A Potential Biomarker for Predicting the Risk of Radiation-Induced Fibrosis in the Lung

Area of Science:

• Biomedical research
• Radiation biology
• Pulmonary medicine

Background:

• Biomarkers are crucial for triage after radiological events, especially with heterogeneous radiation exposure and trauma.
• Assessing downstream pulmonary complications is vital due to lung sensitivity to radiation and potential for morbidity.
• Club cell secretory protein (CCSP) and surfactant protein D (SP-D) are key lung epithelial proteins affected by radiation.

Purpose of the Study:

• To evaluate pulmonary epithelial damage using CCSP and SP-D as biomarkers in radiation-induced lung injury models.
• To determine the utility of the plasma CCSP/SP-D ratio as a specific biomarker for radiation-induced pulmonary fibrosis.

Main Methods:

• Mice (C57BL/6J and C3H/HeJ) were subjected to combined total-body and whole-lung irradiation.
• Lung and plasma samples were collected at various time points post-irradiation (24 h to 26 weeks).
• Changes in CCSP and SP-D levels and the CCSP/SP-D ratio were analyzed in relation to radiation dose and injury severity.

Main Results:

• Radiation exposure reduced bronchiole CCSP coverage and increased plasma CCSP/SP-D ratios in C57 mice, correlating with fibrosis.
• The plasma CCSP/SP-D ratio changes were specific to radiation exposure, unlike responses to LPS or influenza.
• Plasma CCSP/SP-D ratios reflected individual radiation sensitivity and fibrosis development, even at subthreshold doses.

Conclusions:

• The plasma CCSP/SP-D ratio is a sensitive, specific, and early indicator of radiation-induced lung injury.
• This ratio correlates with individual radiation sensitivity and the development of pulmonary fibrosis.
• The CCSP/SP-D ratio holds potential as a valuable biomarker for assessing radiation-induced lung damage and guiding treatment strategies.