Bronchiectasis and pulmonary exacerbations in children and young adults with cystic fibrosis.

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 FEV(1) at 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 FEV(1) both 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 FEV(1). 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.

Cystic fibrosis: are volumetric ultra-low-dose expiratory CT scans sufficient for monitoring related lung disease?

PURPOSE: To assess whether chest computed tomography (CT) scores from ultra-low-dose end-expiratory scans alone could suffice for assessment of all cystic fibrosis (CF)-related structural lung abnormalities. MATERIALS AND METHODS: In this institutional review board-approved study, 20 patients with CF aged 6-20 years (eight males, 12 females) underwent low-dose end-inspiratory CT and ultra-low-dose end-expiratory CT. Informed consent was obtained. Scans were randomized and scored by using the Brody-II CT scoring system to assess bronchiectasis, airway wall thickening, mucus plugging, and opacities. Scoring was performed by two observers who were blinded to patient identity and clinical information. Mean scores were used for all analyses. Statistical analysis included assessment of intra- and interobserver variability, calculation of intraclass correlation coefficients (ICCs), and Bland-Altman plots. RESULTS: Median age was 12.6 years (range, 6.3-20.3 years), median forced expiratory volume in 1 second was 100% (range, 46%-127%) of the predicted value, and median forced vital capacity was 99% (range, 61%-123%) of the predicted value. Very good agreement was observed between end-inspiratory and end-expiratory CT scores for Brody-II total score (ICC = 0.96), bronchiectasis (ICC = 0.98), airway wall thickening (ICC = 0.94), mucus plugging (ICC = 0.96), and opacities (ICC = 0.90). Intra- and interobserver agreement were good to very good (ICC range, 0.70-0.98). Bland-Altman plots showed that differences in scores were independent of score magnitude. CONCLUSION: In this pilot study, CT scores from end-expiratory and end-inspiratory CT match closely, suggesting that ultra-low-dose end-expiratory CT alone may be sufficient for monitoring CF-related lung disease. This would help reduce radiation dose for a single investigation by up to 75%.