Utility of Bronchoalveolar Lavage Fluid Cellular Composition in the Differential Diagnosis of Idiopathic Pulmonary Fibrosis: a preliminary study

Qian Wu^1†, Shangwu Liu^2†, Qi Zhang1, Yanfen Ma1, Xiaoxuan He¹, Thomas Stuart Mughogho³, Ying
Li⁴, Dokani Michael Ndovi⁵, Xiaoqin Wang^1*

1.Department of Clinical Laboratory, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, Shaanxi Province, China.

2. Department of Clinical Laboratory, Shaanxi Provincial Tuberculosis Prevention and Control Hospital, Xi’an,710100, Shaanxi Province, China.
3. Department of Biological Sciences, Faculty of Science, Technology and Innovations, Mzuzu University, Malawi.
4. Department of Clinical Laboratory, Shaanxi Kang Fu Hospital, Xi’an,710065, Shaanxi Province, China.
5. Laboratory Department, Mzuzu Central Hospital, Luwinga, Mzuzu, Malawi.
   † Both authors are co-first authors and have contributed equally to this work
   *Corresponding Author: Xiaoqin Wang; E-mail: 78197594@qq.com

Abstract

Background

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease with poor prognosis. Its early diagnosis is challenging due to nonspecific clinical features and overlap with infectious pulmonary diseases. Bronchoalveolar lavage fluid (BALF) provides direct access to lower respiratory tract cellular components, offering potential adjunctive diagnostic value. This study aimed to evaluate the cytological characteristics of BALF in IPF and assess their utility in differentiating IPF from non-fibrotic pneumonia.

Methods

We retrospectively analyzed 64 IPF patients and 64 age-, sex-, and intensive care unit (ICU) admission–matched patients with community-acquired pneumonia (CAP) who underwent BAL at the First Affiliated Hospital of Xi’an Jiaotong University (January 2021–November 2025). BALF total cell counts and differential cell proportions were measured. Multivariable logistic regression identified independent discriminators, and receiver operating characteristic (ROC) curve analysis evaluated the diagnostic performance of individual and combined BALF parameters.

Results

IPF patients showed significantly higher proportions of macrophages (median 29.55% vs. 11.70%, P<0.001), lymphocytes (7.20% vs. 3.60%, P=0.031), and eosinophils (1.00% vs. 0.40%, P=0.008), and a significantly lower neutrophil proportion (58.50% vs. 80.90%, P<0.001) compared with pneumonia patients. Multivariable analysis confirmed eosinophil percentage (OR=1.871, 95%CI:1.123 2.836) and macrophage percentage (OR=1.139, 95%CI:1.082–1.199) as independent discriminators of IPF. The combined logistic regression model incorporating these two parameters yielded an area under the curve (AUC) of 0.832 (95%CI:0.761–0.903), with a sensitivity of 93.8% and a specificity of 65.6%, outperforming either parameter alone.

Conclusions

BALF cellular profiles differ significantly between IPF and non-fibrotic pneumonia. Macrophage and eosinophil percentages are independent discriminators of IPF, and their combination provides good discriminative performance. Although BALF cytology alone is insufficient for a definitive diagnosis, it serves as a valuable adjunctive tool, particularly when high-resolution computed tomography findings are atypical or when infection is suspected. These findings support the potential utility of BALF cellular analysis in the diagnostic workup of IPF and warrant further prospective validation, including integration with molecular biomarkers.

Keywords: Bronchoalveolar lavage fluid, Idiopathic pulmonary fibrosis, Differential diagnosis, ROC curve