Prognostic biomarkers of clinical outcomes
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DLCO %pred slope of decline was significantly associated with all five of the LPA species (LPA16:0, 16:1, 18:1, 18:2, 20:4), where patients with higher levels of LPA at baseline had greater declines in DLCO %pred (Decline in DLCO percentage predicted and baseline biomarker levels. A multivariate linear regression model adjusted for the following covariates: age, sex, baseline FVC %pred, baseline DLCO %pred, and the geographical region was used to assess the association between (A) LPA and TAG and (B) protein biomarkers, with DLCO %pred decline calculated as slope, where the y-axis indicated the DLCO %pred change per year. ∗∗Combination of prognostic biomarkers and clincial outcomesCI, confidence interval; SE, standard error; uM, microMolar.Values are from multivariate regression models predicting clinical outcomes of interest, using a combination of biomarkers as predictors while adjusting for the following covariates: age, sex, baseline FVC %pred, baseline DLCO %pred, and geographical region.∗FVC %pred decline was not associated with any of the lipid species (Decline in FVC percentage predicted and baseline biomarker levels. A multivariate linear regression model adjusted for the following covariates: age, sex, baseline FVC %pred, baseline DLCO %pred, and geographical region, was used to assess the association between (A) LPA and TAG and (B) protein biomarkers, with FVC %pred decline calculated as slope, where the y-axis indicated FVC %pred change per year. ∗Patients with higher levels (≥ median) of LPA20:4 had an earlier time to exacerbation or respiratory hospitalization compared with the biomarker low subgroups (hazard ratio (95% CI)): LPA20:4-high = 5.71 (1.17–27.72) (Time to first exacerbation or respiratory hospitalization and baseline (A) lipid or (B) protein biomarker profile. Baseline biomarker profile was fitted to a Cox proportional hazards regression model adjusted for the following covariates: age, sex, baseline FVC %pred, baseline DLCO %pred, and geographical region. Multivariate linear regression The TAG species were prognostic of mortality as patients with lower levels (< median) of the TAG species had increased risk of mortality (odd ratio (95% CI)): TAG48:4-FA12:0-low = 8.6 (1.0–71.5) (Risk of mortality and baseline biomarker profile. The baseline biomarker profile was fitted to a multivariate logistic regression model adjusted for the following covariates: age, sex, baseline FVC %pred, baseline DLCO %pred, and geographical region. An odds ratio above 1 denotes higher odds of mortality in patients with higher levels (≥median) of biomarker compared to patients with lower levels (<median) of biomarker; specifically for TAG species, an odds ratio above 1 denotes higher odds of mortality in patients with the lower levels (<median) of TAG compared to patients with higher levels of (≥median) TAG. Line arrows denote censored confidence intervals.