Background: In order to establish a valid surrogate outcome measure, it must be shown that the outcome measure (chest HRCT scores in cystic fibrosis [CF] patients) demonstrates strong statistical association with established endpoints of disease, such as Pseudomonas aeruginosa (Pa) airway acquisition, acute exacerbations, or mortality.
Methods: We estimated and tested the association between Pa infection status (Pa+ vs. Pa-) and baseline chest HRCT scores in 25 children with mild-to-moderate CF lung disease. For comparison, we estimated the association between Pa status and pulmonary function tests (PFTs), chest X-rays (CXR) scores, and BMI. Pa acquisition was determined from respiratory culture results and systematic review of clinic notes.
Results: All subjects had respiratory cultures performed prior to or at baseline with a median of 19 months of retrospective culture observation (SD = 15.7 months, range: 0-52.5 months). The difference between age-adjusted mean total HRCT score for Pa+ versus Pa- was highly significant (P < 0.00001) with a near-perfect separation between scores in Pa+ versus Pa- patients. Similar results were found for several HRCT sub-scores. Among PFTs, only residual volume-to-total lung capacity (RV/TLC) had a significant difference between group means (P = 0.03), but the overlap between groups in RV/TLC measurements was large.
Conclusions: CF HRCT scores correlate highly with Pa acquisition, a clinically meaningful measure of progressing CF lung disease. HRCT scores are highly sensitive at predicting Pa acquisition status, while most PFT measures, chest radiograph (CXR) scores, and body mass index are not. These results provide further evidence that HRCT is appropriate for use in patient care and as an outcome measure in clinical trials.