Bronchoalveolar Lavage Cell Percentages As Diagnostic Markers of Immune Checkpoint Inhibitor Pneumonitis

Authors

Mahnoor Mir
Felipe Soto
Pedro Antonio Amezcua Gomez
Rodrigo Del Rio Arroyo
Adarsh Suresh
Amber Su
Qiong Gan
John Stewart
Roberto Adachi
Diwakar D Balachandran
Lara Bashoura
Roberto F Casal
Burton F Dickey
George A Eapen
Scott E Evans
Horiana Grosu
Carlos A Jimenez
Julie Lin
David E Ost
Bruce F Sabath
Vickie R Shannon
Aung Naing
Jianjun Gao
Jia Wu
Karthik Suresh
Saadia A Faiz
Mehmet Altan
Ajay Sheshadri

Publication Date

1-1-2025

Journal

Frontiers in Medicine

DOI

10.3389/fmed.2025.1582714

PMID

40529125

PMCID

PMC12171021

PubMedCentral® Posted Date

6-2-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Introduction: Diagnostic biomarkers for immune checkpoint inhibitor pneumonitis (ICIP) are lacking. Bronchoalveolar lavage (BAL) lymphocytosis has been associated with ICIP, but studies have not evaluated BAL lymphocytosis as a diagnostic biomarker for ICIP.

Purpose: This study aimed to measure the association of BAL immune cell percentage with ICIP and test its performance as a diagnostic biomarker.

Methods: We performed a retrospective chart review of 476 patients treated with ICIs for solid organ or hematologic malignancies who underwent BAL between 2016 and 2022. Two independent reviewers, blinded to the results of BAL cell percentage, confirmed the diagnosis of ICIP or other conditions (e.g., pneumonia) based on clinical history and radiology. We constructed logistic regression models to assess the relationship between BAL lymphocyte, eosinophil, and neutrophil percentages and the diagnosis of pneumonitis, and the area under the receiver-operator curves (AUROC) was used to assess their discriminatory function. We measured the association of BAL immune cell percentages with 1-year overall survival using Cox proportional hazard models adjusted for age and cancer diagnosis.

Results: Each 1% increase in lymphocyte (OR 1.01, 95% CI 1.01-1.02, p < 0.001) and eosinophil percentage (OR 1.05, 95% CI 1.01-1.11, p = 0.01) were independently associated with pneumonitis, while neutrophil percentage was inversely associated (OR 0.99, 95% CI 0.98-0.99, p = 0.01) with pneumonitis. In multivariable analysis, lymphocyte percentage (OR 1.02, 95% CI 1.009-1.04, p = 0.002) and eosinophil percentage (OR 1.10, 95% CI 1.01-1.23, p = 0.05) were both associated with ICIP. The AUROC for BAL lymphocytes to diagnose ICIP was 0.62 (95% CI 0.57-0.67, optimal cutoff 15.5%, sensitivity 69%, and specificity 52%) and the AUROC for eosinophils was 0.61 (95% CI 0.56-0.66, optimal cutoff 1%, sensitivity 58%, and specificity 62%). In patients with pneumonitis, lymphocyte percentage (HR 0.99, 95% CI 0.97-1.00, p = 0.02), neutrophil percentage (HR 1.01, 95% CI 1.00-1.02, p = 0.05), and eosinophil percentage (HR 0.93, 95% CI 0.86-0.99, p = 0.03) were associated with 1-year survival.

Conclusion: BAL lymphocytosis and eosinophilia are associated with ICIP, but their ability to discriminate ICIP from other conditions is modest. BAL immune cell percentages may have prognostic value for 1-year survival, but this likely reflects the morbidity of other pulmonary diseases that require BAL for evaluation.

Keywords

immune check inhibitor (ICI), BAL (bronchoalveolar lavage), lymphocytosis, pneumonitis, eosinophilia, cell percentage

Comments

This article has been corrected. See Front Med (Lausanne). 2025 Jun 26;12:1646108.

Published Open-Access

yes

Recommended Citation

Mir, Mahnoor; Soto, Felipe; Gomez, Pedro Antonio Amezcua; et al., "Bronchoalveolar Lavage Cell Percentages As Diagnostic Markers of Immune Checkpoint Inhibitor Pneumonitis" (2025). Faculty, Staff and Student Publications. 4341.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/4341