Lung disease at diagnosis in infants with cystic fibrosis detected by newborn screening.
BACKGROUND
The promise of newborn screening (NBS) for cystic fibrosis (CF) has not been fully realized, and the extent of improvement in respiratory outcomes is unclear. We hypothesized that significant lung disease was present at diagnosis.


OBJECTIVE
To determine the extent of lung disease in a geographically defined population of infants with CF diagnosed after detection by NBS.


METHODS
Fifty-seven infants (median age, 3.6 mo) with CF underwent bronchoalveolar lavage and chest computed tomography (CT) using a three-slice inspiratory and expiratory protocol.


RESULTS
Despite the absence of respiratory symptoms in 48 (84.2%) of infants, a substantial proportion had lung disease with bacterial infection detected in 12 (21.1%), including Staphylococcus aureus (n = 4) and Pseudomonas aeruginosa (n = 3); neutrophilic inflammation (41. 4 x 10(3) cells/ml representing 18.7% of total cell count); proinflammatory cytokines, with 44 (77.2%) having detectable IL-8; and 17 (29.8%) having detectable free neutrophil elastase activity. Inflammation was increased in those with infection and respiratory symptoms; however, the majority of those infected were asymptomatic. Radiologic evidence of structural lung disease was common, with 46 (80.7%) having an abnormal CT; 11 (18.6%) had bronchial dilatation, 27 (45.0%) had bronchial wall thickening, and 40 (66.7%) had gas trapping. On multivariate analysis, free neutrophil elastase activity was associated with structural lung disease. Most children with structural lung disease had no clinically apparent lung disease.


CONCLUSIONS
These data support the need for full evaluation in infancy and argue for new treatment strategies, especially those targeting neutrophilic inflammation, if the promise of NBS for CF is to be realized.
Division of Clinical Sciences, Telethon Institute for Child Health Research, PO Box 855, W. Perth, WA 6872, Australia. peters@ichr.uwa.edu.au
Peter D
PD
Sly
Siobhain
S
Brennan
Catherine
C
Gangell
Nicholas
N
de Klerk
Conor
C
Murray
Lauren
L
Mott
Stephen M
SM
Stick
Philip J
PJ
Robinson
Colin F
CF
Robertson
Sarath C
SC
Ranganathan
D001315:Australia; D018893:Bronchoalveolar Lavage; D015331:Cohort Studies; D003550:Cystic Fibrosis / Q000150:complications / Q000175:diagnosis* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D015997:Neonatal Screening; D011014:Pneumonia / Q000175:diagnosis / Q000453:epidemiology* / Q000382:microbiology; D011159:Population Surveillance; D012120:Respiration Disorders / Q000175:diagnosis / Q000453:epidemiology / Q000382:microbiology; D012129:Respiratory Function Tests; D012141:Respiratory Tract Infections / Q000150:complications / Q000175:diagnosis / Q000453:epidemiology*; D014057:Tomography, X-Ray Computed