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

Abstract

Abstract 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.