Quantitative analysis of pathological findings identified clinical heterogeneity in nonspecific interstitial pneumonia with organising pneumonia overlap.

The pathological classification of nonspecific interstitial pneumonia (NSIP) with organizing pneumonia (OP) overlap (NSIP/OP overlap) remains complex due to overlapping pathological features, and its heterogeneity is not well understood. We retrospectively analysed adult patients with interstitial lung disease (ILD) diagnosed with NSIP/OP overlap via surgical lung biopsy. Patients were pathologically subclustered using an unbiased clustering method, and clinical, radiological, and prognostic differences were examined. Among 38 patients, two pathological clusters were identified: Cluster 1, characterized by fibrotic changes with mild inflammation, and Cluster 2, exhibiting intense inflammation with fibrosis. While both clusters initially responded well to treatment, Cluster 2 demonstrated progressive ILD deterioration and a higher frequency of pulmonary fibrosis. Cluster 2 was also associated with hypoxia, reduced pulmonary function, elevated erythrocyte sedimentation rate, and greater consolidation on chest computed tomography. Based on these findings, we have identified NSIP/OP overlap is a heterogeneous and progressive disease and pathological findings at diagnosis significantly influence both initial ILD severity and long-term prognosis. Our findings highlight the need for tailored long-term management strategies based on early histopathological evaluation.