Fig. 4

(a) Representative histologic cross section of cartilage necrosis, bronchial wall fibrosis, and preserved bronchial epithelium. (b-d) Histopathological analysis at 30 days (n = 6 animals, 11 airways), 365 days (n = 5 animals, 10 airways), and 640 (n = 8 animals, 16 airways) of the bronchial anatomy for necrosis (black bars), acute inflammation (open bars), chronic inflammation (diagonal stripe bars) and fibrosis (horizontal stripe bars). Data are presented as mean ± SEM. *p < 0.05 vs 30 day time point, **p < 0.001 vs 30 day timepoint, † p < 0.05 365 day vs 640 day time point, ‡ p < 0.001 365 day and 640 day time point. (b) Semi-quantitative analysis of bronchial wall. The adventitia surrounding the bronchi is the target of TLD therapy because of the presence of bronchial nerves. The semi-quantitative analysis of the bronchial wall at the treatment site, which include the adventitia, demonstrates consistently moderate levels fibrosis over the 640 day time course. Acute inflammation decreased (p < 0.001) at 365 day vs. 30 day and remained low for the time course. Chronic inflammation decreased (p < 0.001) at 640 days vs. 30 day timepoint. (c) Semi-quantitative analysis of bronchial epithelium. The bronchial epithelium at the treatment site demonstrates only minimal treatment related tissue changes that largely resolve over the 640 day time course. Acute inflammation decreases significantly (p < 0.001) at the 640 days versus the 30 day timepoint. Chronic inflammation decreases significantly (p < 0.001) at both 365 and 640 days versus the 30 day timepoint. (d) Semi-quantitative analysis of bronchial cartilage. The cartilage in sheep are located directly below the TLD electrode and are subject to energy levels that are not intended to occur in the human lung. In this way, the sheep serves as a sensitive model that amplifies TLD related tissue effects in the cartilage. Necrosis and fibrosis were elevated (p < 0.001) at the 365 day time point and remained stable out to 640 days