne, Australia
  4. 4Department of Paediatrics, University of Melbourne, Melbourne, Australia
  5. 5Queensland Children's Medical Research Institute, Royal Children's Hospital, University of Queensland, Brisbane, Australia
  6. 6Queensland Children's Respiratory Centre, Royal Children's Hospital, Brisbane, Australia
  7. 7Department of Paediatrics, Monash Medical Centre, Melbourne, Australia
  8. 8Department of Respiratory Medicine, The Children's Hospital at Westmead, Sydney, Australia
  9. 9Department of Infectious Disease, Royal Children's Hospital, Brisbane, Australia
  10. 10Deakin Health Economics, Population Health Strategic Research Centre, Deakin University, Melbourne, Australia
  11. 11Department of Respiratory Medicine, Royal Children's Hospital, Melbourne, Australia
  12. 12Center for Clinical and Translational Research, Seattle Children's Hospital, Seattle, Washington, USA
  13. 13Department of Pediatrics, University of Washington, Seattle, Washington, USA
  14. 14Department of Pediatric Pulmonology, Erasmus Medical Centre, Sophia Children's Hospital, Rotterdam, The Netherlands
  1. Correspondence to Dr Catherine Ann Byrnes, Department of Paediatrics, Faculty of Medical and Health Sciences, University of Auckland, PO Box 92019, Auckland 1301, New Zealand; c.byrnes{at}
  • Received 26 June 2012
  • Revised 16 December 2012
  • Accepted 18 December 2012
  • Published Online First 23 January 2013


Background Newborn screening allows novel treatments for cystic fibrosis (CF) to be trialled in early childhood before irreversible lung injury occurs. As respiratory exacerbations are a potential trial outcome variable, we determined their rate, duration and clinical features in preschool children with CF; and whether they were associated with growth, lung structure and function at age 5 years.

Methods Respiratory exacerbations were recorded prospectively in Australasian CF Bronchoalveolar Lavage trial subjects from enrolment after newborn screening to age 5 years, when all participants underwent clinical assessment, chest CT scans and spirometry.

Results 168 children (88 boys) experienced 2080 exacerbations, at an average rate of 3.66 exacerbations per person-year; 80.1% were community managed and 19.9% required hospital admission. There was an average increase in exacerbation rate of 9% (95% CI 4% to 14%; p<0.001) per year of age. Exacerbation rate differed by site (p<0.001) and was 26% lower (95% CI 12% to 38%) in children receiving 12 months of prophylactic antibiotics. The rate of exacerbations in the first 2 years was associated with reduced forced expiratory volume in 1 s z scores. Ever having a hospital-managed exacerbation was associated with bronchiectasis (OR 2.67, 95% CI 1.13 to 6.31) in chest CT scans, and lower weight z scores at 5 years of age (coefficient −0.39, 95% CI −0.74 to −0.05).

Conclusions Respiratory exacerbations in young children are markers for progressive CF lung disease and are potential trial outcome measures for novel treatments in this age group.

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