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Computed Tomography Correlates with Pulmonary Exacerbations in Children with Cystic Fibrosis

Cincinnati Children's Hospital and Medical Center, Cincinnati, Ohio; Statistical Analysis Unit, Cystic Fibrosis Foundation Therapeutics Development Network Coordinating Center, Seattle, Washington; University of North Carolina School of Medicine, Chapel Hill, North Carolina; University of Vermont, Fletcher Allen Health Care, Burlington, Vermont; and Medical Affairs, Genentech, Inc., South San Francisco, California

Correspondence and requests for reprints should be addressed to Alan S. Brody, M.D., Professor of Radiology and Pediatrics, Department of Radiology, MLC-5031, Cincinnati Children's Hospital, 3333 Burnet Avenue, Cincinnati, OH 45229-3039. E-mail: alan.brody{at}cchmc.org

Rationale: High-resolution computed tomography (HRCT) has been suggested as a potential outcome surrogate for cystic fibrosis (CF) lung disease. An important attribute of a valid outcome surrogate is that the surrogate reflects true clinical outcomes. Objectives: We performed this study to validate HRCT, a proposed surrogate outcome measure for CF lung disease, against a true clinical outcome, the number of respiratory tract exacerbations occurring in 2 yr, and to assess the correlation of CT scores and pulmonary function tests (PFTs) with this clinical outcome. Methods: CTs and PFTs were performed on 6- to 10-yr-old children at the beginning and end of a 2-yr study during which the number of exacerbations were recorded. Spearman correlations and Poisson models were used to assess the correlation of the number of exacerbations with baseline values and changes in PFTs and CT scores. Measurements and Main Results: Nine of 61 subjects had a total of 22 respiratory tract exacerbations. At baseline, PFTs and four CT scores showed significant correlation with number of exacerbations, but no variable by itself predicted exacerbations with high accuracy. For change over the 2-yr period, three CT scores showed significant correlation with exacerbations, whereas no PFTs showed significant correlation. Conclusion: This is the first study showing correlation between CT and a true clinical outcome. Change in CT scores correlates moderately well with the number of exacerbation. Poor correlation between change in FEV₁ and exacerbations suggests that HRCT may be a more appropriate outcome surrogate for longitudinal studies of young children.

Key Words: children • computerized tomography X-ray • forced expiratory volume • pulmonary function tests • surrogate endpoint

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