Objective: Respiratory tract exacerbation rate (RTE-R) is a key clinical efficacy end point in cystic fibrosis (CF) trials. Chest CT scanning holds great potential as a surrogate end point. Evidence supporting the ability of CT scan scores to predict RTE-R is an important step in validating CT scanning as a surrogate end point. The objective of this study was to investigate the association between CT scan scores and RTE-R in a cohort of pediatric patients with CF. Methods: A retrospective review of data from pediatric patients with CF included chest CT scans, spirometry, and 2 years follow-up. RTE-R was defined as the number of IV antibiotics courses per year. CT scans were scored with the Brody-II system, assessing bronchiectasis, airway wall thickening, mucus, and opacities. Results: One hundred fifteen patients contributed 170 CT scans. Median age and FEV1at first CT scan were 12 years (range, 5-20 years) and 90% predicted (range, 23% predicted-132% predicted), respectively. Analyzing exacerbation counts using Poisson regression models, bronchiectasis score and FEV1both were found to be strong independent predictors of RTE-R in the subsequent 2 years. For the bronchiectasis score categorized in quartiles, RTE-R increased by factors of 1.8 (95% CI, 0.6-6.1; P =.31), 5.5 (95% CI, 1.9-15.4; P =.001), and 10.6 (95% CI, 3.8-29.4; P <.001), respectively, for each quartile compared with the quartile with the best (ie, lowest) scores. Similarly, time to first respiratory tract exacerbation was significantly associated with quartiles of both bronchiectasis score and FEV1. Conclusions: The CT scan bronchiectasis score is strongly associated with RTE-R in pediatric patients with CF, providing an important piece of evidence in the validation of CT scans as an end point for CF clinical trials.

dx.doi.org/10.1378/chest.10-1152, hdl.handle.net/1765/33389
Chest: the cardiopulmonary and critical care journal
Erasmus MC: University Medical Center Rotterdam

Loeve, M, Gerbrands, K, Hop, W.C.J, Rosenfeld, M, Hartmann, I.C, & Tiddens, H.A.W.M. (2011). Bronchiectasis and pulmonary exacerbations in children and young adults with cystic fibrosis. Chest: the cardiopulmonary and critical care journal, 140(1), 178–185. doi:10.1378/chest.10-1152