AUTHOR=Zhou Chengzhi , Yang Yilin , Lin Xinqing , Fang Nianxin , Chen Likun , Jiang Juhong , Deng Haiyi , Deng Yu , Wan Minghui , Qiu Guihuan , Sun Ni , Wu Di , Long Xiang , Zhong Changhao , Xie Xiaohong , Xie Zhanhong , Liu Ming , Ouyang Ming , Qin Yinyin , Petrella Francesco , Fiorelli Alfonso , Bravaccini Sara , Kataoka Yuki , Watanabe Satoshi , Goto Taichiro , Solli Piergiorgio , Igai Hitoshi , Saito Yuichi , Tsoukalas Nikolaos , Nakada Takeo , Li Shiyue , Chen Rongchang TITLE=Proposed clinical phases for the improvement of personalized treatment of checkpoint inhibitor–related pneumonitis JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.935779 DOI=10.3389/fimmu.2022.935779 ISSN=1664-3224 ABSTRACT=Background

Checkpoint inhibitor–related pneumonitis (CIP) is a lethal immune-related adverse event. However, the development process of CIP, which may provide insight into more effective management, has not been extensively examined.

Methods

We conducted a multicenter retrospective analysis of 56 patients who developed CIP. Clinical characteristics, radiological features, histologic features, and laboratory tests were analyzed. After a comprehensive analysis, we proposed acute, subacute, and chronic phases of CIP and summarized each phase’s characteristics.

Results

There were 51 patients in the acute phase, 22 in the subacute phase, and 11 in the chronic phase. The median interval time from the beginning of CIP to the different phases was calculated (acute phase: ≤4.9 weeks; subacute phase: 4.9~13.1 weeks; and chronic phase: ≥13.1 weeks). The symptoms relieved from the acute phase to the chronic phase, and the CIP grade and Performance Status score decreased (P<0.05). The main change in radiologic features was the absorption of the lesions, and 3 (3/11) patients in the chronic phase had persistent traction bronchiectasis. For histologic features, most patients had acute fibrinous pneumonitis in the acute phase (5/8), and most had organizing pneumonia in the subacute phase (5/6). Other histologic changes advanced over time, with the lesions entering a state of fibrosis. Moreover, the levels of interleukin-6, interleukin-10 and high-sensitivity C-reactive protein (hsCRP) increased in the acute phase and decreased as CIP progressed (IL-6: 17.9 vs. 9.8 vs. 5.7, P=0.018; IL-10: 4.6 vs 3.0 vs. 2.0, P=0.041; hsCRP: 88.2 vs. 19.4 vs. 14.4, P=0.005).

Conclusions

The general development process of CIP can be divided into acute, subacute, and chronic phases, upon which a better management strategy might be based devised.