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Early Pseudomonas aeruginosa predicts poorer pulmonary function in preschool children with cystic fibrosis

  • Author Footnotes
    1 Joint first authors.
    P. Aurora
    Footnotes
    1 Joint first authors.
    Affiliations
    Infection, Immunity, Inflammation Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, 30 Guilford Street, London WC1N 1EH, United Kingdom

    Respiratory Medicine, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom
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  • Author Footnotes
    1 Joint first authors.
    Julie Anne Duncan
    Correspondence
    Corresponding author.
    Footnotes
    1 Joint first authors.
    Affiliations
    Infection, Immunity, Inflammation Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, 30 Guilford Street, London WC1N 1EH, United Kingdom
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  • S. Lum
    Affiliations
    Infection, Immunity, Inflammation Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, 30 Guilford Street, London WC1N 1EH, United Kingdom
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  • G. Davies
    Affiliations
    Respiratory Medicine, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom

    Clinical Epidemiology, Nutrition and Biostatistics, Population, Policy and Practice Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, London, United Kingdom
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  • A. Wade
    Affiliations
    Clinical Epidemiology, Nutrition and Biostatistics, Population, Policy and Practice Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, London, United Kingdom
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  • J. Stocks
    Affiliations
    Infection, Immunity, Inflammation Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, 30 Guilford Street, London WC1N 1EH, United Kingdom
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  • L. Viviani
    Affiliations
    Infection, Immunity, Inflammation Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, 30 Guilford Street, London WC1N 1EH, United Kingdom
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  • E. Raywood
    Affiliations
    Infection, Immunity, Inflammation Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, 30 Guilford Street, London WC1N 1EH, United Kingdom
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  • C. Pao
    Affiliations
    Department of Paediatric Respiratory Medicine, Royal London Hospital, London, United Kingdom
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  • G. Ruiz
    Affiliations
    Department of Paediatric Respiratory Medicine, King's College Hospital, London, United Kingdom
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  • A. Bush
    Affiliations
    Department of Paediatric Respiratory Medicine, Royal Brompton Hospital, London, United Kingdom

    National Heart and Lung Institute, Imperial College London, London, United Kingdom
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  • On behalf of theLondon Cystic Fibrosis Collaboration (LCFC)
  • Author Footnotes
    1 Joint first authors.

      Highlights

      • Lung clearance index increases in children with CF between 2 years of age and the preschool years.
      • Growth of Pseudomonas aeruginosa in the first six months of life is the strongest clinical predictor of this deterioration in lung function.
      • We suggest more proactive monitoring and treatment of infants with early signs of CF lung disease.

      Abstract

      Background

      We previously reported relatively normal pulmonary function (2 years of age) and computed tomography (CT, 1 year of age) in cystic fibrosis (CF) newborn screened (NBS) infants. We now report follow up of these children to preschool age.

      Methods

      67 NBS children with CF and 41 healthy controls underwent pulmonary function tests in infancy (∼3 months, 1 year and 2 years) and at preschool (3–6 years). Broncho-alveolar lavage (BAL) and CT were undertaken in those with CF at 1 year. Primary outcomes at preschool were lung clearance index (LCI) and forced expired volume (FEV0.75). Risk factors for lung function impairment were identified by regression modelling, emphasising factors that could be identified or measured in the first 2 years of life.

      Results

      At preschool age children with CF had poorer lung function than controls, mean(95% CI) difference in LCI z-score: 1.47(0.96;1.97) and FEV0.75 z-score -0.54(-0.98; -0.10). Isolation of Pseudomonas aeruginosa before 6 months was a highly significant predictor of raised (abnormal) preschool LCI, associated with a mean (95%CI) increase of 1.69(0.43, 2.95) z-scores, compared to those with no Pseudomonas aeruginosa during the first 2 years of life. Including 2 year LCI and 1 year CT data in the predictive model increased the r2 from 13% to 61%.

      Conclusions

      Lung function deteriorates after 2 years in NBS children with CF. Isolation of Pseudomonas aeruginosa before 6 months and minor abnormalities of infant lung function tests and CT in infancy are associated with higher preschool LCI.

      Keywords

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