A framework for translational research in interstitial lung disease (ILD) using bronchoalveolar lavage (BAL)

Bronchoalveolar lavage (BAL) offers a minimally invasive window into the distal airspaces and is an important tool in the study of interstitial lung disease (ILD). As chest imaging has obviated the need for diagnostic surgical biopsies, research tissue is increasingly limited, strengthening the rationale for BAL. By sampling the epithelial lining fluid, BAL captures cellular and acellular host- and microbe-derived signals relevant to inflammation and fibrogenesis, enabling multi-omic mechanistic and biomarker studies. However, variation in technique, dilution, and pre-analytical handling limits reproducibility and cross-center comparability.

Here, we summarize key biological insights gained from BAL fluid-based studies, divided into cellular, acellular and microbiome compartments. We highlight current guidance, methodological challenges, and outline standardized frameworks to maximize translational scientific yield and multi-center validation.

Standardized protocols will maximize the value of BAL samples. Paired multi-compartment analysis can expand actionable readouts: multimodal cellular pipelines combining single-cell RNA and protein profiling, aligned with clinical annotation, may define ILD endotypes and prognostic/predictive biomarkers. Acellular BALF bioassays coupled to transcriptional and proteomic signatures can support mechanistic validation and pharmacological targeting, while microbiome profiling integrated with host multi-omics may improve risk stratification. Ultimately, these data could inform clinical decision-making and regulatory endpoints.