Grant: Travel Awards - Institute Community Support

RATIONALE Previous reports from our laboratory have shown small airways disease is associated an innate and adaptive inflammatory immune response and that it is associated with the massive destruction of terminal bronchioles before emphysema can be recognized on routine thoracic CT scans. The present report identifies a 'hot spot" for terminal bronchiolar destruction in COPD and describes the gene expression profiles associated with it. METHODS Gene expression profiling, MicroCT, and quantitative histology were performed on 40 samples from each of COPD, and control lungs respectively. The immune network was manually collected from distinct public databases on the basis of GO annotation. Cibersort & MMC are run on the expression profile to further validate our discoveries. RESULTS The data presented here identify a hot spot region for the destruction of terminal bronchioles that are located in regions of the lung where the mean linear intercept (Lm) used to estimate the severity of emphysematous destruction, ranges from within its normal range of 250- 500 µm. To the lower limit of the spatial resolution of modern clinical CT scanners which is approximately 1000 µm. Importantly these data also provide molecular evidence of the activation of adaptive immunity within this "Hot spot" that includes IFNG activation, T cell recruitment, as well as the expression pattern of immune checkpoint genes within the hot spot region. The long-term goal of this project is to discover the key molecular mechanisms involved in the destruction of terminal bronchioles and alveolar tissue in the hot spot region, which represents the earliest stages of COPD. CONCLUSIONS The present results extend our previously histological data-based discovery that the adaptive immune response has been already activated in COPD. Further, we identified the fact that the destruction of terminal bronchioles is well advanced but emphysematous destruction cannot be identified on the MDCT scans.