Bronchoalveolar lavage cell percentages as diagnostic markers of immune checkpoint inhibitor pneumonitis
IntroductionDiagnostic 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.PurposeThis study aimed to measure the assoc...
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2025-06-01
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| author | 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 |
| author_facet | 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 |
| author_sort | Mahnoor Mir |
| collection | DOAJ |
| description | IntroductionDiagnostic 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.PurposeThis study aimed to measure the association of BAL immune cell percentage with ICIP and test its performance as a diagnostic biomarker.MethodsWe 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.ResultsEach 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.ConclusionBAL 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. |
| format | Article |
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| institution | Kabale University |
| issn | 2296-858X |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Medicine |
| spelling | doaj-art-e8de039f0d7a4d248cb1cc76e28fe03d2025-08-20T03:29:39ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2025-06-011210.3389/fmed.2025.15827141582714Bronchoalveolar lavage cell percentages as diagnostic markers of immune checkpoint inhibitor pneumonitisMahnoor Mir0Felipe Soto1Pedro Antonio Amezcua Gomez2Rodrigo Del Rio Arroyo3Adarsh Suresh4Amber Su5Qiong Gan6John Stewart7Roberto Adachi8Diwakar D. Balachandran9Lara Bashoura10Roberto F. Casal11Burton F. Dickey12George A. Eapen13Scott E. Evans14Horiana Grosu15Carlos A. Jimenez16Julie Lin17David E. Ost18Bruce F. Sabath19Vickie R. Shannon20Aung Naing21Jianjun Gao22Jia Wu23Karthik Suresh24Saadia A. Faiz25Mehmet Altan26Ajay Sheshadri27Division of Critical Care, Pulmonary, and Sleep Medicine, McGovern Medical School at UTHealth Houston, Houston, TX, United StatesSchool of Medicine, Tecnológico de Monterrey, Monterrey, MexicoSchool of Medicine, Tecnológico de Monterrey, Monterrey, MexicoSchool of Medicine, Tecnológico de Monterrey, Monterrey, MexicoTexas A&M School of Medicine, Houston, TX, United StatesDepartment of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDivision of Cancer Medicine, Department of Genitourinary Medical Oncology, Houston, TX, United StatesDepartment of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, United StatesDepartment of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States0Department of Thoracic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United StatesIntroductionDiagnostic 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.PurposeThis study aimed to measure the association of BAL immune cell percentage with ICIP and test its performance as a diagnostic biomarker.MethodsWe 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.ResultsEach 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.ConclusionBAL 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.https://www.frontiersin.org/articles/10.3389/fmed.2025.1582714/fullimmune check inhibitor (ICI)BAL (bronchoalveolar lavage)lymphocytosispneumonitiseosinophiliacell percentage |
| spellingShingle | 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 Bronchoalveolar lavage cell percentages as diagnostic markers of immune checkpoint inhibitor pneumonitis Frontiers in Medicine immune check inhibitor (ICI) BAL (bronchoalveolar lavage) lymphocytosis pneumonitis eosinophilia cell percentage |
| title | Bronchoalveolar lavage cell percentages as diagnostic markers of immune checkpoint inhibitor pneumonitis |
| title_full | Bronchoalveolar lavage cell percentages as diagnostic markers of immune checkpoint inhibitor pneumonitis |
| title_fullStr | Bronchoalveolar lavage cell percentages as diagnostic markers of immune checkpoint inhibitor pneumonitis |
| title_full_unstemmed | Bronchoalveolar lavage cell percentages as diagnostic markers of immune checkpoint inhibitor pneumonitis |
| title_short | Bronchoalveolar lavage cell percentages as diagnostic markers of immune checkpoint inhibitor pneumonitis |
| title_sort | bronchoalveolar lavage cell percentages as diagnostic markers of immune checkpoint inhibitor pneumonitis |
| topic | immune check inhibitor (ICI) BAL (bronchoalveolar lavage) lymphocytosis pneumonitis eosinophilia cell percentage |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2025.1582714/full |
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