Systemic Inflammatory Response Index (SIRI) in Hypersensitivity Pneumonitis: Association with Clinical Course and Mortality

Objective: Hypersensitivity pneumonitis (HP) is an interstitial lung disease that can range in its course from reversible inflammation to progressive fibrosis. Identifying
reliable biomarkers to predict disease phenotype and prognosis remains a major clinical challenge. This study aimed to evaluate the prognostic significance of the
Systemic Inflammatory Response Index (SIRI) in patients with HP and to investigate its association with clinical parameters, pulmonary function, and mortality.
Materials and Methods: A retrospective analysis was conducted on 73 patients diagnosed with HP between 2014 and 2022. Patients were classified into fibrotic and
non-fibrotic groups based on clinical, radiological, and histopathological criteria. Hematological indices including neutrophil-to-lymphocyte ratio (NLR), monocyteto-
lymphocyte ratio (MLR) and SIRI were calculated. Kaplan–Meier and Cox regression analyses assessed survival outcomes and independent predictors of mortality.
Results: SIRI levels were significantly higher in patients with fibrotic HP and those who died during follow-up. SIRI correlated positively with inflammatory markers,
and negatively with pulmonary function (Forced Vital Capacity), carbon monoxide diffusion capacity (DLCO%)) and 6-minute walk distance. ROC analysis demonstrated
high diagnostic accuracy for SIRI in differentiating fibrotic HP (AUC = 0.858) and predicting mortality (AUC = 0.932), with an optimal mortality cut-off of 1.92. Kaplan–
Meier survival curves illustrated significantly shorter survival in patients with SIRI >1.92 compared to those with SIRI ≤1.92, with a Log-Rank test confirming this
difference (mean survival time 74.6 ± 3.2 months vs. 127.7 ± 2.9 months; p < 0.001). In multivariable Cox analysis, fibrotic phenotype, reduced DLCO%, and SIRI >1.92
were independent predictors of mortality.
Conclusion: SIRI, as a quantitative indicator of systemic inflammation, may be regarded as a meaningful biomarker for predicting disease severity and mortality risk in
patients with hypersensitivity pneumonitis. While more evidence is needed before integration into routine clinical use, it holds potential as a supportive tool for risk
stratification, early detection of fibrotic progression, and long-term management strategy planning.