Abstract Rationale Epithelial injury and abnormal repair are key factors in the development of idiopathic pulmonary fibrosis (IPF), making epithelial-derived proteins like CA-125 (MUC16) and surfactant protein D (SP-D) potential biomarkers of disease activity. Respiratory hospitalizations in patients with IPF reflect acute disease worsening and are associated with mortality. We investigated whether short-term changes in CA-125 and SP-D informed risk of respiratory-related hospitalization, including among patients taking antifibrotic therapy. Methods The cohort came from the IPF-PRO Registry and included participants with biosamples at enrollment and at 6 months (+/- 3 months) post-enrollment (n = 504). CA-125 and SP-D plasma concentrations were measured by immunoassay (Myriad RBM). Associations between absolute change in each protein over 6 months and subsequent respiratory hospitalization were assessed using Cox models, landmarked at the 6-month sample. Models were unadjusted and adjusted for age, sex, FVC % predicted, DLco % predicted, and protein level at enrollment. A prior event indicator was included for patients who experienced a respiratory hospitalization between enrollment and the follow-up blood sample (n = 18). Interaction terms for antifibrotic treatment pattern between the samples (continued antifibrotic therapy, initiated antifibrotic therapy, remained untreated) were included. Results The cohort was 71.4% male with a mean (SD) age of 69.5 (7.7) years. At enrollment, mean FVC % predicted and DLCO % predicted were 74.0 (16.5) and 44.2 (14.3), respectively. About half of patients (47.8%) were taking antifibrotic therapy at both time-points, 31.3% initiated antifibrotic therapy between enrolment and follow-up, and 19.3% were untreated at both time-points. Eight patients (1.6%) discontinued antifibrotic therapy and were excluded. An absolute increase in SP-D over 6 months was independently associated with a higher risk of respiratory hospitalization (Figure). In the adjusted model, a 6 ug/L increase in SP-D level was associated with a 16% increase in the risk of respiratory hospitalization (HR 1.16 95% CI 1.08, 1.25; p 0.001). Absolute change in CA-125 over 6 months was not associated with the risk of respiratory hospitalization in unadjusted or adjusted models. There was no significant interaction between change in SP-D or CA-125 and antifibrotic treatment pattern. Conclusions In patients with IPF, a short-term increase in plasma SP-D — but not CA-125 — was independently associated with higher risk of subsequent respiratory-related hospitalization, regardless of antifibrotic treatment status. These findings support SP-D as a dynamic biomarker of disease activity in patients with IPF and suggest its potential utility in identifying patients at elevated risk of acute clinical deterioration. This abstract is funded by: The IPF-PRO/ILD-PRO Registry is supported by Boehringer Ingelheim Pharmaceuticals, Inc and run in collaboration with the Duke Clinical Research Institute and enrolling centres.
Todd et al. (Fri,) studied this question.