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Bronchoalveolar lavage fluid analysis in patients with checkpoint inhibitor pneumonitis
Ruxuan Chen1, Yujie Shi1, Nan Fang2
1Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, #1 Shuaifuyuan Street, Dongcheng District, Beijing, 100730, China.
Insights
Checkpoint inhibitor pneumonitis (CIP) shows a CD3+CD8+ lymphocytosis pattern in bronchoalveolar lavage fluid. Targeting these lymphocytes may offer a new treatment strategy for CIP.
Area of Science:
- Oncology
- Immunology
- Pulmonology
Background:
- Checkpoint inhibitor pneumonitis (CIP) is a severe immune-related adverse event (irAE) associated with cancer immunotherapy.
- Lung biopsies are rarely performed for CIP, necessitating alternative diagnostic methods like bronchoalveolar lavage fluid (BALF) analysis.
- Previous studies reported inconsistent BALF findings in CIP patients.
Purpose of the Study:
- To investigate the BALF cellular and lymphocyte subset profiles in patients with CIP.
- To identify potential diagnostic biomarkers and therapeutic targets for CIP.
Main Methods:
- Retrospective analysis of 154 patients with malignancies and CIP between July 2018 and December 2022.
- Included patients with available bronchoalveolar lavage (BAL) data.
- Analyzed clinical, laboratory, radiological, and follow-up data, including BALF differential cell counts and lymphocyte subsets.
Main Results:
- Forty-two CIP patients underwent BALF analysis; 81% exhibited a lymphocytic cellular pattern.
- A CD3+CD4+/CD3+CD8+ lymphocyte ratio < 1.0 was observed in 73.8% of patients.
- No significant differences in BALF features were found between low-grade and high-grade CIP.
Conclusions:
- The predominant inflammatory profile in CIP patients' BALF is CD3+CD8+ lymphocytosis.
- Targeting CD3+CD8+ lymphocytes presents a potential therapeutic avenue for managing CIP.
Background:
Checkpoint inhibitor pneumonitis (CIP) is a relatively uncommon but potentially life-threatening immune-related adverse event (irAE). Lung biopsies have not been commonly performed for CIP patients. Bronchoalveolar lavage fluid (BALF) analysis is a useful diagnostic approach for interstitial lung disease. However, BALF features were inconsistent across different studies.
Methods:
We retrospectively reviewed the medical records of 154 patients with pathologically confirmed malignancies and suffering from CIPs between July 2018 and December 2022. Patients who had bronchoalveolar lavage (BAL) data available were enrolled in our study. Patient clinical, laboratory, radiological and follow-up data were reviewed and analyzed.
Results:
The BALF differential cell count and lymphocyte subset analysis were performed for 42 CIP patients. There were 32 males (76.2%). The mean age at diagnosis of CIP was 62.0 ± 10.4 (range: 31-78) years. The median time to onset of CIP was 98.5 days after the start of immunotherapy. There were 18 patients (42.9%) with low-grade CIPs and 24 patients (57.1%) with high-grade CIPs. The mean lymphocyte percentage was 36.7 ± 22.5%. There were 34 (81%) CIP patients with a lymphocytic cellular pattern. The median ratio of CD3+CD4+/CD3+CD8+ lymphocytes was 0.5 (0.3, 1.0). The ratio was less than 1.0 for 31 CIP patients (73.8%). However, there was no significant difference in the BALF features between patients with low-grade CIPs and those with high-grade CIPs.
Conclusions:
The CD3+CD8+ lymphocytosis pattern was the main inflammatory profile in the BALF of CIP patients in this cohort. Targeting CD3+CD8+ lymphocytes might be a treatment option for CIPs.
