Pediatric Pulmonology 31:377–382 (2001) Diagnostic Therapeutic Methods Use of Computerized Tomography and Chest X-Rays in Evaluating Efficacy of Aerosolized Recombinant Human DNase in Cystic Fibrosis Patients Younger Than Age 5 Years: A Preliminary Study Samya Z. Nasr, MD,* Lawrence R. Kuhns, MD, Randall W. Brown, MD, Martin E. Hurwitz, MD, Georgiana M. Sanders, MD, and Peter J. Strouse, MD Summary. The aim of this study was to evaluate the ability of high-resolution computerized tomography (HRCT) of the chest and chest x-rays (CXR) to determine efficacy of inhaled recombinant human DNase (rhDNase) in cystic fibrosis (CF) patients younger than 5 years of age. A randomized, double-blind, placebo-controlled pilot study of 12 patients with CF younger than 5 years of age, attending the University of Michigan Cystic Fibrosis Center (Ann Arbor, MI) was conducted. The changes in the HRCT and CXR score from baseline to day 100 of therapy were assessed using a previously validated scoring system. The mean changes of HRCT scores between the rhDNase and placebo groups were found to be significant at the 95% level, with mean change  SE mean of 1.00  0.53 and 0.58  0.24 for rhDNase and placebo groups, respectively (P  0:02). The difference in CXR score was not significant between the two groups. An analysis was performed to relate HRCT subscores to CXR score; only thickening of the intra-interlobular septae was significantly correlated with the total CXR score (r 0.7, P < 0:01). There was improvement in the parents’ assessments of the patients’ well-being, with improvement in physical activity, decreased cough, sleep quality, and appetite in those subjects receiving rhDNase. We conclude that the administration of rhDNase was associated with improvement in the HRCT scan in CF patients younger than 5 years of age. Findings indicate that HRCT of the chest is useful and sensitive in studying responses to therapy in patients with CF lung disease. To our knowledge, this is the first report of the use of HRCT to assess the effectiveness of a therapeutic modality in so young a CF patient population. Pediatr Pulmonol. 2001; 31:377–382. ß 2001 Wiley-Liss, Inc. Key words: preschool children; cystic fibrosis; high-resolution computed chest tomo- graphy; recombinant human DNase; pulmonary disease. INTRODUCTION Respiratory disease in patients with cystic fibrosis is caused by the accumulation of purulent, infected sputum in the airways and leads to obstruction of the small airways, and a state of chronic low-grade infection. 1 Sputum in CF is rich in leukocyte-derived DNA that greatly contributes to abnormal viscoelasticity of the CF sputum. 2 CF patients younger than 5 years of age have significant amounts of DNA in their airway. 3 Recombi- nant human DNase 1 (rhDNase), a copy of the native human enzyme responsible for hydrolyzing extracellular DNA, dramatically alters the viscoelastic properties of CF sputum in vitro. 4 Aerosol administration of rhDNase Sections of Pediatric Pulmonary and Radiology, Department of Pediatrics, University of Michigan Medical Center, Ann Arbor, Michigan. Grant sponsor: NIH; Grant number: MO1-RR000042; Grant sponsor: Genentech, Inc.; Grant sponsor: Dale Maxwell Memorial Funds. Presented in part at the International Conference for the American Thoracic Society, April 23–28, 1999, and at the North American Annual Cystic Fibrosis Conference, October 7–10, 1999. *Correspondence to: Samya Z. Nasr, M.D., Department of Pediatrics, University of Michigan Medical Center, 1500 E. Medical Center Drive, Ann Arbor, MI 48109-0212. E-mail: snasr@umich.edu Received 29 March 2000; Accepted 12 January 2001. ß 2001 Wiley-Liss, Inc.