Fig. 14

Graphical abstract for this study. A brief summary of the process by which alveolitis was caused by inhalation of CWAAPs is given below. (1) Inhalation of CWAAPs can damage (2) the surfactant layer by retaining water on the alveolar surface causing (3) alveolar collapse with inflammatory cell infiltration, mainly neutrophils, in the acute phase. Alveolar collapse can persist for up to 3 days after a single 4 h exposure to CWAAP-A. Alveolar collapse may recover after cessation of exposure, but persistent exposure can lead to (4) persistent inflammation and alveolar epithelial hypertrophy/proliferation. Immediately after repeated exposure to CWAAP-A, inflammation and alveolar epithelial hypertrophy/proliferation were observed throughout the lungs of the CWAAP-A exposed rats. These findings were accompanied by the appearance alveolar epithelial progenitor (AEP) cells, suggesting a regenerative change after lung injury. After an 18-week recovery period, inflammatory changes in the alveoli (4) partially led to a repaired alveolus (successful repair of alveolus) (6), as evidenced by a decrease in LDH in the BALF, but some developed into (5) alveolitis with fibrous thickening. This change is a "pre-fibrosis lesion" and is considered irreversible (regarded as misrepair of alveoli)