Methods
Study Cohort
- The cohort was drawn from the Idiopathic Pulmonary Fibrosis Prospective Outcomes (IPF-PRO) Registry, a multicenter US registry that enrolled patients with IPF that was diagnosed or confirmed at the enrolling center in the past 6 months.3
- These analyses were based on data from 300 patients enrolled between March 2016 and February 2017.
- Outcomes were ascertained from enrollment to June 2019.
Proteomic assays
- Plasma samples taken at enrollment were assayed using an aptamer-based platform encompassing 1305 proteins.
- Protein data were log2 transformed prior to analysis.
Analyses
- The univariable association between each protein and the composite outcome of respiratory death or lung transplant was determined using Cox proportional hazards modelling.
- Linearity and proportional hazards assumptions associated with the unadjusted model were assessed prior to fitting each model.
- Analyses were adjusted for sex, age, FVC % predicted, DLco % predicted, oxygen use at rest, oxygen use with activity (all assessed at enrollment).
- P-values were corrected for multiple comparisons using the Benjamini-Hochberg method to control the false discovery rate (FDR) at 5%.
- Multivariable analyses were performed to determine a set of candidate predictors for the composite outcome of respiratory death or lung transplant, using Cox regression modelling with the elastic net penalty considering:
- proteins only
- proteins and clinical factors (sex, age, FVC % predicted, DLco % predicted, oxygen use at rest, oxygen use with activity [all assessed at enrollment]).
- Model performance was assessed by Harrell’s C-index, corrected for optimism.