Journal Article

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

Ranganathan, Sarath C, Murray, Conor, Stick, Stephen M, Gangell, Catherine, Brennan, Siobhain, Robinson, Philip J, Mott, Lauren, Sly, Peter D, Robertson, Colin F, on behalf of Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST-CF), de Klerk, Nicholas

2009

Overview

Abstract 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 × 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.

• Publisher: Am Thoracic Soc,Oxford University Press,American Thoracic Society
• Subject: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy / Antibiotics / Australia / Biological and medical sciences / Bronchoalveolar Lavage / Cohort Studies / Cystic fibrosis / Cystic Fibrosis - complications / Cystic Fibrosis - diagnosis / Cystic Fibrosis - physiopathology / Disease prevention / Emergency and intensive care: neonates and children. Prematurity. Sudden death / Female / Humans / Infant / Infant, Newborn / Infections / Inflammation / Intensive care medicine / Lavage / Lung diseases / Male / Medical sciences / Medical screening / Neonatal Screening / Neutrophils / Newborn babies / Pediatrics / Pneumonia - diagnosis / Pneumonia - epidemiology / Pneumonia - microbiology / Population Surveillance / Pulmonary arteries / Regression analysis / Respiration Disorders - diagnosis / Respiration Disorders - epidemiology / Respiration Disorders - microbiology / Respiratory Function Tests / Respiratory Tract Infections - complications / Respiratory Tract Infections - diagnosis / Respiratory Tract Infections - epidemiology / Tomography / Tomography, X-Ray Computed