Free erythrocyte protoporphyrin fluorescence as an underrecognized prognostic marker of mortality in community-acquired pneumonia

Abstract

Abstract Community‑acquired pneumonia (CAP) still carries a high long‑term mortality. Free protoporphyrin in erythrocytes (FPP) is a well-recognized biomarker of erythropoietic porphyrias. However, it also reflects impaired heme synthesis, disturbances in iron metabolism, and inflammation-driven erythropoietic alterations, mechanisms particularly relevant in pneumonia. This pilot study aimed to evaluate, for the first time, the prognostic value of FPP and zinc protoporphyrin (ZnPP), measured in acetone extracts of erythrocytes using fluorescence analysis with 405 nm excitation, in predicting 100-day mortality among 66 patients hospitalized with CAP. The area under the ROC curve for FPP fluorescence in predicting mortality was 0.793 (95% CI 0.657–0.928; p < 0.0001), with 63% sensitivity and 94% specificity. Elevated FPP fluorescence was associated with a tenfold higher mortality risk and over fifteenfold greater odds of death, even after adjustment for age and the Charlson Comorbidity Index (CCI). A single fluorescence measurement at 632 nm (F632) demonstrated identical prognostic accuracy to spectral deconvolution-derived FPP intensity. Furthermore, significant correlations were observed between F632 or FPP fluorescence intensities and multiple clinical parameters reflecting disease severity, systemic inflammation, and erythropoietic stress. Given its accessibility and prognostic potential, prospective studies should further validate the method presented to guide individualized clinical management in CAP.