Serum cholinesterase as a prognostic marker in respiratory critical illness: a narrative review

Prognostication in respiratory critical care rests largely on composite severity scores derived from mixed medical, surgical or sepsis populations. Serum butyrylcholinesterase (pseudocholinesterase) is a liver-synthesized plasma enzyme, a negative acute-phase reactant and an established index of hepatic synthesis and nutrition, and has re-emerged as a candidate prognostic biomarker in critical illness. A direct cytokine-driven mechanism is inferred, not demonstrated, and whether the circulating enzyme modulates the cholinergic anti-inflammatory axis is unproven. This narrative review synthesizes the evidence across community-acquired pneumonia, acute exacerbation of chronic obstructive pulmonary disease and acute respiratory failure including coronavirus disease 2019 (COVID-19). A reproducible inverse association between enzyme activity and mortality or disease severity emerges, but it rests on small, mostly retrospective single-center studies with heterogeneous assays and data-derived thresholds. The review therefore asks one decisive question, almost never addressed in respiratory cohorts: whether the enzyme adds information beyond albumin and established severity scores, judged by incremental discrimination and reclassification. On that test it is a consistent signal in search of methodological rigour rather than an established independent marker. Prospective, setting-specific and adequately adjusted validation is required before clinical adoption, capturing the activity nadir and the slope of any recovery, whose prognostic role is untested. Mislabelling could influence decisions on escalation and limitation of treatment.