BackgroundConnective tissue diseases-associated interstitial lung disease (CTD-ILD) is a heterogeneous condition that impairs quality of life and is associated with premature death. Progressive pulmonary fibrosis (PPF) has been identified as an important risk factor for poor prognosis. However, different criteria for PPF are used in clinical studies, which may complicate comparison between trials and translation of study findings into clinical practice.MethodsThis is a retrospective single center study in patients with CTD-ILD. The prognostic relevance of PPF definitions, including INBUILD, ATS/ERS/JRS/ALAT 2022, and simplified progressive fibrosing (simplified PF) criteria, were examined in this cohort and validated in the other reported Dutch CTD-ILD cohort.ResultsA total of 230 patients with CTD-ILD were included and the median follow-up period was six (3—9) years. Mortality risk was independently associated with age (adjusted HR 1.07, p < 0.001), smoking history (adjusted HR 1.90, p = 0.045), extent of fibrosis on high-resolution computed tomography (HRCT) at baseline (adjusted HR 1.05, p = 0.018) and baseline DLCO (adjusted HR 0.97, p = 0.013). Patients with regular pulmonary function tests in the first 2 years (adjusted HR 0.42, p = 0.002) had a better survival. The prognostic relevance for survival was similar between the three PPF criteria in the two cohorts.ConclusionHigher age, smoking, increased extent of fibrosis and low baseline DLCO were associated with poor prognosis, while regular pulmonary function evaluation was associated with better survival. The INBUILD, ATS/ERS/JRS/ALAT 2022, and simplified PF criteria revealed similar prognostication.

BackgroundProgressive pulmonary fibrosis (PPF) is characterized by deterioration of respiratory symptoms, lung function decline and progressive fibrosis on high-resolution computed tomography (HRCT). It is associated with poor prognosis. Patients with connective tissue disease-related interstitial lung disease (CTD-ILD) may also develop PPF and need intensified clinical management. However, different criteria for PPF are used in trials (i.e. INBUILD and RELIEF) and the ATS/ERS/JRS/ALAT 2022 guideline.[1-3]This variety in criteria complicates study comparison and clinical implication.ObjectivesTo explore the prognostic relevance for mortality of different PPF criteria in patients with CTD-ILD.MethodsThis is a single center retrospective cohort study in patients with CTD-ILD or interstitial pneumonia with autoimmune features between 2005 and 2021. The prognostic relevance was compared between the INBUILD criteria[1], the ATS/ERS/JRS/ALAT 2022 criteria[3], and the simplified progressive fibrosing (simplified PF) criteria used in a previous cohort (≥10% relative decline in FVC, ≥15% relative decline in DLCO, or progression of fibrosis on HRCT within two years)[4]in the time-dependent receiver operator characteristic model.ResultsThe cohort consisted of 230 patients. The median age was 63 years (IQR 54—69), and 122 (53%) were female. The most prevalent CTD was rheumatoid arthritis (n=77, 33%), followed by 38 (17%) patients with idiopathic inflammatory myopathies and 33 (14%) with primary Sjögren’s syndrome. Various HRCT patterns were observed at baseline: UIP in 63 (27%) patients, fibrotic NSIP in 21 (9%), cellular NSIP in 25 (11%), mixed NSIP in 79 (34%), OP in 34 (15%), two (1%) mixed NSIP/OP, and other patterns in six. The median follow-up period was 6 (3—9) years.Mortality risk was independently associated with age (adjusted HR 1.07, p < 0.001), smoking history (adjusted HR 1.90, p = 0.045), extent of fibrosis on HRCT at baseline (adjusted HR 1.05, p = 0.018) and baseline DLCO % of predicted (adjusted HR 0.97, p = 0.013).PPF was observed in 61 (27%) patients meeting INBUILD criteria, 53 (23%) meeting ATS/ERS/JRS/ALAT 2022 criteria, 136 (59%) meeting simplified PF criteria and 125 (54%) when using simplified PF criteria with a threshold for HRCT ≥ 5% increase in the extent of fibrosis. The prognostic relevance for mortality did not differ between simplified PF criteria, INBUILD and ATS/ERS/JRS/ALAT 2022 criteria; the prognostic relevance improved when the simplified PF criteria defined HRCT progression with a ≥5% increase in fibrosis. (Figure 1)ConclusionHigher age, smoking, increased extent of fibrosis and low baseline DLCO were associated with poor prognosis. The prognostic value was similar between the different PPF criteria and increased during the first three years and achieved a plateau thereafter.References[1]KR Flaherty, AU Wells, V Cottin, et al.N Engl J Med.2019;381(18):1718-27.[2]J Behr, A Prasse, M Kreuter, et al.Lancet Respir Med.2021;9(5):476-86.[3]G Raghu, M Remy-Jardin, L Richeldi, et al.Am J Respir Crit Care Med.2022;205(9):e18-e47.[4]YH Chiu, J Spierings, PA de Jong, et al.Respir Med.2021;187:106579.Figure 1.Acknowledgements:NIL.Disclosure of InterestsYu-Hsiang Chiu: None declared, Maaike Koops: None declared, Mareye Voortman: None declared, H. Wouter van Es: None declared, Lucianne Langezaal: None declared, Paco Welsing: None declared, Anna Jamnitski: None declared, Anne Wind: None declared, Jacob M. van Laar Grant/research support from: Grant from Boehringer, Astra Zeneca, MSD, Roche, J.C. Grutters: None declared, Julia Spierings Grant/research support from: A grant from Boehringer.