Published ahead of print on April 16, 2009, doi:10.1164/rccm.200901-0069OC Am. J. Respir. Crit. Care Med., Volume 180, Number 2, July 2009, 146-152 A more recent version of this article appeared on July 15, 2009
Submitted on January 14, 2009 Lung Disease at Diagnosis in Infants with Cystic Fibrosis Detected by Newborn ScreeningPeter D. Sly1*,1 Division of Clinical Sciences, Telethon Institute for Child Health Research and Centre for Child Health Research , University of Western Australia, Perth, Western Australia, Australia; Department of Respiratory Medicine, Princess Margaret Hospital for Children, Perth, Western Australia, Australia, 2 Division of Clinical Sciences, Telethon Institute for Child Health Research and Centre for Child Health Research, University of Western Australia, Perth, Western Australia, Australia, 3 Department of Diagnostic Imaging, Princess Margaret Hospital for Children, Perth, Western Australia, Australia, 4 Department of Respiratory Medicine, Royal Children’s Hospital, Melbourne, Victoria, Australia; Infection, Immunity and Environment Theme, Murdoch Children’s Research Institute, Melbourne, Victoria, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia * To whom correspondence should be addressed. E-mail: peters{at}ichr.uwa.edu.au.
Rationale: The promise of newborn screening (NBS) for cystic fibrosis (CF) has not been fully realised, with improvement in respiratory outcomes unclear. We hypothesised 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 following detection by NBS. Methods: Fifty seven infants (median age 3.6 months) with CF underwent bronchoalveolar lavage (BAL) and chest computed tomography (CT) using a 3-slice inspiratory and expiratory protocol. Main Results: Despite the absence of respiratory symptoms in 48 (84.2%), a substantial proportion of infants had lung disease with: bacterial infection detected in 12 (21.1%), including S. aureus (n=4) and P. aeruginosa (N=3); neutrophilic inflammation (41.4 x103 cells/ml representing 18.7 % of total cell count); pro-inflammatory cytokines with 44 (77.2%) having detectable IL-8 ; and 17 (29.8%) having detectable free neutrophil elastase (NE) activity. Inflammation was increased in those with infection and respiratory symptoms however the majority of those infected were asymptomatic. Radiological 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 NE 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 realised. Key words: pulmonary infection • chest computed tomography scans • bronchoalveolar lavage • neutrophil elastase • pulmonary inflammation
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