Sub-chronic inhalation of reclaimed water-induced fibrotic lesion in a mouse model

When reclaimed water is used as municipal miscellaneous water, acute exposure of the generated aerosol with high levels of endotoxins can cause severe inflammation in the lungs. However, the potential risks of long-term inhalation of reclaimed water remains unclear. To identify the adverse effects of sub-chronic reclaimed water inhalation and explain the underlying mechanisms, a mouse model of 12-week sub-chronic exposure was established, and wastewater before a membrane bioreactor (MBR, positive control) and the MBR effluent (reclaimed water, which met the quality standard of urban use and was currently used for landscape irrigation) were tested in this study. The exposure dose was set to approach the real working scenarios. Lung lavage and histology were analyzed. Obvious epithelial cell apoptosis in the bronchi was observed, along with the accumulation of myofibroblasts and the collagen deposition both in main bronchi and terminal bronchioles. All these symptoms were persistent after 4 weeks of recovery. Inflammation and induced bronchus-associated lymphoid tissues (iBALT) were also observed but diminished after recovery indicating inflammation may not be the direct cause of the symptom. Furthermore, two fibrogenic cytokines (TNF-α and TGF-β) were constantly high in the lung during the study. They might be the biomarkers of lung damage after the inhalation of reclaimed water. Adaptive immune responses were also detected as elevated levels of IgG and IgA, but not for IgE. Inhalation of reclaimed water causes sustained fibrotic lesions in the lungs, which suggests potential health risks during urban application where aerosols generated.