Progressive pulmonary fibrosis (PPF) is a newly recognized clinical phenotype of interstitial lung diseases in the 2022 interstitial pulmonary fibrosis (IPF) guidelines. This category is based entirely on clinical and radiological factors, and the background histopathology is unknown. Our objective was to investigate the histopathological characteristics of PPF and to examine the correlation between usual interstitial pneumonia (UIP) and prognosis in this new disease type. We hypothesized that the presence of UIP-like fibrosis predicts patients' survival in PPF cases. We selected 201 cases fulfilling the clinical criteria of PPF from case archives. Cases diagnosed as IPF by a multidisciplinary team were excluded. Whole slide images were evaluated by three pathologists who were blind to clinical and radiological data. We measured areas of UIP-like fibrosis and calculated what percentage of the total lesion area they occupied. The presence of focal UIP-like fibrosis amounting to 10% or more of the lesion area was seen in 148 (73.6%), 168 (83.6%), and 165 (82.1%) cases for each pathologist respectively. The agreement of the recognition of UIP-like fibrosis in PPF cases was above κ = 0.6 between all pairs. Survival analysis showed that the presence of focal UIP-like fibrosis correlated with worsened survival under all parameters tested (p < 0.001). The presence of UIP-like fibrosis is a core pathological feature of clinical PPF and its presence within diseased areas is associated with poorer prognosis. This study highlights the importance of considering the presence of focal UIP-like fibrosis in the evaluation and management of PPF.

The authors have declared no competing interest.

This study was funded by the Study Group on Diffuse Lung Disease, Scientific Research/Research on Intractable Diseases in the Ministry of Health, Labour and Welfare, Japan.

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IRB of Nagasaki University gave ethical approval for this work (IRB No. 14012746, February 3, 2014).

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