Gwyneth Davies1, Lena P Thia2, Janet Stocks3, Andrew Bush4, Ah-Fong Hoo5, Angie Wade6, The Thanh Diem Nguyen7, Alan S Brody8, Alistair Calder9, Nigel J Klein10, Siobhán B Carr4, Colin Wallis5, Ranjan Suri5, Caroline S Pao11, Gary Ruiz12, Ian M Balfour-Lynn4. 1. Respiratory, Critical Care and Anaesthesia section, UCL Great Ormond Street Institute of Child Health (GOS ICH), London, United Kingdom; Department of Respiratory Medicine, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom. Electronic address: gwyneth.davies@ucl.ac.uk. 2. Respiratory, Critical Care and Anaesthesia section, UCL Great Ormond Street Institute of Child Health (GOS ICH), London, United Kingdom; Department of Paediatric Respiratory Medicine, Cardiff University and Children's Hospital for Wales, Cardiff, United Kingdom. 3. Respiratory, Critical Care and Anaesthesia section, UCL Great Ormond Street Institute of Child Health (GOS ICH), London, United Kingdom. 4. Department of Paediatric Respiratory Medicine, Imperial College & Royal Brompton & Harefield Hospital NHS Foundation Trust, London, United Kingdom. 5. Respiratory, Critical Care and Anaesthesia section, UCL Great Ormond Street Institute of Child Health (GOS ICH), London, United Kingdom; Department of Respiratory Medicine, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom. 6. Clinical Epidemiology, Nutrition and Biostatistics Section, UCL GOS ICH, London, United Kingdom. 7. Respiratory, Critical Care and Anaesthesia section, UCL Great Ormond Street Institute of Child Health (GOS ICH), London, United Kingdom; Department of Respiratory Medicine, Centre Hospitalier Universitaire Sainte-Justine, Montreal, QC, Canada. 8. University of Cincinnati College of Medicine and Cincinnati Children's Hospital, Cincinnati, OH, United States. 9. Department of Radiology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom. 10. Infection, Inflammation and Rheumatology Section, UCL GOS ICH, London, United Kingdom. 11. Department of Paediatric Respiratory Medicine, Royal London Hospital, London, United Kingdom. 12. Department of Paediatric Respiratory Medicine, Kings College Hospital, London, United Kingdom.
Abstract
BACKGROUND: With the widespread introduction of newborn screening for cystic fibrosis (CF), there has been considerable emphasis on the need to develop objective markers of lung health that can be used during infancy. We hypothesised that in a newborn screened (NBS) UK cohort, evidence of airway inflammation and infection at one year would be associated with adverse structural and functional outcomes at the same age. METHODS: Infants underwent lung function testing, chest CT scan and bronchoscopy with bronchoalveolar lavage (BAL) at 1 year of age when clinically well. Microbiology cultures were also available from routine cough swabs. RESULTS: 65 infants had lung function, CT and BAL. Mean (SD) lung clearance index and forced expiratory volume in 0.5 s z-scores were 0.9(1.2) and -0.6(1.1) respectively; median Brody II CF-CT air trapping score on chest CT =0 (interquartile range 0-1, maximum possible score 27). Infants isolating any significant pathogen by 1 yr of age had higher LCI z-score (mean difference 0.9; 95%CI:0.4-1.4; p = 0.001) and a trend towards higher air trapping scores on CT (p = 0.06). BAL neutrophil elastase was detectable in 23% (10/43) infants in whom BAL supernatant was available. This did not relate to air trapping score on CT. CONCLUSIONS: In this UK NBS cohort at one year of age, lung and airway damage is much milder and associations between inflammation, abnormal physiology and structural changes were at best weak, contrary to our hypothesis and previously published reports. Continued follow-up will clarify longer term implications of these very mild structural, functional and inflammatory changes.
BACKGROUND: With the widespread introduction of newborn screening for cystic fibrosis (CF), there has been considerable emphasis on the need to develop objective markers of lung health that can be used during infancy. We hypothesised that in a newborn screened (NBS) UK cohort, evidence of airway inflammation and infection at one year would be associated with adverse structural and functional outcomes at the same age. METHODS: Infants underwent lung function testing, chest CT scan and bronchoscopy with bronchoalveolar lavage (BAL) at 1 year of age when clinically well. Microbiology cultures were also available from routine cough swabs. RESULTS: 65 infants had lung function, CT and BAL. Mean (SD) lung clearance index and forced expiratory volume in 0.5 s z-scores were 0.9(1.2) and -0.6(1.1) respectively; median Brody II CF-CT air trapping score on chest CT =0 (interquartile range 0-1, maximum possible score 27). Infants isolating any significant pathogen by 1 yr of age had higher LCI z-score (mean difference 0.9; 95%CI:0.4-1.4; p = 0.001) and a trend towards higher air trapping scores on CT (p = 0.06). BAL neutrophil elastase was detectable in 23% (10/43) infants in whom BAL supernatant was available. This did not relate to air trapping score on CT. CONCLUSIONS: In this UK NBS cohort at one year of age, lung and airway damage is much milder and associations between inflammation, abnormal physiology and structural changes were at best weak, contrary to our hypothesis and previously published reports. Continued follow-up will clarify longer term implications of these very mild structural, functional and inflammatory changes.
Authors: Drake C Bouzek; Mahmoud H Abou Alaiwa; Ryan J Adam; Alejandro A Pezzulo; Leah R Reznikov; Daniel P Cook; Maria I Aguilar Pescozo; Patrick Ten Eyck; Chaorong Wu; Thomas J Gross; Douglas B Hornick; Eric A Hoffman; David K Meyerholz; David A Stoltz Journal: Am J Respir Crit Care Med Date: 2021-09-15 Impact factor: 30.528