Keith RL, et al. - Given a great potential of lung cancer chemoprevention in reducing lung cancer incidence and mortality, especially in high-risk former smokers and preclinical studies indicating thiazolidinediones as preventive against the development of lung cancer, and lower lung cancer rates among cases with diabetes who were receiving thiazolidinediones, researchers performed a double-blind, randomized, phase 2 placebo-controlled trial of oral pioglitazone in high-risk current or former smokers with sputum cytologic atypia or known endobronchial dysplasia. Biopsies were histologically scored, and primary endpoint analysis tested worst biopsy scores between groups. The trial accrued 92 individuals (47 pioglitazone, 45 placebo); of these 76 completed both bronchoscopies (39 pioglitazone, 37 placebo). While there appeared no statistically significant changes in Dysplasia index (DI) and average score (Avg) in the treatment group, a slight decrease in both Avg and DI was observed in former smokers. Current smokers showed negligible Avg and DI changes. Former smokers with baseline dysplasia receiving pioglitazone showed a trend toward decreased Ki-67 labeling index. Although this high-risk cohort showed no improved endobronchial histology in correlation with receipt of pioglitazone, a histologic improvement was observed in specific lesions, and further study is required to better define responsive dysplasia.