Focal Usual Interstitial Pneumonia-like Fibrosis is a Core Prognostic Factor in Progressive Pulmonary Fibrosis

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. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement 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. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: IRB of Nagasaki University gave ethical approval for this work (IRB No. 14012746, February 3, 2014). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors