Evolution of lung function during the first year of life in newborn screened cystic fibrosis infants.
BACKGROUND
Newborn screening (NBS) for cystic fibrosis (CF) allows early intervention. Design of randomised controlled trials (RCT) is currently impeded by uncertainty regarding evolution of lung function, an important trial end point in such infants.


OBJECTIVE
To assess changes in pulmonary function during the first year of life in CF NBS infants.


METHODS
Observational longitudinal study. CF NBS infants and healthy controls were recruited between 2009 and 2011. Lung Clearance Index (LCI), plethysmographic lung volume (plethysmographic functional residual capacity (FRCpleth)) and forced expired volume (FEV₀.₅) were measured at 3 months and 1 year of age.


RESULTS
Paired measurements were obtained from 72 CF infants and 44 controls. At 3 months, CF infants had significantly worse lung function for all tests. FEV₀.₅ improved significantly (0.59 (95% CI 0.18 to 0.99) z-scores; p<0.01) in CF infants between 3 months and 1 year, and by 1 year, FEV₀.₅ was only 0.52 (0.89 to 0.15) z-scores less than in controls. LCI and FRCpleth remained stable throughout the first year of life, being on average 0.8 z-scores higher in infants with CF. Pulmonary function at 1 year was predicted by that at 3 months. Among the 45 CF infants with entirely normal LCI and FEV₀.₅ at 3 months, 80% remained so at 1 year, while 74% of those with early abnormalities remained abnormal at 1 year.


CONCLUSIONS
This is the first study reporting improvements in FEV₀.₅ over time in stable NBS CF infants treated with standard therapy. Milder changes in lung function occurred by 1 year than previously reported. Lung function at 3 months predicts a high-risk group, who should be considered for intensification of treatment and enrolment into RCTs.
Portex Unit: Respiratory Physiology and Medicine, UCL Institute of Child Health, London, UK Department of Respiratory Medicine, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada.
The Thanh-Diem
TT
Nguyen
Portex Unit: Respiratory Physiology and Medicine, UCL Institute of Child Health, London, UK.
Lena P
LP
Thia
Portex Unit: Respiratory Physiology and Medicine, UCL Institute of Child Health, London, UK Respiratory Unit, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
Ah-Fong
AF
Hoo
Department of Paediatric Respiratory Medicine, Imperial College & Royal Brompton & Harefield Hospital NHS Foundation Trust, London, UK.
Andrew
A
Bush
Portex Unit: Respiratory Physiology and Medicine, UCL Institute of Child Health, London, UK Respiratory Unit, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
Paul
P
Aurora
Centre for Paediatric Epidemiology and Biostatistics, UCL Institute of Child Health, MRC Centre for Epidemiology of Child Health, London, UK.
Angie
A
Wade
Portex Unit: Respiratory Physiology and Medicine, UCL Institute of Child Health, London, UK Respiratory Unit, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
Jane
J
Chudleigh
Portex Unit: Respiratory Physiology and Medicine, UCL Institute of Child Health, London, UK.
Sooky
S
Lum
Portex Unit: Respiratory Physiology and Medicine, UCL Institute of Child Health, London, UK.
Janet
J
Stocks
D003550:Cystic Fibrosis / Q000175:diagnosis / Q000453:epidemiology / Q000503:physiopathology*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005865:Gestational Age; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008176:Lung Volume Measurements; D008297:Male; D008450:Maximal Midexpiratory Flow Rate / Q000502:physiology*; D015997:Neonatal Screening / Q000379:methods*; D011237:Predictive Value of Tests; D015995:Prevalence; D012129:Respiratory Function Tests; D012189:Retrospective Studies; D013997:Time Factors; D006113:United Kingdom / Q000453:epidemiology
Cystic Fibrosis; Lung Physiology; Paediatric Lung Disaese