TY - JOUR
T1 - Bronchoalveolar lavage cell percentages as diagnostic markers of immune checkpoint inhibitor pneumonitis
AU - Mir, Mahnoor
AU - Soto, Felipe
AU - Gomez, Pedro Antonio Amezcua
AU - Arroyo, Rodrigo Del Rio
AU - Suresh, Adarsh
AU - Su, Amber
AU - Gan, Qiong
AU - Stewart, John
AU - Adachi, Roberto
AU - Balachandran, Diwakar D.
AU - Bashoura, Lara
AU - Casal, Roberto F.
AU - Dickey, Burton F.
AU - Eapen, George A.
AU - Evans, Scott E.
AU - Grosu, Horiana
AU - Jimenez, Carlos A.
AU - Lin, Julie
AU - Ost, David E.
AU - Sabath, Bruce F.
AU - Shannon, Vickie R.
AU - Naing, Aung
AU - Gao, Jianjun
AU - Wu, Jia
AU - Suresh, Karthik
AU - Faiz, Saadia A.
AU - Altan, Mehmet
AU - Sheshadri, Ajay
N1 - Publisher Copyright:
Copyright © 2025 Mir, Soto, Gomez, Arroyo, Suresh, Su, Gan, Stewart, Adachi, Balachandran, Bashoura, Casal, Dickey, Eapen, Evans, Grosu, Jimenez, Lin, Ost, Sabath, Shannon, Naing, Gao, Wu, Suresh, Faiz, Altan and Sheshadri.
PY - 2025
Y1 - 2025
N2 - 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.
AB - 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.
KW - BAL (bronchoalveolar lavage)
KW - cell percentage
KW - eosinophilia
KW - immune check inhibitor (ICI)
KW - lymphocytosis
KW - pneumonitis
UR - https://www.scopus.com/pages/publications/105008229808
UR - https://www.scopus.com/pages/publications/105008229808#tab=citedBy
U2 - 10.3389/fmed.2025.1582714
DO - 10.3389/fmed.2025.1582714
M3 - Article
C2 - 40529125
AN - SCOPUS:105008229808
SN - 2296-858X
VL - 12
JO - Frontiers in Medicine
JF - Frontiers in Medicine
M1 - 1582714
ER -