C104-01 Utility of Radiographic Fibrosis as Theragnostic Marker for Immunomodulatory Therapy in Hypersensitivity Pneumonitis

Abstract Background Hypersensitivity pneumonitis (HP) is an interstitial lung disease (ILD) caused by exposure to inhaled allergens, triggering an immune-mediated “inflammatory response” with subsequent lung injury and often resulting in lung fibrosis. It is widely accepted that the first-line therapy in HP is antigen avoidance, however, there are still meaningful decisions regarding treatment choice when patients experience progression. Treatment selection in chronic hypersensitivity pneumonitis (HP) remains empiric due to a lack of randomized trial data and clinicians lack any validated markers that meaningfully identify those HP patients most likely to positively respond to immunomodulation versus those who are most likely to benefit from an antifibrotic approach. This study aims to address that gap by evaluating the association between forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO) response to immunomodulation and the visual extent of fibrosis on pre-treatment computed tomography (CT) scans in patients with HP. Methods The retrospective cohort study included 108 patients with HP from two ILD referral centers who received ≥3 months of immunomodulatory therapy (prednisone, azathioprine, mycophenolate mofetil and rituximab) and had pre- and post-treatment pulmonary function tests (PFTs) and pretreatment CT for review. Fibrosis extent was classified as ≥ 10% or 10% based on blinded thoracic radiologist interpretations. Linear spline mixed-effects models were used to estimate FVC and DLCO % predicted trajectory before and after immunomodulation, with patients serving as their own controls. The primary analysis evaluated whether fibrosis extent modified the association between immunomodulation and lung function trajectory. Results Overall, immunomodulation was associated with a modest FVC improvement at 12-months (+2.63%, 95% CI: 0.72 to 4.54; p 0.01) across the entire cohort. Among patients with 10% fibrosis, immunomodulation was associated with improvements in both FVC (+5.83%, p 0.01) and DLCO (+13.9%, p 0.01). In contrast, no improvement in FVC (+0.81%, p = 0.42) or DLCO (-4.3%, p = 0.17) was observed in patients with ≥10% fibrosis at 12-months (Figure). Baseline demographics, smoking history, and antigen identification status were similar between fibrosis groups. Conclusion Visual fibrosis extent is associated with differential pulmonary function response to immunomodulatory therapy in chronic HP. Patients with limited fibrosis experienced improved pulmonary function compared to those with greater radiographic fibrosis. These findings may support the use of fibrosis extent as a clinical tool for treatment stratification and highlight the need for prospective trials to validate radiographic markers in guiding HP management. This abstract is funded by: None