Bronchoalveolar lavage lymphocyte patterns in hypersensitivity pneumonitis and nonspecific interstitial pneumonia: a systematic review.

BACKGROUND

Bronchoalveolar lavage (BAL) is an important adjunctive tool in the multidisciplinary evaluation of interstitial lung diseases (ILDs), particularly hypersensitivity pneumonitis (HP) and nonspecific interstitial pneumonia (NSIP). However, considerable overlap in BAL cellular profiles and inconsistent lymphocyte thresholds limit its independent diagnostic value. This systematic review summarizes current evidence regarding the diagnostic and prognostic utility of BAL cellular analysis in differentiating HP from NSIP.

METHODS

A systematic literature search of PubMed/MEDLINE, Embase, CENTRAL identified studies evaluating BAL cellular, immunophenotypic, and biomarker findings in HP and NSIP. Study selection followed PRISMA recommendations. Owing to methodological heterogeneity, the evidence was synthesized narratively.

RESULTS

Twenty-one studies met the inclusion criteria. BAL lymphocytosis consistently supported the diagnosis of HP, particularly at thresholds above 30%, although higher cut-offs improved specificity at the expense of sensitivity. Considerable overlap between HP and NSIP was observed, especially in fibrotic disease, limiting the diagnostic performance of isolated lymphocyte percentages. Emerging BAL biomarkers, including CD4/CD8 ratio, NK/NKT-cell subsets, IL-9 signaling, KL-6, and flow cytometric immunophenotyping, showed potential to improve differential diagnosis. In addition, higher BAL lymphocyte counts were associated with favorable treatment response and improved prognosis in selected HP and NSIP populations.

CONCLUSION

BAL cellular analysis remains a valuable complementary diagnostic tool rather than a standalone test for distinguishing HP from NSIP. Accurate interpretation requires integration with exposure history, high-resolution computed tomography, histopathology when available, and multidisciplinary discussion. Standardized BAL protocols and prospective validation of advanced immunophenotypic biomarkers are needed to improve diagnostic precision and clinical decision-making in fibrotic ILDs.

SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420261397405, identifier PROSPERO (CRD420261397405).