BAL lymphocytosis as a predictive marker for drug response and long-term outcome in fibrotic ILD: systematic review.

BACKGROUND

Fibrotic interstitial lung diseases (fILDs) encompass a heterogeneous group of disorders characterised by varying degrees of inflammation and/or fibrosis. The role of bronchoalveolar lavage lymphocytosis (BALL) as a prognostic biomarker and predictor of corticosteroid (CS) response remains uncertain. We investigated whether, in patients with fILD, increased BALL can serve as a marker for CS responsiveness and whether increased BALL may also predict better long-term outcomes following CS therapy compared with patients with lower BALL levels.

METHODS

A systematic review was conducted. MEDLINE, Embase, Web of Science and Google Scholar were searched up to 4 August 2025. Eligible studies included mainly observational clinical studies evaluating BALL in fILD, with a focus on short-term CS response (<6 months) as well as long-term survival (>6 months) after treatment, including changes in lung function parameters, radiological response and overall and progression-free survival. Study selection, data extraction and quality assessment were performed independently by two reviewers. Disagreements were resolved by consensus.

RESULTS

30 studies involving a total of 3083 patients were included. Increased BALL was associated with better CS response as reflected by improved lung function and increased survival in fILD subtypes, such as hypersensitivity pneumonitis and non-specific interstitial pneumonia. However, BALL thresholds varied, and study heterogeneity precluded meta-analysis. Most studies showed moderate to high risk of bias.

CONCLUSIONS

Increased BALL may predict CS responsiveness and treatment outcome prediction in fILD; however, clinical implementation remains limited due to insufficient evidence, predominantly observational studies, inconsistent BALL thresholds and heterogeneous results across disease entities. Standardisation and prospective validations are needed to better integrate BALL findings into clinical routine.

PROSPERO REGISTRATION NUMBER: CRD420251057631.