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Lung Disease at Diagnosis in Infants with Cystic Fibrosis Detected by Newborn Screening

¹ Division of Clinical Sciences, Telethon Institute for Child Health Research and Centre for Child Health Research, University of Western Australia, Perth; ² Department of Respiratory Medicine, and ³ Department of Diagnostic Imaging, Princess Margaret Hospital for Children, Perth; ⁴ Department of Respiratory Medicine, Royal Children's Hospital, Melbourne; ⁵ Infection, Immunity and Environment Theme, Murdoch Children's Research Institute, Melbourne; and ⁶ Department of Paediatrics, University of Melbourne, Australia

Correspondence and requests for reprints should be addressed to Peter D. Sly, M.D., Telethon Institute for Child Health Research, PO Box 855, W. Perth, WA 6872, Australia. E-mail: peters{at}ichr.uwa.edu.au

Rationale: 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.

Objectives: 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.

Measurements and Main 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 10³ 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.

Key Words: pulmonary infection • chest computed tomography scans • bronchoalveolar lavage • neutrophil elastase • pulmonary inflammation

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject There have been no previous population-based surveys of lung disease at diagnosis after newborn screening in infants with cystic fibrosis. What This Study Adds to the Field This study shows that infection, inflammation, and abnormal chest computed tomography findings are already present in a significant proportion of infants with cystic fibrosis at 3 months of age.